Publications by authors named "Guido Biasco"

157 Publications

Does Delirium Phenomenology in Persons with Advanced Cancer follow a Specific Pattern?

J Palliat Med 2021 Apr 16. Epub 2021 Apr 16.

ATLANTES Research Programme, Institute for Culture and Society, University of Navarra, Pamplona, Spain.

Recognizing delirium phenomenology (DP) aids the early diagnosis of this syndrome and improves quality of life in patients with advanced cancer. The aim of this study was to identify the neurobehavioral and cognitive patterns of delirium-related symptoms in persons with advanced cancer. We conducted an observational comparative prospective study on delirium in patients with advanced cancer in different palliative care settings, assessing the presentation/evolution of DP with the Memorial delirium assessment scale (MDAS). Two hundred twenty-seven patients were enrolled on hospital/hospice admission. Of these, 57 were admitted with delirium, 170 without delirium, and 31 developed delirium during hospitalization. Of the 88 patients admitted with delirium or who developed it during hospitalization, only 32 underwent two consecutive MDAS evaluations (at diagnosis and after one week). Delirium resolved in 22 patients (first average MDAS score 10.08 vs. second 3.6 [ < 0.001]). Disorientation, short-term memory, and memory span were altered in all patients with unresolved delirium. The same features were altered in 18 (80%), 17 (80%), and 16 (70%) of the patients with resolved delirium, respectively, and in 58 (35%), 114 (67%), and 38 (23%) of no-delirium patients, respectively. Cognitive-related symptoms appear to be the most prevalent and earliest signs of DP in patients with advanced cancer.
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http://dx.doi.org/10.1089/jpm.2020.0473DOI Listing
April 2021

Genetic Factors associated with Pain Severity, Daily Opioid Dose Requirement, and Pain Response among Advanced Cancer Patients receiving Supportive Care.

J Pain Symptom Manage 2021 Apr 10. Epub 2021 Apr 10.

Department of Palliative care, Rehabilitation Medicine, and Integrative Medicine UT MD Anderson Cancer Center, Houston, United States.

Background: Current understanding of genetic factors associated with pain severity, and improvement of pain with opioids in advanced cancer patients (AC) is inadequate for delivery of personalized pain therapy(PPT). Therefore, the aim of this study was to determine the genetic factors associated with pain severity, daily opioid dose, and pain response in AC patients receiving supportive care.

Methods: In this prospective study, AC patients were eligible if they had cancer pain ≥4/10 on Edmonton Symptom Assessment Scale (ESAS) - Pain Item and needed opioid rotation for pain control by specialist at the outpatient supportive care center. Pain phenotype was assessed using logistic regression models and SKATO (Gene-block) analysis.

Results: 174/178 (98%) patient samples were analyzed. After adjustment for demographic and clinical variables, pain severity was negatively associated with intron variant alleles in OPRM1 rs9322446, P = 0.02; rs2270459, P=0.038; rs62052210, P= 0.038. Opioid daily dose was positively associated NFKBIA rs2233419 P=0.008, rs2233417 P=0.007, rs3138054 P=0.008, rs1050851, P= 0.015;ORPM1 rs9479759, P= 0.046, rs2003185, P= 0.047, rs636433, P= 0.044; COMT (rs9306234, P= 0.014, rs165728, P= 0.014, rs2020917, P= 0.036, rs165728, P= 0.034); ARRB2 (rs1045280, P= 0.045); and pain response to opioids was negatively associated OPRM1 rs1319339 p=0.024, rs34427887 P=0.048, and COMT rs4646316 P=0.03, rs35478083 P=0.028 respectively. SKATO analysis showed association between pain severity and CXCL8 (P=0.0056), and STAT6 (P=0.0297) genes respectively, and pain response with IL-6 (P=0.00499).

Conclusions: This study identified that SNPs of OPRM1, COMT, NFKBIA, CXCL8, IL-6, STAT6,and ARRB2 genes were associated with pain severity, opioid daily dose, and pain response in AC receiving supportive care. Additional studies are needed to validate our findings for PPT.

