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Malta

Cancer Statistics
Population in 2012: 0.4m
People newly diagnosed with cancer (excluding NMSC) / yr: 1,900
Age-standardised rate, incidence per 100,000 people/yr: 242.9
Risk of getting cancer before age 75:23.7%
People dying from cancer /yr: 800
Data from IARC GlobalCan (2012)
Malta Cancer Organisations and Resources
Latest Research Publications Related to Malta

Malta Cancer Organisations and Resources (2 links)


Latest Research Publications Related to Malta

Fang C, Cortis K, Yusuf GT, et al.
Complications from percutaneous microwave ablation of liver tumours: a pictorial review.
Br J Radiol. 2019; 92(1099):20180864 [PubMed] Article available free on PMC after 01/07/2020 Related Publications
Percutaneous microwave ablation of liver tumours is a well-established technique that has been proven to be effective in the curative and palliative treatment of small volume primary and secondary liver tumours. Microwave ablation is designed to achieve larger areas of necrosis compared to radiofrequency ablation and has a good safety profile among liver tumour treatments. Mortality is unreported and major complications are rare. Knowledge of potential complications is essential for interventional radiologists performing liver ablation in order to reduce patient morbidity. The aim of this review is to illustrate major complications post microwave ablation in a pictorial format as well as a discussion on how best to avoid these complications.

Marmarà D, Marmarà V, Hubbard G
Predicting reattendance to the second round of the Maltese national breast screening programme: an analytical descriptive study.
BMC Public Health. 2019; 19(1):189 [PubMed] Article available free on PMC after 01/07/2020 Related Publications
BACKGROUND: A range of barriers influence women's uptake to a first breast screening invitation. Few studies however, have examined factors associated with second screening uptake. This study follows Maltese women to explore predictors and behaviours to re-attendance, and to determine if uptake of first invitation to the Maltese Breast Screening Programme (MBSP) is a significant predictor of second screening uptake.
METHODS: A prospective study was conducted to determine factors associated with re-attendance for 100 women invited to the second MBSP round. Records of women's second attendance to the MBSP were extracted in January 2016 from the MBSP database. Data were analyzed using chi-square tests, Independent Samples t-test, Mann Whitney test, Shapiro Wilk test and logistic regression.
RESULTS: There were no significant associations for sociodemographic or health status variables with second screening uptake (p > 0.05), except breast condition (Fisher's exact test, p = 0.046). Non-attendees at second screening were most unsure of screening frequency recommendations (χ2 = 9.580, p = 0.048). Attendees were more likely to perceive their susceptibility to breast cancer (p = 0.041), believed breast cancer to be life changing (p = 0.011) and considered cues to action to aid attendance (p = 0.028). Non-attendees were in stronger agreement on mammography pain (p = 0.008) and were less likely to consider cues to action (15.4% non-attendees vs 1.4% attendees) (p = 0.017 respectively). 'Perceived barriers', 'breast cancer identity', 'causes' and 'consequences' were found to be significant predictors of second screening uptake, with 'perceived barriers' being the strongest. The inclusion of illness perception items improved the regression model's accuracy in predicting non-attendance to the second screening round (84.6% vs 30.8%). First screening uptake was found to be a significant predictor of subsequent uptake (OR = 0.102; 95% CI = 0.037, 0.283; p = 0.000).
CONCLUSIONS: Interventions to increase uptake should target first invitees since attending for the first time is a strong predictor of uptake to the second cycle. Further research is required given the small sample. Particular attention should be paid to women who did not respond to their first invite or are unsure or reluctant participants initially.

Catania AM, Sammut Scerri C, Catania GJ
Men's experience of their partners' breast cancer diagnosis, breast surgery and oncological treatment.
J Clin Nurs. 2019; 28(9-10):1899-1910 [PubMed] Related Publications
AIMS AND OBJECTIVES: To investigate the experiences of male partners of female breast cancer patients who had undergone surgery and oncological treatment and who were still raising children.
BACKGROUND: Research on the psychological effects of breast cancer has focused primarily on the patients undergoing treatment, neglecting the effect of such a condition on their closest family members. This study addresses this gap by focusing on understanding the effects of this disease on male partners of these patients.
DESIGN: An interpretative phenomenological approach was used.
METHODS: Eight males whose female partners were diagnosed with primary breast cancer between the ages of 30 and 55 and who had young children still living at home at the time were interviewed by the first author of this article. Interviews were transcribed verbatim and analyzed using an interpretative phenomenological framework, in accordance with the guidelines in the COREQ checklist for qualitative studies.
RESULTS: Participants emphasized the difficulties they faced in trying to juggle work and family responsibilities while offering support to their partners, a task they felt ill-prepared for. At times, they felt excluded by their partners and worried about the impact of the disease on their children. A common fear was that of recurrence of the disease, and while some discussed the financial difficulties associated with treating the disease, others saw it as enhancing the potential for their personal and couple growth.
CONCLUSIONS: This study adds to the topic by uncovering the perspectives of male partners of breast cancer patients and the effects of their partner's condition on them and their families.
RELEVANCE TO CLINICAL PRACTICE: The results of this study can be used to inform policy when providing holistic care. They also highlight the importance of counselling and support interventions for partners of breast cancer patients.

Schembri EL, Mifsud S, Gauci J, et al.
An unusual presentation of multiple myeloma.
BMJ Case Rep. 2018; 11(1) [PubMed] Related Publications
The authors report a case of a 58-year-old woman, ex-smoker, who was referred to the respiratory clinic with a presumed unresolving airspace shadowing in the right lung. Further evaluation of the shadowing with a CT thorax revealed rib lesions, a pancreatic lesion and multiple liver lesions, making the diagnosis of metastatic pancreatic carcinoma most likely. However, further blood investigations and imaging eventually revealed the cause for the shadowing to be multiple myeloma, since the unresolving shadowing was actually a rib lesion.

