Publications by authors named "Sergio Faria"

88 Publications

Computational search for drug repurposing to identify potential inhibitors against SARS-COV-2 using Molecular Docking, QTAIM and IQA methods in viral Spike protein - Human ACE2 interface.

J Mol Struct 2021 May 8;1232:130076. Epub 2021 Feb 8.

Universidade Paulista, Av. Comendador Enzo Ferrari, 280-Swift, Campinas, SP, 13045-770, Brazil.

With the advancement of the Covid-19 pandemic, this work aims to find molecules that can inhibit the attraction between the Spike proteins of the SARS-COV-2 virus and human ACE2. The results of molecular docking positioned four molecules at the interaction site Tyr-491(Spike)-Glu-37(ACE2) and one at the site Gly-488(Spike)-Lys-353(ACE2). The QTAIM and IQA data showed that the 1629 molecule had a significant inhibitory effect on the Gly488-Ly353 site, decreasing the Laplacian of the electronic density of the BCP O-N. The molecule 2542 showed an inhibitory effect in two regions of interaction of the Tyr491-Glu37 site, acting on the BCPs H-H and O-H while the ligand 2600, in conformation 26, presented a similar effect only on the BCP O-H of that same interactive site. Thus, the data suggest laboratory tests of a combination of molecules that can act at two sites of interaction simultaneously, using the combination of 1629/2542 and 1629/2600 ligands.
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http://dx.doi.org/10.1016/j.molstruc.2021.130076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870108PMC
May 2021

Long-Term Results of Moderate Hypofractionation to Prostate and Pelvic Nodes Plus Androgen Suppression in High-Risk Prostate Cancer.

Pract Radiat Oncol 2020 Nov - Dec;10(6):e514-e520. Epub 2020 Jul 29.

Department of Radiation Oncology, McGill University, Quebec, Canada.

Purpose: Moderate hypofractionated radiation therapy (HypoRT) is an attractive alternative to conventionally fractionated radiation therapy for prostate cancer. However, most studies using HypoRT only included the prostate as the target volume. We report long-term outcomes of patients with high-risk prostate cancer treated with androgen deprivation therapy (ADT) and HypoRT to the prostate and nodal areas with a simultaneous integrated boost technique.

Methods And Materials: Patients with localized, high-risk prostate cancer entered a prospective phase I/II study with a HypoRT regimen of 60 Gy/20 fractions (4 weeks) to the prostate volume while the nodal areas received 44 Gy in the same 20 fractions delivered with intensity modulated radiation therapy with a simultaneous integrated boost technique. ADT started 2 to 3 months before HypoRT. Toxicity was prospectively assessed according to the Common Terminology Criteria for Adverse Events v3. Outcomes rates were calculated by the actuarial method of Kaplan-Meier from the date of last radiation treatment until date of event.

Results: We report on the first 105 patients treated between October 2010 and February 2014. Median follow-up was 74 months, with 97% of patients followed for more than 36 months. Median ADT duration was 18 months. The worst grade 2 or higher late gastrointestinal or genitourinary toxicity was seen in 7% and 9%, respectively. There was no grade 4 or 5 toxicity. At the last follow-up, the rates of grade ≥2 gastrointestinal or genitourinary toxicity were 2% and 3%, respectively, with no residual grade ≥3 toxicity. The 5- and 7-year actuarial overall survival and relapse free survival were 91% and 85% and 87% and 81%, respectively.

Conclusions: The longest follow-up report of moderate HypoRT (plus ADT) to the prostate and pelvic nodes shows that this approach is feasible, well tolerated, and effective. It is convenient for patients and the health system. A larger randomized trial using this approach is warranted.
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http://dx.doi.org/10.1016/j.prro.2020.06.012DOI Listing
July 2020

Mycorrhizal networks facilitate the colonization of legume roots by a symbiotic nitrogen-fixing bacterium.

Mycorrhiza 2020 May 25;30(2-3):389-396. Epub 2020 Mar 25.

Embrapa Agrobiologia, Rodovia BR 465, km 7, Seropédica, RJ, 23891-000, Brazil.

Arbuscular mycorrhizal fungi (AMF) absorb and translocate nutrients from soil to their host plants by means of a wide network of extraradical mycelium (ERM). Here, we assessed whether nitrogen-fixing rhizobia can be transferred to the host legume Glycine max by ERM produced by Glomus formosanum isolate CNPAB020 colonizing the grass Urochloa decumbens. An H-bridge experimental system was developed to evaluate the migration of ERM and of the GFP-tagged Bradyrhizobium diazoefficiens USDA 110 strain across an air gap compartment. Mycorrhizal colonization, nodule formation in legumes, and occurrence of the GFP-tagged strain in root nodules were assessed by optical and confocal laser scanning microscopy. In the presence of non-mycorrhizal U. decumbens, legume roots were neither AMF-colonized nor nodulated. In contrast, G. formosanum ERM crossing the discontinuous compartment connected mycorrhizal U. decumbens and G. max roots, which showed 30-42% mycorrhizal colonization and 7-11 nodules per plant. Fluorescent B. diazoefficiens cells were detected in 94% of G. max root nodules. Our findings reveal that, besides its main activity in nutrient transfer, ERM produced by AMF may facilitate bacterial translocation and the simultaneous associations of plants with beneficial fungi and bacteria, representing an important structure, functional to the establishment of symbiotic relationships.
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http://dx.doi.org/10.1007/s00572-020-00948-wDOI Listing
May 2020

Comparing local control and distant metastasis in NSCLC patients between CyberKnife and conventional SBRT.

Radiother Oncol 2020 Mar 7;144:201-208. Epub 2020 Feb 7.

Medical Physics Unit, McGill University and Cedars Cancer Center, Montréal, Canada.

Background And Purpose: Previous literature suggests that the dose proximally outside the PTV could have an impact on the incidence of distant metastasis (DM) after SBRT in stage I NSCLC patients. We investigated this observation (along with local failure) in deliveries made by different treatment modalities: robotic mounted linac SBRT (CyberKnife) vs conventional SBRT (VMAT/CRT).

Materials And Methods: This study included 422 stage I NSCLC patients from 2 institutions who received SBRT: 217 treated conventionally and 205 with CyberKnife. The dose behavior outside the PTV of both sub-cohorts were compared by analyzing the mean dose in continuous shells extending 1, 2, 3, …, 100 mm from the PTV. Kaplan-Meier analysis was performed between the two sub-cohorts with respect to DM-free survival and local progression-free survival. A multivariable Cox proportional hazards model was fitted to the combined cohort (n = 422) with respect to DM incidence and local failure.

