Optimization of treatment workflow for 0.35T MR-Linac system.

PURPOSE: This study presents a novel and comprehensive framework for evaluating magnetic resonance guided radiotherapy (MRgRT) workflow by integrating the Failure Modes and Effects Analysis (FMEA) approach with Time-Driven Activity-Based Costing (TDABC). We assess the workflow for safety, quality, and economic implications, providing a holistic understanding of the MRgRT implementation. The aim is to offer valuable insights to healthcare practitioners and administrators, facilitating informed decision-making regarding the 0.35T MRIdian MR-Linac system's clinical workflow. METHODS: For FMEA, a multidisciplinary team followed the TG-100 methodology to assess the MRgRT workflow's potential failure modes. Following the mitigation of primary failure modes and workflow optimization, a treatment process was established for TDABC analysis. The TDABC was applied to both MRgRT and computed tomography guided RT (CTgRT) for typical five-fraction stereotactic body RT (SBRT) treatments, assessing total workflow and costs associated between the two treatment workflows. RESULTS: A total of 279 failure modes were identified, with 31 categorized as high-risk, 55 as medium-risk, and the rest as low-risk. The top 20% risk priority numbers (RPN) were determined for each radiation oncology care team member. Total MRgRT and CTgRT costs were assessed. Implementing technological advancements, such as real-time multi leaf collimator (MLC) tracking with volumetric modulated arc therapy (VMAT), auto-segmentation, and increasing the Linac dose rate, led to significant cost savings for MRgRT. CONCLUSION: In this study, we integrated FMEA with TDABC to comprehensively evaluate the workflow and the associated costs of MRgRT compared to conventional CTgRT for five-fraction SBRT treatments. FMEA analysis identified critical failure modes, offering insights to enhance patient safety. TDABC analysis revealed that while MRgRT provides unique advantages, it may involve higher costs. Our findings underscore the importance of exploring cost-effective strategies and key technological advancements to ensure the widespread adoption and financial sustainability of MRgRT in clinical practice.

Cucurbitacin B modulates M2 macrophage differentiation and attenuates osteosarcoma progression via PI3K/AKT pathway.

Osteosarcoma is a common malignant bone tumour characterised by an aggressive metastatic potential. The tumour microenvironment, particularly the M2-polarised macrophages, is crucial for tumour progression. Cucurbitacin B (CuB), a triterpenoid derivative, is recognised for its anti-inflammatory and antitumour properties. This study investigates CuB and its effect on M2 macrophage differentiation and osteosarcoma progression, aiming to contribute to new treatment strategies. In vitro, THP-1 monocytes were stimulated with PMA, IL-13 and IL-4 to induce differentiation into M2 macrophages. Additionally, the influence of CuB on the proliferation, migration and invasion of osteosarcoma cells in the context of M2 macrophages was scrutinised. Crucial signalling pathways, especially the PI3K/AKT pathway, affected by CuB were identified and validated. In vivo, the osteosarcoma model was employed to gauge the effects of CuB on tumour weight, lung metastasis, angiogenesis, cell proliferation and M2 macrophage markers. The results showed that CuB inhibited M2 macrophage differentiation, leading to reduced proliferation, migration and invasion of osteosarcoma cells. CuB manifested an inhibitory effect on the PI3K/AKT pathway during the differentiation of M2 macrophages. In mouse models, CuB markedly reduced the tumour weight and the number of lung metastases. It also reduced the expression of angiogenesis and cell proliferation markers in tumour tissues, decreased the quantity of M2 macrophages and their associated markers and pathway proteins. In conclusion, CuB impedes osteosarcoma progression by inhibiting M2 macrophage differentiation via the PI3K/AKT pathway, presenting the potential for therapeutic advancements in osteosarcoma treatment.

Circulating vascular endothelial growth factor and cancer risk: A bidirectional mendelian randomization.

