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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.

Highlights • Combination of PRRT and EBRT is feasible and safe in meningioma. • Combined therapy resulted in disease stabilization in 7 of 10 patients. • Future prospective validation of this new approach in larger cohorts is warranted., Background The combination of somatostatin receptor-directed peptide receptor radionuclide therapy (PRRT) in combination with external beam radiotherapy (EBRT) might prove a feasible treatment option in patients with advanced meningioma. Patients and methods From May 2010 to May 2011, 10 patients with unresectable meningioma (6 × WHO grade I, 2 × WHO grade II, 2 × WHO grading not available) were treated with one cycle of PRRT followed by EBRT. Long-term toxicity and efficacy were assessed according to Common Terminology Criteria for Adverse Events version 5.0 and magnetic resonance imaging-based Response Assessment in Neuro-Oncology Working Group criteria, respectively. Results During long-term follow-up of a median of 105.0 months (range, 38.2–111.4 m), combined PRRT and EBRT was well-tolerated with no severe acute or chronic toxicity. Kidney or bone marrow function was not affected in any patient. Combination of PRRT and EBRT resulted in disease stabilization in 7 of the 10 patients with a median progression-free survival of 107.7 months (range, 47.2–111.4 m) vs. 26.2 months (range, 13.8–75.9 m) for the patients with meningioma progression. Conclusions The combination of PRRT and EBRT is a feasible and safe therapeutic option in meningioma patients. In this pilot cohort, the multimodality treatment demonstrated good disease stabilization.

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.

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.

Optimal doses for the treatment of adrenal metastases with stereotactic radiotherapy (SBRT) are unknown. We aimed to identify dose-volume cut-points associated with decreased local recurrence rates (LRR). A multicenter database of patients with adrenal metastases of any histology treated with SBRT (biologically effective dose, BED10 ≥50 Gy, ≤12 fractions) was analyzed. Details on dose-volume parameters were required (planning target volume: PTV-D98%, PTV-D50%, PTV-D2%; gross tumor volume: GTV-D50%, GTV-mean). Cut-points for LRR were optimized using the R maxstat package. One hundred and ninety-six patients with 218 lesions were included, the largest histopathological subgroup was adenocarcinoma (n=101). Cut-point optimization resulted in significant cut-points for PTV-D50% (BED10: 73.2 Gy; P= .003), GTV-D50% (BED10: 74.2 Gy; P= .006), GTV-mean (BED10: 73.0 Gy; P= .007), and PTV-D2% (BED10: 78.0 Gy; P= .02) but not for the PTV-D98% (P= .06). Differences in LRR were clinically relevant (LRR ≥ doubled for cut-points that were not achieved). Further dose-escalation was not associated with further improved LRR. PTV-D50%, GTV-D50%, and GTV-mean cut-points were also associated with significantly improved LRR in the adenocarcinoma subgroup. Separate dose optimizations indicated a lower cut-point for the PTV-D50% (BED10: 69.1 Gy) in adenocarcinoma lesions, other values were similar (73.2 Gy (adenocarcinoma: 69.1 Gy) should be considered.

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.

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.

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.

Purpose To report long-term outcome of fractionated stereotactic body radiation therapy (SBRT) for painful spinal metastases. Methods and Materials This prospective, single-arm, multicenter phase 2 clinical trial enrolled 57 patients with 63 painful, unirradiated spinal metastases between March 2012 and July 2015. Patients were treated with 48.5 Gy in 10 SBRT fractions (long life expectancy [Mizumoto score ≤4]) or 35 Gy in 5 SBRT fractions (intermediate life expectancy [Mizumoto score 5-9]). Pain response was defined as pain improvement of a minimum of 2 points on a visual analog scale, and net pain relief was defined as the sum of time with pain response (complete and partial) divided by the overall follow-up time. Results All 57 patients received treatment per protocol; 32 and 25 patients were treated with 10- and 5-fraction SBRT, respectively. The median follow-up of living patients was 60 months (range, 33-74 months). Of evaluable patients, 82% had complete or partial pain response (responders) at 3 months’ follow-up (primary endpoint), and pain response remained stable over 5 years. Net pain relief was 74% (95% CI, 65%-80%). Overall survival rates of 1, 3, and 5 years were 59.6% (95% CI, 47%-72%), 33.3% (95% CI, 21%-46%), and 21% (95% CI, 10%-32%), respectively. Freedom from local spinal-metastasis progression was 82% at the last imaging follow-up. Late grade-3 toxicity was limited to pain in 2 patients (nonresponders). There were no cases of myelopathy. SBRT resulted in long-term improvements of all dimensions of the 5-level EuroQol 5-Dimension Questionnaire except anxiety/depression. Conclusions Fractionated SBRT achieved durable pain response and improved quality of life at minimum late toxicity.

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.

