Genomic Characterization of a Rare, de Novo Unbalanced ins(3;1)(p25.3;q21.3q23.3) in a Female Child with Multiple Congenital Anomalies.

"Simple" 1-way interchromosomal insertions involving an interstitial 1q segment are rare, and therefore, their characterization at the base pair level remains understudied. Here, we describe the genomic characterization of a previously unreported de novo interchromosomal insertion (3;1) entailing an about 12-Mb pure gain of 1q21.3q23.3 that causes typical (microcephaly, developmental delay, and facial dysmorphism) and atypical (interauricular communication, small feet with bilateral deep plantar creases, syndactyly of II-IV toes, and mild pachyonychia of all toes) clinical manifestations associated with this region. Based on our analyses, we hypothesize that the duplication of a subset of morbid genes (including LMNA, USF1, VANGL2, LOR, and POGZ) could account for most clinical findings in our patient. Furthermore, the apparent disruption of a promoter region (between CPNE9 and BRPF1) and a topologically associated domain also suggests likely pathogenic reconfiguration/position effects to contribute to the patient's phenotype. In addition to further expanding the clinical spectrum of proximal 1q duplications and evidencing the phenotypical heterogeneity among similar carriers, our genomic findings and observations suggest that randomness - rather than lethality issues - may account for the paucity of "simple" interchromosomal insertions involving the 1q21.3q23.3 region as genomic donor and distal 3p25.3 as receptor. Moreover, the microhomology sequence found at the insertion breakpoint is consistent with a simple nonhomologous end-joining mechanism, in contrast to a chromothripsis-like event, which has previously been seen in other nonrecurrent insertions. Taken together, the data gathered in this study allowed us to inform this family about the low recurrence risk but not to predict the reproductive prognosis for hypothetical carriers. We highlight that genomic-level assessment is a powerful tool that allows the visualization of the full landscape of sporadic chromosomal injuries and can be used to improve genetic counseling.

Circulating blood levels of IL-6, IFN-γ, and IL-10 as potential diagnostic biomarkers in gastric cancer: a controlled study.

BACKGROUND: Gastric adenocarcinoma is the third most common cause of cancer-associated death worldwide. Helicobacter pylori infection activates a signaling cascade that induces production of cytokines and chemokines involved in the chronic inflammatory response that drives carcinogenesis. We evaluated circulating cytokines and chemokines as potential diagnostic biomarkers for gastric cancer. METHODS: We included 201 healthy controls and 162 patients with distal gastric cancer who underwent primary surgical resection between 2009 and 2012 in Mexico City. The clinical and pathological data of patients were recorded by questionnaire, and the cancer subtype was classified as intestinal or diffuse. Pathological staging of cancer was based on the tumor-node-metastasis staging system of the International Union Against Cancer. Concentrations of IL-1ß, IL-6, TNF-α, IL-10, and MCP-1 in serum were measured using multiplex analyte profiling technology and concentrations of IL-8, IFN-γ, and TGF-ß in plasma were measured using enzyme-linked immunosorbent assay. RESULTS: Levels of IL-1ß, IL-6, IFN-γ, and IL-10 were significantly higher and that of MCP-1 was lower in gastric cancer patients compared with controls. No differences in IL-8 or TNF-α levels were observed between gastric cancer and controls. IFN-γ and IL-10 were significantly higher in both intestinal and diffuse gastric cancer, whereas IL-1ß and IL-6 were higher and TGF-ß lower only in intestinal gastric cancer; MCP-1 was lower only in diffuse gastric cancer. IFN-γ and IL-10 levels were significantly higher in early (I/II) and late stage (III/IV) gastric cancer; IL-1ß and IL-8 were higher and MCP-1 was lower only in late stage (IV) patients. Receiver-operating characteristic analysis showed that for diagnosis of GC, IL-6 had high specificity (0.97) and low sensitivity (0.39), IL-10 had moderate specificity (0.82) and low sensitivity (0.48), and IL-1ß and IFN-γ showed low specificity (0.43 and 0.53, respectively) and moderate sensitivity (0.76 and 0.71, respectively). CONCLUSIONS: Increased levels of IL-6, IFN-γ, and IL-10 might be useful as diagnostic biomarkers for GC; however, this needs to be confirmed with larger number of patients and with control groups other than blood donors, properly age paired. IL-1ß, IL-6, MCP-1, and TGF-ß differentiate intestinal from diffuse GC. IFN-γ and IL-10 might be useful for diagnosis of early stage GC, and IL-1ß, IL-8, and MCP-1 for late stages of the disease.