Rich A, Baldwin D, Alfageme I, et al.
Achieving Thoracic Oncology data collection in Europe: a precursor study in 35 Countries.
BMC Cancer. 2018; 18(1):1144 [PubMed] Article available free on PMC after 01/07/2020 Related Publications
BACKGROUND: A minority of European countries have participated in international comparisons with high level data on lung cancer. However, the nature and extent of data collection across the continent is simply unknown, and without accurate data collection it is not possible to compare practice and set benchmarks to which lung cancer services can aspire.
METHODS: Using an established network of lung cancer specialists in 37 European countries, a survey was distributed in December 2014. The results relate to current practice in each country at the time, early 2015. The results were compiled and then verified with co-authors over the following months.
RESULTS: Thirty-five completed surveys were received which describe a range of current practice for lung cancer data collection. Thirty countries have data collection at the national level, but this is not so in Albania, Bosnia-Herzegovina, Italy, Spain and Switzerland. Data collection varied from paper records with no survival analysis, to well-established electronic databases with links to census data and survival analyses.
CONCLUSION: Using a network of committed clinicians, we have gathered validated comparative data reporting an observed difference in data collection mechanisms across Europe. We have identified the need to develop a well-designed dataset, whilst acknowledging what is feasible within each country, and aspiring to collect high quality data for clinical research.

Kuhara K, Tokuda K, Kitagawa T, et al.
CUB Domain-containing Protein 1 (CDCP1) Is Down-regulated by Active Hexose-correlated Compound in Human Pancreatic Cancer Cells.
Anticancer Res. 2018; 38(11):6107-6111 [PubMed] Related Publications
BACKGROUND/AIM: We have previously reported that treatment of pancreatic cancer cells with active hexose-correlated compound (AHCC), an extract of a basidiomycete mushroom, decreases the levels of tumor-associated proteins including heat-shock protein 27 (HSP27), heat shock factor 1 (HSF1) and sex-determining region Y-box 2 (SOX2). The transmembrane glycoprotein, CUB domain-containing protein 1 (CDCP1) has been reported to be up-regulated in various cancers, and be associated with invasion and metastasis. The aim of this study was to examine the effect of AHCC on the expression of CDCP1 in KLM1-R cells.
MATERIALS AND METHODS: Gemcitabine-resistant pancreatic cancer cells (KLM1-R) were treated with AHCC (10 mg/ml) for 48 h. Western blot analysis of cell extracts with anti-CDCP1 or anti-actin antibodies was performed to assess the expression of CDCP1.
RESULTS: Expression of CDCP1 was reduced by AHCC treatment of KLM1-R cells, whereas expression of actin was not affected. The ratio of intensities of CDCP1/actin in AHCC-treated KLM1-R cells was significantly suppressed (p<0.05) compared to untreated cells.
CONCLUSION: AHCC down-regulated CDCP1 expression and inhibited the malignant progression of pancreatic cancer cells.

Mercieca S, Belderbos JSA, van Baardwijk A, et al.
The impact of training and professional collaboration on the interobserver variation of lung cancer delineations: a multi-institutional study.
Acta Oncol. 2019; 58(2):200-208 [PubMed] Related Publications
BACKGROUND: To assess the impact of training and interprofessional collaboration on the interobserver variation in the delineation of the lung gross tumor volume (GTVp) and lymph node (GTVln).
MATERIAL AND METHODS: Eight target volume delineations courses were organized between 2008 and 2013. Specialists and trainees in radiation oncology were asked to delineate the GTVp and GTVln on four representative CT images of a patient diagnosed with lung cancer individually prior each course (baseline), together as group (interprofessional collaboration) and post-training. The mean delineated volume and local standard deviation (local SD) between the contours for each course group were calculated and compared with the expert delineations.
RESULTS: A total 410 delineations were evaluated. The average local SD was lowest for the interprofessional collaboration (GTVp = 0.194 cm, GTVln = 0.371 cm) followed by the post-training (GTVp = 0.244 cm, GTVln = 0.607 cm) and baseline delineations (GTVp = 0.274 cm, GTVln: 0.718 cm). The mean delineated volume was smallest for the interprofessional (GTVp = 4.93 cm
CONCLUSION: Our findings indicate that image interpretational differences can lead to large interobserver variation particularly when delineating the GTVln. Interprofessional collaboration was found to have the greatest impact on reducing interobserver variation in the delineation of the GTVln. This highlights the need to develop a clinical workflow so as to ensure that difficult cases are reviewed routinely by a second radiation oncologist or radiologist so as to minimize the risk of geographical tumor miss and unnecessary irradiation to normal tissue.

Conti L, Pisani D, Gatt A, Montefort S
Unusual case of primary pulmonary Hodgkin's lymphoma presenting with a continuous murmur.
BMJ Case Rep. 2018; 2018 [PubMed] Related Publications
Systemic to pulmonary fistulas are an unusual entity, even more so in association with Hodgkin's lymphoma. We herein report a case of a 33-year-old woman that presented with an incidental lung lesion on a chest radiograph with an associated high-frequency continuous murmur over the lesion. The diagnosis of primary pulmonary Hodgkin's lymphoma, nodular sclerosis type, was obtained by a CT transthoracic biopsy. We achieved an excellent response after polychemotherapy with near-complete disappearance of the mass and a residual faint systolic murmur over the lesion.