Purpose To identify frequency, clinical relevance and risk factors for vertebral compression fracture (VCF) after spine stereotactic body radiation therapy (SBRT) with long-term follow up (FU). Methods From 2012 to 2015, 61 lesions (56 patients) were treated within a prospective multicenter phase 2 study (NCT01594892) of SBRT for painful vertebral metastases. Post-SBRT VCF were identified. Anatomical segments, normal and tumor tissue of treated vertebrae were segmented for volumetric analyses. Predictive factors for VCF were identified by logistic regression. Results Median clinical and radiological FU for all patients was 16.2 months (range, 0–68.2) and 7.8 months (range, 0–66.9), respectively. Local metastasis control was observed in 82% of lesions at last imaging FU. Post-SBRT VCF occurred in 21 lesions (34.4%): 16.4% showed a progressive VCF, while a new VCF occurred in 18.0%. 3/56 (5.4%) patients developed painful VCF defined as pain increase by ≥2 on the visual analogue scale (VAS) and 2 (3.6%) patients required surgical stabilization. Pre-SBRT VCF, localization in the thoracic spine, Bilsky score >0, SINS score, pre-SBRT osteolytic volume and metastatic vertebral body (VB) involvement were predictive factors for VCF on univariate analysis. Relative VB involvement, osteolytic volume and pre-SBRT VCF remained in the multivariate logistic regression model that had AUC = 0.930, 83.3% sensitivity and 96.6% specificity. Conclusion Spine SBRT resulted in favorable long-term pain and local metastasis control. Despite post-SBRT VCF being observed after one third of treatments, this was symptomatic in only 5% of patients. Predictive factors for developing VCF were identified which could contribute to better selection of patients for spine SBRT.

BACKGROUND: The objective of this study was to prospectively evaluate dose-intensified hypofractionated stereotactic body radiation therapy (SBRT) in patients with painful spinal metastases in a multicenter, single-arm, phase 2 study. METHODS: Patients with 2 or fewer distinct, noncontiguous, painful, mechanically stable, unirradiated spinal metastases from a solid tumor with a Karnofsky performance status >= 60 were eligible. Patients with a long (Mizumoto score

Summary Background We have found that a ketogenic diet (KD) during the course of radiotherapy (RT) was feasible and led to a preservation or favorable changes of body composition. Based on these observations and theoretical considerations, we initiated a study to investigate the impact of a KD or a ketogenic breakfast intervention in patients undergoing RT. Methods All patients presenting for curative RT with age between 18 and 75, body mass index between 18 and 34 kg/m 2 and a histologically confirmed cancer of the breast, colorectum or head and neck region are considered for inclusion. Exclusion criteria are Karnofsky index ® , vitaflo, Bad Homburg, Germany) plus (ii) 5–15 g amino acids (MAP, dr. reinwald healthcare gmbh+co kg, Schwarzenbruck, Germany). If willing to undertake a complete KD for the duration of RT, patients are entered into intervention group 2. Intervention group 2 does not have to fast prior to RT fractions but will be supplemented with MAP analogous to intervention group 1. The control group will not receive dietary advice to follow a KD or reduce carbohydrate intake. The objective is twofold: (i) to test whether the ketogenic interventions are feasibly, as measured by the number of dropouts; (ii) to see whether intervention groups 1 and 2 attain a better preservation of BIA phase angle than the control group. Endpoints Primary endpoints are the feasibility of the interventions (measured through dropout rates), and changes in body weight and composition (measured through BIA). Secondary endpoints are changes in quality of life (EORTC questionnaires) and blood parameters as well as the occurrence and grade of toxicities and grade of regression after surgery in case of colorectal carcinomas. Trial registration Registered under ClinicalTrials.gov Identifier no. NCT00123456 .

To report the development of an ultimately fatal occurrence of Fournier’s gangrene in a rectal cancer patient undergoing neoadjuvant radiotherapy without chemotherapy. A 53-year-old male patient with G2 cT3 cN1a cM0 stage IIIB adenocarcinoma of the lower rectum and several comorbidities including ulcerative colitis was treated with 56 Gy to the primary tumor in 28 fractions because he declined the recommended simultaneous chemotherapy. He was also enrolled in the ketogenic diet arm of our KETOCOMP study, so that prospective measurements of blood parameters, quality of life, and body composition were made. The patient died 6 days after completion of radiotherapy due to septic shock associated with Fournier’s gangrene reaching from the right buttock into the gluteal muscles and descending into the scrotum. In retrospect, there were several signs probably indicating the development of the gangrene: (i) a decline in bioelectrical phase angle; (ii) an accelerated weight and fat-free mass loss starting in the third week of radiotherapy; (iii) an increase in C-reactive protein (CRP) and concurrent drop in high-density lipoprotein (HDL) cholesterol and insulin-like growth factor(IGF)-1 concentrations; and (iv) the occurrence of a sharp pain in the perianal region reported in the fifth week of radiotherapy. Notably, his self-reported quality of life score was the same at the end of as before radiotherapy. This case highlights the occurrence of Fournier’s gangrene as an extremely rare but life-threatening complication during neoadjuvant radiotherapy for rectal cancer which should be refreshed in the awareness of radiation oncologists and radiologists.