In observational studies, circulating vascular endothelial growth factor (VEGF) has been reported to be associated with certain types of cancer. The purpose of this study was to verify whether there is a causal relationship between circulating VEGF and different types of cancer and the direction of the causal relationship. Summary statistical data were obtained from the corresponding genome-wide association studies (GWASs) to investigate the causal relationship between circulating VEGF and the risk of several cancers, including breast cancer, ovarian cancer, lung cancer, colorectal cancer, anus and anal canal cancer, prostate cancer, esophageal cancer, kidney cancer, bladder cancer, thyroid cancer, malignant neoplasm of the brain and malignant neoplasm of the liver and intrahepatic bile ducts. A two-sample bidirectional Mendelian randomization (MR) analysis and sensitivity tests were used to evaluate the validity of causality. A causal relationship was detected between circulating VEGF and colorectal cancer (OR 1.21, 95% CI 1.11-1.32, p < 0.000) and colon adenocarcinoma (OR 1.245, 95% CI 1.10-1.412, p < 0.000). Suggestive evidence of association was detected in VEGF on malignant neoplasms of the rectum (OR 1.16, 95% CI 1.00-1.34, p = 0.049). No causal relationship was found between circulating VEGF and other types of cancer, nor was there a reverse causal relationship from tumors to VEGF (p > 0.05). Circulating VEGF has a causal relationship with specific types of cancer. Our findings highlight and confirm the importance of circulating VEGF in the prevention and treatment of colorectal cancer.

Proton induced DNA double strand breaks at the Bragg peak: Evidence of enhanced LET effect.

Purpose: To investigate DNA double strand breaks (DSBs) induced by therapeutic proton beams in plateau and Bragg peak to demonstrate DSB induction due to the higher LET in the Bragg peak. Materials and Methods: pUC19 plasmid DNA samples were irradiated to doses of 1000 and 3000 Gy on a Mevion S250i proton system with a monoenergetic, 110 MeV, proton beam at depths of 2 and 9.4 cm, corresponding to a position on the plateau and distal Bragg peak of the beam, respectively. The irradiated DNA samples were imaged by atomic force microscopy for visualization of individual DNA molecules, either broken or intact, and quantification of the DNA fragment length distributions for each of the irradiated samples. Percentage of the broken DNA and average number of DSBs per DNA molecule were obtained. Results: Compared to irradiation effects in the plateau region, DNA irradiated at the Bragg peak sustained more breakage at the same dose, yielding more short DNA fragments and higher numbers of DSB per DNA molecule. Conclusion: The higher LET of proton beams at the Bragg peak results in more densely distributed DNA DSBs, which supports an underlying mechanism for the increased cell killing by protons at the Bragg peak.

Is adaptive planning necessary for patients with large tumor position displacements observed on daily image guidance during lung SBRT?

For patients undergoing stereotactic body radiation therapy for lung cancer, their tumor positions may vary due to anatomical changes. This study is to investigate whether adaptive re-planning is necessary for patients with large tumor position displacements observed from daily kV-cone-beam computed tomography (kV-CBCT). We selected 16 fractions from 16 patients with recorded treatment couch shifts greater than 1.5 cm under kV-CBCT guidance. The treatment positions for these patients were manually restored in kV-CBCTs via bone-to-bone alignments (B2B) and tumor-to-tumor alignments (T2T) with corresponding planning CTs. The tumor volumes, including PTVs, ITVs, and GTVs, were transferred from the planning CTs to these kV-CBCTs. With the planned beam configurations and treatment isocenters, kV-CBCTs were imported into the treatment planning system for dose recalculations. To minimize uncertainties of the Hounsfield Unit (HU) in kV-CBCTs, uniformed HU values were assigned to the externals, ITVs, and lungs. The percentage volumes of GTVs, ITVs, and PTVs receiving the prescription dose (VRx) and the dose to the normal structures were analyzed. Seven out of the 16 patients were identified with >5mm tumor position displacements after subtracting the recorded couch shifts from the shifts of B2B alignment. For T2T alignments, 9 out of 16 (56.3%) patients had VRx of PTV <95% (the planning goal) with 91.4% as the lowest, while VRx of the GTV and ITV remained 100% for all 16 patients. For B2B alignments, 14 out of 16 (87.5%) patients have VRx of PTV <95%; 5 patients (31.3%) had VRx of ITV <95%; and 4 patients (25.0%) had VRx of GTV <99%. T2T alignment with 5 mm PTV margin was found superior to B2B alignment, resulting in adequate dose coverage to the ITVs, even for tumors with large positional changes. Adaptive re-planning may not be necessary under these scenarios.

Is there a volume threshold of brain metastases for Linac-based stereotactic radiotherapy?

