Gastric cancer is a significant global health problem. It is the fifth most common cancer and third leading cause of cancer-related death worldwide (Torre et al. in CA Cancer J Clin 65(2):87–108,
...2015
). Despite advances in treatment, overall prognosis remains poor, due to tumour relapse and metastasis. There is an urgent need for novel therapeutic approaches to improve clinical outcomes in gastric cancer. The cancer stem cell (CSC) model has been proposed to explain the high rate of relapse and subsequent resistance of cancer to current systemic treatments (Vermeulen et al. in Lancet Oncol 13(2):e83–e89,
2012
). CSCs have been identified in many solid malignancies, including gastric cancer, and have significant clinical implications, as targeting the CSC population may be essential in preventing the recurrence and spread of a tumour (Dewi et al. in J Gastroenterol 46(10):1145–1157,
2011
). This review seeks to summarise the current evidence for CSC in gastric cancer, with an emphasis on candidate CSC markers, clinical implications, and potential therapeutic approaches.
The ectonucleotidases CD39 and CD73 are present on immune cells and play important roles in cancer progression by suppressing antitumour immunity. As such, CD39 and CD73 on peripheral blood ...mononuclear cells (PBMCs) are emerging as potential biomarkers to predict disease outcomes and treatment responses in cancer patients. This study aimed to examine T and B cells, including CD39 and CD73 expressing subsets, by flow cytometry in PBMCs from 28 patients with head and neck squamous cell carcinoma (HNSCC) and to assess the correlation with the treatment modality, human papillomavirus (HPV) status, and relapse-free survival (RFS). The PBMCs were examined pre-, mid-, and post-radiotherapy with concurrent cisplatin chemotherapy or anti-epidermal growth factor receptor antibody (cetuximab) therapy. Combination radiotherapy caused changes to T and B cell populations, including CD39 and CD73 expressing subsets, but no such differences were observed between concurrent chemotherapy and cetuximab. Pretreatment PBMCs from HPV+ patients contained increased proportions of CD39−CD73−CD4+ T cells and reduced proportions of CD39−/+CD73+CD4+ T cells compared to the equivalent cells from HPV− patients. Notably, the pretreatment CD4+:CD8+ T cell ratios and CD39+CD73+CD19+ B cell proportions below the respective cohort medians corresponded with an improved RFS. Collectively, this study supports the notion that CD39 and CD73 may contribute to disease outcomes in HNSCC patients and may assist as biomarkers, either alone or as part of immune signatures, in HNSCC. Further studies of CD39 and CD73 on PBMCs from larger cohorts of HNSCC patients are warranted.
Despite the acceptability and efficacy of e-patient-reported outcome (ePRO) systems, implementation in routine clinical care remains challenging.
This pragmatic trial implemented the PROMPT-Care ...(Patient Reported Outcome Measures for Personalized Treatment and Care) web-based system into existing clinical workflows and evaluated its effectiveness among a diverse population of patients with cancer.
Adult patients with solid tumors receiving active treatment or follow-up care in four cancer centers were enrolled. The PROMPT-Care intervention supported patient management through (1) monthly off-site electronic PRO physical symptom and psychosocial well-being assessments, (2) automated electronic clinical alerts notifying the care team of unresolved clinical issues following two consecutive assessments, and (3) tailored online patient self-management resources. Propensity score matching was used to match controls with intervention patients in a 4:1 ratio for patient age, sex, and treatment status. The primary outcome was a reduction in emergency department presentations. Secondary outcomes were time spent on chemotherapy and the number of allied health service referrals.
From April 2016 to October 2018, 328 patients from four public hospitals received the intervention. Matched controls (n=1312) comprised the general population of patients with cancer, seen at the participating hospitals during the study period. Emergency department visits were significantly reduced by 33% (P=.02) among patients receiving the intervention compared with patients in the matched controls. No significant associations were found in allied health referrals or time to end of chemotherapy. At baseline, the most common patient reported outcomes (above-threshold) were fatigue (39%), tiredness (38.4%), worry (32.9%), general wellbeing (32.9%), and sleep (24.1%), aligning with the most frequently accessed self-management domain pages of physical well-being (36%) and emotional well-being (23%). The majority of clinical feedback reports were reviewed by nursing staff (729/893, 82%), largely in response to the automated clinical alerts (n=877).
Algorithm-supported web-based systems utilizing patient reported outcomes in clinical practice reduced emergency department presentations among a diverse population of patients with cancer. This study also highlighted the importance of (1) automated triggers for reviewing above-threshold results in patient reports, rather than passive manual review of patient records; (2) the instrumental role nurses play in managing alerts; and (3) providing patients with resources to support guided self-management, where appropriate. Together, these factors will inform the integration of web-based PRO systems into future models of routine cancer care.
