Brain glucose hypometabolism and hippocampal inflammation in Goto-Kakizaki rats

Brain glucose hypometabolism and neuroinflammation are early pathogenic manifestations in neurological disorders. Neuroinflammation may also disrupt leptin signaling, an adipokine that centrally regulates appetite and energy balance by acting on the hypothalamus and exerting neuroprotection in the hippocampus. The Goto-Kakizaki (GK) rat is a non-obese type 2 diabetes mellitus (T2DM) animal model used to investigate diabetes-associated molecular mechanisms without obesity jeopardizing effects. Wistar and GK rats received the maintenance adult rodent diet. Also, an additional control group of Wistar rats received a high-fat and high-sugar diet (HFHS) provided by free consumption of condensed milk. All diets and water were provided ad libitum for eight weeks. Brain glucose uptake was evaluated by 2-deoxy-2-[fluorine-18] fluoro-D-glucose under basal (saline administration) or stimulated (CL316,243, a selective β3-AR agonist) conditions. The animals were fasted for 10-12 h, anesthetized, and euthanized. The brain was quickly dissected, and the hippocampal area was sectioned and stored at -80°C in different tubes for protein and RNA analyses on the same animal. GK rats exhibited attenuated brain glucose uptake compared to Wistar animals and the HFHS group under basal conditions. Also, the hippocampus of GK rats displayed upregulated leptin receptor, IL-1β, and IL-6 gene expression and IL-1β and the subunit of the transcription factor NF-κB (p-p65) protein expression. No significant alterations were detected in the hippocampus of HFHS rats. Our data indicated that a genetic predisposition to T2DM has significant brain deteriorating features, including brain glucose hypometabolism, neuroinflammation, and leptin signaling disruption in the hippocampal area.

Stereotactic Re-irradiation in Recurrent Prostate Cancer after Previous Postoperative or Definitive Radiotherapy: Long-term Results after a Median Follow-up of 4 Years.

AIMS: In 2018, we published early results from a cohort of patients treated with stereotactic body radiotherapy (SBRT) after previous radiotherapy with definitive or postoperative intent. We sought to provide extended follow-up of this cohort to confirm the safety and efficacy of this approach in a real-world scenario. MATERIALS AND METHODS: Fifty patients affected by local relapse after previous definitive or postoperative radiotherapy were treated with SBRT. Treatment provided a total dose of 30 Gy in five fractions. Data about biochemical relapse-free survival (BRFS) and metastasis-free survival (MFS), together with adverse events, were analysed. Toxicity was reported according to Common Terminology Criteria for Adverse Events (CTCAE) score v.4.03. RESULTS: After a median follow-up of 48.2 months, the median BRFS was 43 months. A Gleason score >7 and concomitant androgen deprivation therapy were shown to be predictors of the worst BRFS (hazard ratio 2.42, 95% confidence interval 1.09-5.41, P = 0.02; hazard ratio 2.83, 95% confidence interval 1.17-6.8, P = 0.02, respectively). The median MFS was not reached; concomitant androgen deprivation therapy was confirmed to be predictive of the worst MFS (hazard ratio 4.75, 95% confidence interval 1.52-14.8, P = 0.007). Late grade 1 and 2 rectal and bladder toxicity occurred in three (6%) and 13 (26%) patients, respectively. One patient experienced both grade 3 acute and chronic bladder toxicity. CONCLUSION: Salvage SBRT re-irradiation after previous postoperative or definitive radiotherapy for local prostate cancer recurrence confirmed promising results in terms of oncological outcomes and the safety of this approach.

