•Accurate Synthetic-CT (sCT) generation for anorectal cancers.•Deep learning sCT generation with varied input data.•T2-SPACE MRI sequence use for generalisable pelvic synthetic-CT.
Comprehensive ...dosimetric analysis is required prior to the clinical implementation of pelvic MR-only sites, other than prostate, due to the limited number of site specific synthetic-CT (sCT) dosimetric assessments in the literature. This study aims to provide a comprehensive assessment of a deep learning-based, conditional generative adversarial network (cGAN) model for a large ano-rectal cancer cohort. The following challenges were investigated; T2-SPACE MR sequences, patient data from multiple centres and the impact of sex and cancer site on sCT quality.
RT treatment position CT and T2-SPACE MR scans, from two centres, were collected for 90 ano-rectal patients. A cGAN model trained using a focal loss function, was trained and tested on 46 and 44 CT-MR ano-rectal datasets, paired using deformable registration, respectively. VMAT plans were created on CT and recalculated on sCT. Dose differences and gamma indices assessed sCT dosimetric accuracy. A linear mixed effect (LME) model assessed the impact of centre, sex and cancer site.
A mean PTV D95% dose difference of 0.1% (range: −0.5% to 0.7%) was found between CT and sCT. All gamma index (1%/1 mm threshold) measurements were >99.0%. The LME model found the impact of modality, cancer site, sex and centre was clinically insignificant (effect ranges: −0.4% and 0.3%). The mean dose difference for all OAR constraints was 0.1%.
Focal loss cGAN models using T2-SPACE MR sequences from multiple centres can produce generalisable, dosimetrically accurate sCTs for ano-rectal cancers.
Maintenance of energy homeostasis depends on the highly regulated storage and release of triacylglycerol primarily in adipose tissue, and excessive storage is a feature of common metabolic disorders. ...CIDEA is a lipid droplet (LD)-protein enriched in brown adipocytes promoting the enlargement of LDs, which are dynamic, ubiquitous organelles specialized for storing neutral lipids. We demonstrate an essential role in this process for an amphipathic helix in CIDEA, which facilitates embedding in the LD phospholipid monolayer and binds phosphatidic acid (PA). LD pairs are docked by CIDEA trans-complexes through contributions of the N-terminal domain and a C-terminal dimerization region. These complexes, enriched at the LD-LD contact site, interact with the cone-shaped phospholipid PA and likely increase phospholipid barrier permeability, promoting LD fusion by transference of lipids. This physiological process is essential in adipocyte differentiation as well as serving to facilitate the tight coupling of lipolysis and lipogenesis in activated brown fat.
This study reports the 10-year experience of permanent brachytherapy monotherapy at a single UK center.
Between March 1995 and September 2004, 1,298 patients underwent trans-rectal ultrasound (TRUS) ...planned transperineal brachytherapy delivering 145 Gy using I-125. No patient received supplemental external beam; 44.2% received neoadjuvant hormones. In 688, CT postimplant dosimetry was available. Outcome data were analyzed in terms of overall survival (OS), disease specific survival (DSS), and PSA relapse-free survival (PSA-RFS).
The mean age was 62.9 (range, 34-83) years. Median follow-up was 4.9 years (range, 2.03-11.7 years). OS and DSS were 85% and 95%, respectively, at 10 years. Twenty-one patients died from prostate cancer (1.6%) and 34 (2.5%) from unrelated causes. Seventy-four (5.7%) developed evidence of clinical failure. Overall PSA-RFS was 79.9% and 72.1% at 10 years (American Society for Therapeutic Radiology and Oncology ASTRO and Nadir+2 definitions, respectively). Higher presenting PSA or Gleason score and use of neoadjuvant hormones were associated with an increased risk of biochemical failure (p <0.01). Biochemical control was achieved in 86.4%, 76.7%, and 60.6% (ASTRO) and 72.3%, 73.5%, and 57.6% (Nadir+2) of patients in low-, intermediate-, and high-risk groups, respectively. Biochemical control was achieved in 88% of patients with D(90) > or =140 Gy and in 78% of patients with D(90) <140 Gy (p <0.01).