Australian New Zealand Clinical Trials Registry ACTRN12616000615482; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370633.
RR2-10.1186/s12885-018-4729-3.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
This paper reports a high-level python package for selecting machine learning algorithms and ensembles of machine learning algorithms parameters by using the particle swarm optimization (PSO) ...algorithm named PSPSO. The first version of PSPSO supports four algorithms: Support Vector Machine (SVM), Multi-Layer Perceptron (MLP), Extreme Gradient Boosting (XGBoost) and Gradient Boosting Decision Trees (GBDT). PSPSO provides an easy framework for building machine learning algorithms using PSO and a new platform for researchers to investigate their selection methods. In addition, it provides a basis for establishing new selection ideas and can be easily extended to support other algorithms.
Right sided colon cancer (RsCC) is proposed to be a distinct disease entity to left sided colon cancer (LsCC). We seek to confirm primary tumour location as an independent prognostic factor in ...locoregional colorectal cancer.
All patients with stage I - III primary adenocarcinoma of colon were identified from the New South Wales (NSW) clinical cancer registry (2006-2013). Primary tumour location (RsCC vs LsCC) survival analyses were conducted using the Kaplan-Meier method, and adjusted hazard ratios for 5-year all-cause mortality (OS) and 5-year cancer specific mortality (CSS) were obtained using Cox proportional hazards regression.
We identified 9509 patients including 5051 patients with RsCC and 4458 with LsCC. Patients with RsCC were more likely to be older, female, have a higher Charlson comorbidity index, and have worse tumour prognostic factors. In univariate analysis of all stages combined, those patients with RsCC had a worse overall survival (OS, HR 1.20 95% CI 1.11-1.29, p < 0.0001), although this was not significant in the multivariate analysis (HR 0.96 95% CI 0.89-1.04, p = 0.35). Stage I patients with RsCC had a trend to improved OS (multivariate HR 0.84 95% CI 0.69-1.01, p = 0.07) and a significantly improved CSS (multivariate HR 0.51 95% CI 0.35-0.75, p = 0.0006). In stage II patients with RsCC there was a significantly improved OS (multivariate HR 0.85 95% CI 0.75-0.98, p = 0.02) and CSS (multivariate HR 0.59 95% CI 0.45-0.78, p = 0.0002) compared to LsCC. In stage III patients, those with RsCC had a worse OS (multivariate HR 1.13 95% CI 1.01-1.26, p = 0.032) and a trend to worse CSS (multivariate HR 1.12 95% CI 0.94-1.33, p = 0.22).
Primary tumour location is an important prognostic factor in locoregional colon cancer with an effect that varies by stage. RsCC is associated with lower all-cause mortality in stage II, and higher all-cause mortality in stage III.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In progressing the use of big data in health systems, standardised nomenclature is required to enable data pooling and analyses. In many radiotherapy planning systems and their data archives, target ...volumes (TV) and organ-at-risk (OAR) structure nomenclature has not been standardised. Machine learning (ML) has been utilised to standardise volumes nomenclature in retrospective datasets. However, only subsets of the structures have been targeted. Within this paper, we proposed a new approach for standardising all the structures nomenclature by using multi-modal artificial neural networks. A cohort consisting of 1613 breast cancer patients treated with radiotherapy was identified from Liverpool & Macarthur Cancer Therapy Centres, NSW, Australia. Four types of volume characteristics were generated to represent each target and OAR volume: textual features, geometric features, dosimetry features, and imaging data. Five datasets were created from the original cohort, the first four represented different subsets of volumes and the last one represented the whole list of volumes. For each dataset, 15 sets of combinations of features were generated to investigate the effect of using different characteristics on the standardisation performance. The best model reported 99.416% classification accuracy over the hold-out sample when used to standardise all the nomenclatures in a breast cancer radiotherapy plan into 21 classes. Our results showed that ML based automation methods can be used for standardising naming conventions in a radiotherapy plan taking into consideration the inclusion of multiple modalities to better represent each volume.
CD39 and CD73 are ecto-nucleotidases present on human peripheral blood mononuclear cells (PBMCs) and are emerging biomarkers on these cells in various disorders including cancer. Many factors ...influence PBMC quality, so it is essential to validate sample processing methods prior to incorporation in clinical studies. This study examined the impact of both PBMC cryopreservation and PBMC isolation using SepMate density gradient centrifugation on CD39 and CD73 expressing subsets. First, PBMCs were isolated from the peripheral blood of 11 healthy donors by routine Ficoll-Paque density gradient centrifugation, cryopreserved and compared with freshly isolated PBMCs by flow cytometry. The proportions of T and B cells expressing combinations of CD39 and CD73 were relatively stable over 6-month cryopreservation, although some T cell combinations revealed small but significant changes. Second, peripheral blood was collected from six healthy donors to compare PBMCs isolated by SepMate or Ficoll-Paque density gradient centrifugation. Compared with Ficoll-Paque, the more rapid SepMate method yielded 9.1% less PBMCs but did not alter cell viability or proportions of T and B cells expressing combinations of CD39 and CD73. The present study reveals that cryopreservation is suitable for studying T and B cells expressing combinations of CD39 and CD73. However, caution should be exercised when observing small differences in these cryopreserved subsets between different cohorts. Further, SepMate and Ficoll-Paque methods of PBMC isolation show similar results for T and B cell subset analysis; however, SepMate is a faster and easier approach.