BackgroundKetogenic therapy (KT) in the form of ketogenic diets (KDs) and/or supplements that induce nutritional ketosis have gained interest as a complementary treatment for cancer patients. Besides putative anti-tumor effects, preclinical and preliminary clinical data indicate that KT could induce favorable changes in body composition of the tumor bearing host. Here we present first results of our ongoing KETOCOMP study (NCT02516501) study concerning body composition changes among rectal, breast and head & neck cancer (HNC) patients who underwent concurrent KT during standard-of-care radiotherapy (RT).MethodsEligible patients were assigned to one of three groups: (i) a standard diet group; (ii) a ketogenic breakfast group taking 50-250 ml of a medium-chain triglyceride (MCT) drink plus 10 g essential amino acids in the morning of RT days; (iii) a complete KD group supplemented with 10 g essential amino acids on RT days. Body composition was to be measured prior to and weekly during RT using 8-electrode bioimpedance analysis. Longitudinal data were analyzed using mixed effects linear regression.ResultsA total of 17 patients underwent KT during RT thus far (rectal cancer: n=6; HNC: n=6; breast cancer: n=5). All patients consuming a KD (n=14) reached nutritional ketosis and finished the study protocol with only minor problems reported. Compared to control subjects, the ketogenic intervention in rectal and breast cancer patients was significantly associated with a decline in fat mass over time (−0.3 and −0.5 kg/week, respectively), with no significant changes in skeletal muscle mass. In HNC patients, concurrent chemotherapy was the strongest predictor of body weight, fat free and skeletal muscle mass decline during radiotherapy, while KT showed significant opposite associations. Rectal cancer patients who underwent KT during neoadjuvant RT had significantly better tumor response at the time of surgery as assessed by the Dworak regression grade (median 3 versus 2, p=0.04483).ConclusionsWhile sample sizes are still small our results already indicate some significant favorable effects of KT on body composition. These as well as a putative radiosensitizing effect on rectal tumor cells need to be confirmed once the final analysis of our study becomes possible.

To evaluate the prognostic value of O-(2-[(18)F]fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) uptake intensity in World Health Organisation (WHO) tumor grade II-IV gliomas.We studied 28 patients with WHO tumor grade II-IV gliomas who were referred to our department for radiation therapy. We acquired a FET-PET in all patients, as well as magnetic resonance imaging (MRI) of the brain consisting of at least T2-weighted imaging, flair and pre- and post-contrast T1-weighted imaging. SUVmax was measured and the tumor-to-brain uptake ratio (TBR) of all lesions was calculated based on the SUVmax (TBRmax) or SUVmean (TBRmean) of the contralateral healthy tissue. For this study, volumes were calculated using MRI alone, MRI + the volume with a SUVmax on FET-PET ≥ 2.2 as well as MRI + the volume with an uptake of at least 40 % of the SUVmax.Tumor volumes were a median (range) of 88.6 (2.6-467.4) ml (MRI alone), 84.2 (2.8-474.4) ml (MRI + SUVmax on FET-PET ≥ 2.2) and 101.5 (4.0-512.1) ml (MRI + FET-PET uptake ≥ 40 % SUVmax), respectively. TBR-SUVmean was 2.36 (1.46-4.08); TBR-SUVmax was 1.71 (0.97-2.85). During a follow-up of 18.7 (2.5-36.1) months after FET-PET, 12 patients died of malignant glioma. Patients with a SUVmax ≥ 2.6 had a significantly worse tumor-related mortality (p = 0.005) and progression-free survival (p = 0.038) than those with a lower SUVmax. Multivariate analysis showed that WHO tumor grade (p = 0.001) and SUVmax ≥ 2.6 (p0.001) were independent predictors for tumor-related mortality, but not tumor volume or TBRmax or TBRmean. SUVmax ≥ 2.6 (p = 0.007) and being treated for a recurrence rather than for a primary tumor manifestation (p = 0.014) were predictors for progression-free survival, but not TBRmax or TBRmean.In this heterogeneous patient population, higher tracer uptake in FET-PET appears to be associated with a worse tumor-related mortality and a shorter duration of the disease-free interval.

SummaryAim: The objective of this study was to assess the feasibility, dosimetry, tolerability and efficacy of systemically administrated p-[131I] - iodo-L-phenylalanine (131IPA) combined with hypo-fractionated external beam radiation therapy (EBRT) in patients with recurrent glioblastoma multiforme (GBM). Patients, methods: Five patients (2 women, 3 men, aged 27-69) with recurrent GBM and exhaustion of regular therapy options were included. All had a positive O-(2-[18F]Fluoroethyl)- L-tyrosine positron emission tomography (FET-PET) and pretherapeutic dosimetry was performed. Tumour targeting was verified by 131IPA-SPECT up to six days after radiotracer administration. After 131IPA therapy, patients were treated with hypo-fractionated EBRT in six fractions of 5 Gy (n = 4) or in eleven fractions of 2 Gy in one case. Results: Based on the individual dosimetry, the patients received a single intravenous administration of 2 to 7 GBq of 131IPA, resulting in radiation absorbed doses to the blood of 0.80–1.47 Gy. The treatment was well tolerated; only minor complaints of nausea and vomiting that responded to ondansetron and pantoprazol were noticed in the first two patients. After preventive medication, the last three patients had no complaints during therapy. In none of the patients a decrease of leukocyte or thrombocyte counts below the baseline level or the lower normal limit was observed. Tumour doses from 131IPA were low (≤ 1 Gy) and all patients died three to eight (median 5.5) months after therapy. Conclusion: In this initial experience, treatment of GBM with 131IPA in combination with EBRT was demonstrated to be safe and well tolerated, but less effective than suggested by the animal studies.

Background Based on promising preclinical data, ketogenic diets (KDs) have been proposed as supplementary measures for cancer patients undergoing standard-of-care therapy. However, data is still scarce on the tolerability and effects of KDs on cancer patients undergoing radiotherapy (RT). Here we present six cases of patients who underwent RT and concurrently consumed a self-administered KD in our clinic within a busy community hospital setting. Methods All patients were followed prospectively with measurements of blood parameters, quality of life and body weight and composition using bioelectrical impedance analysis. Results No adverse diet-related side effects occurred. Two patients had no elevated ketone body levels in serum despite self-reporting compliance to the diet. There was consensus that the KD was satiating and weight loss occurred in all patients, although this was only significant in two patients. Our data indicate that weight loss was mainly due to fat mass loss with concurrent preservation of muscle mass. Overall quality of life remained fairly stable, and all subjects reported feeling good on the diet. Tumor regression occurred as expected in five patients with early stage disease; however one subject with metastatic small cell lung cancer experienced slight progression during three cycles of combined chemotherapy + KD and progressed rapidly after ending the KD. Conclusions Our data lend support to the hypothesis that KDs administered as supportive measures during standard therapy are safe and might be helpful in preservation of muscle mass. Further studies with control groups are needed to confirm these findings and address questions regarding any putative anti-tumor effects. Based on the experience with these six cases we implemented further steps to improve issues with KD compliance and initiated a clinical study that is described in a companion paper.