Toll-like receptors and cytokines are upregulated during Helicobacter pylori infection in children.

BACKGROUND AND AIM: Helicobacter pylori infection is mainly acquired during childhood, and establishes a chronic infection that may lead to peptic ulcer or gastric cancer during adulthood. Toll-like receptors (TLRs) are expressed by distinct cell types throughout the gastrointestinal tract, and play an important role in regulation of the innate immune response. Few works have addressed TLRs expression in gastric epithelia of adults, and scarce studies have done it in children. The aim of this work was to analyze the expression of TLR2, TLR4, TLR5, TLR9, and IL-8, IL-10 and TNF-α in the gastric mucosa of children with and without H. pylori infection. METHODS: Gastric biopsies were collected by endoscopy from 50 children with recurrent abdominal pain, 25 with H. pylori infection and 25 without infection. In the gastric biopsies the expression of TLRs and cytokines was studied by immunohistochemistry, and the degree of mucosal inflammation was determined using the Sydney system. RESULTS: We found that H. pylori infection was associated with a significant increased expression of TLRs 2, 4, 5 and 9, although expression varied between surface epithelia and glands. Epithelial cells expressing IL-8, IL-10 and TNF-α were increased in gastric mucosa of children with H. pylori infection. CONCLUSION: This study shows the gastric epithelia of children respond to H. pylori infection by increasing the expression of TLR2, TLR4, TLR5, TLR9 and the cytokines IL-8, IL-10 and TNF-α.

First Report of Mexican Patients with PACS1-Related Neurodevelopmental Disorder and Review of the PACS1-, PACS2-, and WDR37-Related Ophthalmological Manifestations.

Introduction: PACS1-related neurodevelopmental disorder (PACS1-related NDD) is caused by pathogenic variants in the PACS1 gene and is characterized by a distinctive facial appearance, intellectual disability, speech delay, seizures, feeding difficulties, cryptorchidism, hernias, and structural anomalies of the brain, heart, eye, and kidney. There is a marked facial resemblance and a common multisystem affectation with patients carrying pathogenic variants in the WDR37 and PACS2 genes, although they vary in terms of severity and eye involvement. Case Presentation: Here, we describe 4 individuals with PACS1-related NDD from Mexico, all of them carrying a de novo PACS1 variant c.607C>T; p.(Arg203Trp) identified by exome sequencing. In addition to eye colobomata, this report identified corneal leukoma, cataracts, and tortuosity of retinal vessels as ophthalmic manifestations not previously reported in patients with PACS1-related NDD. Discussion: We reviewed the ocular phenotypes reported in 74 individuals with PACS1-related NDD and the overlaps with WDR37- and PACS2-related syndromes. We found that the 3 syndromes have in common the presence of colobomata, ptosis, nystagmus, strabismus, and refractive errors, whereas microphthalmia, microcornea, and Peters anomaly are found only among individuals with PACS1-related NDD and WDR37 syndrome, being more severe in the latter. This supports the previous statement that the so-called WDR37-PACS1-PACS2 axis might have an important role in ocular development and also that the specific ocular findings could be useful in the clinical differentiation between these related syndromes.

Sensitivity of a helical diode array device to delivery errors in IMRT treatment and establishment of tolerance level for pretreatment QA.

The aim of this study is to determine the gantry angle and multileaf collimator (MLC) gap error-detection threshold of a diode helical array with an inserted micro-ionization chamber in order to use this device for the pretreatment quality assurance (QA) of intensity-modulated radiation therapy (IMRT) treatments. Implications on the dose-volume histograms (DVHs) of the patient treatments will also be considered for the establishment of a QA protocol with a reasonable tolerance level. Three dynamic IMRT HN (head and neck) and prostate treatments were studied. Random and systematic variations of gantry angle and systematic errors in MLC gap width of the clinical treatments were analyzed in order to establish the detection sensitivity of the array. The associated clinical significance was studied introducing the same errors in the treatment plan based on the patients' computed tomography (CT) and calculating the corresponding DVHs. The Gamma (3%/3 mm) presented a 4% variation in failure rate for a rotation error of 1° for both types of treatment. Both systematic and random errors in gantry rotation angle have little effect on the patients' DVHs. MLC gap width errors of 1 mm and 2 mm in the prostate treatments imply a mean variation in isocenter-measured absorbed dose of 2.1% and 4.1%, respectively. In the case of HN, these errors entail a change in measured isocenter dose of 4.7% and 8.6%, respectively. The variation observed in the DVHs of the patients was, basically, a global displacement of the curves proportional to the isocenter dose variation caused by the gap width error. According to the array sensitivity to the analyzed errors and its implication in patient DVHs, a tolerance of 95% point passing rate for the gamma criterion 3%/2 mm and an agreement of 2% in isocenter absolute dose have been established as tolerance criteria for our pretreatment IMRT QA protocol.