Results: The shell-averaged dose fall-off beyond the PTV was found to be significantly more modest in CyberKnife plans than in conventional SBRT plans. In a 30 mm shell around the PTV, the mean dose delivered with CyberKnife (38.1 Gy) is significantly larger than with VMAT/CRT (22.8 Gy, p<10). For 95% of CyberKnife plans, this region receives a mean dose larger than the 21 Gy threshold dose discovered in our previous study. In contrast, this occurs for only 75% of VMAT/CRT plans. The DM-free survival of the entire CyberKnife cohort is superior to that of the 25% of VMAT/CRT patients receiving less than the threshold dose (VMAT/CRT), with a hazard ratio of 5.3 (95% CI: 3.0-9.3, p<10). The 2 year DM-free survival rates were 87% (95% CI: 81%-91%) and 44% (95% CI: 28%-58%) for CyberKnife and the below-threshold dose conventional cohorts, respectively. A multivariable analysis of the combined cohort resulted in the confirmation that threshold dose was a significant predictor of DM(HR = 0.28, 95% CI: 0.15-0.55, p<10) when adjusted for other clinical factors. CyberKnife was also found to be superior to the entire VMAT/CRT with respect to local control (HR = 3.44, CI: 1.6-7.3). The 2-year local progression-free survival rates for the CyberKnife cohort and the VMAT/CRT cohort were 96% (95% CI: 92%-98%) and 88% (95% CI: 82%-92%) respectively.

Conclusions: In standard-of-care CyberKnife treatments, dose distributions that aid distant control are achieved 95% of the time. Although similar doses could be physically achieved by conventional SBRT, this is not always the case with current prescription practices, resulting in worse DM outcomes for 25% of conventional SBRT patients. Furthermore, CyberKnife was found to provide superior local control compared to VMAT/CRT.
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http://dx.doi.org/10.1016/j.radonc.2020.01.017DOI Listing
March 2020

Correction to: Tracing Rhizophagus irregularis isolate IR27 in Ziziphus mauritiana roots under field conditions.

Mycorrhiza 2020 01;30(1):171

Laboratoire des Symbioses Tropicales et Méditerranéennes UMR113 INRA/AGRO-M/CIRAD/IRD/UM2-TA10/J, Campus International de Baillarguet, 34398, Montpellier, France.

The authors of the above-mentioned published article inadvertently omitted Dirk Redecker, Dioumacor Fall and Diaminatou Sanogo from the list of authors. The names and their affiliations presented in this paper.
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http://dx.doi.org/10.1007/s00572-020-00935-1DOI Listing
January 2020

Light Field Image Dataset of Skin Lesions.

Annu Int Conf IEEE Eng Med Biol Soc 2019 Jul;2019:3905-3908

Light field imaging technology has been attracting increasing interest because it enables capturing enriched visual information and expands the processing capabilities of traditional 2D imaging systems. Dense multiview, accurate depth maps and multiple focus planes are examples of different types of visual information enabled by light fields. This technology is also emerging in medical imaging research, like dermatology, allowing to find new features and improve classification algorithms, namely those based on machine learning approaches. This paper presents a contribution for the research community, in the form of a publicly available light field image dataset of skin lesions (named SKINL2 v1.0). This dataset contains 250 light fields, captured with a focused plenoptic camera and classified into eight clinical categories, according to the type of lesion. Each light field is comprised of 81 different views of the same lesion. The database also includes the dermatoscopic image of each lesion. A representative subset of 17 central view images of the light fields is further characterised in terms of spatial information (SI), colourfulness (CF) and compressibility. This dataset has high potential for advancing medical imaging research and development of new classification algorithms based on light fields, as well as in clinically-oriented dermatology studies.
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http://dx.doi.org/10.1109/EMBC.2019.8856578DOI Listing
July 2019

Novel knowledge-based treatment planning model for hypofractionated radiotherapy of prostate cancer patients.

Phys Med 2020 Jan 6;69:36-43. Epub 2019 Dec 6.

McGill University Health Centre, Montreal, QC, Canada.

Purpose: To demonstrate the strength of an innovative knowledge-based model-building method for radiotherapy planning using hypofractionated, multi-target prostate patients.

Material And Methods: An initial RapidPlan model was trained using 48 patients who received 60 Gy to prostate (PTV60) and 44 Gy to pelvic nodes (PTV44) in 20 fractions. To improve the model's goodness-of-fit, an intermediate model was generated using the dose-volume histograms of best-spared organs-at-risk (OARs) of the initial model. Using the intermediate model and manual tweaking, all 48 cases were re-planned. The final model, trained using these re-plans, was validated on 50 additional patients. The validated final model was used to determine any planning advantage of using three arcs instead of two on 16 VMAT cases and tested on 25 additional cases to determine efficacy for single-PTV (PTV60-only) treatment planning.

Results: For model validation, PTV V of 99.9% was obtained by both clinical and knowledge-based planning. D was lower for model plans: by 1.23 Gy (PTV60, CI = [1.00, 1.45]), and by 2.44 Gy (PTV44, CI = [1.72, 3.16]). OAR sparing was superior for knowledge-based planning: ΔD = 3.70 Gy (bladder, CI = [2.83, 4.57]), and 3.22 Gy (rectum, CI = [2.48, 3.95]); ΔD = 1.17 Gy (bowel bag, CI = [0.64, 1.69]), and 4.78 Gy (femoral heads, CI = [3.90, 5.66]). Using three arcs instead of two, improvements in OAR sparing and PTV coverage were statistically significant, but of magnitudes < 1 Gy. The model failed at reliable DVH predictions for single PTV plans.

Conclusions: Our knowledge-based model delivers efficient, consistent plans with excellent PTV coverage and improved OAR sparing compared to clinical plans.
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http://dx.doi.org/10.1016/j.ejmp.2019.11.023DOI Listing
January 2020

Consumption of meat, eggs and dairy products is associated with aerobic and anaerobic performance in Brazilian athletes - A cross-sectional study.

Nutr Hosp 2019 Dec;36(6):1375-1383

Universidade Federal de Mato Grosso do Sul.

Introduction: To associate food consumption according to the groups that make up the food pyramid with the aerobic and anaerobic performance of Brazilian athletes. A cross-sectional study of 168 athletes with a mean age and BMI of 20.84 ± 7.74 years and 22.88 ± 3.1 kg/m², respectively. Maximum power output was significantly associated with the meat and eggs groups (β = 0.31; p < 0.05). VO2max exhibited a positive relationship with the fruit group (β = 0.29; p < 0.05). A significant inverse relation between VO2max and the legumes group was observed (β = -0.76; p < 0.05). The meat and eggs group and the dairy products group had an inverse and significant association with VO2max (β = -0.43; p < 0.01). Consumption of meat and eggs showed a positive association with anaerobic performance, whereas the same group and the dairy products group had a negative association with aerobic performance.
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http://dx.doi.org/10.20960/nh.02718DOI Listing
December 2019

Mimosa caesalpiniifolia Benth. adapts to rhizobia populations with differential taxonomy and symbiotic effectiveness outside of its location of origin.

FEMS Microbiol Ecol 2019 08;95(8)

EMBRAPA, Centro Nacional de Pesquisa de Agrobiologia, Rodovia BR 465, km 7, s/n, Ecologia, Seropedica - RJ, 23891-000, Brazil.