Restivo V, Costantino C, Marras A, et al.
Pap Testing in a High-Income Country with Suboptimal Compliance Levels: A Survey on Acceptance Factors among Sicilian Women.
Int J Environ Res Public Health. 2018; 15(9) [PubMed] Article available free on PMC after 01/07/2020 Related Publications
Cervical cancer screening is uncommon, especially in low-income countries and among lower socioeconomic status people in high-income countries. The aims of this study were to examine the adherence of Sicilian women to Pap testing and to identify the determinants of this in a population with a secondary prevention attitude lower than high-income countries and the national average. A cross-sectional study called "Save Eva in Sicily" was conducted among all women aged 25⁻64 years, with a sample drawn by the list of general practitioners (GPs), using a proportional sampling scheme, stratified by age and resident population. The study outcome was performing a Pap test within the past three years. The association between the outcome and Pap test determinants was analyzed through a multivariable logistic regression. Among the 365 interviewed women, 66% (

Baldacchino S, Saliba C, Scerri J, et al.
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material.
J Vis Exp. 2018; (138) [PubMed] Article available free on PMC after 01/07/2020 Related Publications
Nucleic acid degradation in archival tissue, tumor heterogeneity, and a lack of fresh frozen tissue specimens can negatively impact cancer diagnostic services in pathology laboratories worldwide. Gene amplification and expression diagnostic testing using archival material or material that requires transportation to servicing laboratories, needs a more robust and accurate test adapted to current clinical workflows. Our research team optimized the use of Invitrogen™ QuantiGene™ Plex Assay (Thermo Fisher Scientific) to quantify RNA in archival material using branched-DNA (bDNA) technology on Luminex xMAP

Chircop D, Scerri J
The lived experience of patients with non-Hodgkin's lymphoma undergoing chemotherapy.
Eur J Oncol Nurs. 2018; 35:117-121 [PubMed] Related Publications
PURPOSE: Patients with non-Hodgkin's lymphoma face many challenges when undergoing chemotherapy. However, there is a dearth of literature targeting the experiences of this patient group. Hence, the aim of this study was to explore the lived experience of patients with non-Hodgkin's lymphoma during the initial stages of chemotherapy (i.e. from commencement to mid-treatment).
METHOD: This study adopted a qualitative research design. Semi-structured interviews were conducted with six adult patients having non-Hodgkin's lymphoma and undergoing chemotherapy. Data collection was undertaken between July 2016 and December 2016. The interviews were audio-recorded and transcribed verbatim. The data was analysed using Interpretative Phenomenological Analysis.
RESULTS: Three themes emerged: 'Living an emotional rollercoaster', 'Becoming dependent on others' and 'Facing an uncertain future'. This study highlights that, whilst undergoing chemotherapy, the participants experienced a rollercoaster of emotions, such as fear, relief, acceptance and depression, in addition to physical dysfunction. Moreover, two participants described feeling so overwhelmed emotionally that they even considered committing suicide. Nevertheless, all the participants stated that they hoped that their life would revert back to normal on completion of their treatment.
CONCLUSIONS: The findings of this study may help guide the formulation of interventions that target the needs of patients undergoing chemotherapy for non-Hodgkin's lymphoma. Such interventions may include the introduction of community services where health care providers can provide domestic support to these patients. Additionally, the information generated can also inform hospital policies, such as the introduction of screening programs to monitor for psychological distress in this patient group during treatment.

Doganis D, Panagopoulou P, Tragiannidis A, et al.
Survival and mortality rates of Wilms tumour in Southern and Eastern European countries: Socioeconomic differentials compared with the United States of America.
Eur J Cancer. 2018; 101:38-46 [PubMed] Related Publications
BACKGROUND: Despite recent therapeutic advancements, Wilms tumour (WT) presents remarkable survival variations. We explored mortality and survival patterns for children (0-14 years) with WT in 12 Southern and Eastern European (SEE) countries in comparison with the United States of America (USA).
METHODS: A total of 3966 WT cases (0-14 years) were registered by a network of SEE childhood cancer registries (N:1723) during available registration periods circa 1990-2016 and surveillance, epidemiology, and end results program (SEER) (N:2243; 1990-2012); mortality data were provided by the respective national statistical services. Kaplan-Meier curves and Cox proportional hazards models were used to assess the role of age, sex, year of diagnosis, urbanisation and Human Development Index (HDI) on overall survival (OS).
RESULTS: Persisting regional variations shape an overall 78% 5-year OS in the participating SEE countries, lagging behind the USA figure (92%, p=0.001) and also reflected by higher SEE mortality rates. Worth mentioning is the gradually escalating OS in SEE (hazard ratio [HR]
CONCLUSIONS: Children with WT residing in SEE countries do not equally enjoy the substantial survival gains, especially for those living in rural areas and in lower HDI countries. Noteworthy are steep and sizeable survival gains in SEE along with the newly presented Greek data pointing to achievable survival goals in SEE despite the financial crisis.

Sommariva A, Forsea AM, Agius D, et al.
Quality assurance in melanoma care: The EU-MELACARE study.
Eur J Surg Oncol. 2018; 44(11):1773-1778 [PubMed] Related Publications
BACKGROUND: A significant disparity regarding survival outcome for melanoma among European regions is well recognized and access to high quality care for European melanoma patients needs to be improved. There is an unmet need for the implementation of minimal standard of care within defined clinical pathways and Quality Assurance (QA) indicators.
OBJECTIVE: The EU-MELACARE study aims to identify shared variables for cutaneous melanoma cases recorded in melanoma registries across Europe.
MATERIAL AND METHODS: Opinion leaders involved in melanoma data registration and care quality analysis in 34 European countries were invited to respond to an expert survey covering questions regarding the melanoma registration practice in their countries and the characteristics, coverage and variables collected by the relevant melanoma registries.
RESULTS: Data regarding 13 melanoma registries from 11 European countries contributed to the study. The majority (61,5%) were population based registries and more than half (62%) had national coverage. The included registries collected a median of 38 variables (Interquartile Range, IRQ 21-76). We identified 24 shared variables available in >70% of registries.
CONCLUSIONS: This study provides valuable specific information on information recorded for melanoma cases are registered within Europe. A core of shared variables has been identified, which will constitute the basis for a standardized set of QA indicators for assessing and monitoring melanoma care across European countries.