Reviewing physical exercise in non-obese diabetic Goto-Kakizaki rats

There is a high incidence of non-obese type 2 diabetes mellitus (non-obese-T2DM) cases, particularly in Asian countries, for which the pathogenesis remains mainly unclear. Interestingly, Goto-Kakizaki (GK) rats spontaneously develop insulin resistance (IR) and non-obese-T2DM, making them a lean diabetes model. Physical exercise is a non-pharmacological therapeutic approach to reduce adipose tissue mass, improving peripheral IR, glycemic control, and quality of life in obese animals or humans with T2DM. In this narrative review, we selected and analyzed the published literature on the effects of physical exercise on the metabolic features associated with non-obese-T2DM. Only randomized controlled trials with regular physical exercise training, freely executed physical activity, or skeletal muscle stimulation protocols in GK rats published after 2008 were included. The results indicated that exercise reduces plasma insulin levels, increases skeletal muscle glycogen content, improves exercise tolerance, protects renal and myocardial function, and enhances blood oxygen flow in GK rats.

Poor prognosis indicators of type-2 diabetic COVID-19 patients

Diabetes is associated with a worse prognosis and a high risk of morbidity and mortality in COVID-19 patients. We aimed to evaluate the main factors involved in the poor prognosis in diabetic patients. A total of 984 patients diagnosed with COVID-19 admitted to the hospital were included in this study. Patients were first divided into type-2 diabetic (DM+) and non-diabetic (DM-) groups. The participants were analyzed based on the National Early Warning Score (NEWS) and on the Quick-Sequential Organ Failure Assessment (qSOFA) to find the best prognostic risk score for our study. The DM+ and DM- groups were divided into non-severe and severe groups. Comparative and correlative analyses were used to identify the physiological parameters that could be employed for creating a potential risk indicator for DM+ COVID-19 patients. We found a poorer prognosis for the DM+ COVID-19 patients with a higher ICU admission rate, mechanical ventilation rate, vasopressor use, dialysis, and longer treatment times compared with the DM- group. DM+ COVID-19 patients had increased plasma glucose, lactate, age, urea, NEWS, and D-dimer levels, herein referred to as the GLAUND set, and worse prognosis and outcomes when compared with infected DM- patients. The NEWS score was a better indicator for assessing COVID-19 severity in diabetic patients than the q-SOFA score. In conclusion, diabetic COVID-19 patients should be assessed with the NEWS score and GLAUND set for determining their prognosis COVID-19 prognosis.

Spatial Bloch Oscillations of a Quantum Gas in a "Beat-Note" Superlattice.

We report the experimental realization of a new kind of optical lattice for ultracold atoms where arbitrarily large separation between the sites can be achieved without renouncing to the stability of ordinary lattices. Two collinear lasers, with slightly different commensurate wavelengths and retroreflected on a mirror, generate a superlattice potential with a periodic "beat-note" profile where the regions with large amplitude modulation provide the effective potential minima for the atoms. To prove the analogy with a standard large spacing optical lattice we study Bloch oscillations of a Bose Einstein condensate with negligible interactions in the presence of a small force. The observed dynamics between sites separated by ten microns for times exceeding one second proves the high stability of the potential. This novel lattice is the ideal candidate for the coherent manipulation of atomic samples at large spatial separations and might find direct application in atom-based technologies like trapped-atom interferometers and quantum simulators.

A high-carbohydrate diet induces greater inflammation than a high-fat diet in mouse skeletal muscle.

We previously reported that both the high-carbohydrate diet (HCD) and high-fat diet (HFD) given for two months promote lipid deposition and inflammation in the liver and brain of mice. The results obtained indicate a tissue-specific response to both diets. Herein, we compared the effects of HCD and HFD on fatty acid (FA) composition and inflammation in the gastrocnemius muscle. Male Swiss mice were fed with HCD or HFD for 1 or 2 months. Saturated FA (SFA), monounsaturated FA (MUFA), n-3 polyunsaturated FA (n-3 PUFA), and n-6 PUFA were quantified. The activities of stearoyl-CoA desaturase 1 (SCD-1), Δ-6 desaturase (D6D), elongase 6, and de novo lipogenesis (DNL) were estimated. As for indicators of the inflammatory tissue state, we measured myeloperoxidase (MPO) activity and gene expression of F4/80, tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-6, and IL-10. The HCD led to a lower deposition of SFA, MUFA, n-3 PUFA, and n-6 PUFA compared to HFD. However, the HCD increased arachidonic acid levels, SFA/n-3 PUFA ratio, DNL, SCD-1, D6D, and MPO activities, and expression of IL-6, contrasting with the general idea that increased lipid deposition is associated with more intense inflammation. The HCD was more potent to induce skeletal muscle inflammation than the HFD, regardless of the lower lipid accumulation.