Re-irradiation is probably the most challenging situation in radiotherapy because the radiation tolerance of the normal tissue is significantly reduced compared with the first treatment series. Results with traditional radiotherapy techniques have been disappointing because of the poor conformality of the dose distributions: radiation doses were either insufficiently low resulting in poor rates of tumor control or substantial toxicity was the consequence of high-dose re-irradiation. This chapter will focus on modern techniques of radiation treatment planning and delivery, which make improved sparing of the normal tissue possible. All techniques will be discussed in the context of re-irradiation and theoretical and clinical data supporting the use of these technologies will be presented. Palliative reirradiation to moderate doses might be feasible without using advanced technology. However, under many circumstances 2D or 3D conformal approaches cannot fulfill the required normal tissue constraints. The present chapter discusses the advantages and challenges associated with more complex planning and delivery methods.

The purpose of this work was to perform a single institution comparison between preoperative short-course radiotherapy (SC-RT) and long-course radiochemotherapy (LC-RCHT) for locally advanced rectal cancer. A total of 225 patients with clinical stage UICC II–III rectal cancer were treated with SC-RT (29 Gy in 10 twice daily fractions followed by immediate surgery; n = 108) or LC-RCHT (54 Gy in 28 fractions with simultaneous 5-fluorouracil (5-FU) ± oxaliplatin chemotherapy followed by delayed surgery; n = 117). All patients in the LC-RCHT cohort and patients in the SC-RT with pathological UICC stage ≥ II received adjuvant chemotherapy. Before 2004, the standard of care was SC-RT with LC-RCHT reserved for patients where downstaging was considered as required for sphincter preservation or curative resection. In the later period, SC-RT was practiced only for patients unfit for radiochemotherapy. Patients in the LC-RCHT cohort had a significantly higher proportion of cT4 tumors, clinical node positivity, and lower tumor location. The 5-year local control (LC) and overall survival (OS) were 91% and 66% without differences between the SC-RT and LC-RCHT groups. Acute toxicity was increased during LC-RCHT (grade ≥ II 1% vs. 33%) and there were no differences in postoperative complications. Severe late toxicity grade ≥ III was increased after SC-RT (12% vs. 3%). Of patients aged > 80 years, 7 of 7 patients and 4 of 9 patients received curative surgery after SC-RT and LC-RCHT, respectively. Despite the fact that patients with worse prognostic factors were treated with LC-RCHT, there were no significant differences in LC and OS between the SC-RT and LC-RCHT group. Age > 80 years was identified as a significant risk factor for LC-RCHT and these patients could be treated preferably with SC-RT.

To investigate whether the tumour uptake of radionuclide in peptide receptor radionuclide therapy (PRRT) of meningioma can be predicted by a PET scan with (68)Ga-labelled somatostatin analogue.In this pilot trial, 11 meningioma patients with a PET scan indicating somatostatin receptor expression received PRRT with 7.4 GBq (177)Lu-DOTATOC or (177)Lu-DOTATATE, followed by external beam radiotherapy. A second PET scan was scheduled for 3 months after therapy. During PRRT, multiple whole-body scans and a SPECT/CT scan of the head and neck region were acquired and used to determine the kinetics and dose in the voxel with the highest radionuclide uptake within the tumour. Maximum voxel dose and retention of activity 1 h after administration in PRRT were compared to the maximum standardized uptake values (SUV(max)) in the meningiomas from the PET scans before and after therapy.The median SUV(max) in the meningiomas was 13.7 (range 4.3 to 68.7), and the maximum fractional radionuclide uptake in voxels of size 0.11 cm³ was a median of 23.4 × 10(-6) (range 0.4 × 10(-6) to 68.3 × 10(-6)). A strong correlation was observed between SUV(max) and the PRRT radionuclide tumour retention in the voxels with the highest uptake (Spearman's rank test, P0.01). Excluding one patient who showed large differences in biokinetics between PET and PRRT and another patient with incomplete data, linear regression analysis indicated significant correlations between SUV(max) and the therapeutic uptake (r = 0.95) and between SUV(max) and the maximum voxel dose from PRRT (r = 0.76). Observed absolute deviations from the values expected from regression were a median of 5.6 × 10(-6) (maximum 9.3 × 10(-6)) for the voxel fractional radionuclide uptake and 0.40 Gy per GBq (maximum 0.85 Gy per GBq) (177)Lu for the voxel dose from PRRT.PET with (68)Ga-labelled somatostatin analogues allows the pretherapeutic assessment of tumour radionuclide uptake in PRRT of meningioma and an estimate of the achievable dose.