PURPOSE: To investigate whether there is a volume threshold in target volume of brain metastases below which a small cone size and sharp penumbra in Gamma Knife (GK) may provide improved plan quality when compared to Volumetric Modulated Arc Therapy (VMAT)-based stereotactic radiosurgery (SRS). METHODS: For patients treated on GK SRS for brain metastases in 2018-2019 in our institution, 121 patients with two and three targets were identified. Twenty-six patients with two or three brain metastases (total of 76 lesions) were selected for this study. Two VMAT plans, SmartArc (Pinnacle) and HyperArc (Eclipse), were generated retrospectively for each patient. Plan quality was evaluated based on RTOG conformity index (CI), Paddick gradient index (GI), normal tissue (NT) V12Gy and V4.5Gy. By using the receiver operating characteristic (ROC) curve for both VMAT plans (SmartArc and HyperArc) and metrics of RTOG CI and NT V12Gy, we compared GK plans to SmartArc and HyperArc plans separately to determine the threshold volume. RESULTS: For SmartArc plans, both ROC curve analyses showed a threshold volume of 0.4 cc for both CI and NT V12Gy. For HyperArc plans, the threshold volumes were 0.2 cc for the CI and 0.5 cc for NT V12Gy. GK plans produced improved dose distribution compared to VMAT for targets ≤0.4 cc, but HyperArc was found to have competing results with GK in terms of CI and NT V12Gy. For targets > 0.4 cc, both SmartArc and HyperArc showed better plan quality when compared to the GK plans. CONCLUSIONS: Target volumes ≤0.4 cc may require a small cone size and sharp penumbra in GK while for target volumes >0.4 cc, VMAT-based SRS can provide improved overall plan quality and faster treatment delivery.

Impact of prostate focused alignment on planned pelvic lymph node dose.

PURPOSE: Prostate patients with positive lymph node margins receive an initial course of 45 Gy to the planning target volume (PTV) comprised of prostate, seminal vesicles, and lymph nodes with a 1-cm margin. The prostate is localized via implanted fiducial markers before each fraction is delivered using portal-imaging. However, the pelvic lymph nodes are affixed to the bony anatomy and are not mobile in concert with the prostate. The aim of this study was to determine whether a significant difference in pelvic lymph node coverage exists between planned and delivered external beam therapy treatments for these patients. METHODS: The recorded prostate motions were gathered for 19 patients; conjointly the pelvic lymph node motions were determined by manual registration of the bony anatomy in the kV-images. The difference between the prostate and the bony anatomy coordinates was input into Eclipse as field shifts to represent the deviation in planned vs delivered pelvic lymph node coverage. RESULTS: Structure volume at V(100) was recorded for each patient for two structures: summed pelvic lymph nodes (LN CTV) and pelvic lymph nodes +1 cm margin (LN PTV) to express their contribution to the PTV. For the LN PTV, the average difference between the planned coverage and calculated delivered coverage was 3.5%, with a paired t-test value of P = 0.005. Based upon bony anatomy registration, 26% of patients received less than 95% dose coverage using V(100) criteria for LN PTV. Dose value differences between the two plans at minimum were 6.96 ± 6.23 Gy, at mean were 0.54 ± 0.40 Gy, and at maximum were 0.10 ± 0.29 Gy. For the LN CTV, the average difference between the planned coverage and calculated delivered coverage was 1%, with a paired t-test value of P = 0.53. CONCLUSIONS: The results indicate a significant difference exists between the planned coverage and calculated delivered coverage for the LN PTV. There was no significant difference found for the LN CTV. We conclude that lymph node motion must be considered with the prostate motion when aligning patients before each fraction.

Dosimetric impact and modeling of prone breast positioning device and couch structures.

In prone breast radiation, as the medial tangential beam usually passes through the immobilization board and couch, it is necessary to quantify the attenuation effect and the potential skin dose enhancement from these external structures. The prone breast board studied consists of an insert on which the contralateral breast rests and a board base indexed to the couch. Two different Varian couch systems were also studied. Transmission factors (TF) of the board were measured using a Farmer chamber at 4 cm depth. Couch TFs were measured using a thimble chamber centered in a cylindrical phantom. A custom support model was created in the treatment planning system (TPS). TFs were then computed in the TPS for comparison. Selected clinical plans were recomputed in the TPS incorporating external structures for target coverage evaluation. The correction for the attenuation effect in the TPS was also demonstrated. Skin dose effects were evaluated using a Markus parallel plate chamber with a 1 mm buildup cap. Measured insert TFs ranged 0.976 to 0.983 for 6 MV and 0.990 to 0.999 for 23 MV. Board base TFs ranged 0.979 to 0.985 for 6 MV and 0.989 to 0.998 for 23 MV. TPS values agreed within 0.9% and 0.5% for the insert and board base, respectively. Assigned Hounsfield units (HUs) providing the best agreement were 200, -100, and -900 for the insert, the board "base shell" and "base inside," respectively. Varian Exact Couch and Exact IGRT Couch TFs varied with respect to couch angle, with minimum values of 0.837 and 0.956, respectively, for 6 MV. The clinical treatment volume (CTV) and whole breast receiving 95% of the prescription dose (CTV-V95 and WB-V95) of selected patients demonstrated reduced coverage due to attenuation of external structures. Close proximity to the base increased skin dose by up to 25% to 30%. Contacting the insert increased skin dose by 65% to 93% for 6 MV and 117% to 157% for 23 MV, respectively. Results have shown reduced coverage by attenuating external structures. Proper modeling of immobilization devices and couch structures in the TPS should be implemented for accurate dose calculation. Increased surface doses were observed due to direct contact to the insert or close proximity to the base. Further study is required to quantify such a skin dose enhancement effect and its correlation to clinically apparent skin effects and toxicity.

