Varian ethos online adaptive radiotherapy for prostate cancer: Early results of contouring accuracy, treatment plan quality, and treatment time.

The Varian Ethos system allows for online adaptive treatments through the utilization of artificial intelligence (AI) and deformable image registration which automates large parts of the anatomical contouring and plan optimization process. In this study, treatments of intact prostate and prostate bed, with and without nodes, were simulated for 182 online adaptive fractions, and then a further 184 clinical fractions were delivered on the Ethos system. Frequency and magnitude of contour edits were recorded, as well as a range of plan quality metrics. From the fractions analyzed, 11% of AI generated contours, known as influencer contours, required no change, and 81% required minor edits in any given fraction. The frequency of target and noninfluencer organs at risk (OAR) contour editing varied substantially between different targets and noninfluencer OARs, although across all targets 72% of cases required no edits. The adaptive plan was the preference in 95% of fractions. The adaptive plan met more goals than the scheduled plan in 78% of fractions, while in 15% of fractions the number of goals met was the same. The online adaptive recontouring and replanning process was carried out in 19 min on average. Significant improvements in dosimetry are possible with the Ethos online adaptive system in prostate radiotherapy.

Comparison of semiautomated tangential VMAT with 3DCRT for breast or chest wall and regional nodes.

Radiotherapy to the breast after surgery sometimes requires adjoining nodes to be included in the treatment volume. In these cases, the traditional approach has been a complex 3-Dimensional Conformal Radiotherapy (3DCRT) beam arrangement which can result in significant dose heterogeneity at the beam junctions. A Volumetric Modulated Arc Therapy (VMAT) beam arrangement has previously been proposed for breast cases, where the chest wall/breast is treated with a limited angle (partial arc) tangential VMAT technique (Virén et al. [2015] Radiat Oncol. 10:79). In our study, this approach is extended to breast and chest wall cases with adjoining nodes by adding a separate conventional VMAT arc field specifically limited to the superior nodes. This VMAT method was implemented using a semiautomated approach on 27 patients, and the resultant plan compared to a monoisocentric 3DCRT plan. Plan statistics, Dose-Volume Histogram (DVH) analysis and Radiation Oncologist (RO) preference were assessed. When compared to the 3DCRT technique, the VMAT planning method was found to result in better target volume coverage, high doses to organs at risk (OAR) were reduced but greater OAR volumes received low doses. Having said that, the volume receiving low doses with this tangential VMAT technique was less than that of other VMAT planning methods described in the literature, and the integral dose was less than the 3DCRT method. The VMAT technique also resulted in more robust junction doses that the 3DCRT method. RO review found that the VMAT technique was preferred in 81% of cases. Specifically, the VMAT plans were preferred in all categories of patients except left chest wall cases where the intermammary nodes were also treated. The VMAT technique described here is a useful addition to the treatment options available for breast/chest wall and nodal patients.

The influence of dissolved oxygen level and medium on biofilm formation by Campylobacter jejuni.

Campylobacter jejuni survival in aerobic environments has been suggested to be mediated by biofilm formation. Biofilm formation by eight C. jejuni strains under both aerobic and microaerobic conditions in different broths (Mueller-Hinton (MH), Bolton and Brucella) was quantified. The dissolved oxygen (DO) content of the broths under both incubation atmospheres was determined. Biofilm formation for all strains was highest in MH broth under both incubation atmospheres. Four strains had lower biofilm formation in MH under aerobic as compared to microaerobic incubation, while biofilm formation by the other four strains did not differ under the 2 atm. Two strains had higher biofilm formation under aerobic as compared to microaerobic atmospheres in Bolton broth. Biofilm formation by all other strains in Bolton, and all strains in Brucella broth, did not differ under the 2 atm. Under aerobic incubation DO levels in MH > Brucella > Bolton broth. Under microaerobic conditions levels in MH = Brucella > Bolton broth. Levels of DO in MH and Brucella broth were lower under microaerobic conditions but those of Bolton did not differ under the 2 atm. Experimental conditions and especially the DO of broth media confound previous conclusions drawn about aerobic biofilm formation by C. jejuni.