To evaluate toxicity after dose-escalated radiotherapy for prostate cancer using intensity-modulated treatment planning (IMRT) and image-guided treatment (IGRT) delivery. 100 patients were treated with simultaneous integrated boost (SIB) IMRT for prostate cancer: doses of 76.23 Gy and 60 Gy in 33 fractions were prescribed to the prostate and the seminal vesicles, respectively, for intermediate- and high-risk patients (n = 74). The total dose was 73.91 Gy in 32 fractions for low-risk patients and after transurethral resection of the prostate (n = 26). The pelvic lymphatics were treated with 46 Gy in 25 fractions in patients with high risk of lymph node metastases using an SIB to the prostate (n = 25). IGRT was practiced with cone-beam computed tomography. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated prospectively (CTCAE v3.0). Treatment was completed as planned by all patients. Acute GI and GU toxicity grade ≥ 2 was observed in 12% and 42% of the patients, respectively, with 4% suffering from GU toxicity grade 3. 6 weeks after treatment, the incidence of acute toxicity grade ≥ 2 had decreased to 12%. With a median follow-up of 26 months, late GI and GU toxicity grade ≥ 2 was seen in 1.5% and 7.7% of the patients at 24 months. Four patients developed late toxicity grade 3 (GI n = 1; GU n = 3). Presence of acute GI and GU toxicity was significantly associated with late GI (p = 0.0007) and GU toxicity (p = 0.006). High-dose radiotherapy for prostate cancer using IMRT and IGRT resulted in low rates of acute toxicity and preliminary results of late toxicity are promising.

Purpose To evaluate the outcomes after dose-escalated radiotherapy (RT) for spinal metastases and paraspinal tumors. Methods and Materials A total of 14 patients, 12 with spinal metastases and a long life expectancy and 2 with paraspinal tumors, were treated for 16 lesions with intensity-modulated, image-guided RT. A median biologic effective dose of 74 Gy 10 (range, 55–86) in a median of 20 fractions (range, 3–34) was prescribed to the target volume. The spinal canal was treated to 40 Gy in 20 fractions using a second intensity-modulated RT dose level in the case of epidural involvement. Results After median follow-up of 17 months, one local recurrence was observed, for an actuarial local control rate of 88% after 2 years. Local control was associated with rapid and long-term pain relief. Of 11 patients treated for a solitary spinal metastasis, 6 developed systemic disease progression. The actuarial overall survival rate for metastatic patients was 85% and 63% after 1 and 2 years, respectively. Acute Grade 2-3 skin toxicity was seen in 2 patients with no late toxicity greater than Grade 2. No radiation-induced myelopathy was observed. Conclusion Dose-escalated irradiation of spinal metastases was safe and resulted in excellent local control. Oligometastatic patients with a long life expectancy and epidural involvement are considered to benefit the most from fractionated RT.

To evaluate intra-fractional uncertainties during intensity-modulated radiotherapy (IMRT) of prostate cancer.During IMRT of 21 consecutive patients, kilovolt (kV) cone-beam computed tomography (CBCT) images were acquired prior to and immediately after treatment: a total of 252 treatment fractions with 504 CBCT studies were basis of this analysis. The prostate position in anterior-posterior (AP) direction was determined using contour matching; patient set-up based on the pelvic bony anatomy was evaluated using automatic image registration. Internal variability of the prostate position was the difference between absolute prostate and patient position errors. Intra-fractional changes of prostate position, patient position, rectal distension in AP direction and bladder volume were analyzed.With a median treatment time of 16 min, intra-fractional drifts of the prostate were5 mm in 12% of all fractions and a margin of 6 mm was calculated for compensation of this uncertainty. Mobility of the prostate was independent from the bony anatomy with poor correlation between absolute prostate motion and motion of the bony anatomy (R2=0.24). A systematic increase of bladder filling by 41 ccm on average was observed; however, these changes did not influence the prostate position. Small variations of the prostate position occurred independently from intra-fractional changes of the rectal distension; a weak correlation between large internal prostate motion and changes of the rectal volume was observed (R2=0.55).Clinically significant intra-fractional changes of the prostate position were observed and margins of 6 mm were calculated for this intra-fractional uncertainty. Repeated or continuous verification of the prostate position may allow further margin reduction.

Purpose To evaluate a novel four-dimensional (4D) image-guided radiotherapy (IGRT) technique in stereotactic body RT for liver tumors. Methods and Materials For 11 patients with 13 intrahepatic tumors, a respiratory-correlated 4D computed tomography (CT) scan was acquired at treatment planning. The target was defined using CT series reconstructed at end-inhalation and end-exhalation. The liver was delineated on these two CT series and served as a reference for image guidance. A cone-beam CT scan was acquired after patient positioning; the blurred diaphragm dome was interpreted as a probability density function showing the motion range of the liver. Manual contour matching of the liver structures from the planning 4D CT scan with the cone-beam CT scan was performed. Inter- and intrafractional uncertainties of target position and motion range were evaluated, and interobserver variability of the 4D-IGRT technique was tested. Results The workflow of 4D-IGRT was successfully practiced in all patients. The absolute error in the liver position and error in relation to the bony anatomy was 8 ± 4 mm and 5 ± 2 mm (three-dimensional vector), respectively. Margins of 4–6 mm were calculated for compensation of the intrafractional drifts of the liver. The motion range of the diaphragm dome was reproducible within 5 mm for 11 of 13 lesions, and the interobserver variability of the 4D-IGRT technique was small (standard deviation, 1.5 mm). In 4 patients, the position of the intrahepatic lesion was directly verified using a mobile in-room CT scanner after application of intravenous contrast. Conclusion The results of our study have shown that 4D image guidance using liver contour matching between respiratory-correlated CT and cone-beam CT scans increased the accuracy compared with stereotactic positioning and compared with IGRT without consideration of breathing motion.