A high-carbohydrate diet induces greater inflammation than a high-fat diet in mouse skeletal muscle

We previously reported that both the high-carbohydrate diet (HCD) and high-fat diet (HFD) given for two months promote lipid deposition and inflammation in the liver and brain of mice. The results obtained indicate a tissue-specific response to both diets. Herein, we compared the effects of HCD and HFD on fatty acid (FA) composition and inflammation in the gastrocnemius muscle. Male Swiss mice were fed with HCD or HFD for 1 or 2 months. Saturated FA (SFA), monounsaturated FA (MUFA), n-3 polyunsaturated FA (n-3 PUFA), and n-6 PUFA were quantified. The activities of stearoyl-CoA desaturase 1 (SCD-1), Δ-6 desaturase (D6D), elongase 6, and de novo lipogenesis (DNL) were estimated. As for indicators of the inflammatory tissue state, we measured myeloperoxidase (MPO) activity and gene expression of F4/80, tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-6, and IL-10. The HCD led to a lower deposition of SFA, MUFA, n-3 PUFA, and n-6 PUFA compared to HFD. However, the HCD increased arachidonic acid levels, SFA/n-3 PUFA ratio, DNL, SCD-1, D6D, and MPO activities, and expression of IL-6, contrasting with the general idea that increased lipid deposition is associated with more intense inflammation. The HCD was more potent to induce skeletal muscle inflammation than the HFD, regardless of the lower lipid accumulation.

Stereotactic radiotherapy in oligoprogressive and oligorecurrent urothelial cancer patients: A retrospective experience.

Urothelial cancer is one of the most common malignancies; after relapse or disease progression available therapeutic options are limited. We analyze efficacy and toxicity of local treatment on metastases using stereotactic body radiation therapy (SBRT) in selected patients with oligometastatic disease from urothelial cancer. A significant percentage of treated lesions achieved local control, with a promising overall response rate. OBJECTIVES: to analyze efficacy and toxicity of local treatment on metastases using stereotactic body radiation therapy (SBRT) in selected patients with oligometastatic disease from urothelial cancer. MATERIALS AND METHODS: Data from clinical records of 19 patients treated in our institution since May 2011 to October 2017 with SBRT for oligometastatic/oligoprogressive urothelial carcinoma were retrospectively collected. Clinical outcomes in terms of local control (LC), response rate, symptoms control, progression free and overall survival (PFS and OS), and adverse events were analyzed and reported. RESULTS: Nineteen patients were treated on 25 metastatic lesions; 5 of them received treatment on multiple sites. After an average follow up of 11.5 months, LC was achieved in 17 lesions (68%) and there was no local recurrence in lesions with complete or partial response. OS was 13.8 months. Adverse events were reported only in 3 patients (5 overall events). No late toxicity was reported. CONCLUSIONS: An approach consisting in SBRT for local treatment of oligometastatic or persistent disease can be effective and safe in selected patients. Prospective studies are needed, to find correct selection criteria and optimal dose and fractionation.

Adipose tissue is less responsive to food restriction anti-inflammatory effects than liver, muscle, and brain in mice

High caloric intake promotes chronic inflammation, insulin resistance, and chronic diseases such as type-2 diabetes, which may be prevented by food restriction (FR). The effect of FR on expression of pro-inflammatory and anti-inflammatory genes in adipose tissue, liver, muscle, and brain was compared. Male Swiss mice were submitted to FR (FR group) or had free access to food (control group) during 56 days. The liver, gastrocnemius muscle, brain, and epididymal white adipose tissue (WAT) were collected for analysis of gene expressions. FR attenuated inflammation in the liver, brain, and gastrocnemius muscle but did not markedly change inflammatory gene expression in epididymal WAT. We concluded that adipose tissue was less responsive to FR in terms of gene expression of pro-inflammatory and anti-inflammatory genes.