The Influence of Prior Modes of Growth, Temperature, Medium, and Substrate Surface on Biofilm Formation by Antibiotic-Resistant Campylobacter jejuni.

Campylobacter jejuni is one of the most common causes of bacterial gastrointestinal food-borne infection worldwide. It has been suggested that biofilm formation may play a role in survival of these bacteria in the environment. In this study, the influence of prior modes of growth (planktonic or sessile), temperatures (37 and 42 °C), and nutrient conditions (nutrient broth and Mueller-Hinton broth) on biofilm formation by eight C. jejuni strains with different antibiotic resistance profiles was examined. The ability of these strains to form biofilm on different abiotic surfaces (stainless steel, glass, and polystyrene) as well as factors potentially associated with biofilm formation (bacterial surface hydrophobicity, auto-aggregation, and initial attachment) was also determined. The results showed that cells grown as sessile culture generally have a greater ability to form biofilm (P < 0.05) compared to their planktonic counterparts. Biofilm was also greater (P < 0.05) in lower nutrient media, while growth at different temperatures affects biofilm formation in a strain-dependent manner. The strains were able to attach and form biofilms on different abiotic surfaces, but none of them demonstrated strong, complex, or structured biofilm formation. There were no clear trends between the bacterial surface hydrophobicity, auto-aggregation, attachment, and biofilm formation by the strains. This finding suggests that environmental factors did affect biofilm formation by C. jejuni, and they are more likely to persist in the environment in the form of mixed-species rather than monospecies biofilms.

Does Campylobacter jejuni form biofilms in food-related environments?

Campylobacter jejuni is one of the most frequent causes of bacterial gastrointestinal food-borne infection worldwide. This species is part of the normal flora of the gastrointestinal tracts of animals used for food production, including poultry, which is regarded as the primary source of human Campylobacter infections. The survival and persistence of C. jejuni in food processing environments, especially in poultry processing plants, represent significant risk factors that contribute to the spread of this pathogen through the food chain. Compared to other food-borne pathogens, C. jejuni is more fastidious in its growth requirements and is very susceptible to various environmental stressors. Biofilm formation is suggested to play a significant role in the survival of C. jejuni in the food production and processing environment. The aims of this minireview were (i) to examine the evidence that C. jejuni forms biofilms and (ii) to establish the extent to which reported and largely laboratory-based studies of C. jejuni biofilms provide evidence for biofilm formation by this pathogen in food processing environments. Overall existing studies do not provide strong evidence for biofilm formation (as usually defined) by most C. jejuni strains in food-related environments under the combined conditions of atmosphere, temperature, and shear that they are likely to encounter. Simple attachment to and survival on surfaces and in existing biofilms of other species are far more likely to contribute to C. jejuni survival in food-related environments based on our current understanding of this species.

The influence of antibiotic resistance gene carriage on biofilm formation by two Escherichia coli strains associated with urinary tract infections.

Urinary tract infections (UTI) caused by uropathogenic Escherichia coli are one of the most common forms of human disease. In this study, the effect of the presence of newly acquired antibiotic resistance genes on biofilm formation of UTI-associated E. coli strains was examined. Two clinical UTI-associated E. coli strains (SMC18 and SMC20) carrying different combinations of virulence genes were transformed with pGEM-T, pGEM-T::KmΔAmp, or pGEM-T::Km to construct ampicillin-resistant (Km(S)Amp(R)), kanamycin-resistant (Km(R)Amp(S)), or ampicillin- and kanamycin-resistant (Km(R)Amp(R)) strains. Transformed and wild-type strains were characterized for biofilm formation, bacterial surface hydrophobicity, auto-aggregation, morphology, and attachment to abiotic surfaces. Transformation with a plasmid carrying an ampicillin resistance gene alone decreased (p < 0.05) biofilm formation by SMC18 (8 virulence marker genes) but increased (p < 0.05) biofilm formation by SMC20 (5 virulence marker genes). On the other hand, transformation with a plasmid carrying a kanamycin resistance gene alone or both ampicillin and kanamycin resistance genes resulted in a decrease (p < 0.05) in biofilm formation by SMC18 but did not affect (p > 0.05) the biofilm formation by SMC20. Our results suggest that transformation of UTI-associated E. coli with plasmids carrying different antibiotic resistance gene(s) had a significant impact on biofilm formation and that these effects were both strain dependent and varied between different antibiotics.