Mimosa caesalpiniifolia Benth. is a legume native to the semi-arid region of Brazil, in the Northeast. Its successful adaptation to other locations, such as the Atlantic Forest in the Southeast region, may be related to its ability to establish symbiosis with nitrogen-fixing bacteria, especially β-rhizobia of the genus Paraburkholderia. The objective of this work was to determine whether M. caesalpiniifolia adapted to bacterial symbionts in locals where it was introduced. Bacteria were recovered from nodules of M. caesalpiniifolia and characterized at the genetic level by BOX-PCR and sequencing of the 16S rRNA, recA, nifH, and nodC genes. Their symbiotic effectiveness was assessed under axenic conditions. M. caesalpiniifolia nodulated mainly with Paraburkholderia sabiae and a few strains of Rhizobium in the Southeast. On the other hand, the symbionts found in the Northeast were, predominantly, Paraburkholderia diazotrophica. Regardless of its origin, P. diazotrophica promoted a superior accumulation of plant biomass than other bacterial species. The results presented here demonstrate the ability of M. caesalpiniifolia to adapt to bacterial populations outside its location of origin, and indicate that, in this case, the symbiotic effectiveness was associated with the taxonomical classification of the strains.
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http://dx.doi.org/10.1093/femsec/fiz109DOI Listing
August 2019

Two herbicides, two fungicides and spore-associated bacteria affect Funneliformis mosseae extraradical mycelium structural traits and viability.

Mycorrhiza 2019 Jul 12;29(4):341-349. Epub 2019 Jun 12.

CNR-Institute of Agricultural Biology and Biotechnology UOS Pisa, Pisa, Italy.

The extraradical mycelium (ERM) produced by arbuscular mycorrhizal fungi is fundamental for the maintenance of biological fertility in agricultural soils, representing an important inoculum source, together with spores and mycorrhizal root fragments. Its viability and structural traits, such as density, extent and interconnectedness, which are positively correlated with the growth and nutrition of host plants, may be affected by different agronomic practices, including the use of pesticides and by different mycorrhizospheric communities. This work, carried out using a whole-plant experimental model system, showed that structural traits of ERM, such as length and density, were strongly decreased by the herbicides dicamba and glufosinolate and the fungicides benomyl and fenhexamid, while anastomosis frequency and hyphal branching were differentially modulated by singly inoculated mycorrhizospheric bacteria, depending on their identity.
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http://dx.doi.org/10.1007/s00572-019-00901-6DOI Listing
July 2019

Tolerance doses for late adverse events after hypofractionated radiotherapy for prostate cancer on trial NRG Oncology/RTOG 0415.

Radiother Oncol 2019 06 5;135:19-24. Epub 2019 Mar 5.

Cedars-Sinai Medical Center, United States.

Purpose/objective: Hypofractionated radiotherapy (HRT) regimens for prostate cancer are emerging, but tolerance doses for late adverse events are scarce. The purpose of this study is to define dose-volume predictors for late gastrointestinal and genitourinary (GI and GU) toxicities after HRT in the multi-center NRG Oncology/RTOG 0415 low-risk prostate cancer trial (N = 521).

Material/methods: Treatment in the studied HRT arm was delivered as 70 Gy at 2.5 Gy/fraction with 3D-CRT/IMRT (N = 108/413). At a median follow-up of 5.9 years, the crude late ≥Grade 2 GI and GU toxicities were 19% and 29%, respectively. For modeling, the complete HRT cohort was randomly split into training and validation (70% and 30%; preserved toxicity rates). Within training, dose-response modeling was based on dose-volume cut-points (EQD2Gy; bladder/rectum: α/β = 6 Gy/3Gy), age, acute ≥Grade 2 toxicity, and treatment technique using univariate and multivariate logistic regression on bootstrapping (UVA and MVA). Candidate predictors were determined at p ≤ 0.05, and the selected MVA models were explored on validation where model generalizability was judged if the area under the receiver-operating curve in validation (AUC) was within AUC ± SD with p ≤ 0.05, and with an Hosmer-Lemeshow p-value (p) > 0.05.

Results: Three candidate predictors were suggested for late GI toxicity: the minimum dose to the hottest 5% rectal volume (D5%[Gy]), the absolute rectal volume <35 Gy, and acute GI toxicity (AUC = 0.59-0.63; p = 0.02-0.04). The two generalizable MVA models, i.e., D5%[Gy] with or without acute GI toxicity (AUC = 0.64, 0.65; p = 0.01, 0.03; p = 0.45-0.56), suggest that reducing late GI toxicity from 20% to 10% would require reducing D5%[Gy] from ≤65 Gy to ≤62 Gy (logistic function argument: 17+(0.24D5%[Gy])). Acute GU toxicity showed only a trend to predict late GU toxicity (AUC = 0.57; p = 0.07).

Conclusion: Late GI toxicity, following moderate HRT for low-risk prostate cancer, increases with higher doses to small rectal volumes. This work provides quantitative evidence that limiting small rectal dose 'hotspots' in clinical practice of such HRT regimens is likely to further reduce the associated rates of GI toxicity.
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http://dx.doi.org/10.1016/j.radonc.2019.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582638PMC
June 2019

Tracing Rhizophagus irregularis isolate IR27 in Ziziphus mauritiana roots under field conditions.

Mycorrhiza 2019 Jan 21;29(1):77-83. Epub 2018 Nov 21.

Laboratoire des Symbioses Tropicales et Méditerranéennes UMR113 INRA/AGRO-M/CIRAD/IRD/UM2-TA10/J, Campus International de Baillarguet, 34398, Montpellier, France.

Arbuscular mycorrhizal fungi (AMF) play a major role as biofertilizer for sustainable agriculture. Nevertheless, it is still poorly documented whether inoculated AMF can successfully establish in field soils as exotic AMF and improve plant growth and productivity. Further, the fate of an exogenous inoculum is still poorly understood. Here, we pre-inoculated two cultivars (Tasset and Gola) of the fruit tree Ziziphus mauritiana (jujube) with the exotic AM fungus Rhizophagus irregularis isolate IR27 before transplantation in the field. In two experiments, tracking and quantification of R. irregularis IR27 were assessed in a 13-month-old jujube and an 18-month-old jujube in two fields located in Senegal. Our results showed that the inoculant R. irregularis IR27 was quantitatively traced and discriminated from native R. irregularis isolates in roots by using a qPCR assay targeting a fragment of the RNA polymerase II gene (RPB1), and that the inoculum represented only fractions ranging from 11 to 15% of the Rhizophagus genus in the two plantations 13 and 18 months after transplantation, respectively. This study validates the use of the RPB1 gene as marker for a relative quantification of a mycorrhizal inoculant fungus isolate in the field.
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http://dx.doi.org/10.1007/s00572-018-0875-3DOI Listing
January 2019

Anisotropic Bladder Planning Target Volume in Bladder Radiation Therapy.

Pract Radiat Oncol 2019 Jan 7;9(1):24-28. Epub 2018 Aug 7.