Phosphate wasting disorders in adults.

A cause of hypophosphatemia is phosphate wasting disorders. Knowledge concerning mechanisms involved in phosphate wasting disorders has greatly increased in the last decade by the identification of phosphatonins, among them FGF-23. FGF-23 is a primarily bone derived factor decreasing renal tubular reabsorption of phosphate and the synthesis of calcitriol. Currently, pharmacological treatment of these disorders offers limited efficacy and is potentially associated to gastrointestinal, renal, and parathyroid complications; therefore, efforts have been directed toward newer pharmacological strategies that target the FGF-23 pathway. This review focuses on phosphate metabolism, its main regulators, and phosphate wasting disorders in adults, highlighting the main issues related to diagnosis and current and new potential treatments.

Robotic Stereotactic Retreatment for Biochemical Control in Previously Irradiated Patients Affected by Recurrent Prostate Cancer.

AIMS: Robotic stereotactic body radiotherapy (rSBRT) to local recurrences emerged as a valuable option for exclusive local failure after prior external beam radiation therapy (EBRT) for localised prostate cancer. The aim of this study was to assess the efficacy and safety of rSBRT in patients experiencing locally recurrent prostate cancer after prior definitive or postoperative radiotherapy using the Cyberknife. MATERIALS AND METHODS: Data from 50 patients were retrospectively reviewed. Local recurrence was assessed by 18F-choline positron emission tomography and pelvic magnetic resonance imaging; a dose of 30 Gy was delivered in five fractions. Prostate-specific antigen (PSA) was assessed at 2 months, 6 months and every 4 months thereafter. Toxicity was assessed according to CTCAE v.4.03. RESULTS: All patients received prior EBRT. The median EQD2 total dose was 74 Gy (60-80 Gy). Eleven patients were receiving androgen deprivation after prior biochemical failure. At 6 months, 41 patients showed a median PSA decline of -77.1% (14.3-99.3%), whereas nine patients experienced a median PSA elevation of +58.7% (0-2300.0%). Biochemical relapse-free survival (BRFS) was 80.0%. Impaired BRFS was correlated with the high-risk category at diagnosis (P = 0.014, hazard ratio 5.61) and ongoing androgen deprivation (P = 0.025, hazard ratio 2.98). Neither clinical variables nor dosimetric parameters were found to be predictive for toxicity. CONCLUSION: Focal rSBRT can achieve durable remission in locally relapsing patients and systemic treatment can be postponed with acceptable toxicity. Accurate patient selection is mandatory to maximise disease control.

Improving patient outcomes in fibrous dysplasia/McCune-Albright syndrome: an international multidisciplinary workshop to inform an international partnership.

To develop consensus on improving the management of patients, we convened an international workshop involving patients, clinicians, and researchers. Key findings included the diagnostic delay and variability in subsequent management with agreement to develop an international natural history study. We now invite other stakeholders to join the partnership. PURPOSE: The aim of this study was develop a consensus on how to improve the management of patients with fibrous dysplasia and prioritize areas for research METHODS: An international workshop was held over 3 days involving patients, clinicians, and researchers. Each day had a combination of formal presentations and facilitated discussions that focused on clinical pathways and research. RESULTS: The patient workshop day highlighted the variability of patients' experience in getting a diagnosis, the knowledge of general clinical staff, and understanding long-term outcomes. The research workshop prioritized collaborations that improved understanding of the contemporary natural history of fibrous dysplasia/McCune-Albright syndrome (FD/MAS). The clinical workshop outlined the key issues around diagnostics, assessment of severity, treatment and monitoring of patients. CONCLUSIONS: In spite of advances in understanding the genetic and molecular underpinnings of fibrous dysplasia/McCune-Albright syndrome, clinical management remains a challenge. From the workshop, a consensus was reached to create an international, multi-stakeholder partnership to advance research and clinical care in FD/MAS. We invite other stakeholders to join the partnership.