Intrafraction Motion and Margin Assessment for Ethos Online Adaptive Radiotherapy Treatments of the Prostate and Seminal Vesicles.

Purpose: Online adaptive radiation therapy (OART) uses daily imaging to identify changes in the patient's anatomy and generate a new treatment plan adapted to these changes for each fraction. The aim of this study was to determine the intrafraction motion and planning target volume (PTV) margins required for an OART workflow on the Varian Ethos system. Methods and Materials: Sixty-five fractions from 13 previously treated OART patients were analyzed for this retrospective study. The prostate and seminal vesicles were contoured by a radiation oncologist on 2 cone beam computed tomography scans (CBCT) for each fraction, the initial CBCT at the start of the treatment session, and the verification CBCT immediately before beam-on. In part 1 of the study, PTVs of different sizes were defined on the initial CBCT, and the geometric overlap with the clinical target volume (CTV) on the verification CBCT was used to determine the optimal OART margin. This was performed with and without a patient realignment shift by registering the verification CBCT to the initial CBCT. In part 2 of the study, the margins determined in part 1 were used for simulated Ethos OART treatments on all 65 fractions. The resultant coverage to the CTV on the verification CBCT, was compared with an image guided radiation therapy (IGRT) workflow with 7-mm margins. Results: Part 1 of the study found, if a verification CBCT and shift is performed, a 4-mm margin on the prostate and 5 mm on the seminal vesicles resulted in 95% of the CTV covered by the PTV in >90% of fractions, and 98% of the CTV covered by the PTV in >80% of fractions. Part 2 of the study found when these margins were used in an Ethos OART workflow, they resulted in CTV coverage that was superior to an IGRT workflow with 7-mm margins. Conclusions: A 4mm prostate margin and 5-mm seminal vesicles margin in an OART workflow with verification imaging are adequate to ensure coverage on the Varian Ethos system. Larger margins may be required if using an OART workflow without verification imaging.

Performance of Ga-68 PSMA PET/CT for diagnosis and grading of local prostate cancer.

BACKGROUND: We aimed to evaluate the utility of prostate-specific membrane antigen (PSMA) PET/CT for the detection of local disease within the prostate. METHODS: This is a retrospective review of a single-center experience evaluating intraprostatic detection rates compared with final histopathology in a radical prostatectomy (RP) population. Seventy-two patients had PSMA PET/CT scan performed as part of their primary staging. Intraprostatic PSMA PET/CT avidity was assessed. PSMA PET/CT uptake was retrospectively correlated with patient characteristics including final histopathology, MRI Prostate Imaging Reporting and Data System (PI-RADS) score, clinical tumor stage, prostate-specific antigen (PSA) level, and patient age. RESULTS: The sensitivity of PSMA PET/CT for the detection of RP-confirmed prostate cancer was 81.2%. Much higher sensitivity was found within certain subpopulations. The patient characteristics that most strongly correlated with focal intraprostatic PSMA PET/CT uptake were patient age (Kendall's tau coefficient τb = 0.24, p < 0.05) and clinical T stage (τb = 0.21, p < 0.05).The International Society of Urological Pathology (ISUP) grade group from final RP was predicted by standardized uptake value (SUVmax) and to a lesser extent PSA and the maximal dimension of PET-avid lesions. SUVmax monotonically increased with ISUP grade group. If SUVmax was above 10 g/mL, the final RP histopathology had a relative risk of 2.3 (95% CI 1.3-4.1) of being ISUP grade group 5. CONCLUSION: This trial provides early evidence that PSMA PET/CT assists in the grading of prostate cancer and suggests that the imaging modality is particularly accurate in subpopulations including the elderly and those with palpable disease.