Chircop D, Scerri J
The use of metaphors in non-Hodgkin's lymphoma patients undergoing chemotherapy.
J Adv Nurs. 2018; 74(11):2622-2629 [PubMed] Related Publications
AIM: The aim of this study was to explore the use of metaphors by non-Hodgkin's lymphoma (NHL) patients undergoing chemotherapy in a haematology ward setting.
BACKGROUND: There is a dearth of literature exploring the use of metaphors in people with cancer undergoing aggressive treatment. Hence, this study aims to explore the use of metaphors in NHL patients undergoing chemotherapy and additionally, examining whether the use of such metaphors has an empowering/disempowering effect.
DESIGN: A qualitative design was used.
METHODS: The participants were six adult patients diagnosed with NHL and undergoing chemotherapy. Data collection was undertaken between July 2016-December 2016. Each participant was interviewed twice using semi-structured interviews. The data were analysed using Pragglejaz method for finding metaphors.
FINDINGS: The participants used metaphors 17 times per 1,000 words to describe their experience of undergoing chemotherapy for NHL. The metaphors cited focused on aspects relating to "war", "prison" and a "journey".
CONCLUSIONS: The findings demonstrate that certain metaphors used by the study participants, such as those pertaining to "war" or a "journey", concur with those described in narratives of people with cancer in general. However, the use of the "prison" metaphor by NHL patients undergoing chemotherapy relates particularly to their context of being isolated while undergoing treatment for fear of infection. Consequently, there is the need to interpret metaphors in relation to the specific type of illness and context. Furthermore, the findings of this study suggest that the impact of metaphors in empowering/disempowering people with cancer depends on the unique interpretation of the individual patient.

Shimada T, Nanimoto Y, Baron B, et al.
Enzyme-treated Asparagus Extract Down-regulates Heat Shock Protein 27 of Pancreatic Cancer Cells.
In Vivo. 2018 Jul-Aug; 32(4):759-763 [PubMed] Article available free on PMC after 01/07/2020 Related Publications
BACKGROUND/AIM: From the standpoint of cancer therapy, it is valuable to enhance the anticancer effects of chemotherapy. Our previous reports revealed that up-regulation of heat-shock protein 27 (HSP27) has been linked to gemcitabine resistance of pancreatic cancer cells. Enzyme-treated asparagus extract (ETAS) is an extract that is produced from asparagus. The purpose of this study was to investigate the effect of ETAS on the expression of HSP27 and other HSPs in the gemcitabine-resistant pancreatic cancer cell line KLM1-R.
MATERIALS AND METHODS: KLM1-R cells were treated with ETAS, and expression levels of HSPs, including HSP27, were investigated by western blotting.
RESULTS: ETAS down-regulated HSP27 and pHSP27 (serine 78) in KLM1-R cells, but, HSP70 and GRP78 levels were not altered.
CONCLUSION: This study suggests the potential therapeutic benefit of ETAS in enhancing anticancer effects by its combination with gemcitabine for patients with pancreatic cancer.

Hubbard G, Kyle RG, Neal RD, et al.
Promoting sunscreen use and skin self-examination to improve early detection and prevent skin cancer: quasi-experimental trial of an adolescent psycho-educational intervention.
BMC Public Health. 2018; 18(1):666 [PubMed] Article available free on PMC after 01/07/2020 Related Publications
BACKGROUND: Skin cancer rates are increasing. Interventions to increase adolescent sunscreen use and skin self-examination (SSE) are required.
METHODS: Quasi-experimental design; 1 control and 4 intervention group schools in Scotland, UK. Participants were 15-16 year old students on the school register. The intervention was a theoretically-informed (Common-Sense Model and Health Action Process Approach) 50-min presentation, delivered by a skin cancer specialist nurse and young adult skin cancer survivor, to students in a classroom, supplemented by a home-based assignment. Outcome variables were sunscreen use intention, SSE intention/behaviour, planning, illness perceptions and skin cancer communication behaviour, measured 2 weeks pre- and 4 weeks post- intervention using self-completed pen and paper survey. School attendance records were used to record intervention up-take; students self-reported completion of the home-based assignment. Pearson's chi-square test, analysis of variance, and non-parametric Wilcoxon Signed Ranks Test were used to measure outcomes and associations between variables. Focus groups elicited students' (n = 29) views on the intervention. Qualitative data were analysed thematically.
RESULTS: Five of 37 invited schools participated. 639 (81%) students in intervention schools received the intervention; 33.8% completed the home-based assignment. 627 (69.6%) of students on the school register in intervention and control schools completed a questionnaire at baseline; data for 455 (72.6%) students were available at baseline and follow-up. Focus groups identified four themes - personal experiences of skin cancer, distaste for sunscreen, relevance of SSE in adolescence, and skin cancer conversations. Statistically significant (p < 0.05) changes were observed for sunscreen use, SSE, planning, and talk about skin cancer in intervention schools but not the control. Significant associations were found between sunscreen use, planning and 2 illness perceptions (identity and consequence) and between SSE, planning and 3 illness perceptions (timeline, causes, control).
CONCLUSIONS: It is feasible to promote sunscreen use and SSE in the context of an adolescent school-based psychoeducation intention. Further research is required to improve study uptake, intervention adherence and effectiveness.
TRIAL REGISTRATION: ISRCTN11141528.