Monte Carlo simulated corrections for beam commissioning measurements with circular and MLC shaped fields on the CyberKnife M6 System: a study including diode, microchamber, point scintillator, and synthetic microdiamond detectors.

Monte Carlo simulation was used to calculate correction factors for output factor (OF), percentage depth-dose (PDD), and off-axis ratio (OAR) measurements with the CyberKnife M6 System. These include the first such data for the InCise MLC. Simulated detectors include diodes, air-filled microchambers, a synthetic microdiamond detector, and point scintillator. Individual perturbation factors were also evaluated. OF corrections show similar trends to previous studies. With a 5 mm fixed collimator the diode correction to convert a measured OF to the corresponding point dose ratio varies between -6.1% and -3.5% for the diode models evaluated, while in a 7.6 mm × 7.7 mm MLC field these are -4.5% to -1.8%. The corresponding microchamber corrections are +9.9% to +10.7% and +3.5% to +4.0%. The microdiamond corrections have a maximum of -1.4% for the 7.5 mm and 10 mm collimators. The scintillator corrections are <1% in all beams. Measured OF showed uncorrected inter-detector differences >15%, reducing to <3% after correction. PDD corrections at d > d max were <2% for all detectors except IBA Razor where a maximum 4% correction was observed at 300 mm depth. OAR corrections were smaller inside the field than outside. At the beam edge microchamber OAR corrections were up to 15%, mainly caused by density perturbations, which blurs the measured penumbra. With larger beams and depths, PTW and IBA diode corrections outside the beam were up to 20% while the Edge detector needed smaller corrections although these did vary with orientation. These effects are most noticeable for large field size and depth, where they are dominated by fluence and stopping power perturbations. The microdiamond OAR corrections were <3% outside the beam. This paper provides OF corrections that can be used for commissioning new CyberKnife M6 Systems and retrospectively checking estimated corrections used previously. We recommend the PDD and OAR corrections are used to guide detector selection and inform the evaluation of results rather than to explicitly correct measurements.

CyberKnife stereotactic radiotherapy for isolated recurrence in the prostatic bed.

PURPOSE: To report a clinical experience of stereotactic body radiation therapy (SBRT) for isolated recurrence in the prostatic bed from prostate cancer. MATERIALS AND METHODS: Between November 2011 and November 2013, 16 patients were treated with SBRT for a macroscopic isolated recurrence of prostate cancer in the prostatic bed. All patients were initially treated with radical prostatectomy, and half of them also received radiotherapy. Two schedules of SBRT were used: 30 Gy in 5 fractions in previously irradiated patients, 35 Gy in five fractions in radiotherapy-naïve patients. RESULTS: At a median follow-up of 10 months (range 2-21 months), a significant biochemical response was found in all but one patient. At imaging evaluation, no local progression was noted: 10 patients showed partial response while four stable disease. At the moment of analysis, all 16 patients were alive. Seven of them experienced distant relapse, while nine maintained biochemical control, with no further therapy. Median time to relapse was 9.3 months (range 3-15.2 months). The treatment was well tolerated: One patient experienced G2 acute genitourinary and gastrointestinal toxicity. CONCLUSIONS: Our experience shows that SBRT with CyberKnife for isolated nodal relapse is a safe and well-tolerated treatment.

Taxonomy of rare genetic metabolic bone disorders.