To evaluate survival and toxicity rates after primary external-beam radiation for the treatment of prostate cancer. Data of 306 patients treated with conformal external beam radiation between 1996 and 2001 were collected. These were evaluated in terms of overall, cause-specific and disease-free survival as well as toxicity. Furthermore, an investigation of possible risk factors was performed. Toxicity rates compared favorably with other series with 5.2% RTOG 1–2 and no RTOG > 2 long-term side effects. Actuarial 5-year overall survival rates with and without biochemical failure were 77% versus 78%, cancer-specific survival was 85.41% versus 100%, and disease-free survival was 71.54%, respectively. Potential risk factors for cancer-related death were biochemical failure, initial serum prostate-specific antigen (PSA) and Gleason score. Toxicity rates were found to be surprisingly low compared to other series, which is likely due to low daily dose and consistent MR-based treatment planning. In terms of survival, no significant differences to other trials could be observed. Initial PSA and Gleason score were significant predictors for treatment outcome in terms of survival.

Radiosurgery in the base of skull region can be especially challenging due to immediate proximity of critical structures such as brainstem and critical nerves such as those of the optic system. This chapter should guide clinicians in understanding the technical possibilities, determining feasibility, and risks of radiosurgery as well as critical organ dose limits for primary or repeat radiosurgery in this region. Specifically, radiosurgery of rare tumors of this region such as chordomas and chondrosarcomas, glomus jugulare tumors, esthesioneuroblastomas and angiofibromas are discussed according to current literature. Many of these tumors are quite amenable to radiosurgery depending upon histology, size, and location. However, ideally, modern techniques of (sometimes multimodality) imaging should be used to determine precise tumor-extent prior to the recommendation for radiosurgery, as in general, tumors larger than 3 cm or those abutting critical structures may benefit more from alternative precision therapies.

Precise reproducible patient positioning is a prerequisite for conformal fractionated radiotherapy. A fixation system based on double-vacuum technology is presented which can be used for conventional as well as hypofractionated stereotactic extracranial radiotherapy. To form the actual vacuum mattress, the patient is pressed into the mattress with a vacuum foil which can also be used for daily repositioning and fixation. A stereotactic frame can be positioned over the region of interest on an indexed base plate. Repositioning accuracy was determined by comparing daily, pretreatment, orthogonal portal images to the respective digitally reconstructed radiographs (DRRs) in ten patients with abdominal and pelvic lesions receiving extracranial fractionated (stereotactic) radiotherapy. The three-dimensional (3-D) vectors and 95% confidence intervals (CI) were calculated from the respective deviations in the three axes. Time required for initial mold production and daily repositioning was also determined. The mean 3-D repositioning error (187 fractions) was 2.5 ± 1.1 mm. The largest single deviation (10 mm) was observed in a patient treated in prone position. Mold production took an average of 15 min (10–30 min). Repositioning times are not necessarily longer than using no positioning aid at all. The presented fixation system allows reliable, flexible and efficient patient positioning for extracranial stereotactic radiotherapy.

To present a simple and precise method of combining functional information of cranial SPECT and PET images with CT and MRI, in any combination. Material and Methods: Imaging is performed with a hockey mask-like reference frame with image modality-specific markers in precisely defined positions. This frame is reproducibly connected to the VBH vacuum mouthpiece, granting objectively identical repositioning of the frame with respect to the cranium. Using these markers, the desired 3-D imaging modalities can then be manually or automatically registered. This information can be used for diagnosis, treatment planning, and evaluation of follow-up, while the same vacuum mouthpiece allows precisely reproducible stereotactic head fixation during radiotherapy. Results: 244 CT and MR data sets of 49 patients were registered to a root square mean error (RSME) of 0.9 mm (mean). 64 SPECT-CT fusions on 18 of these patients gave an RMSE of 1.4 mm, and 40 PET-CT data sets of eight patients were registered to 1.3 mm. An example of the method is given by means of a case report of a 52-year-old patient with bilateral optic nerve meningioma. Conclusion: This technique is a simple, objective and accurate registration tool to combine diagnosis, treatment planning, treatment, and follow-up, all via an individualized vacuum mouthpiece. Especially for low-resolution PET and even more so for some very diffuse SPECT data sets, activity can now be accurately correlated to anatomic structures.

The aim of the study was to implement a vibrotactile stimulator using functional magnetic resonance imaging (fMRI). A fMRI compatible vibration device consisting of a pneumatically driven dual membrane pump was developed. Brain activation during 50 Hz vibrotactile stimulation of the right hand-palm were compared to a right 2 Hz finger-to-thumb-tapping in ten healthy, right-handed male volunteers. The vibration paradigm showed a comparable activation pattern with respect to finger-to-thumb-tapping in the contralateral perirolandic region. The advantage of the new vibration device is the possibility to elicit the vibratory-tonic-reflex due to the higher amplitude in context with the high frequency than established devices. This reflex is considered to be responsible for the activation in the primary motor cortex and the current paradigm might prove useful in future neurosurgical planning in patients with perirolandic lesions.