Association of some Campylobacter jejuni with Pseudomonas aeruginosa biofilms increases attachment under conditions mimicking those in the environment.

Campylobacter jejuni is a microaerophilic bacterial species which is a major food-borne pathogen worldwide. Attachment and biofilm formation have been suggested to contribute to the survival of this fastidious bacteria in the environment. In this study the attachment of three C. jejuni strains (C. jejuni strains 2868 and 2871 isolated from poultry and ATCC 33291) to different abiotic surfaces (stainless steel, glass and polystyrene) alone or with Pseudomonas aeruginosa biofilms on them, in air at 25°C and under static or flow conditions, were investigated using a modified Robbins Device. Bacteria were enumerated and scanning electron microscopy was carried out. The results indicated that both C. jejuni strains isolated from poultry attached better to Pseudomonas aeruginosa biofilms on abiotic surfaces than to the surfaces alone under the different conditions tested. This suggests that biofilms of other bacterial species may passively protect C. jejuni against shear forces and potentially oxygen stress which then contribute to their persistence in environments which are detrimental to them. By contrast the C. jejuni ATCC 33291 strain did not attach differentially to P. aeruginosa biofilms, suggesting that different C. jejuni strains may have alternative strategies for persistence in the environment. This study supports the hypothesis that C. jejuni do not form biofilms per se under conditions they encounter in the environment but simply attach to surfaces or biofilms of other species.

Growth in the presence of specific antibiotics induces biofilm formation by a Campylobacter jejuni strain sensitive to them but not in resistant strains.

OBJECTIVE: Campylobacter jejuni (C. jejuni) are among the most frequently identified bacteria associated with human gastroenteritis worldwide. Exposure to antibiotics may induce or inhibit biofilm formation in some bacterial species. Little work has been reported on the influence of antibiotics on biofilm formation by C. jejuni. METHODS: This study investigated the effect of six different classes of antibiotics with different modes of action (ampicillin, ciprofloxacin, erythromycin, nalidixic acid, rifampicin and tetracycline) on biofilm formation in vitro by seven C. jejuni from poultry with different antibiotic resistance profiles. RESULTS: The results indicated that in the presence of most of the tested antibiotics, biofilm formation by C. jejuni strains, which are resistant to them, was reduced but biofilm formation in sensitive strains was increased. CONCLUSION: The ability of certain antibiotics to induce biofilm formation by a tested C. jejuni strain is of concern, with respect to the effective control of disease caused by this pathogen; however, further work is required to confirm how widespread this feature is.

Implementing user-defined atlas-based auto-segmentation for a large multi-centre organisation: the Australian Experience.

INTRODUCTION: Contouring has become an increasingly important aspect of radiation therapy due to inverse planning, and yet is extremely time-consuming. To improve contouring efficiency and reduce potential inter-observer variation, the atlas-based auto-segmentation (ABAS) function in Velocity was introduced to ICON cancer centres (ICC) throughout Australia as a solution for automatic contouring. METHODS: This paper described the implementation process of the ABAS function and the construction of user-defined atlas sets and compared the contouring efficiency before and after the introduction of ABAS. RESULTS: The results indicate that the main limitation to the ABAS performance was Velocity's sub-optimal atlas selection method. Three user-defined atlas sets were constructed. Results suggested that the introduction of the ABAS saved at least 5 minutes of manual contouring time (P < 0.05), although further verification was required due to limitations in the data collection method. The pilot rollout adopting a 'champion' approach was successful and provided an opportunity to improve the user-defined atlases prior to the national implementation. CONCLUSION: The implementation of user-defined ABAS for head and neck (H&N) and female thorax patients at ICCs was successful, which achieved at least 5 minutes of efficiency gain.

Identification of potential Campylobacter jejuni genes involved in biofilm formation by EZ-Tn5 Transposome mutagenesis.