Multidisciplinary evidence of an isolated Neanderthal occupation in Abric del Pastor (Alcoi, Iberian Peninsula).

Testing Neanderthal behavioural hypotheses requires a spatial-temporal resolution to the level of a human single occupation episode. Yet, most of the behavioural data on Neanderthals has been obtained from coarsely dated, time-averaged contexts affected by the archaeological palimpsest effect and a diversity of postdepositional processes. This implies that time-resolved Neanderthal behaviour remains largely unknown. In this study, we performed archaeostratigraphic analysis on stratigraphic units IVe, IVf, IVg, Va, Vb and Vc from Abric del Pastor (Alcoi, Iberian Peninsula). Further, we isolated the archaeological remains associated with the resulting archaeostratigraphic unit and applied raw material, technological, use-wear, archaeozoological and spatial analyses. Our results show a low-density accumulation of remains from flintknapping, flint tool-use and animal processing around a hearth. These data provide a time-resolved human dimension to previous high-resolution environmental and pyrotechnological data on the same hearth, representing the first comprehensive characterisation of a Neanderthal single occupation episode. Our integrated, multidisciplinary method also contributes to advance our understanding of archaeological record formation processes.

New insights of tricuspid regurgitation: a large-scale prospective cohort study.

AIMS: To evaluate the burden of tricuspid regurgitation (TR) in a large cohort, determine the right ventricle involvement of patients with TR and determine the characteristics of isolated TR. METHODS AND RESULTS: Prospective study where consecutive patients undergoing an echocardiographic study in 10 centres were included. All studies with significant TR (at least moderate) were selected. We considered that patients with one of pulmonary systolic hypertension >50 mmHg, left ventricular ejection fraction <35%, New York Heart Association III-IV, or older than 85 years, had a high surgical risk. A total of 35 088 echocardiograms were performed. Significant TR was detected in 6% of studies. Moderate TR was found in 69.6%, severe in 25.5%, massive in 3.9%, and torrential in 1.0% of patients. Right ventricle was dilated in 81.7% of patients with massive/torrential TR, in 55.9% with severe TR, and in 29.3% with moderate TR (P < 0.001). Primary TR was present in 7.4% of patients whereas secondary TR was present in 92.6%. Mitral or aortic valve disease was the most common aetiology (54.6%), following by isolated TR (16%). Up to 51.9% of patients with severe, massive, or torrential primary TR and 57% of patients with severe, massive, or torrential secondary TR had a high surgical risk. CONCLUSION: Significant TR is a prevalent condition and a high proportion of these patients have an indication for valve intervention. More than a half of patients with severe, massive, or torrential TR had a high surgical risk. Massive/torrential TR may have implications regarding selection and monitoring patients for percutaneous treatment.

Fire and brief human occupations in Iberia during MIS 4: Evidence from Abric del Pastor (Alcoy, Spain).

There is a relatively low amount of Middle Paleolithic sites in Europe dating to MIS 4. Of the few that exist, several of them lack evidence for anthropogenic fire, raising the question of how this period of global cooling may have affected the Neanderthal population. The Iberian Peninsula is a key area to explore this issue, as it has been considered as a glacial refugium during critical periods of the Neanderthal timeline and might therefore yield archaeological contexts in which we can explore possible changes in the behaviour and settlement patterns of Neanderthal groups during MIS 4. Here we report recent data from Abric del Pastor, a small rock shelter in Alcoy (Alicante, Spain) with a stratified deposit containing Middle Palaeolithic remains. We present absolute dates that frame the sequence within MIS 4 and multi-proxy geoarchaeological evidence of in situ anthropogenic fire, including microscopic evidence of in situ combustion residues and thermally altered sediment. We also present archaeostratigraphic evidence of recurrent, functionally diverse, brief human occupation of the rock shelter. Our results suggest that Neanderthals occupied the Central Mediterranean coast of the Iberian Peninsula during MIS 4, that these Neanderthals were not undergoing climatic stress and they were habitual fire users.