Division of Radiation Oncology, Cedars Cancer Centre, McGill University Health Centre, Montreal, Quebec, Canada. Electronic address:

Purpose: This study aimed to investigate 3 planning target volume (PTV) margin expansions and determine the most appropriate volume to be used in bladder preservation therapy when using daily cone beam computed tomography (CBCT). We aimed to establish whether a smaller PTV expansion is feasible without risking geographical miss.

Methods And Materials: The study included patients with bladder cancer who were treated with a hypofractionated course of radiation therapy delivered with intensity modulated radiation therapy. The clinical target volume (CTV) was the whole empty bladder, and the PTV consisted of a 1.5-cm margin around the bladder (PTV). Patients underwent daily CBCT imaging before treatment to assess the bladder volume and ensure accurate positioning. We investigated 2 additional smaller PTV margin expansions to determine the most appropriate volume to be used with CBCT as a daily image guided radiation therapy modality. These margins were created retrospectively on every CBCT. The first additional volume was a uniform PTV margin of the surrounding 1 cm (PTV1 cm). When considering that the majority of the internal bladder movement was due to the variation in filling that occurs in the superior and anterior directions, a second volume of an anisotropic PTV margin with a 1.5-cm superior/anterior and 1 cm in other directions (PTV1/1.5 cm) was created. We recorded the frequency and measured the volume of bladder falling out of each PTV based on the daily CBCT.

Results: For the purpose of this study, we considered an arbitrary 5 cm of CTV falling out of the designated PTV as a clinically significant volumetric miss. The frequency of such a miss when applying the uniform PTV1 cm was 1%. However, when applying the uniform PTV1.5 cm and anisotropic PTV1/1.5 cm margins, the frequency was 0.5% and 0.5%, respectively.

Conclusions: The anisotropic PTV expansion of 1.5 cm superiorly and anteriorly and 1 cm in all other directions around the bladder (CTV) provides a safe PTV approach when daily CBCT imaging is used to localize an empty bladder.
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http://dx.doi.org/10.1016/j.prro.2018.07.006DOI Listing
January 2019

Can dose outside the PTV influence the risk of distant metastases in stage I lung cancer patients treated with stereotactic body radiotherapy (SBRT)?

Radiother Oncol 2018 09 22;128(3):513-519. Epub 2018 May 22.

Medical Physics Unit, McGill University Health Centre, Canada.

Background And Purpose: In an era where little is known about the "abscopal" (out-of-the-field) effects of lung SBRT, we investigated correlations between the radiation dose proximally outside the PTV and the risk of cancer recurrence after SBRT in patients with primary stage I non-small cell lung cancer (NSCLC).

Materials And Methods: This study included 217 stage I NSCLC patients across 2 institutions who received SBRT. Correlations between clinical and dosimetric factors were investigated. The clinical factors considered were distant metastasis (DM), loco-regional control (LRC) and radiation pneumonitis (RP). The dose (converted to EQD2) delivered to regions of varying size directly outside of the PTV was computed. For each feature, area under the curve (AUC) and odds ratios with respect to the outcome parameters DM, LRC and RP were estimated; Kaplan-Meier (KM) analysis was also performed.

Results: Thirty-seven (17%) patients developed DM after a median follow-up of 24 months. It was found that the mean dose delivered to a shell-shaped region of thickness 30 mm outside the PTV had an AUC of 0.82. Two years after treatment completion, the rate of DM in patients where the mean dose delivered to this region was higher than 20.8 Gy was 5% compared to 60% in those who received a dose lower than 20.8 Gy. KM analysis resulted in a hazard ratio of 24.2 (95% CI: 10.7, 54.4); p < 10. No correlations were found between any factor and either LRC or RP.

Conclusions: The results of this study suggest that the dose received by the region close to the PTV has a significant impact on the risk of distant metastases in stage I NSCLC patients treated with SBRT. If these results are independently confirmed, caution should be taken, particularly when a treatment plan results in a steep dose gradient extending outwards from the PTV.
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http://dx.doi.org/10.1016/j.radonc.2018.05.012DOI Listing
September 2018

Interdependency of efficient nodulation and arbuscular mycorrhization in Piptadenia gonoacantha, a Brazilian legume tree.

Plant Cell Environ 2018 09 17;41(9):2008-2020. Epub 2017 Nov 17.

CIRAD, UMR LSTM, F-34398, Montpellier, France.

Tripartite interactions between legumes and their root symbionts (rhizobia and arbuscular mycorrhizal fungi, AMF) are poorly understood, although it is well established that only specific combinations of symbionts lead to optimal plant growth. A classic example in which to investigate such interactions is the Brazilian legume tree Piptadenia gonoacantha (Caesalpinioideae), for which efficient nodulation has been described as dependent on the presence of AMF symbiosis. In this study, we compared the nodulation behaviour of several rhizobial strains with or without AMF inoculation, and performed analyses on nodulation, nodule cytology, N-fixing efficiency, and plant growth response. Nodulation of P. gonoacantha does not rely on the presence of AMF, but mycorrhization was rhizobial strain-dependent, and nodule effectiveness and plant growth were dependent on the presence of specific combinations of rhizobial strains and AMF. The co-occurrence of both symbionts within efficient nodules and the differentiation of bacteroids within nodule cells were also demonstrated. Novel close interactions and interdependency for the establishment and/or functioning of these symbioses were also revealed in Piptadenia, thanks to immunocytochemical analyses. These data are discussed in terms of the evolutionary position of the newly circumscribed mimosoid clade within the Caesalpinioid subfamily and its relative proximity to non-nodulated (but AMF-associated) basal subfamilies.
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http://dx.doi.org/10.1111/pce.13095DOI Listing
September 2018

Lossless Compression of Medical Images Using 3-D Predictors.

IEEE Trans Med Imaging 2017 11 9;36(11):2250-2260. Epub 2017 Jun 9.

This paper describes a highly efficient method for lossless compression of volumetric sets of medical images, such as CTs or MRIs. The proposed method, referred to as 3-D-MRP, is based on the principle of minimum rate predictors (MRPs), which is one of the state-of-the-art lossless compression technologies presented in the data compression literature. The main features of the proposed method include the use of 3-D predictors, 3-D-block octree partitioning and classification, volume-based optimization, and support for 16-b-depth images. Experimental results demonstrate the efficiency of the 3-D-MRP algorithm for the compression of volumetric sets of medical images, achieving gains above 15% and 12% for 8- and 16-bit-depth contents, respectively, when compared with JPEG-LS, JPEG2000, CALIC, and HEVC, as well as other proposals based on the MRP algorithm.
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http://dx.doi.org/10.1109/TMI.2017.2714640DOI Listing
November 2017

Study on molecular structure, spectroscopic properties (FTIR and UV-Vis), NBO, QTAIM, HOMO-LUMO energies and docking studies of 5-fluorouracil, a substance used to treat cancer.

Spectrochim Acta A Mol Biomol Spectrosc 2017 Sep 27;184:169-176. Epub 2017 Apr 27.

Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, São Paulo, Brazil; Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, São Paulo, Brazil. Electronic address:

Cancer cells can expand to other parts of body through blood system and nodes from a mechanism known as metastasis. Due to the large annual growth of cancer cases, various biological targets have been studied and related to this disorder. A very interesting target related to cancer is human epidermal growth factor receptor 2 (HER2). In this study, we analyzed the main intermolecular interactions between a drug used in the cancer treatment (5-fluorouracil) and HER2. Molecular modeling methods were also employed to assess the molecular structure, spectroscopic properties (FTIR and UV-Vis), NBO, QTAIM and HOMO-LUMO energies of 5-FU. From the docking simulations it was possible to analyze the interactions that occur between some residues in the binding site of HER2 and 5-FU. To validate the choice of basis set that was used in the NBO and QTAIM analyses, theoretical calculations were performed to obtain FT-IR and UV/Vis spectra, and the theoretical results are consistent with the experimental data, showing that the basis set chosen is suitable. For the maximum λ from the theoretical calculation (254.89nm) of UV/Vis, the electronic transition from HOMO to LUMO occurs at 4.89eV. From NBO analyses, we observed interactions between Asp863 and 5-FU, i.e. the orbitals with high transfer of electrons are LP O (donor NBO) and BD* (π) N-H (acceptor NBO), being that the value of this interaction is 7.72kcal/mol. Results from QTAIM indicate one main intermolecular H bond, which is necessary to stabilize the complex formed between the ligands and the biological target. Therefore, this study allowed a careful evaluation on the main structural, spectroscopic and electronic properties involved in the interaction between 5-FU and HER2, an important biological complex related to the cancer treatment.
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http://dx.doi.org/10.1016/j.saa.2017.04.070DOI Listing
September 2017

Long-term Outcomes of Induction Carboplatin and Gemcitabine Followed by Concurrent Radiotherapy With Low-dose Paclitaxel and Gemcitabine for Stage III Non-small-cell Lung Cancer.

Clin Lung Cancer 2017 09 1;18(5):565-571. Epub 2017 Mar 1.

Department of Radiation Oncology, McGill University Health Centre, Montreal, Quebec, Canada.

Background: Standard treatment for unresectable stage III non-small-cell lung cancer (NSCLC) is concurrent chemo-radiation (CRT). A regimen of induction carboplatin and gemcitabine followed by CRT was developed at the McGill University Health Centre to prevent delays in treatment initiation. We report the long-term outcomes with this regimen based on a pooled analysis of both protocol patients from a phase II study and nonprotocol patients.

Methods And Materials: Outcomes and toxicity data were retrieved for 142 patients with stage III NSCLC: 43 patients treated on protocol between January 2003 and November 2004, and 101 patients treated off-protocol between December 2004 and August 2013. Patients received 2 cycles of carboplatin with an area under the curve of 5 intravenously (IV) on day 1 and gemcitabine 1000 mg/m IV on days 1 and 8 every 3 weeks, followed on day 50 by CRT, 60 Gy/30 over 6 weeks, concomitantly with 2 cycles of paclitaxel 50 mg/m IV and gemcitabine 100 mg/m IV on days 1 and 8 every 3 weeks.

Results: The median overall survival was 23.2 months. With a median follow-up of 23.8 months, the 3-, 4-, and 5-year overall survival was 38%, 30%, and 26%, respectively. The median and 5-year progression-free survival rates were 12.5 months and 25%, respectively. Rates of grade ≥ 3 hematologic, esophageal, and respiratory toxicity were 20%, 10%, and 10%, respectively. Forty-eight patients received further lines of chemotherapy.

Conclusion: The present analysis affirms the favorable toxicity profile of this novel induction chemotherapy, without apparent compromise in clinical outcomes, when compared with regimens using immediate concurrent CRT.
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http://dx.doi.org/10.1016/j.cllc.2017.02.003DOI Listing
September 2017

Genetic diversity of symbiotic Paraburkholderia species isolated from nodules of Mimosa pudica (L.) and Phaseolus vulgaris (L.) grown in soils of the Brazilian Atlantic Forest (Mata Atlântica).

FEMS Microbiol Ecol 2017 04;93(4)

Soil Biotechnology Laboratory, Embrapa Soja, C.P. 231, 86001-970, Londrina, PR, Brazil.

Some species of the genus Paraburkholderia that are able to nodulate and fix nitrogen in symbiosis with legumes are called β-rhizobia and represent a group of ecological and biotechnological importance. We used Mimosa pudica and Phaseolus vulgaris to trap 427 rhizobial isolates from rhizospheric soil of Mimoseae trees in the Brazilian Atlantic Forest. Eighty-four representative strains were selected according to the 16S rRNA haplotypes and taxonomically characterized using a concatenated 16S rRNA-recA phylogeny. Most strains were assembled in the genus Paraburkholderia, including Paraburkholderia sabiae and Pa. nodosa. Mesorhizobium (α-rhizobia) and Cupriavidus (β-rhizobia) were also isolated, but in smaller proportions. Multilocus sequence analysis and BOX-PCR analyses indicated that six clusters of Paraburkholderia represent potential new species. In the phylogenetic analysis of the nodC gene, the majority of the strains were positioned in the same groups as in the 16S rRNA-recA tree, indicative of stability and vertical inheritance, but we also identified horizontal transfer of nodC in Pa. sabiae. All α- and β-rhizobial species were trapped by both legumes, although preferences of the host plants for specific rhizobial species have been observed.
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http://dx.doi.org/10.1093/femsec/fix027DOI Listing
April 2017

Acute and late toxicity in high-risk prostate cancer patients treated with androgen suppression and hypofractionated pelvic radiation therapy.

Pract Radiat Oncol 2017 Jul - Aug;7(4):264-269. Epub 2017 Jan 20.

McGill University Health Centre, Department of Radiation Oncology, Montreal, Quebec, Canada.

Purpose: To report acute and late toxicity rates in patients with high-risk prostate cancer treated with androgen deprivation therapy (ADT) and moderate hypofractionated radiation therapy (HypoRT) to the prostate and nodal areas.

Methods And Materials: Patients with localized, high-risk prostate cancer were treated with a HypoRT regimen of 60 Gy in 20 fractions (4 weeks) to the prostate volume while the nodal areas received 44 Gy in the same 20 fractions delivered with intensity modulated RT with a simultaneous integrated boost technique. ADT started 2 to 3 months before HypoRT and was given to all patients. Acute and late toxicity were prospectively assessed and graded according to the Common Terminology Criteria for Adverse Events, version 3.

Results: A total of 105 patients treated between September 2010 and November 2013 were reviewed. Median follow-up was 41 months, with 97% of patients followed for more than 26 months. Median ADT duration was 18 months. Acute grade 2 or higher gastrointestinal (GI) or genitourinary (GU) toxicity was seen in 18 (17%) and 19 (17%) patients, respectively, with only 1 and 3 patients experiencing either a GI or GU acute grade 3 toxicity. The worst grade 2 or higher late GI and GU toxicity were seen in 7 (7%) and 8 (8%) patients, respectively. There was no grade 4 or 5 toxicity. At the last follow-up, the rate of grade 2 GI and GU toxicity was 5% and 3%, respectively, with no residual grade ≥3 toxicity. The 48-month actuarial progression free survival is 82%.