BACKGROUND: Biofilm formation has been suggested to play a role in the survival of Campylobacter jejuni in the environment and contribute to the high incidence of human campylobacteriosis. Molecular studies of biofilm formation by Campylobacter are sparse. RESULTS: We attempted to identify genes that may be involved in biofilm formation in seven C. jejuni strains through construction of mutants using the EZ-Tn5 Transposome system. Only 14 mutants with reduced biofilm formation were obtained, all from one strain of C. jejuni. Three different genes of interest, namely CmeB (synthesis of multidrug efflux system transporter proteins), NusG (transcription termination and anti-termination protein) and a putative transmembrane protein (involved in membrane protein function) were identified. The efficiency of the EZ::TN5 transposon mutagenesis approach was strain dependent and was unable to generate any mutants from most of the strains used. CONCLUSIONS: A diverse range of genes may be involved in biofilm formation by C. jejuni. The application of the EZ::TN5 system for construction of mutants in different Campylobacter strains is limited.

A Feasibility Study on the Use of TomoTherapy Megavoltage Computed Tomography Images for Palliative Patient Treatment Planning.

Dedicated rapid access palliative radiation therapy improves patients' access to care, allowing more timely treatment which would positively impact on quality of life. The TomoTherapy (Accuray, Sunnyvale, CA) system provides megavoltage (MV) fan-beam computed tomography (FBCT) as the image guidance technique, and a module called "statRT" that allows the use of these MV FBCT images for direct planning. The possibility of using this imaging modality for palliative radiotherapy treatment planning is assessed against accepted planning CT standards by performing tests following AAPM TG 66 and an end-to-end measurement. Results have shown that MV FBCT images acquired by TomoTherapy are of sufficient quality for the purpose of target delineation and dose calculation for palliative treatments. Large image noise and extended scan acquisition time are the two main drawbacks, so this imaging modality should only be used for palliative treatments at areas with well-known, easily distinguishable, and relatively immobile targets such as spine and whole brain.

Static beam tomotherapy as an optimisation method in whole-breast radiation therapy (WBRT).

INTRODUCTION: TomoTherapy (Accuray, Sunnyvale, CA) has recently introduced a static form of tomotherapy: TomoDirect™ (TD). This study aimed to evaluate TD against a contemporary intensity modulated radiation therapy (IMRT) alternative through comparison of target and organ at risk (OAR) doses in breast cancer cases. A secondary objective was to evaluate planning efficiency by measuring optimisation times. METHODS: Treatment plans of 27 whole-breast radiation therapy (WBRT) patients optimised with a tangential hybrid IMRT technique were replanned using TD. Parameters included a dynamic field width of 2.5 cm, a pitch of 0.251 and a modulation factor of 2.000; 50 Gy in 25 fractions was prescribed and planning time recorded. The planning metrics used in analysis were ICRU based, with the mean PTV minimum (D99 ) used as the point of comparison. RESULTS: Both modalities met ICRU50 target heterogeneity objectives (TD D99 = 48.0 Gy vs. IMRT = 48.1 Gy, P = 0.26; TD D1 = 53.5 Gy vs. IMRT = 53.0 Gy, P = 0.02; Homogeneity index TD = 0.11 vs. IMRT = 0.10, P = 0.03), with TD plans generating higher median doses (TD D50 = 51.1 Gy vs. IMRT = 50.9 Gy, P = 0.03). No significant difference was found in prescription dose coverage (TD V50 = 85.5% vs. IMRT = 82.0%, P = 0.09). TD plans produced a statistically significant reduction in V5 ipsilateral lung doses (TD V5 = 23.2% vs. IMRT = 27.2%, P = 0.04), while other queried OARs remained comparable (TD ipsilateral lung V20 = 13.2% vs. IMRT = 14.6%, P = 0.30; TD heart V5 = 2.7% vs. IMRT = 2.8%, P = 0.47; TD heart V10 = 1.7% vs. IMRT = 1.8%, P = 0.44). TD reduced planning time considerably (TD = 9.8 m vs. IMRT = 27.6 m, P < 0.01), saving an average planning time of 17.8 min per patient. CONCLUSIONS: TD represents a suitable WBRT treatment approach both in terms of plan quality metrics and planning efficiency.