Long-term Outcomes and Patterns of Failure Following Trimodality Treatment With Bladder Preservation for Invasive Bladder Cancer.

OBJECTIVE: To report long-term results on survival, toxicity, and patterns of failure of 3 different organ-sparing strategies for patients with muscle invasive bladder cancer. MATERIALS AND METHODS: This is a monoinstitutional prospective analysis of 3 consecutive bladder-sparing protocols combining maximal transurethral resection of bladder tumor (mTURBT), radiotherapy (RT), and cisplatin-based chemotherapy. Protocol 1 consisted of neoadjuvant methotrexate-cisplatin-vinblastine followed by endoscopic re-evaluation and consolidative RT 60 Gy in complete responders. Protocol 2 involved altered-fractionation RT 64.8 Gy and concurrent weekly cisplatin with re-evaluation after 40.8 Gy. Protocol 3 consisted of RT 64.8 Gy with concomitant weekly cisplatin. Nonresponders underwent radical cystectomy. Probabilities for overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS) were calculated using Kaplan-Meier product limited estimates. A Cox regression multivariate analysis was performed to detect potential risk factors for OS, CSS, and MFS. RESULTS: The 10-year bladder preservation rate was 79%. The 10-year OS, CSS, and MFS rates were 43.2%, 76.3% and 79.2%, respectively. There was no statistically significant difference in OS between the different treatment protocols. On multivariate analysis, mTURBT of the bladder and the complete response after induction therapy were independent correlates of improved OS and of MFS. The development of invasive bladder recurrence was independently associated with worse CSS and MFS. CONCLUSION: Ten-year results indicate that bladder-sparing treatment is a successful approach for muscle invasive bladder cancer in selected patients. The mTURBT of the bladder tumor and complete response after induction therapy remain the most relevant predictive factors.

Lewis antigen expression by Helicobacter pylori strains colonizing different regions of the stomach of individual patients.

The diversity in the expression of Lewis antigens (Le) of 226 single colonies of Helicobacter pylori isolated from four regions of the stomach of eight adults is shown. Le(y) was expressed more in strains colonizing antrum than in strains colonizing fundus, whereas Le(x) was more common in fundus strains. cagA(+) strains were more associated with Le-negative strains.

Study of the uncertainty in the determination of the absorbed dose to water during external beam radiotherapy calibration.

To achieve a good clinical outcome in radiotherapy treatment, a certain accuracy in the dose delivered to the patient is required. Therefore, it is necessary to keep the uncertainty in each of the steps of the process inside some acceptable values, which implies a global uncertainty as low as possible. This work is focused on the uncertainty evaluation of absorbed dose to water in the routine calibration for clinical beams, in the range of energies used in external radiotherapy. With this aim, different uncertainty components (corrected electrometer reading, calibration factor, beam quality correction factor and reference conditions) associated to beam calibration have been considered. Results show a typical uncertainty in the determination of absorbed dose to water during beam calibration around 1.3% for photon beams and 1.5% for electron beams (k=1 in both cases) when the N(D,w) formalism is used and is theoretically calculated. These values may be different depending on the uncertainty provided by the standards laboratory for calibration factor, which is shown in the work. If the total application of the N(D,w) formalism, that is to say, specific calibrations of each chamber in the user's beam qualities, is taken into account the uncertainty in this step of the process could be placed close to 1.0%. Furthermore, the possibility of an uncertainty reduction with the absorbed dose to water formalism adoption against the air kerma one is discussed.

First deep screening of bacterial assemblages associated with corals of the Tropical Eastern Pacific.

Bacterial assemblages associated with the hermatypic corals Pocillopora damicornis and P. verrucosa, the surrounding seawater and the sediment at six coral reef sites in the north section of the Tropical Eastern Pacific were assessed using MiSeq Illumina sequencing of the V4 region of the 16S rDNA. The bacterial microbiota in both coral species, seawater and sediment were stable to seasonal variations. Bacterial assemblages between the same substrates were not significantly different from each other in the six sites sampled. Interestingly, the bacterial composition between substrates within the same site was significantly different, or not, depending on the conservation status of the site. Moreover, we found species-specific bacterial OTUs in both coral species. Analyzing the relationship between bacterial composition and environmental variables revealed a positive correlation between bacterial assemblages and dissolved oxygen, ammonium and silicate.