Armbruster M, D'Anastasi M, Holzner V, et al.
Improved detection of a tumorous involvement of the mesorectal fascia and locoregional lymph nodes in locally advanced rectal cancer using DCE-MRI.
Int J Colorectal Dis. 2018; 33(7):901-909 [PubMed] Related Publications
PURPOSE: The prediction of an infiltration of the mesorectal fascia (MRF) and malignant lymph nodes is essential for treatment planning and prognosis of patients with rectal cancer. The aim of this study was to assess the additional diagnostic value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the detection of a malignant involvement of the MRF and of mesorectal lymph nodes in patients with locally advanced rectal cancer.
METHODS: In this prospective study, 22 patients with locally advanced rectal cancer were examined with 1.5-T MRI between September 2012 and April 2015. Histopathological assessment of tumor size, tumor infiltration to the MRF, and malignant involvement of locoregional lymph nodes served as standard of reference. Sensitivity and specificity of detecting MRF infiltration and malignant nodes (nodal cut-off size [NCO] ≥ 5 and ≥ 10 mm, respectively) was determined by conventional MRI (cMRI; precontrast and postcontrast T1-weighted, T2-weighted, and diffusion-weighted images) and by additional semi-quantitative DCE-MRI maps (cMRI+DCE-MRI).
RESULTS: Compared to cMRI, additional semi-quantitative DCE-MRI maps significantly increased sensitivity (86 vs. 71% [NCO ≥ 5 mm]/29% [NCO ≥ 10 mm]) and specificity (90 vs. 70% [NCO ≥ 5 mm]) of detecting malignant lymph nodes (p < 0.05). Moreover, DCE-MRI significantly augmented specificity (91 vs. 82%) of discovering a MRF infiltration (p < 0.05), while there was no change in sensitivity (83%; p > 0.05).
CONCLUSION: DCE-MRI considerably increases both sensitivity and specificity for the detection of small mesorectal lymph node metastases (≥ 5 mm but < 10 mm) and sufficiently improves specificity of a suspected MRF infiltration in patients with locally advanced rectal cancer.

Winter KS, Hofmann FO, Thierfelder KM, et al.
Towards volumetric thresholds in RECIST 1.1: Therapeutic response assessment in hepatic metastases.
Eur Radiol. 2018; 28(11):4839-4848 [PubMed] Related Publications
OBJECTIVES: To empirically determine thresholds for volumetric assessment of response and progress of liver metastases in line with the unidimensional RECIST thresholds.
METHODS: Patients with metastatic colorectal cancer initially enrolled in a multicentre clinical phase-III trial were included. In all CT scans, the longest axial diameters and volumes of hepatic lesions were determined semi-automatically. The sum of diameters and volumes of 1, ≤2 and ≤5 metastases were compared to all previous examinations. Volumetric thresholds corresponding to RECIST 1.1 thresholds were predicted with loess-regression. In sensitivity analysis, the concordances of proposed thresholds, weight-maximizing thresholds and thresholds from loess-regression were compared. Classification concordance for measurements of ≤2 metastases was further analyzed.
RESULTS: For measurements of ≤2 metastases, 348 patients with 629 metastases were included, resulting in 4,773 value pairs. Regression analysis yielded volumetric thresholds of -65.3% for a diameter change of -30%, and +64.6% for a diameter change of +20%. When comparing measurements of unidimensional RECIST assessment with volumetric measurements, there was a concordance of significant progress (≥+20% and ≥+65%) in 88.3% and of significant response (≤-30% and ≤-65%) in 85.0%.
CONCLUSIONS: In patients with hepatic metastases, volumetric thresholds of +65% and -65% were yielded corresponding to RECIST thresholds of +20% and -30%.
KEY POINTS: • Volumes and diameters of liver metastases from colorectal cancer were determined. • Volumetric thresholds of +65%/-65% corresponding to RECIST 1.1 are proposed. • Comparing both measurements, concordance was 88.3% (significant progress) and 85.0% (significant response).

Panagopoulou P, Georgakis MK, Baka M, et al.
Persisting inequalities in survival patterns of childhood neuroblastoma in Southern and Eastern Europe and the effect of socio-economic development compared with those of the US.
Eur J Cancer. 2018; 96:44-53 [PubMed] Related Publications
AIM: Neuroblastoma outcomes vary with disease characteristics, healthcare delivery and socio-economic indicators. We assessed survival patterns and prognostic factors for patients with neuroblastoma in 11 Southern and Eastern European (SEE) countries versus those in the US, including-for the first time-the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumours (NARECHEM-ST)/Greece.
METHODS: Overall survival (OS) was calculated in 13 collaborating SEE childhood cancer registries (1829 cases, ∼1990-2016) and Surveillance, Epidemiology, and End Results (SEER), US (3072 cases, 1990-2012); Kaplan-Meier curves were used along with multivariable Cox regression models assessing the effect of age, gender, primary tumour site, histology, Human Development Index (HDI) and place of residence (urban/rural) on survival.
RESULTS: The 5-year OS rates varied widely among the SEE countries (Ukraine: 45%, Poland: 81%) with the overall SEE rate (59%) being significantly lower than in SEER (77%; p < 0.001). In the common registration period within SEE (2000-2008), no temporal trend was noted as opposed to a significant increase in SEER. Age >12 months (hazard ratio [HR]: 2.8-4.7 in subsequent age groups), male gender (HR: 1.1), residence in rural areas (HR: 1.3), living in high (HR: 2.2) or medium (HR: 2.4) HDI countries and specific primary tumour location were associated with worse outcome; conversely, ganglioneuroblastoma subtype (HR: 0.28) was associated with higher survival rate.
CONCLUSIONS: Allowing for the disease profile, children with neuroblastoma in SEE, especially those in rural areas and lower HDI countries, fare worse than patients in the US, mainly during the early years after diagnosis; this may be attributed to presumably modifiable socio-economic and healthcare system performance differentials warranting further research.