Conclusions: ADT with moderate HypoRT delivered with IMRT and an integrated simultaneous boost to the prostate (60 Gy) and pelvic nodes (44 Gy) in 20 fractions is feasible and well tolerated. This approach shortens treatment duration and is convenient for patients and the health system, and its results support a randomized trial.
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http://dx.doi.org/10.1016/j.prro.2017.01.003DOI Listing
March 2018

Physical analysis of an Antarctic ice core-towards an integration of micro- and macrodynamics of polar ice.

Philos Trans A Math Phys Eng Sci 2017 Feb;375(2086)

AWI-Glaciology, Alfred-Wegener-Institute Helmholtz-Centre for Polar and Marine Research, Bremerhaven, Germany.

Microstructures from deep ice cores reflect the dynamic conditions of the drill location as well as the thermodynamic history of the drill site and catchment area in great detail. Ice core parameters (crystal lattice-preferred orientation (LPO), grain size, grain shape), mesostructures (visual stratigraphy) as well as borehole deformation were measured in a deep ice core drilled at Kohnen Station, Dronning Maud Land (DML), Antarctica. These observations are used to characterize the local dynamic setting and its rheological as well as microstructural effects at the EDML ice core drilling site (European Project for Ice Coring in Antarctica in DML). The results suggest a division of the core into five distinct sections, interpreted as the effects of changing deformation boundary conditions from triaxial deformation with horizontal extension to bedrock-parallel shear. Region 1 (uppermost approx. 450 m depth) with still small macroscopic strain is dominated by compression of bubbles and strong strain and recrystallization localization. Region 2 (approx. 450-1700 m depth) shows a girdle-type LPO with the girdle plane being perpendicular to grain elongations, which indicates triaxial deformation with dominating horizontal extension. In this region (approx. 1000 m depth), the first subtle traces of shear deformation are observed in the shape-preferred orientation (SPO) by inclination of the grain elongation. Region 3 (approx. 1700-2030 m depth) represents a transitional regime between triaxial deformation and dominance of shear, which becomes apparent in the progression of the girdle to a single maximum LPO and increasing obliqueness of grain elongations. The fully developed single maximum LPO in region 4 (approx. 2030-2385 m depth) is an indicator of shear dominance. Region 5 (below approx. 2385 m depth) is marked by signs of strong shear, such as strong SPO values of grain elongation and strong kink folding of visual layers. The details of structural observations are compared with results from a numerical ice sheet model (PISM, isotropic) for comparison of strain rate trends predicted from the large-scale geometry of the ice sheet and borehole logging data. This comparison confirms the segmentation into these depth regions and in turn provides a wider view of the ice sheet.This article is part of the themed issue 'Microdynamics of ice'.
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http://dx.doi.org/10.1098/rsta.2015.0347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5179957PMC
February 2017

Paraburkholderia piptadeniae sp. nov. and Paraburkholderia ribeironis sp. nov., two root-nodulating symbiotic species of Piptadenia gonoacantha in Brazil.

Int J Syst Evol Microbiol 2017 Feb 16;67(2):432-440. Epub 2017 Mar 16.

Laboratory of Microbiology, Department of Biochemistry and Microbiology, Ghent University, K. L. Ledeganckstraat 35, B-9000 Ghent, Belgium.

During a survey of root-nodulating symbionts of Mimosoid species in the south-east region of Brazil, eight Paraburkholderia isolates were obtained from nodules of the legume species Piptadenia gonoacantha, either from the field or following a soil trapping method with the same plant host. 16S rRNA gene as well as recA and gyrB phylogenetic markers placed these strains in two new clades within the genus Burkholderia sensu lato. DNA-DNA hybridization values and analyses of average nucleotide identities of the whole genome sequence of selected strains in each clade (STM 7183 and STM 7296) showed that the two clades represented novel species of the genus Paraburkholderia. All eight isolates were further characterized using DNA base content determination, chemotaxonomic and biochemical profiling and symbiotic properties, which allowed to distinguish the novel species from known diazotrophic species of the genus Paraburkholderia. Based on genomic and phenotypic data, the names Paraburkholderia piptadeniae sp. nov. with type strain STM 7183T (=DSM 101189T=LMG 29163T) and Paraburkholderia ribeironis sp. nov. with type strain STM 7296T (=DSM 101188T=LMG 29351T) are proposed.
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http://dx.doi.org/10.1099/ijsem.0.001648DOI Listing
February 2017

Patient-reported quality of life after stereotactic body radiation therapy versus moderate hypofractionation for clinically localized prostate cancer.

Radiother Oncol 2016 11 24;121(2):294-298. Epub 2016 Nov 24.

Department of Therapeutic Radiology, Yale School of Medicine, New Haven, United States; Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale School of Medicine, New Haven, United States. Electronic address:

Background And Purpose: Evaluate changes in bowel, urinary and sexual patient-reported quality of life following treatment with moderately hypofractionated radiotherapy (<5Gray/fraction) or stereotactic body radiation therapy (SBRT;5-10Gray/fraction) for prostate cancer.

Materials And Methods: In a pooled multi-institutional analysis of men treated with moderate hypofractionation or SBRT, we compared minimally detectable difference in bowel, urinary and sexual quality of life at 1 and 2years using chi-squared analysis and logistic regression.

Results: 378 men received moderate hypofractionation compared to 534 men who received SBRT. After 1year, patients receiving moderate hypofractionation were more likely to experience worsening in bowel symptoms (39.5%) compared to SBRT (32.5%; p=.06), with a larger difference at 2years (37.4% versus 25.3%, p=.002). Similarly, patients receiving moderate fractionation had worsening urinary symptom score compared to patients who underwent SBRT at 1 and 2years (34.7% versus 23.1%, p<.001; and 32.8% versus 14.0%, p<.001). There was no difference in sexual symptom score at 1 or 2years. After adjusting for age and cancer characteristics, patients receiving SBRT were less likely to experience worsening urinary symptom scores at 2years (odds ratio: 0.24[95%CI: 0.07-0.79]).

Conclusions: Patients who received SBRT or moderate hypofractionation have similar patient-reported change in bowel and sexual symptoms, although there was worse change in urinary symptoms for patients receiving moderate hypofractionation.
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http://dx.doi.org/10.1016/j.radonc.2016.10.013DOI Listing
November 2016

Canadian Phase III Randomized Trial of Stereotactic Body Radiotherapy Versus Conventionally Hypofractionated Radiotherapy for Stage I, Medically Inoperable Non-Small-Cell Lung Cancer - Rationale and Protocol Design for the Ontario Clinical Oncology Group (OCOG)-LUSTRE Trial.

Clin Lung Cancer 2017 03 3;18(2):250-254. Epub 2016 Oct 3.

Department of Oncology, McMaster University, Hamilton, Ontario, Canada; Ontario Clinical Oncology Group, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.