Identification of Mycobacterium tuberculosis in the cerebrospinal fluid of patients with meningitis using nested PCR.

Tuberculous meningitis (TBM) is the most severe form of tuberculosis. It is caused by Mycobacterium tuberculosis (M. tuberculosis; MT) and it is very difficult to diagnose. The symptoms are similar to other infectious neurological diseases, such as neurocysticercosis, neuroborreliosis, or herpes viral infection. The aim of this study was to identify tuberculosis (TB) in cases of meningitis with clinical and laboratory evidence suggestive of TBM, and to confirm our findings with molecular tests for TB infection. We recruited patients with neurological symptoms who were examined at the neurology services of Hospitals of Instituto Mexicano del Seguro Social (IMSS) in Mexico City. A total of 144 consecutive patients with suggestive infectious meningitis were initially included; 94 cases of meningitis with clinical and laboratory evidence suggestive of TBM were included, but only 50 of these cases fulfilled the criteria for probable TBM. As the controls, we included 50 cases of meningitis with clinical and laboratory evidence suggestive of non-TBM. Cerebrospinal fluid (CSF) was collected from all 100 patients (cases and controls) and tested for TB by multiplex and nested PCR analyses. Nested PCR detected 0.1 fg of M. tuberculosis DNA. TB infection was confirmed with molecular tests in 49 patients from the 50 cases suggestive of TBM and in 1 of the 50 non-TBM cases. The analysis exhibited a sensitivity of 98.0%, a specificity of 92.0%, a positive predictive value of 88.0% and a negative predictive value of 98.0%. The use CSF for the analyses proved to be effective for the rapid diagnosis of TBM using a developed system of multiplex and nested PCR analyses in patients presenting neurological symptoms.

Correction: Coral Reef Health Indices versus the Biological, Ecological and Functional Diversity of Fish and Coral Assemblages in the Caribbean Sea.

[This corrects the article DOI: 10.1371/journal.pone.0161812.].

Coral Reef Health Indices versus the Biological, Ecological and Functional Diversity of Fish and Coral Assemblages in the Caribbean Sea.

This study evaluated the relationship between the indices known as the Reef Health Index (RHI) and two-dimensional Coral Health Index (2D-CHI) and different representative metrics of biological, ecological and functional diversity of fish and corals in 101 reef sites located across seven zones in the western Caribbean Sea. Species richness and average taxonomic distinctness were used to asses biological estimation; while ecological diversity was evaluated with the indices of Shannon diversity and Pielou´s evenness, as well as by taxonomic diversity and distinctness. Functional diversity considered the number of functional groups, the Shannon diversity and the functional Pielou´s evenness. According to the RHI, 57.15% of the zones were classified as presenting a "poor" health grade, while 42.85% were in "critical" grade. Based on the 2D-CHI, 28.5% of the zones were in "degraded" condition and 71.5% were "very degraded". Differences in fish and coral diversity among sites and zones were demonstrated using permutational ANOVAs. Differences between the two health indices (RHI and 2D-CHI) and some indices of biological, ecological and functional diversity of fish and corals were observed; however, only the RHI showed a correlation between the health grades and the species and functional group richness of fish at the scale of sites, and with the species and functional group richness and Shannon diversity of the fish assemblages at the scale of zones. None of the health indices were related to the metrics analyzed for the coral diversity. In general, our study suggests that the estimation of health indices should be complemented with classic community indices, or should at least include diversity indices of fish and corals, in order to improve the accuracy of the estimated health status of coral reefs in the western Caribbean Sea.

Clinical impact of the detector size effect in 3D-CRT.