Jantsch MF, Quattrone A, O'Connell M, et al.
Positioning Europe for the EPITRANSCRIPTOMICS challenge.
RNA Biol. 2018; 15(6):829-831 [PubMed] Article available free on PMC after 01/07/2020 Related Publications
The genetic alphabet consists of the four letters: C, A, G, and T in DNA and C,A,G, and U in RNA. Triplets of these four letters jointly encode 20 different amino acids out of which proteins of all organisms are built. This system is universal and is found in all kingdoms of life. However, bases in DNA and RNA can be chemically modified. In DNA, around 10 different modifications are known, and those have been studied intensively over the past 20 years. Scientific studies on DNA modifications and proteins that recognize them gave rise to the large field of epigenetic and epigenomic research. The outcome of this intense research field is the discovery that development, ageing, and stem-cell dependent regeneration but also several diseases including cancer are largely controlled by the epigenetic state of cells. Consequently, this research has already led to the first FDA approved drugs that exploit the gained knowledge to combat disease. In recent years, the ~150 modifications found in RNA have come to the focus of intense research. Here we provide a perspective on necessary and expected developments in the fast expanding area of RNA modifications, termed epitranscriptomics.

Rapisarda V, Loreto C, Castorina S, et al.
Occupational exposure to fluoro-edenite and prevalence of anti-nuclear autoantibodies.
Future Oncol. 2018; 14(6s):59-62 [PubMed] Related Publications
An environmental contamination due to an asbestiform mineral fiber, fluoro-edenite (FE), caused a significantly increased mortality rate for malignant mesothelioma in Biancavilla, Italy. Exposure to fluoro-edenite has been associated with inflammatory processes as an early response to inhaled fibers. The aim was to explore prevalence of anti-nuclear autoantibodies (ANA) in a group of construction workers residing and working in the contaminated area. Prevalences for samples positive to ANA were 60% (n = 9) and 13% (n = 2), for exposed and nonexposed, respectively (p-value <0.05), the odds ratio was 9.75 (95% CI: 1.59-59.69). The significance of elevated ANAs in subjects exposed to fibers is unknown; additional studies may provide a better opportunity to establish a correlation between autoimmunity and environmental exposure.

Doganis D, Panagopoulou P, Tragiannidis A, et al.
Childhood nephroblastoma in Southern and Eastern Europe and the US: Incidence variations and temporal trends by human development index.
Cancer Epidemiol. 2018; 54:75-81 [PubMed] Related Publications
BACKGROUND: Despite advances in the management of nephroblastoma (Wilms' tumor, WT), the etiology of the tumor remains obscure. We aimed to compare nephroblastoma incidence rates and time trends among children (0-14 years) in 12 Southern and Eastern European (SEE) countries and the Surveillance, Epidemiology, and End Results Program (SEER), USA, in relation to the human development index (HDI).
METHODS: In total 1776 WT cases were recorded in 13 SEE collaborating registries (circa 1990-2016), whereas data on 2260 cases (1990-2012) were extracted from the SEER database. Age-standardized incidence rates (AIRs) were calculated and correlated with HDI, whereas temporal trends were evaluated using Poisson regression and Joinpoint analyses.
RESULTS: The overall SEE AIR (9.2/10
CONCLUSIONS: Variations in incidence and time trends across the examined registries, changing male-to-female patterns with advancement in age, and positive associations with the HDI imply a plausible role for environmental and genetic factors in disease etiology, and these need to be explored further.

Marmarà D, Marmarà V, Hubbard G
A national cross-sectional study of adherence to timely mammography use in Malta.
BMC Cancer. 2018; 18(1):346 [PubMed] Article available free on PMC after 01/07/2020 Related Publications
BACKGROUND: Routine mammography improves survival. To achieve health benefits, women must attend breast screening regularly at recommended time intervals. Maltese women are routinely invited to undergo mammography at three-year intervals at an organized breast screening programme (MBSP) or can opt to attend a private clinic. Previous research shows that health beliefs, particularly perceived barriers, were the most significant predictors of uptake to the first MBSP invitation. Whether these beliefs and other factors are predictive of adherence with recommended time intervals for mammography at organized or private screening in Malta is unknown. For the first time, this paper explores the predictors for Maltese women screened within or exceeding the recommended three-year frequency in organized or private screening in Malta.
METHODS: Information was obtained from a cross-sectional survey of 404 women, aged 50 to 60 years at the time of their first MBSP invitation, where women's characteristics, knowledge, health beliefs and illness perceptions were compared. The main variable of interest was women's mammography attendance within a three-year interval (ADHERENT) or exceeding three years (NON-ADHERENT). Data were analysed using descriptive statistics, chi-square test, Mann Whitney test, Independent Samples t-test and Shapiro Wilk test.
RESULTS: At the time of the survey, 80.2% (n = 324) had been screened within three years (ADHERENT), 5.9% (n = 24) had exceeded the three-year frequency (NON-ADHERENT) while 13.9% (n = 56) never had a mammogram. No significant associations were found between ADHERENT or NON-ADHERENT women in relation to sociodemographic or health status variables (p > 0.05). Knowledge of screening frequency was significantly associated with women's mammography adherence (χ2 = 5.5, p = 0.020). Health beliefs were the strongest significant predictors to describe the variance between ADHERENT and NON-ADHERENT screeners. When Mann Whitney test and Independent Samples t-test were applied on mammography adherence, perceived barriers and cues to action were found to be the most important predictors (p = 0.000, p = 0.039 respectively).
CONCLUSIONS: To increase routine and timely mammography practices, women who are non-adherent to recommended time frequency guidelines should be targeted, together with their health beliefs, predominantly perceived barriers and cues to action.