We describe a Canadian phase III randomized controlled trial of stereotactic body radiotherapy (SBRT) versus conventionally hypofractionated radiotherapy (CRT) for the treatment of stage I medically inoperable non-small-cell lung cancer (OCOG-LUSTRE Trial). Eligible patients are randomized in a 2:1 fashion to either SBRT (48 Gy in 4 fractions for peripherally located lesions; 60 Gy in 8 fractions for centrally located lesions) or CRT (60 Gy in 15 fractions). The primary outcome of the study is 3-year local control, which we hypothesize will improve from 75% with CRT to 87.5% with SBRT. With 85% power to detect a difference of this magnitude (hazard ratio = 0.46), a 2-sided α = 0.05 and a 2:1 randomization, we require a sample size of 324 patients (216 SBRT, 108 CRT). Important secondary outcomes include overall survival, disease-free survival, toxicity, radiation-related treatment death, quality of life, and cost-effectiveness. A robust radiation therapy quality assurance program has been established to assure consistent and high quality SBRT and CRT delivery. Despite widespread interest and adoption of SBRT, there still remains a concern regarding long-term control and risks of toxicity (particularly in patients with centrally located lesions). The OCOG-LUSTRE study is the only randomized phase III trial testing SBRT in a medically inoperable population, and the results of this trial will attempt to prove that the benefits of SBRT outweigh the potential risks.
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http://dx.doi.org/10.1016/j.cllc.2016.08.002DOI Listing
March 2017

Nitrogen-fixing bacteria and arbuscular mycorrhizal fungi in Piptadenia gonoacantha (Mart.) Macbr.

Braz J Microbiol 2017 Jan - Mar;48(1):95-100. Epub 2016 Nov 8.

Embrapa Agrobiologia, Seropédica, RJ, Brazil.

The family Leguminosae comprises approximately 20,000 species that mostly form symbioses with arbuscular mycorrhizal fungi (AMF) and nitrogen-fixing bacteria (NFB). This study is aimed at investigating and confirming the dependence on nodulation and biological nitrogen fixation in the specie Piptadenia gonoacantha (Mart.) Macbr., which belongs to the Piptadenia group. Two consecutive experiments were performed in a greenhouse. The experiments were fully randomized with six replicates and a factorial scheme. For the treatments, the two AMF species and three NFB strains were combined to nodulate P. gonoacantha in addition to the control treatments. The results indicate this species' capacity for nodulation without the AMF; however, the AMF+NFB combinations yielded a considerable gain in P. gonoacantha shoot weight compared with the treatments that only included inoculating with bacteria or AMF. The results also confirm that the treatment effects among the AMF+NFB combinations produced different shoot dry weight/root dry weight ratios. We conclude that AMF is not necessary for nodulation and that this dependence improves species development because plant growth increases upon co-inoculation.
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http://dx.doi.org/10.1016/j.bjm.2016.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221347PMC
February 2017

Image Coding Using Generalized Predictors Based on Sparsity and Geometric Transformations.

IEEE Trans Image Process 2016 09 20;25(9):4046-60. Epub 2016 Jun 20.

Directional intra prediction plays an important role in current state-of-the-art video coding standards. In directional prediction, neighbouring samples are projected along a specific direction to predict a block of samples. Ultimately, each prediction mode can be regarded as a set of very simple linear predictors, a different one for each pixel of a block. Therefore, a natural question that arises is whether one could use the theory of linear prediction in order to generate intra prediction modes that provide increased coding efficiency. However, such an interpretation of each directional mode as a set of linear predictors is too poor to provide useful insights for their design. In this paper, we introduce an interpretation of directional prediction as a particular case of linear prediction, which uses the first-order linear filters and a set of geometric transformations. This interpretation motivated the proposal of a generalized intra prediction framework, whereby the first-order linear filters are replaced by adaptive linear filters with sparsity constraints. In this context, we investigate the use of efficient sparse linear models, adaptively estimated for each block through the use of different algorithms, such as matching pursuit, least angle regression, least absolute shrinkage and selection operator, or elastic net. The proposed intra prediction framework was implemented and evaluated within the state-of-the-art high efficiency video coding standard. Experiments demonstrated the advantage of this predictive solution, mainly in the presence of images with complex features and textured areas, achieving higher average bitrate savings than other related sparse representation methods proposed in the literature.
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http://dx.doi.org/10.1109/TIP.2016.2582422DOI Listing
September 2016

Moderate hypofractionated external beam radiotherapy alone for intermediate risk prostate cancer: long term outcomes.

Can J Urol 2016 Apr;23(2):8209-14

Division of Radiation Oncology and Medical Physics, McGill University Health Center, Montreal, Quebec, Canada.

Introduction: To report long term toxicity and efficacy of patients with intermediate risk prostate cancer treated with moderate hypofractionated radiotherapy (HypoRT).

Materials And Methods: We studied the first consecutive 100 men with intermediate risk (stage T2b-T2c, or PSA = 10-20 ug/L, or Gleason score = 7) adenocarcinoma of the prostate treated between October 2002 and May 2010 in our institution with moderate HypoRT. Patients were treated using three-dimensional conformal HypoRT to a dose of 66 Gy in 22 daily fractions prescribed to the isocenter. Androgen suppression was not given to any patient. A uniform 7 mm margin was created around the prostate for the planning target volume. Daily ultrasound was used to guide the radiotherapy. Common Terminology Criteria for Adverse Events, version 3.0, was used to prospectively score toxicity. Biochemical failure was defined as the nadir PSA level plus 2 ng/m.

Results: After a median follow up time of 80 months (range: 7-152), the 8 year actuarial freedom from biochemical relapse survival rate was 90%. The 8 year cancer specific survival and overall survival rates were 96% and 84%, respectively. Only 2 patients died from prostate cancer. The worst grade ≥ 2 late genitourinary (GU) or gastrointestinal (GI) toxicities ever documented were 19% and 20%, respectively. At the last follow up the incidence of grade ≥ 2 late GI or GU toxicity was of only 2% and 3%, respectively. No grade 4 or 5 late toxicity was seen.

Conclusion: Our long term experience with HypoRT delivering 66 Gy/22 fractions prescribed to the isocenter using three-dimensional conformal radiotherapy shows excellent tumor control with acceptable toxicity.
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April 2016

Randomized Phase III Noninferiority Study Comparing Two Radiotherapy Fractionation Schedules in Patients With Low-Risk Prostate Cancer.

J Clin Oncol 2016 07 4;34(20):2325-32. Epub 2016 Apr 4.