Draft Genome Sequences of Three Multiantibiotic-Resistant Campylobacter jejuni Strains (2865, 2868, and 2871) Isolated from Poultry at Retail Outlets in Malaysia.

Campylobacter jejuni is a frequent cause of human bacterial gastrointestinal foodborne disease worldwide. Antibiotic resistance in this species is of public health concern. The draft genome sequences of three multiantibiotic-resistant C. jejuni strains (2865, 2868, and 2871) isolated from poultry at retail outlets in Malaysia are presented here.

Rectal ulcer associated with SpaceOAR hydrogel insertion during prostate brachytherapy.

We present a case of rectal ulceration associated with SpaceOAR hydrogel insertion during low-dose-rate (LDR) brachytherapy in a patient with prostate cancer.

Migration of a strand of four seeds in low-dose-rate brachytherapy.

We report a case of stranded-seed migration (one strand of four seeds), via the prostatic venous plexus to the internal pudendal vein, in low-dose-rate (LDR) prostate brachytherapy. A 70-year-old man with low-risk prostate adenocarcinoma underwent transperineal permanent seed implantation. A total of 93 iodine-125 seeds were implanted (91 stranded seeds and 2 loose seeds). Immediate postimplantation fluoroscopic image and day 1 postimplantation CT scan indicated all implanted seeds to be within the vicinity of the prostate as planned. Day 30 pelvic X-ray and CT scan revealed migration of a strand of four seeds to the right pelvis (adjacent to ischial spine). At 2 years postimplantation, the patient continues to have good disease control with prostate specific antigen level of 0.69 µg/L, and asymptomatic. To the best of our knowledge, this is the first report of migration of an entire strand of seeds following LDR prostate brachytherapy.

Concomitant intensity modulated boost during whole breast hypofractionated radiotherapy--a feasibility and toxicity study.

BACKGROUND: Breast cancer sensitivity to large fraction size may be enhanced using hypofractionated concomitant boost radiotherapy (CBRT), thereby shortening overall treatment time. This ethics approved, prospective single cohort feasibility study was designed to evaluate the dosimetry and toxicity of CBRT using an intensity-modulated radiotherapy (IMRT) technique, compared with a standard sequential boost technique (SBT). METHODS: Fifteen women (11 right-sided; 4 left-sided) received 42.4 Gy to the whole breast and an additional 10.08 Gy to the tumor bed in 16 daily fractions, using IMRT and standard dose constraints. Each patient was replanned with the SBT, using mixed photon-electrons. Clinical target volume (CTV), dose evaluation volume (DEV), and organs at risk (OAR) dose distributions were compared with the SBT. Toxicity and treatment times were prospectively recorded. RESULTS: All 15 CBRT plans achieved the desired CTV (V(49.9Gy) ≥ 99%) and DEV (V(49.9Gy) ≥ 95%), coverage of the boost, compared with only 10 (66.7%, p=0.03), and 12 (80%, p=0.125) SBT plans, respectively. Ipsilateral lung (p<0.0001), and heart (right-sided, p=0.001; left-sided, p=0.13) doses were lower. Grade 3 acute toxicity occurred in 1 (6.7%) patient. At 1 year, two (13.3%) additional patients had overall grade 2 late toxicity, compared with baseline. No grade 3-4 late toxicity was observed. CONCLUSIONS: CBRT using IMRT improved boost coverage and lowered OAR doses, compared with SBT. Toxicities were acceptable using a daily boost of 3.28 Gy. While resource utilization was greater, overall treatment time was reduced.

The effect of local breast radiotherapy on circulating CD34(+) cells.

The number of circulating CD34(+) (hematopoietic stem) cells (HSCs) was observed to decline by 15% in breast cancer patients after starting adjuvant radiation therapy, regardless of age or preceding chemotherapy. These data demonstrate that local radiation therapy can profoundly affect HSC homeostasis, which might have a myriad of important implications.