I-125 brachytherapy alone achieved excellent rates of medium-term biochemical control in both low- and selected intermediate-risk localized prostate cancer patients. Postimplant dosimetry improved with experience and longer follow-up, confirming the relationship of D(90) with biochemical control.
The evidence in the field of diagnosis, staging, and treatment of localised prostate cancer (PCa) is evolving rapidly. The 2024 European Association of Urology (EAU)-European Association of Nuclear ...Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines on PCa summarise the most recent findings and advice for their use in clinical practice. These PCa guidelines reflect the multidisciplinary nature of PCa management.
The European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines provide recommendations for the management of clinically localised prostate cancer (PCa). This paper aims to present a summary of the 2024 version of the EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on the screening, diagnosis, and treatment of clinically localised PCa.
The panel performed a literature review of all new data published in English, covering the time frame between May 2020 and 2023. The guidelines were updated, and a strength rating for each recommendation was added based on a systematic review of the evidence.
A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is considered, a combination of targeted and regional biopsies should be performed. Prostate-specific membrane antigen positron emission tomography imaging is the most sensitive technique for identifying metastatic spread. Active surveillance is the appropriate management for men with low-risk PCa, as well as for selected favourable intermediate-risk patients with International Society of Urological Pathology grade group 2 lesions. Local therapies are addressed, as well as the management of persistent prostate-specific antigen after surgery. A recommendation to consider hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term intensified hormonal treatment.
The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. These PCa guidelines reflect the multidisciplinary nature of PCa management.
This article is the summary of the guidelines for “curable” prostate cancer. Prostate cancer is “found” through a multistep risk-based screening process. The objective is to find as many men as possible with a curable cancer. Prostate cancer is curable if it resides in the prostate; it is then classified into low-, intermediary-, and high-risk localised and locally advanced prostate cancer. These risk classes are the basis of the treatments. Low-risk prostate cancer is treated with “active surveillance”, a treatment with excellent prognosis. For low-intermediary-risk active surveillance should also be discussed as an option. In other cases, active treatments, surgery, or radiation treatment should be discussed along with the potential side effects to allow shared decision-making.
To investigate boosting dominant intraprostatic lesions (DILs) in the context of stereotactic ablative radiation therapy (SABR) and to examine the impact on tumor control probability (TCP) and normal ...tissue complication probability (NTCP).
Ten prostate datasets were selected. DILs were defined using T2-weighted, dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging. Four plans were produced for each dataset: (1) no boost to DILs; (2) boost to DILs, no seminal vesicles in prescription; (3) boost to DILs, proximal seminal vesicles (proxSV) prescribed intermediate dose; and (4) boost to DILs, proxSV prescribed higher dose. The prostate planning target volume (PTV) prescription was 42.7 Gy in 7 fractions. DILs were initially prescribed 115% of the PTVProstate prescription, and PTVDIL prescriptions were increased in 5% increments until organ-at-risk constraints were reached. TCP and NTCP calculations used the LQ-Poisson Marsden, and Lyman-Kutcher-Burman models respectively.
When treating the prostate alone, the median PTVDIL prescription was 125% (range: 110%-140%) of the PTVProstate prescription. Median PTVDIL D50% was 55.1 Gy (range: 49.6-62.6 Gy). The same PTVDIL prescriptions and similar PTVDIL median doses were possible when including the proxSV within the prescription. TCP depended on prostate α/β ratio and was highest with an α/β ratio = 1.5 Gy, where the additional TCP benefit of DIL boosting was least. Rectal NTCP increased with DIL boosting and was considered unacceptably high in 5 cases, which, when replanned with an emphasis on reducing maximum dose to 0.5 cm3 of rectum (Dmax0.5cc), as well as meeting existing constraints, resulted in considerable rectal NTCP reductions.