UNLABELLED: This article reports a taxonomic classification of rare skeletal diseases based on metabolic phenotypes. It was prepared by The Skeletal Rare Diseases Working Group of the International Osteoporosis Foundation (IOF) and includes 116 OMIM phenotypes with 86 affected genes. INTRODUCTION: Rare skeletal metabolic diseases comprise a group of diseases commonly associated with severe clinical consequences. In recent years, the description of the clinical phenotypes and radiographic features of several genetic bone disorders was paralleled by the discovery of key molecular pathways involved in the regulation of bone and mineral metabolism. Including this information in the description and classification of rare skeletal diseases may improve the recognition and management of affected patients. METHODS: IOF recognized this need and formed a Skeletal Rare Diseases Working Group (SRD-WG) of basic and clinical scientists who developed a taxonomy of rare skeletal diseases based on their metabolic pathogenesis. RESULTS: This taxonomy of rare genetic metabolic bone disorders (RGMBDs) comprises 116 OMIM phenotypes, with 86 affected genes related to bone and mineral homeostasis. The diseases were divided into four major groups, namely, disorders due to altered osteoclast, osteoblast, or osteocyte activity; disorders due to altered bone matrix proteins; disorders due to altered bone microenvironmental regulators; and disorders due to deranged calciotropic hormonal activity. CONCLUSIONS: This article provides the first comprehensive taxonomy of rare metabolic skeletal diseases based on deranged metabolic activity. This classification will help in the development of common and shared diagnostic and therapeutic pathways for these patients and also in the creation of international registries of rare skeletal diseases, the first step for the development of genetic tests based on next generation sequencing and for performing large intervention trials to assess efficacy of orphan drugs.

Human Preosteoblastic Cell Culture from a Patient with Severe Tumoral Calcinosis-Hyperphosphatemia Due to a New GALNT3 Gene Mutation: Study of In Vitro Mineralization.

Human disorders of phosphate (Pi) handling and skeletal mineralization represent a group of rare bone diseases. One of these disease is tumoral calcinosis (TC). In this study, we present the case of a patient with TC with a new GALNT3 gene mutation. We also performed functional studies using an in vitro cellular model. Genomic DNA was extracted from peripheral blood collected from a teenage Caucasian girl affected by TC, and from her parents. A higher capability to form mineralization nodules in vitro was found in human preosteoblastic cells of mutant when compared to wild-type controls. We found a novel homozygous inactivating splice site mutation in intron I (c.516-2a>g). A higher capability to form mineralization nodules in vitro was found in the mutant cells in human preosteoblastic cells when compared to wild-type controls. Understanding the functional significance and molecular physiology of this novel mutation will help to define the role of FGF23 in the control of Pi homeostasis in normal and in pathological conditions.

Cyberknife treatment for low and intermediate risk prostate cancer.

Cyberknife is an emerging treatment for early stage prostate cancer. Between October 2012 and January 2014, 32 patients were treated in our institution. Prescribed dose was 35-36.25 Gy in five fractions. Biochemical response was observed in 22 patients. Four patients experienced G2 acute genitourinary toxicity and in two cases we recorded G3 acute GU toxicity. 5 patients experienced G2 acute proctitis. At last follow up visit, all patients were still alive. 29 remained free of disease at last follow up appointment, while three developed a biochemical recurrence. Our experience confirms the efficacy and safety of Cyberknife for localized prostate cancer.

Stereotactic radiotherapy for isolated nodal recurrence of prostate cancer.

PURPOSE: To report a clinical experience in stereotactic body radiation therapy (SBRT) for isolated nodal metastases from prostate cancer. MATERIALS AND METHODS: Between November 2011 and December 2013, 30 patients (39 lesions) were treated with SBRT, delivered using Cyberknife, for recurrent prostate cancer with isolated nodal metastases. Prescribed doses and schedules of fractionation varied, ranging from 24 Gy in 1 fraction to 36 Gy in 3 fractions. Most commonly used schedules were 30 Gy in 3 fractions and 36 in Gy in 3 fractions on alternating days. Biochemical response, acute and late toxicity were analyzed. RESULTS: At a median follow-up of 12 months (range 2-24.9), a significant reduction of PSA was observed in 24 cases, while PSA was stable in 1 case and raised in 9 cases. At the time of analysis, among the 30 patients treated, two were dead for systemic disease; 12 patients experienced a relapse of disease in other sites. Sixteen patients were still free of disease. In 24 cases, imaging evaluation 3 months after treatment was available. No in-field recurrence was detected. SBRT was well tolerated: One patient experienced G2 acute genitourinary toxicity. Late toxicity was evaluated in patients with more than 6 months of follow-up, and only one complained G1 proctitis. We did not observe any acute or late severe toxicity (≥G3). CONCLUSIONS: Our experience shows that SBRT for isolated nodal relapse from prostate cancer is a safe treatment, with promising results in terms of efficacy.