PEG-Ceramide Nanomicelles Induce Autophagy and Degrade Tau Proteins in N2a Cells.

PURPOSE: Alzheimer's disease (AD) is a neurodegenerative disorder that manifests as abnormal behavior and a progressive decline in memory. Although the pathogenesis of AD is due to the excessive deposition of amyloid ß protein (Aß) outside the neurons in the brain, evidence suggests that tau proteins may be a better target for AD therapy. In neurodegenerative diseases, a decrease in autophagy results in the failure to eliminate abnormally deposited or misfolded proteins. Therefore, induction of autophagy may be an effective way to eliminate tau proteins in the treatment of AD. We investigated the effects of polyethylene glycol (PEG)-ceramide nanomicelles on autophagy and on tau proteins in N2a, a murine neuroblastoma metrocyte cell line. METHODS: Ceramide is a sphingolipid bioactive molecule that induces autophagy. PEG-ceramide is a polymer that is composed of the hydrophobic chain of ceramide and the hydrophilic chain of PEG-2000. In this study, we prepared PEG-ceramide nanomicelles that were 10-20 nm in size and had nearly neutral zeta potential. RESULTS: The results show that PEG-ceramide nanomicelles caused an increase in the LC3-II/LC3-I ratio, while p62 protein levels decreased. Confocal microscopy revealed a significant increase in the number of dots corresponding to autophagosomes and autolysosomes, which indicated autophagic activation. Moreover, PEG-ceramide nanomicelles induced tau degradation in N2a cells through autophagy. CONCLUSION: In summary, we have confirmed that PEG-ceramide nanomicelles enhanced autophagic flux and degraded overexpressed human tau proteins in N2a cells by regulating the autophagy pathway. Thus, PEG-ceramide nanomicelles show great promise as agents to induce autophagy and degrade tau proteins in the treatment of AD.

Image artifacts caused by incorrect bowtie filters in cone-beam CT image-guided radiotherapy.

Certain models of cone beam computed tomography (CBCT) image-guided radiotherapy (IGRT) systems require manually placing the appropriate bowtie filter according to the relevant imaging protocol. Inadvertently using a wrong bowtie filter or no bowtie filter could cause unexpected image artifacts. In this work, CBCT image artifact patterns caused by different bowtie filter placement were evaluated. CBCT images of CT phantoms, that is, a Body Norm phantom, a Catphan® phantom and an anthropomorphic RANDO® phantom, were acquired at a Varian Trilogy® unit with an On-Board Imager® (OBI) system. Three image acquisition protocols were evaluated. For Standard Head protocol, half-fan bowtie and no bowtie filter were studied for comparison with the correct full-fan bowtie acquisition. For Pelvis and Low-Dose Thorax protocols, full-fan bowtie and no bowtie were studied for comparison with the correct half-fan bowtie acquisition. In addition, the possibility of reversed direction half-fan bowtie was also discussed. All possible scenarios of bowtie filter misplacement caused distinct artifacts regardless of protocols. These artifact patterns are different from the characteristic crescent artifact when correct bowtie filter was placed. Based on the artifact patterns described in this study we recommend reviewing image artifacts at time of image acquisition. If unexpected artifacts appear in the CBCT images, one should verify the correct placement of the bowtie filter and retake the image if necessary. However, it should also be stressed that using a wrong bowtie filter or forgetting to place the bowtie filter can cause increased patient dose. It is always a good practice to verify the bowtie filter placement before acquiring CBCT images for image-guided radiotherapy.

Clinical and dosimetric evaluation of recurrent breast cancer patients treated with hyperthermia and radiation.