Purpose: Primary skull base tumors of the developing child are rare and present a formidable challenge to both surgeons and radiation oncologists. Gross total resection with negative margins is rarely achieved, and the risks of functional, structural, and cosmetic deficits limit the radiation dose using conventional radiation techniques. Twenty-nine children and adolescents treated with conformal proton radiotherapy (proton RT) were analyzed to assess treatment efficacy and safety. Methods and Materials: Between July 1992 and April 1999, 29 patients with mesenchymal tumors underwent fractionated proton (13 patients) or fractionated combined proton and photon (16 patients) irradiation. The age at treatment ranged from 1 to 19 years (median 12); 14 patients were male and 15 female. Tumors were grouped as malignant or benign. Twenty patients had malignant histologic findings, including chordoma ( n = 10), chondrosarcoma ( n = 3), rhabdomyosarcoma ( n = 4), and other sarcomas ( n = 3). Target doses ranged between 50.4 and 78.6 Gy/cobalt Gray equivalent (CGE), delivered at doses of 1.8–2.0 Gy/CGE per fraction. The benign histologic findings included giant cell tumors ( n = 6), angiofibromas ( n = 2), and chondroblastoma ( n = 1). RT doses for this group ranged from 45.0 to 71.8 Gy/CGE. Despite maximal surgical resection, 28 (97%) of 29 patients had gross disease at the time of proton RT. Follow-up after proton RT ranged from 13 to 92 months (mean 40). Results: Of the 20 patients with malignant tumors, 5 (25%) had local failure; 1 patient had failure in the surgical access route and 3 patients developed distant metastases. Seven patients had died of progressive disease at the time of analysis. Local tumor control was maintained in 6 (60%) of 10 patients with chordoma, 3 (100%) of 3 with chondrosarcoma, 4 (100%) of 4 with rhabdomyosarcoma, and 2 (66%) of 3 with other sarcomas. The actuarial 5-year local control and overall survival rate was 72% and 56%, respectively, and the overall survival of the males was significantly superior to that of the female patients ( p = 0.002). Of the patients with benign tumors, 1 patient (giant cell tumor) had local failure at 10 months. The other 8 patients continued to have local tumor control; all 9 patients were alive at last follow-up (actuarial 5-year local control and overall survival rate of 89% and 100%, respectively). Severe late effects (motor weakness and sensory deficits) were observed in 2 (7%) of 29 patients. Conclusion: Proton RT for children with aggressively recurring tumors after major skull base surgery can offer a considerable prospect of tumor control and survival. Longer follow-up is necessary to assess the real value of protons, in particular with regard to bone growth and cosmetic outcome.

To evaluate the usefulness of virtual endoscopy (VE) in planning neuroendoscopic intraventricular surgeries, the technique was applied in 20 of 22 consecutive procedures. Thirteen endoscopic third ventriculostomies (ETV) in 12 patients, 3 endoscopic colloid cyst removals, 1 third ventricular arachnoidal cyst fenestration, 1 endoscopic ventricul-cysto-cisternostomy (suprasellar arachnoidal cyst), 1 endoscopic tumor biopsy, one third ventricular gross total tumor removal and 2 septostomies at the foramen of Monro due the septal occlusion were performed. Contrast medium-enhanced MR images (3DMPRAGE, Siemens, Germany) were semi-automatically segmented with a surface-rendering technique ("Navigator" software, General Electric Medical, Buc, France) to produce the virtual endoluminal views. Surgery was performed with cerebral ventriculoscopes by Wolf (Richard Wolf, Knittlingen, Germany). VE was feasible in all patients and the virtual endoscopic images were comparable with the real intraventricular views obtained by standard rod lens systems. After contrast medium administration intra- and paraventricular vessels such as the thalamocaudate vein, the septal veins, the basilar artery and its branches (distal BA complex) and the choroid plexus were identified on the virtual endoscopic images. In 8 patients, the additional anatomic information provided by VE profoundly influenced surgical planning. VE provides the neurosurgeon with additional morphological information supporting the planning process of neuroendoscopic intraventricular surgeries, contributing to the safety of the procedures.

Purpose: To demonstrate why conventional non-invasive mouthpiece-based fixation has not achieved the expected accuracy and to suggest a solution of the problem. Patients and Methods: The Vogele Bale Hohner (VBH) head holder is a non-invasive vacuum mouthpiece-based head fixation system. Feasibility and repositioning accuracy were evaluated by portal image analysis in 12 patients with cranial tumors intended for stereotactic procedures, fixated with the newest version (VBH HeadFix-ARC®). Results: Portal image analysis (8 patients evaluated in 2-D, 4 patients in 3-D) showed that even in routine external beam radiation therapy, treatment can be applied to within a mean 2-D and 3-D accuracy of under 2 mm (SD 0.92 mm and 1.2 mm, respectively) with cost and repositioning time per patient and patient comfort comparable to that of common thermoplastic masks. Conclusion: These preliminary results show that high repositioning accuracy does not rule out simple and quick application and patient comfort. Paramount, however, is tensionless repositioning via the vacuum mouthpiece.

PURPOSE To fully utilize the technical capabilities of radiation diagnostics and planning, a precise and reproducible method of head fixation is a prerequisite. METHOD We have adapted the Vogele-Bale-Hohner (VBH) head holder (Wellhofer Dosimetrie, Schwarzenbruck, Germany), originally designed for frameless stereotactic operations, to the requirements of external beam radiotherapy. A precise and reproducible head fixation is attained by an individualized vacuum upper-dental cast which is connected over 2 hydraulic arms to an adjustable head- and rigid base-plate. Radiation field and patient alignment lasers are marked on a relocatable clear PVC localization box. RESULTS The possibility of craniocaudal adjustment of the head plate on the base plate allows the system to adapt to the actual position of the patient on the radiotherapy couch granting tensionless repositioning. The VBH head holder has proven itself to be a precise yet practicable method of head fixation. Duration of mouthpiece production and daily repositioning is comparable to that of the thermoplastic mask. CONCLUSION The new head holder is in routine use at our hospital and quite suitable for external beam radiation of patients with tumors of the head and neck.