Rare diseases in clinical endocrinology: a taxonomic classification system.

PURPOSE: Rare endocrine-metabolic diseases (REMD) represent an important area in the field of medicine and pharmacology. The rare diseases of interest to endocrinologists involve all fields of endocrinology, including rare diseases of the pituitary, thyroid and adrenal glands, paraganglia, ovary and testis, disorders of bone and mineral metabolism, energy and lipid metabolism, water metabolism, and syndromes with possible involvement of multiple endocrine glands, and neuroendocrine tumors. Taking advantage of the constitution of a study group on REMD within the Italian Society of Endocrinology, consisting of basic and clinical scientists, a document on the taxonomy of REMD has been produced. METHODS AND RESULTS: This document has been designed to include mainly REMD manifesting or persisting into adulthood. The taxonomy of REMD of the adult comprises a total of 166 main disorders, 338 including all variants and subtypes, described into 11 tables. CONCLUSIONS: This report provides a complete taxonomy to classify REMD of the adult. In the future, the creation of registries of rare endocrine diseases to collect data on cohorts of patients and the development of common and standardized diagnostic and therapeutic pathways for each rare endocrine disease is advisable. This will help planning and performing intervention studies in larger groups of patients to prove the efficacy, effectiveness, and safety of a specific treatment.

Quality assurance of volumetric modulated arc therapy: evaluation and comparison of different dosimetric systems.

PURPOSE: To compare and evaluate different dosimetric techniques and devices for the QA of VMAT plans created by two treatment planning systems (TPSs). METHODS: A total of 50 VMAT plans were optimized for treatment of anatomical sites of various complexities by two TPSs which use rather different approaches to VMAT optimization. Dosimetric plan verifications were performed both as part of commissioning and as patient specific QA of clinical treatments. Absolute point doses were measured for all plans by a micro ion chamber inserted in a dedicated water-filled cylindrical phantom. Delivered dose distributions were verified by four techniques based on different detectors: radiographic and gafchromic films, two systems based on 2D diode arrays and an ion chamber array. Gamma index analysis with various tolerance levels (3%, 3 mm and 3%, 2 mm) was used to analyze differences between calculated and delivered doses. Sensitivity to possible delivery errors was also evaluated for three of the considered devices introducing +/-3 mm shifts along the three directions and a 3 degrees gantry offset. RESULTS: Ion chamber measured point doses were within 3% of calculated ones for 48 out of 50 values. For delivered dose distribution, the average fraction of passed gamma values using 3% and 3 mm criteria was above 95% for both TPSs and all detectors except gafchromic film which yielded on average of 91.4%. For 49 out of 50 plans, a pass-rate above 94% was obtained by at least one of the four techniques. Shrinking the tolerance to 3% and 2 mm, the average pass-rate by all detectors (except film) was still above 95% for one of the two TPSs, but lower for the other one. The detector sensitivity to 3 mm shifts and to gantry angle offset was strongly plan and partially detector dependent: the obtained pass-rate reduction ranged from 2% to 30%. CONCLUSIONS: The presented results for VMAT plans QA assess the reliability of the delivered doses for both TPSs. The slightly lower pass-rate obtained for one of the considered TPS can be attributed to a higher level of complexity of the optimized plans. The results by different dosimetric techniques are coherent, apart from a few measurements by gafchromic films. The detector sensitivity to delivery errors, being strongly plan dependent, is not easy to evaluate.