Rada-Fernandez de Jauregui D, Evans CEL, Jones P, et al.
Common dietary patterns and risk of cancers of the colon and rectum: Analysis from the United Kingdom Women's Cohort Study (UKWCS).
Int J Cancer. 2018; 143(4):773-781 [PubMed] Article available free on PMC after 01/07/2020 Related Publications
Few prospective cohort studies in the UK have specifically focused on the associations between commonly consumed dietary patterns and colorectal cancer (CRC). The aim of our study was to assess whether red meat, poultry, fish and vegetarian dietary patterns are associated with differences in the incidence of cancers of colon and rectum in the UKWCS. Four common dietary patterns were defined based on a hierarchy of consumption of red meat, poultry and fish for each cohort participant, using a 217-item food frequency questionnaire. Cox proportional hazards regression was used to provide adjusted hazard ratios (HR) and 95% confidence intervals (CI) for CRC. A total of 32,147 women recruited and surveyed between 1995 and 1998 were followed up for a mean of 17.2 years (426,798 person-years). A total of 462 incident CRC cases were documented; 335 colon cancers (172 proximal and 119 distal) and 152 in the rectum. In multivariable-adjusted models, there was no evidence of a reduction in risk of overall CRC (HR = 0.86, 95% CI: 0.66-1.12), colon cancer (HR = 0.77, 95% CI: 0.56-1.05) or rectal cancer (HR = 1.04, 95% CI: 0.66-1.63) when comparing grouped red meat free diets with diets containing red meat. Exploratory analysis suggested a reduced risk of distal colon cancer in grouped red meat free diets (HR = 0.56, 95% CI: 0.34-0.95), though numbers with this outcome were small. These results indicate that a protective association of red meat free diets specifically on distal colon cancer merits confirmation in a larger study.

James WH, Grech V
Can sex ratios at birth be used in the assessment of public health, and in the identification of causes of selected pathologies?
Early Hum Dev. 2018; 118:15-21 [PubMed] Related Publications
This paper will consist of two parts. In the first, further support is given to the proposal that offspring sex ratios (proportions male) may usefully be regarded as indicators of public health. In the second, it is shown that sex ratios may help in the identification of the causes and effects of several pathologies that seriously impinge on public health viz. autism, testicular cancer, hepatitis B and toxoplasmosis.

D'Arco F, O'Hare P, Dashti F, et al.
Volumetric assessment of tumor size changes in pediatric low-grade gliomas: feasibility and comparison with linear measurements.
Neuroradiology. 2018; 60(4):427-436 [PubMed] Related Publications
PURPOSE: We report a retrospective comparison between bi-dimensional RANO criteria and manual volumetric segmentation (MVS) in pediatric low-grade gliomas.
METHODS: MRI FLAIR or T1 post contrast images were used for assessment of tumor response. Seventy patients were included in this single center study, for each patient two scans were assessed ("time 0" and "end of therapy") and response to therapy was evaluated for both methods. Inter-reader variability and average time for volumetric assessment were also calculated.
RESULTS: Fourteen (20%) of the 70 patients had discordant results in terms of response assessment between the bi-dimensional measurements and MVS. All volumetric response assessments were in keeping with the subjective analysis of tumor (radiology report). Of the 14 patients, 6 had stable disease (SD) on MVS and progressive disease (PD) on 2D assessment, 5 patients had SD on MVS and partial response (PR) on 2D assessment, 2 patients had PD on MVS and SD on 2D assessment, and 1 patient had PR on MVS and SD on 2D analysis. The number of discordant results rises to 21(30%) if minor response is integrated in the response assessment. MVS was relatively fast and showed high inter-reader concordance.
CONCLUSION: Our analysis shows that therapeutic response classification may change in a significant number of children by performing a volumetric tumor assessment. Furthermore, MVS is not particularly time consuming and has very good inter-reader concordance.

Georgakis MK, Dessypris N, Baka M, et al.
Neuroblastoma among children in Southern and Eastern European cancer registries: Variations in incidence and temporal trends compared to US.
Int J Cancer. 2018; 142(10):1977-1985 [PubMed] Related Publications
Neuroblastoma comprises the most common neoplasm during infancy (first year of life). Our study describes incidence of neuroblastoma in Southern-Eastern Europe (SEE), including - for the first time - the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST)/Greece, compared to the US population, while controlling for human development index (HDI). Age-adjusted incidence rates (AIR) were calculated for 1,859 childhood (0-14 years) neuroblastoma cases, retrieved from 13 collaborating SEE registries (1990-2016), and were compared to those of SEER/US (N = 3,166; 1990-2012); temporal trends were assessed using Poisson regression and Joinpoint analyses. The overall AIR was significantly lower in SEE (10.1/million) compared to SEER (11.7 per million); the difference was maximum during infancy (43.7 vs. 53.3 per million, respectively), when approximately one-third of cases were diagnosed. Incidence rates of neuroblastoma at ages <1 and 1-4 years were positively associated with HDI, whereas lower median age at diagnosis was correlated with higher overall AIR. Distribution of primary site and histology was similar in SEE and SEER. Neuroblastoma was slightly more common among males compared to females (male-to-female ratio: 1.1), mainly among SEE infants. Incidence trends decreased in infants in Slovenia, Cyprus and SEER and increased in Ukraine and Belarus. The lower incidence in SEE compared to SEER, especially in infants living in low HDI countries possibly indicates a lower level of overdiagnosis in SEE. Hence, increases in incidence rates in infancy noted in some subpopulations should be carefully monitored to avoid the unnecessary costs health impacts of tumors that could potentially spontaneously regress.