Boosting DILs in the context of SABR is technically feasible but should be approached with caution. If this therapy is adopted, strict rectal constraints are required including Dmax0.5cc. If the α/β ratio of prostate cancer is 1.5 Gy or less, then high TCP and low NTCP can be achieved by prescribing SABR to the whole prostate, without the need for DIL boosting.
Short chain fatty acids (SCFA) are gut microbiota-derived metabolites that contribute to the gut-brain axis and may impact stroke outcomes following gut dysbiosis. We evaluated plasma SCFA ...concentrations against stroke severity parameters and identified SCFA-associated protein networks.
The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC), a continuously enrolling tissue bank, was used to obtain stroke samples. Arterial blood distal and proximal to the thrombus was obtained from Acute Ischemic Stroke (AIS) Patients (n=53) during thrombectomy. Patient demographics, stroke presentation and outcome parameters were reported. The SCFAs were isolated from proximal plasma
chemical derivatization UHPLC coupled tandem mass spectrometry using electrospray ionization and multiple reaction monitoring. Proteomic levels for 184 cardioembolic and inflammatory proteins was quantified from systemic and intracranial plasma by Olink. Arterial blood from cerebrovascular patients undergoing elective neurointerventional procedures was used as controls.
Acetate positively correlated with time from last known normal (LKN) and was significantly lower in stroke patients compared to control. Isobutyrate, Butyrate and 2-Methylbutyrate negatively correlated with %ΔNIHSS. Isobutyrate and 2-Methylbutyrate positively correlated with NIHSS discharge. SCFA concentrations were not associated with NIHSS admission, infarct volume, or edema volume. Multiple SCFAs positively associated with systemic and pro-inflammatory cytokines, most notably IL-6, TNF-α, VCAM1, IL-17, and MCP-1.
Plasma SCFA concentrations taken at time of stroke are not associated with stroke severity at presentation. However, higher levels of SCFAs at the time of stroke are associated with increased markers of inflammation, less recovery from admission to discharge, and worse symptom burden at discharge.
Cover Image, Volume 531, Issue 8 Arasaratnam, Christine J.; Song, Jennifer J.; Yoshida, Tomoko ...
Journal of comparative neurology,
June 2023, 2023-06-00, 20230601, Letnik:
531, Številka:
8
Journal Article
Recenzirano
Odprti dostop
The cover image is based on the Research Article DARPP‐32 cells and neuropil define striosomal system and isolated matrix cells in human striatum by Christine Arasaratnam et al., ...https://doi.org/10.1002/cne.25488
Reirradiation using brachytherapy (BT) and external beam radiation therapy (EBRT) are salvage strategies with locally radiorecurrent prostate cancer. This systematic review describes the oncologic ...and toxicity outcomes for salvage BT and EBRT including Stereotactic Body Radiation Therapy (SBRT).
An International Prospective Register of Systematic Reviews (PROSPERO) registered (#211875) study was conducted using Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. EMBASE and MEDLINE databases were searched from inception to December 2020. For BT, both low dose rate (LDR) and high dose rate (HDR) BT techniques were included. Two authors independently assessed study quality using the 18-item Modified Delphi technique.
A total of 39 eligible studies comprising 1967 patients were included (28 BT and 11 SBRT). In 35 studies (90%), the design was single centre and/or retrospective and no randomised prospective studies were found. Twelve BT studies used LDR only, 11 HDR only, 4 LDR or HDR and 1 pulsed-dose rate only. All EBRT studies used SBRT exclusively, four with Cyberknife alone and 7 using both Cyberknife and conventional linear accelerator treatments. Median (range) modified Delphi quality score was 15 (6-18). Median (range) follow-up was 47.5 months (13-108) (BT) and 25.4 months (21-44) (SBRT). For the LDR-BT studies, the median (range) 2-year and 5-year bRFS rates were 71% (48-89.5) and 52.5% (20-79). For the HDR-BT studies, the median (range) 2-year and 5-year bRFS rates were 74% (63-89) and 51% (45-65). For the SBRT studies, the median (range) 2-year bRFS for the SBRT group was 54.9% (40-80). Mean (range) acute and late grade≥3 GU toxicity rates for LDR-BT/HDR-BT/SBRT were 7.4%(0-14)/2%(0-14)/2.7%(0-8.7) and 13.6%(0-30)/7.9%(0-21.3%)/2.7%(0-8%). Mean (range) acute and late grade≥3 GI toxicity rates for LDR-BT/HDR-BT/SBRT were 6.5%(0-19)/0%/0.5%(0-4%) and 6.4%(0-20)/0.1%(0-0.9)/0.2%(0-1.5). One third of studies included Patient Reported Outcome Measures (PROMs).