Background: Stereotactic body radiotherapy and radiosurgery are rapidly emerging treatment options for both malignant and benign spine tumors. Proper institutional credentialing by physicians and medical physicists as well as other personnel is important for the safe and effective adoption of spine radiosurgery. This article describes the methods for institutional credentialing for spine radiosurgery at seven highly experienced international institutions. Methods: All institutions (n = 7) are members of the Elekta Spine Radiosurgery Research Consortium and have a dedicated research and clinical focus on image-guided spine radiosurgery. A questionnaire consisting of 24 items covering various aspects of institutional credentialing for spine radiosurgery was completed by all seven institutions. Results: Close agreement was observed in most aspects of spine radiosurgery credentialing at each institution. A formal credentialing process was believed to be important for the implementation of a new spine radiosurgery program, for patient safety and clinical outcomes. One institution has a written policy specific for spine radiosurgery credentialing, but all have an undocumented credentialing system in place. All institutions rely upon an in-house proctoring system for the training of both physicians and medical physicists. Four institutions require physicians and medical physicists to attend corporate sponsored training. Two of these 4 institutions also require attendance at a non-corporate sponsored academic society radiosurgery course. Corporate as well as non-corporate sponsored training were believed to be complimentary and both important for training. In 5 centers, all cases must be reviewed at a multidisciplinary conference prior to radiosurgery treatment. At 3 centers, neurosurgeons are not required to be involved in all cases if there is no evidence for instability or spinal cord compression. Backup physicians and physicists are required at only 1 institution, but all institutions have more than one specialist trained to perform spine radiosurgery. All centers believed that credentialing should also be device specific, and all believed that professional societies should formulate guidelines for institutions on the requirements for spine radiosurgery credentialing. Finally, in 4 institutions radiation therapists were required to attend corporate-sponsored device specific training for credentialing, and in only 1 institution were radiation therapists required to also attend academic society training for credentialing. Conclusions: This study represents the first multi-national report of the current practice of institutional credentialing for spine radiosurgery. Key methodologies for safe implementation and credentialing of spine radiosurgery have been identified. There is strong agreement among experienced centers that credentialing is an important component of the safe and effective implementation of a spine radiosurgery program.

The goal of this study was to evaluate accelerated radiotherapy with and without temozolomide (TMZ) for glioblastoma multiforme (GBM). This retrospective analysis evaluated 86 patients with histologically proven GBM who were treated with accelerated radiotherapy of 1.8 Gy twice daily to a total dose of 54 Gy within 3 weeks. Median age was 62 years and median Karnofsky index was 90. A total of 41 patients received radiotherapy only from 2002–2005 and 45 patients were treated with TMZ concomitantly and after radiotherapy from 2005–2007. Median overall survival (OS) was 12.5 months and 2-year OS was 15.4%. Patient characteristics were well balanced between the two groups except for better performance status (p = 0.05) and higher frequency of retreatment for the first recurrence (p = 0.02) in the TMZ group. Age at diagnosis (HR 2.83) and treatment with TMZ (HR 0.60) were correlated with OS in the multivariate analysis: treatment with and without TMZ resulted in median OS of 16 months and 11.3 months, respectively. Hematological toxicity grade > II was observed in 2/45 patients and 5/37 patients during simultaneous radiochemotherapy and adjuvant TMZ. TMZ added to accelerated radiotherapy for GBM resulted in prolonged overall survival with low rates of severe hematological toxicity.

Background To introduce a novel method of patient positioning for high precision intracranial radiotherapy. Methods An infrared(IR)-array, reproducibly attached to the patient via a vacuum-mouthpiece(vMP) and connected to the table via a 6 degree-of-freedom(DoF) mechanical arm serves as positioning and fixation system. After IR-based manual prepositioning to rough treatment position and fixation of the mechanical arm, a cone-beam CT(CBCT) is performed. A robotic 6 DoF treatment couch (HexaPOD™) then automatically corrects all remaining translations and rotations. This absolute position of infrared markers at the first fraction acts as reference for the following fractions where patients are manually prepositioned to within ± 2 mm and ± 2° of this IR reference position prior to final HexaPOD-based correction; consequently CBCT imaging is only required once at the first treatment fraction. The preclinical feasibility and attainable repositioning accuracy of this method was evaluated on a phantom and human volunteers as was the clinical efficacy on 7 pilot study patients. Results Phantom and volunteer manual IR-based prepositioning to within ± 2 mm and ± 2° in 6DoF was possible within a mean(± SD) of 90 ± 31 and 56 ± 22 seconds respectively. Mean phantom translational and rotational precision after 6 DoF corrections by the HexaPOD was 0.2 ± 0.2 mm and 0.7 ± 0.8° respectively. For the actual patient collective, the mean 3D vector for inter-treatment repositioning accuracy (n = 102) was 1.6 ± 0.8 mm while intra-fraction movement (n = 110) was 0.6 ± 0.4 mm. Conclusions This novel semi-automatic 6DoF IR-based system has been shown to compare favourably with existing non-invasive intracranial repeat fixation systems with respect to handling, reproducibility and, more importantly, intra-fraction rigidity. Some advantages are full cranial positioning flexibility for single and fractionated IGRT treatments and possibly increased patient comfort.