The urokinase plasminogen activation (uPA) system is a crucial pathway for tumour invasion and establishment of metastasis. Although there is good evidence that uPA system expression is a clinically ...relevant biomarker in some solid tumours, its role in gastroesophageal cancer is uncertain.
We identified 22 studies encompassing 1966 patients which fulfilled the inclusion criteria. uPA, uPAR, or PAI-1 expression is significantly associated with high risk clinicopathological features. High uPA expression is associated with a shorter RFS (HR 1.90 95% 1.16-3.11, p = 0.01) and OS (HR 2.21 95% CI 1.74-2.80, p < 0.0001). High uPAR expression is associated with poorer OS (HR 2.21 95%CI 1.82-2.69, p < 0.0001). High PAI-1 expression is associated with shorter RFS (HR 1.96 96% CI 1.07-3.58, p = 0.03) and OS (HR 1.84 95%CI 1.28-2.64, p < 0.0001). There was no significant association between PAI-2 expression and OS (HR 0.97 95%CI 0.48-1.94, p < 0.92) although data was limited.
We undertook a systematic review evaluating expression of uPA, urokinase plasminogen activator receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1/SerpinE1) and plasminogen activator inhibitor-2 (PAI-2/SerpinB2) on primary oesophageal, gastro-oesophageal junction, and gastric adenocarcinomas. We performed a meta-analysis of clinicopathological associations, overall survival (OS) and recurrence free survival (RFS).
We conclude that the uPA system is a clinically relevant biomarker in primary gastroesophageal cancer, with higher expression of uPA, uPAR and PAI-1 associated with higher risk disease and poorer prognosis. This also highlights the potential utility of the uPA system as a therapeutic target for improved treatment strategies.
Purpose
This study aims to investigate the 2D monolithic silicon diode array size of 52 × 52 mm2 (MP512) angular response. An angular correction method has been developed that improves the accuracy ...of dose measurement in a small field.
Methods
The MP512 was placed at the center of a cylindrical phantom, irradiated using 6 MV and 10 MV photons and incrementing the incidence of the beam angle in 15° steps from 0° to 180°, and then in 1° steps between 85° and 95°. The MP512 response was characterized for square field sizes varying between 1 × 1 cm2 and 10 × 10 cm2. The angular correction factor was obtained as the ratio of MP512 response to EBT3 film measured doses as a function of the incidence angle (Ɵ) and was normalized at 0° incidence angle. Beam profiles of the corrected MP512 responses were compared with the EBT3 responses to verify the effectiveness of the method adopted.
Results
The intrinsic angular dependence of the MP512 shows maximum relative deviation from the response normalized to 0° of 18.5 ± 0.5% and 15.5 ± 0.5% for 6 MV and 10 MV, respectively, demonstrating that the angular response is sensitive to the energy. In contrast, the variation of angular response is less affected by field size. Comparison of cross‐plane profiles measured by the corrected MP512 and EBT3 shows an agreement within ±2% for all field sizes when the beams irradiated the array at 0°, 45°, 135°, and 180° angles of incidence from the normal to the detector plane. At 90° incidence, corresponding to a depth dose measurement, up to a 6% discrepancy was observed for a 1 × 1 cm2 field of 6 MV.
Conclusion
An angular correction factor can be adopted for small field sizes. Measurements discrepancies could be encountered when irradiating with very small fields parallel to the detector plane. Using this approach, the MP512 is shown to be a suitable detector for 2D dose mapping of small field size photon beams.
Cherenkov radiation is the primary source of unwanted light in a scintillator dosimetry system. In this work we compare two techniques for temporally separating Cherenkov radiation from a slow ...scintillator signal. These techniques are applicable to a pulsed radiation beam. We found that by analysing the rising edge of the light pulse to identify the fast Cherenkov light only removed 74% of the Cherenkov light. By integrating the tail of the signal where only scintillation light is present a more accurate result is achieved. The average of the results of the two methods provides up to a 90% improvement in the accuracy of the relative dose when compared to ionisation chamber, in certain measurements. This work demonstrates an alternative methodology for the removal of Cherenkov light using signal analysis, while preserving all the scintillation light signal and minimising the bulk of the experimental equipment.
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