Background: Treatment for locally recurrent breast cancer poses a significant challenge because the benefits in local control must be weighed against the increased risk of side effects of the treatment. Frequently, patients have been heavily pre-treated with radiation and several types of chemotherapy. Moreover, they often present with large volumes of bulky disease, further complicating management. Hyperthermia can be used to improve the efficacy of radiation, particularly in the setting of recurrent disease. Methods: We reviewed our clinical and dosimetric experience of breast cancer patients who received hyperthermia and radiation for recurrent breast cancer from 2011 to 2017. Thirty-six patients were treated with hyperthermia and radiation. Median follow-up was 11 months. Thirty patients (83.3%) received prior radiotherapy. The most commonly used radiation fraction scheme was 32 Gy in 8 fractions. The median radiation dose at the time of recurrence was 35.5 Gy (range 20-64 Gy). Mild temperature hyperthermia was delivered two times per week. Results: The median repeat radiation volume was 574 cc (range 11-3620 cc). Electrons, conventional photons, and IMRT radiation techniques were used. IMRT was used for large and complex treatment volumes and showed acceptable doses to organs at risk. The overall response rate was 61.1%. Complete response was observed in 17 patients (47.2%), partial response in 5 patients (13.9%), stable disease in 11 patients (30.6%), and progressive disease in 3 patients (8.3%). Twenty-six patients experienced acute grade 1 and 2 toxicities, primarily pain and erythema; and 26 experienced long-term grade 1 and 2 toxicities, mainly hyperpigmentation and lymphedema. Three patients developed new ulcerations that healed with conservative management. One patient developed pulmonary fibrosis resulting in mild dyspnea on exertion. Conclusion: Hyperthermia and radiation provide good local control with a favorable side effect profile. Thermoradiotherapy may be offered to patients with recurrent breast cancer, including those with extensive volumes of disease.

A Mini-System Integrated with Metal-Oxide-Semiconductor Sensor and Micro-Packed Gas Chromatographic Column.

In this work, a mini monitoring system integrated with a microfabricated metal oxide array sensor and a micro packed gas chromatographic (GC) column was developed for monitoring environmental gases. The microfabricated packed GC column with a 1.6 m length was used to separate the environmental gas, and the metal oxide semiconductor (MOS) array sensor, fabricated with nano-sized SnO-SnO2 sensitive materials, was able to effectively detect each component separated by GC column. The results demonstrate that the monitoring system can detect environmental gas with high precision.

Technical and dosimetric implications of respiratory induced density variations in a heterogeneous lung phantom.

BACKGROUND: Stereotactic Body Radiotherapy (SBRT) is an ablative dose delivery technique which requires the highest levels of precision and accuracy. Modeling dose to a lung treatment volume has remained a complex and challenging endeavor due to target motion and the low density of the surrounding media. When coupled together, these factors give rise to pulmonary induced tissue heterogeneities which can lead to inaccuracies in dose computation. This investigation aims to determine which combination of imaging techniques and computational algorithms best compensates for time dependent lung target displacements. METHODS: A Quasar phantom was employed to simulate respiratory motion for target ranges up to 3 cm. 4DCT imaging was used to generate Average Intensity Projection (AIP), Free Breathing (FB), and Maximum Intensity Projection (MIP) image sets. In addition, we introduce and compare a fourth dataset for dose computation based on a novel phase weighted density (PWD) technique. All plans were created using Eclipse version 13.6 treatment planning system and calculated using the Analytical Anisotropic Algorithm and Acuros XB. Dose delivery was performed using Truebeam STx linear accelerator where radiochromic film measurements were accessed using gamma analysis to compare planned versus delivered dose. RESULTS: In the most extreme case scenario, the mean CT difference between FB and MIP datasets was found to be greater than 200 HU. The near maximum dose discrepancies between AAA and AXB algorithms were determined to be marginal (< 2.2%), with a greater variability occurring within the near minimum dose regime (< 7%). Radiochromatic film verification demonstrated all AIP and FB based computations exceeded 98% passing rates under conventional radiotherapy tolerances (gamma 3%, 3 mm). Under more stringent SBRT tolerances (gamma 3%, 1 mm), the AIP and FB based treatment plans exhibited higher pass rates (> 85%) when compared to MIP and PWD (< 85%) for AAA computations. For AXB, however, the delivery accuracy for all datasets were greater than 85% (gamma 3%,1 mm), with a corresponding reduction in overall lung irradiation. CONCLUSIONS: Despite the substantial density variations between computational datasets over an extensive range of target movement, the dose difference between CT datasets is small and could not be quantified with ion chamber. Radiochromatic film analysis suggests the optimal CT dataset is dependent on the dose algorithm used for evaluation. With AAA, AIP and FB resulted in the best conformance between measured versus calculated dose for target motion ranging up to 3 cm under both conventional and SBRT tolerance criteria. With AXB, pass rates improved for all datasets with the PWD technique demonstrating slightly better conformity over AIP and FB based computations (gamma 3%, 1 mm). As verified in previous studies, our results confirm a clear advantage in delivery accuracy along with a relative decrease in calculated dose to the lung when using Acuros XB over AAA.