OBJECTIVE: The detector size artificially increases the measured penumbra of radiotherapy fields. The aim of this work is to determine the influence of the detector size when planning three-dimensional conformal radiation therapy (3D-CRT) treatments. MATERIAL AND METHODS: Two anatomical sites of interest in 3D-CRT were studied: prostate and hypophysis chordoma. Conventional 3D-CRT treatments for two cases in these locations were planned with a FOCUS 4.0.0 (Computerized Medical Systems, USA) treatment planning system (TPS) equipped with Fast Fourier Transform Convolution (FFTC) and Multigrid Superposition (MGS) algorithms, making use of beams modelled from radiation profiles measured either with a 2.0 mm diameter detector (PFD(3G) diode) or with a 5.5 mm diameter detector (PTW-31002 ionisation chamber). These detectors cover up the range of detector sizes commonly used to measure radiation profiles for 3D-CRT. Dose-volume histograms (DVHs), radiobiological indexes, tumor control probability (TCP) and normal tissue complication probability (NTCP) were analysed and compared for planning target volumes (PTVs) and organs at risk (OAR) studied. RESULTS: Important differences in DVH were found. OAR received higher dose levels when a 5.5 mm detector was used to measure profiles compared to the case in which a 2.0 mm detector was used. A 2 Gy increment in the mean rectal dose was found when the larger detector was used. In the same way, NTCP of brain stem in hypophysis chordoma treatments was doubled when this detector was used. CONCLUSION: The current use of ionisation chambers of about 5 mm active diameter to get the necessary data to model treatment machines in radiotherapy treatment planning systems (TPS) implies a significant overirradiation of OAR close to the PTV in 3D-CRT treatments due to errors in the measured penumbra of beam profiles. To avoid this overirradiation, the measured profiles should either being acquired with a suitable detector size (2-3 mm active diameter) or being deconvoluted.

Statistical analysis of dose-volume and dose-wall histograms for rectal toxicity following 3D-CRT in prostate cancer.

The purpose of this paper is to determine the correlation between dose-volume histogram (DVH) and dose wall-histogram (DWH) in the evaluation of rectal complications for prostate cancer patients treated with three-dimensional conformal radiotherapy (3D-CRT). A retrospective analysis of DVHs and DWHs of a subset of 25 prostate cancer patients treated with 3D-CRT was performed. For every patient the rectum and the rectal wall (inner and outer surface) were contoured. Median ICRU radiation dose of 79.4 Gy was administered. Correlation between DVHs and DWHs parameters was investigated by the nonparametric Spearman test and by linear regression analysis. The results showed a statistically significant linear correlation between pairs of DVH and DWH dosimetric parameters with Spearman correlation values (S) bigger than 0.8, with p values better than 0.0005 (two-sided) when the emptied rectum is considered. The variation of S and linear fit slope values [b(1)] showed a very similar functional shape with a minimum at 91% ICRU dose [S =0.83, b(1)=0.65]. The present study confirms a high correlation (>80%) between DVH and DWH of the rectum following 3D-CRT for prostate cancer. The derived advantage is that the contouring of inner surface of rectum could be obviated in almost 90% of patients when performing predictive models for rectal complications based on dosimetric variables under the standard treatment conditions specified in this study.

Experimental validation tests of fast Fourier transform convolution and multigrid superposition algorithms for dose calculation in low-density media.

BACKGROUND AND PURPOSE: Modern conformal radiotherapy treatments require accurate dose calculation in any relevant clinical situation. One of these situations is the treatment of lung tumors, where irradiation has to be planned under challenging conditions for dose calculation. In this study we assess the errors in dose values predicted by fast Fourier transform convolution (FFTC) and multigrid superposition (MGS) algorithms implemented in a commercial treatment planning system (TPS). MATERIALS AND METHODS: FFTC and MGS algorithms were used in a FOCUS 3.0.0 (Computerized Medical Systems, USA) to calculate doses in treatment plans using photon beams of 6 and 25 MV nominal energy from a Saturne 43 linac (GE Medical Systems, USA). A 10x10-cm beam irradiating a mediastinum-lung and a thoracic wall-lung-thoracic wall modeled geometry was assessed. The calculated data were compared with measurements performed with radiographic films and ionization chamber. RESULTS: FFTC algorithm leads to an average deviation from ionometric dose measurements of over 10%. Discrepancies between measured and calculated beam fringe values (distance between 50 and 90% isodose lines) of up to 8 mm were observed. For MGS algorithm, all the points assessed in both geometries fulfilled the 3%-3 mm accuracy criteria and the average deviation of absolute dose was about 1%. A maximum of 3 mm deviation in the beam fringe for any depth was found and was within 2 mm beyond the buildup region. Deviations between ionometric and film measurements were within 3%. CONCLUSIONS: MGS algorithm assesses with reasonable accuracy dose distributions and absolute dose in inhomogeneous regions like the lung region. Therefore, and respecting the inhomogeneity dose calculation, the system could be used in routine clinical practice and in dose-escalation programs. This is not true in the case of FFTC algorithm which leads to errors greater than 10% in the absolute dose calculation and underestimates the beam fringe by up to 8 mm.