Salvage reirradiation of radiorecurrent prostate cancer using HDR-BT or SBRT provides similar biochemical control and acceptable late toxicity. Salvage LDR-BT is associated with higher late GU/GI toxicity. Challenges exist in comparing BT and SBRT from inconsistencies in reporting with missing data, and prospective randomised trials are needed.
Background: Latinx individuals have over a 50% chance of developing type II diabetes within their lifetime compared to 40% of the general population1,2. Further, a lack of diabetes education ...significantly contributes to poor health literacy surrounding diabetes treatment and management among ethnic minorities3.
Methods: The study utilized a pre and posttest design using the General Nutrition Knowledge Questionnaire-Revised to assess changes in the nutrition knowledge of individuals 18 years or older, after receiving a tailored nutrition education presentation based on U.S. Department of Agriculture MyPlate's dietary guidelines. The difference between pre and posttest nutrition knowledge scores was measured using paired samples t-test for the overall survey and separately for three questions that assessed the diet-diabetes relationship.
Results: Most participants were Spanish-speaking Latinx/Hispanic females between the ages of 40-49, where 66% reported middle school education or lower, 26.4% reported being diagnosed with diabetes, and 56% had a family history of diabetes. The paired t-test of the pre and posttests (n=82) resulted in one and two-sided p-values < 0.001. The comparative pre versus posttest analysis for the diabetes knowledge-related questions showed that the diabetes-related questions one, two, and three resulted in p-values <0.227, <0.02, and <0.03, respectively.
Conclusion: Latinx individuals in rural communities face systemic barriers, including poor medical coverage, low health literacy rates, language and immigration barriers4. Our study brought together promotoras to create and deliver culturally-conscious, evidence-based nutrition education material through platicas. Increased access to nutrition and diabetes education contributes to improved patient health knowledge and addresses negatively impactful social determinants of health among rural Latinx American populations.
Disclosure
S.C.Marin: None. I.Marquez: None. R.R.Flores: None. D.Lee: None. D.Wraich: None. H.Duran: None. A.M.Cheney: None.
Funding
University of California, Riverside School of Medicine
To perform a systematic review regarding the use of stereotactic ablative radiotherapy (SABR) for the re-irradiation of recurrent malignant disease within the pelvis, to guide the clinical ...implementation of this technique.
A systematic search strategy was adopted using the MEDLINE, EMBASE and Cochrane Library databases.
195 articles were identified, of which 17 were appropriate for inclusion. Studies were small and data largely retrospective. In total, 205 patients are reported to have received pelvic SABR re-irradiation. Dose and fractionation schedules and re-irradiated volumes are highly variable. Little information is provided regarding organ at risk constraints adopted in the re-irradiation setting. Treatment appears well-tolerated overall, with nine grade 3 and six grade 4 toxicities amongst thirteen re-irradiated patients. Local control at one year ranged from 51% to 100%. Symptomatic improvements were also noted.
For previously irradiated patients with recurrent pelvic disease, SABR re-irradiation could be a feasible intervention for those who otherwise have limited options. Evidence to support this technique is limited but shows initial promise. Based on the available literature, suggestions for a more formal SABR re-irradiation pathway are proposed. Prospective studies and a multidisciplinary approach are required to optimise future treatment.
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