Recommendation of fiducial marker implantation for better target tracking using MV imager in prostate radiotherapy.

PURPOSE: The aim of this study was to develop a model that optimizes the fiducial marker locations in the prostate to increase detectability of the markers in the projected EPID images during VMAT treatments. METHODS AND MATERIALS: The fiducial marker tracking capability for each arc was evaluated through a proposed formula. The output of the formula, a detectability score, was calculated with the in-house developed software written in MATLAB (The Mathworks, Inc., Natick, MA, USA). Three unique weighting factors were added to penalize the detectability score. The detectability scores of four different patterns containing 40 combinations of simulated fiducial marker locations were evaluated with 101 previously treated prostate treatment plans (containing 202 individual arcs). The results were analyzed for each pattern group and each marker separation distance on the transverse plane. RESULTS: The maximum detectability of the markers occurred when they were placed between 10 and 15 mm from the center of the prostate in the transverse plane and 6-13 mm in the superior-inferior direction. The detectability decreased when the markers were placed beyond 20 mm in both directions. CONCLUSIONS: The fiducial marker-based detectability score can be used to predict the real-time tracking capability. Suggestions for optimal insertion locations were given to improve prostate motion management using MV imaging.

Accuracy of one algorithm used to modify a planned DVH with data from actual dose delivery.

Detection and accurate quantification of treatment delivery errors is important in radiation therapy. This study aims to evaluate the accuracy of DVH based QA in quantifying delivery errors. Eighteen previously treated VMAT plans (prostate, H&N, and brain) were randomly chosen for this study. Conventional IMRT delivery QA was done with the ArcCHECK diode detector for error-free plans and plans with the following modifications: 1) induced monitor unit differences up to ± 3.0%, 2) control point deletion (3, 5, and 8 control points were deleted for each arc), and 3) gantry angle shift (2° uniform shift clockwise and counterclockwise). 2D and 3D distance-to-agreement (DTA) analyses were performed for all plans with SNC Patient software and 3DVH software, respectively. Subsequently, accuracy of the reconstructed DVH curves and DVH parameters in 3DVH software were analyzed for all selected cases using the plans in the Eclipse treatment planning system as standard. 3D DTA analysis for error-induced plans generally gave high pass rates, whereas the 2D evaluation seemed to be more sensitive to detecting delivery errors. The average differences for DVH parameters between each pair of Eclipse recalculation and 3DVH prediction were within 2% for all three types of error-induced treatment plans. This illustrates that 3DVH accurately quantifies delivery errors in terms of actual dose delivered to the patients. 2D DTA analysis should be routinely used for clinical evaluation. Any concerns or dose discrepancies should be further analyzed through DVH-based QA for clinically relevant results and confirmation of a conventional passing-rate-based QA.

[A meta-analysis of fish intake and the risk of renal cell cancer].

OBJECTIVE: To explore the association of fish intake with the risk of renal cancer. METHODS: PubMed, Embase, CNKI and CA databases were searched for case-control studies or cohort studies examining the relationship between fish or fish products intake and renal cancer. Heterogeneity among the selected studies was assessed using I2 score, and the publication bias was assessed using funnel plots. RESULTS: Seventeen articles were included in the analysis with a heterogeneity across the studies (P=0.003, I(2)=52.3%). A random-effects model was used to generate the pooled risk ratio (RR) and 95% confidence interval (CI), and no statistically significant association was found between the risk of renal cancer and fish intake (RR=0.90; 95% CI, 0.78-1.02). In subgroup analysis, no evidence was found that the study design, study region or publication date influenced the results; but in the gender subgroup analysis, fish intake we found to decrease the risk of renal cancer in men but not in women. CONCLUSION: The results of meta-analysis do not support an association between fish intake and a lowered risk of renal cancer.