W. Robert Lee and Bridget F. Koontz, Duke University Medical Center, Durham, NC; James J. Dignam, University of Chicago, Chicago, IL; Mahul B. Amin and Howard M. Sandler, Cedars-Sinai Medical Center; Daniel Low, University of California, Los Angeles, Los Angeles; Samantha A. Seaward, Kaiser Permanente Northern California, Santa Clara, CA; Deborah W. Bruner, Emory University, Atlanta, GA; Gregory P. Swanson, Baylor Scott & White Healthcare Temple Clinic, Temple, TX; Amit B. Shah, York Cancer Center, York; James J. Dignam and Rebecca Paulus, NRG Oncology Statistics and Data Management Center, Philadelphia, PA; David P. D'Souza, London Regional Cancer Program, London, Ontario; Ian S. Dayes, McMaster University, Hamilton, Ontario; Sergio L. Faria, McGill University Health Center, Montreal, Quebec, Canada; Jeff M. Michalski, Washington University School of Medicine, St Louis, MO; William A. Hall, Medical College of Wisconsin, Milwaukee, WI; Paul L. Nguyen, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA; Thomas M. Pisansky, Mayo Clinic, Rochester, MN; and Yuhchyau Chen, University of Rochester, Rochester, NY.

Purpose: Conventional radiotherapy (C-RT) treatment schedules for patients with prostate cancer typically require 40 to 45 treatments that take place from > 8 to 9 weeks. Preclinical and clinical research suggest that hypofractionation-fewer treatments but at a higher dose per treatment-may produce similar outcomes. This trial was designed to assess whether the efficacy of a hypofractionated radiotherapy (H-RT) treatment schedule is no worse than a C-RT schedule in men with low-risk prostate cancer.

Patients And Methods: A total of 1,115 men with low-risk prostate cancer were randomly assigned 1:1 to C-RT (73.8 Gy in 41 fractions over 8.2 weeks) or to H-RT (70 Gy in 28 fractions over 5.6 weeks). This trial was designed to establish (with 90% power and an α of .05) that treatment with H-RT results in 5-year disease-free survival (DFS) that is not worse than C-RT by more than 7.65% (H-RT/C-RT hazard ratio [HR] < 1.52).

Results: A total of 1,092 men were protocol eligible and had follow-up information; 542 patients were assigned to C-RT and 550 to H-RT. Median follow-up was 5.8 years. Baseline characteristics were not different according to treatment assignment. The estimated 5-year DFS was 85.3% (95% CI, 81.9 to 88.1) in the C-RT arm and 86.3% (95% CI, 83.1 to 89.0) in the H-RT arm. The DFS HR was 0.85 (95% CI, 0.64 to 1.14), and the predefined noninferiority criterion that required that DFS outcomes be consistent with HR < 1.52 was met (P < .001). Late grade 2 and 3 GI and genitourinary adverse events were increased (HR, 1.31 to 1.59) in patients who were treated with H-RT.

Conclusion: In men with low-risk prostate cancer, the efficacy of 70 Gy in 28 fractions over 5.6 weeks is not inferior to 73.8 Gy in 41 fractions over 8.2 weeks, although an increase in late GI/genitourinary adverse events was observed in patients treated with H-RT.
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http://dx.doi.org/10.1200/JCO.2016.67.0448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981980PMC
July 2016

FDG-PET-based differential uptake volume histograms: a possible approach towards definition of biological target volumes.

Br J Radiol 2016 Jun 23;89(1062):20150388. Epub 2016 Mar 23.

2 Department of Radiation Oncology, Montreal General Hospital, McGill University, Montréal, QC, Canada.

Objective: Integration of fluorine-18 fludeoxyglucose ((18)F-FDG)-positron emission tomography (PET) functional data into conventional anatomically based gross tumour volume delineation may lead to optimization of dose to biological target volumes (BTV) in radiotherapy. We describe a method for defining tumour subvolumes using (18)F-FDG-PET data, based on the decomposition of differential uptake volume histograms (dUVHs).

Methods: For 27 patients with histopathologically proven non-small-cell lung carcinoma (NSCLC), background uptake values were sampled within the healthy lung contralateral to a tumour in those image slices containing tumour and then scaled by the ratio of mass densities between the healthy lung and tumour. Signal-to-background (S/B) uptake values within volumes of interest encompassing the tumour were used to reconstruct the dUVHs. These were subsequently decomposed into the minimum number of analytical functions (in the form of differential uptake values as a function of S/B) that yielded acceptable net fits, as assessed by χ(2) values.

Results: Six subvolumes consistently emerged from the fitted dUVHs over the sampled volume of interest on PET images. Based on the assumption that each function used to decompose the dUVH may correspond to a single subvolume, the intersection between the two adjacent functions could be interpreted as a threshold value that differentiates them. Assuming that the first two subvolumes spread over the tumour boundary, we concentrated on four subvolumes with the highest uptake values, and their S/B thresholds [mean ± standard deviation (SD)] were 2.88 ± 0.98, 4.05 ± 1.55, 5.48 ± 2.06 and 7.34 ± 2.89 for adenocarcinoma, 3.01 ± 0.71, 4.40 ± 0.91, 5.99 ± 1.31 and 8.17 ± 2.42 for large-cell carcinoma and 4.54 ± 2.11, 6.46 ± 2.43, 8.87 ± 5.37 and 12.11 ± 7.28 for squamous cell carcinoma, respectively.

Conclusion: (18)F-FDG-based PET data may potentially be used to identify BTV within the tumour in patients with NSCLC. Using the one-way analysis of variance statistical tests, we found a significant difference among all threshold levels among adenocarcinomas, large-cell carcinoma and squamous cell carcinomas. On the other hand, the observed significant variability in threshold values throughout the patient cohort (expressed as large SDs) can be explained as a consequence of differences in the physiological status of the tumour volume for each patient at the time of the PET/CT scan. This further suggests that patient-specific threshold values for the definition of BTVs could be determined by creation and curve fitting of dUVHs on a patient-by-patient basis.

Advances In Knowledge: The method of (18)F-FDG-PET-based dUVH decomposition described in this work may lead to BTV segmentation in tumours.
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http://dx.doi.org/10.1259/bjr.20150388DOI Listing
June 2016

Rhizobial characterization in revegetated areas after bauxite mining.

Braz J Microbiol 2016 Apr-Jun;47(2):314-21. Epub 2016 Mar 2.

Embrapa Agrobiologia, Seropédica, RJ, Brazil.

Little is known regarding how the increased diversity of nitrogen-fixing bacteria contributes to the productivity and diversity of plants in complex communities. However, some authors have shown that the presence of a diverse group of nodulating bacteria is required for different plant species to coexist. A better understanding of the plant symbiotic organism diversity role in natural ecosystems can be extremely useful to define recovery strategies of environments that were degraded by human activities. This study used ARDRA, BOX-PCR fingerprinting and sequencing of the 16S rDNA gene to assess the diversity of root nodule nitrogen-fixing bacteria in former bauxite mining areas that were replanted in 1981, 1985, 1993, 1998, 2004 and 2006 and in a native forest. Among the 12 isolates for which the 16S rDNA gene was partially sequenced, eight, three and one isolate(s) presented similarity with sequences of the genera Bradyrhizobium, Rhizobium and Mesorhizobium, respectively. The richness, Shannon and evenness indices were the highest in the area that was replanted the earliest (1981) and the lowest in the area that was replanted most recently (2006).
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http://dx.doi.org/10.1016/j.bjm.2016.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874681PMC
December 2016