Mercieca S, Belderbos JSA, De Jaeger K, et al.
Interobserver variability in the delineation of the primary lung cancer and lymph nodes on different four-dimensional computed tomography reconstructions.
Radiother Oncol. 2018; 126(2):325-332 [PubMed] Related Publications
PURPOSE: The study compared interobserver variation in the delineation of the primary tumour (GTVp) and lymph nodes (GTVln) between three different 4DCT reconstruction types; Maximum Intensity Projection (MIP), Mid-Ventilation (Mid-V) and Mid-Position (Mid-P).
MATERIAL AND METHODS: Seven radiation oncologists delineated the GTVp and GTVln on the MIP, Mid-V and Mid-P 4DCT image reconstructions of 10 lung cancer patients. The volumes, the mean standard deviation (SD) and distribution of SD (SD/area) over the median surface contour were compared for different tumour regions.
RESULTS: The overall mean delineated volume on the MIP was significantly larger (p < 0.001) than the Mid-V and Mid-P. For the GTVp the Mid-P had the lowest interobserver variation (SD = 0.261 cm), followed by Mid-V (SD = 0.314 cm) and MIP (SD = 0.330 cm) For GTVln the Mid-V had the lowest interobserver variation (SD = 0.425 cm) followed by the MIP (SD = 0.477 cm) and Mid-P (SD = 0.543 cm). The SD/area distribution showed a statistically significant difference between the MIP versus Mid-P and Mid-P versus Mid-V for both GTVp and GTVln (p < 0.001), with outliers indicating interpretation differences for GTVp located close to the mediastinum and GTVln.
CONCLUSION: The Mid-P reduced the interobserver variation for the GTVp. Delineation protocols must be improved to benefit from the improved image quality of Mid-P for the GTVln.

Worku T, Bhattarai D, Ayers D, et al.
Long Non-Coding RNAs: the New Horizon of Gene Regulation in Ovarian Cancer.
Cell Physiol Biochem. 2017; 44(3):948-966 [PubMed] Related Publications
Long non-coding RNAs (lncRNAs), a class of non-coding transcripts, have recently been emerging with heterogeneous molecular actions, adding a new layer of complexity to gene-regulation networks in tumorigenesis. LncRNAs are considered important factors in several ovarian cancer histotypes, although few have been identified and characterized. Owing to their complexity and the lack of adapted molecular technology, the roles of most lncRNAs remain mysterious. Some lncRNAs have been reported to play functional roles in ovarian cancer and can be used as classifiers for personalized medicine. The intrinsic features of lncRNAs govern their various molecular mechanisms and provide a wide range of platforms to design different therapeutic strategies for treating cancer at a particular stage. Although we are only beginning to understand the functions of lncRNAs and their interactions with microRNAs (miRNAs) and proteins, the expanding literature indicates that lncRNA-miRNA interactions could be useful biomarkers and therapeutic targets for ovarian cancer. In this review, we discuss the genetic variants of lncRNAs, heterogeneous mechanisms of actions of lncRNAs in ovarian cancer tumorigenesis, and drug resistance. We also highlight the recent developments in using lncRNAs as potential prognostic and diagnostic biomarkers. Lastly, we discuss potential approaches for linking lncRNAs to future gene therapies, and highlight future directions in the field of ovarian cancer research.

Baldacchino S, Wastall LM, Saliba C, et al.
CIP2A expression predicts recurrences of tamoxifen-treated breast cancer.
Tumour Biol. 2017; 39(10):1010428317722064 [PubMed] Related Publications
CIP2A is emerging as an oncoprotein overexpressed commonly across many tumours and generally correlated with higher tumour grade and therapeutic resistance. CIP2A drives an oncogenic potential through inhibiting protein phosphatase 2A, stabilizing MYC, and promoting epithelial-to-mesenchymal transition, although further biological mechanisms for CIP2A are yet to be defined. CIP2A protein expression was studied by immunohistochemistry in oestrogen receptor-positive primary breast cancers (n = 250) obtained from the Leeds Tissue Bank. In total, 51 cases presented with a relapse or metastasis during adjuvant treatment with tamoxifen and were regarded as tamoxifen resistant. CIP2A expression was scored separately for cytoplasmic, nuclear, or membranous staining, and scores were tested for statistically significant relationships with clinicopathological features. Membranous CIP2A was preferentially expressed in cases who experienced a recurrence during tamoxifen treatment thus predicting a worse overall survival (log rank = 8.357, p = 0.004) and disease-free survival (log rank = 21.766, p < 0.001). Cox multivariate analysis indicates that it is an independent prognostic indicator for overall survival (hazard ratio = 4.310, p = 0.013) and disease-free survival (hazard ratio = 5.449, p = 0.002). In this study, we propose the assessment of membranous CIP2A expression as a potential novel prognostic and predictive indicator for tamoxifen resistance and recurrence within oestrogen receptor-positive breast cancer.

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