Key Message: This study shows unique SNPs of OPRM1, COMT, NFKBIA, CXCL8, IL-6, STAT6, and ARRB2 genes were associated with cancer pain severity, and pain response after supportive care consultation in advanced cancer patients. Additional studies are needed to validate our findings for personalized pain therapy.
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http://dx.doi.org/10.1016/j.jpainsymman.2021.03.024DOI Listing
April 2021

Home palliative care professionals perception of challenges during the Covid-19 outbreak: A qualitative study.

Palliat Med 2021 05 8;35(5):862-874. Epub 2021 Apr 8.

Department of Palliative Care, Rehabilitation and Integrative Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Home palliative care services have played an essential role during the first wave of the SARS-CoV-2 outbreak by providing symptom control, drug procurement, and psychological support for frail patients and their families unable to leave their homes.

Aim: To understand how home palliative care professionals were affected by the outbreak, describing changes and challenges in their daily work as well as their reactions to the Covid-19 pandemic in Italy.

Design: Qualitative study conducted using telephone semi-structured interviews, with thematic analysis.

Setting/participants: Thirty home care professionals working for an Italian non-profit organization which provides home palliative care for cancer patients and their families.

Results: Three main themes were identified. The first theme showed both and challenges participants faced in their daily work, requiring the implementation of different communication methods and patient and family education on risk prevention. The second theme showed the perception of increased responsibility and being the only landmark for family played a decisive role in participants' positive attitude. The third theme highlighted the participants' perception of the critical role of a home care setting in this emergency situation.

Conclusions: The first wave of the Covid-19 pandemic brought many challenges and stressors for home palliative care professionals. On the other side, they reported a satisfaction with their critical role in carrying out their work with patients at risk.
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http://dx.doi.org/10.1177/02692163211008732DOI Listing
May 2021

Journalistic Denial of Death during the Very First Traumatic Period of the Italian COVID-19 Pandemic.

Behav Sci (Basel) 2021 Mar 23;11(3). Epub 2021 Mar 23.

Department of Specialistic, Diagnostic and Experimental Medicine (DIMES), University of Bologna, 40126 Bologna, Italy.

Exactly one year ago, between February and March 2020, the COVID-19 infection went from an epidemic confined to China to a worldwide pandemic that was particularly lethal in Italy. This study examined the media accounts during that period by analysing the representation of death-related constructs in Corriere della Sera, the most widely read newspaper in Italy. A textual and thematic analysis of articles published between period A (epidemic: 23 January-22 February 2020) and period B (pandemic: 23 February-31 March 2020) was conducted using Nvivo-11. A total of 141 articles comprising 48,524 words were collected. The most utilised words and meanings linked to COVID-19 were computed. In the rank distribution, 'China' and 'virus' were the terms most frequently used in both periods. The terms 'death' and 'dead' were completely absent in period A and appeared in the 535th position in period B. The term 'dead' was used primarily to indicate the number of deceased. From a Terror Management Theory perspective, it is possible that the minimal reference to death-related issues was a reflection of death denial and a manifestation of efforts to deny death to manage terror. These findings highlight the ambiguities and ambivalence surrounding any issue pertaining to death; on the one side, undue alarmism may provoke exaggerated reactions, such as moral panic, while on the other denial-based messages that minimise references to mortality may reduce safe behaviour during a pandemic.
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http://dx.doi.org/10.3390/bs11030041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004840PMC
March 2021

Caring Advanced Cancer Patients at Home During COVID-19 Outbreak: Burnout and Psychological Morbidity Among Palliative Care Professionals in Italy.

J Pain Symptom Manage 2021 02 27;61(2):e4-e12. Epub 2020 Nov 27.

Department of Palliative Care, Rehabilitation and Integrative Medicine, Houston, Texas.

Context: Providing palliative care (PC) at home for patients with advanced cancer has become essential during the COVID-19 emergency. Nevertheless, the home PC professionals (PCPs) faced a challenging situation because of increased number of discharged patients, reduced availability of health-care facilities, and physical/relational barriers between them and patients.

Objectives: This study aimed to investigate the impact of COVID-19 pandemic on burnout and psychological morbidity among home PCPs in Italy.

Methods: One hundred and ninety-eight PC physicians and nurses working in home assistance in Italy were invited to participate. The results obtained by the investigation conducted during the COVID-19 emergency (COVID2020) were compared with data collected in 2016 in the same setting (BURNOUT2016). The questionnaires (socio-demographics, Maslach Burnout Inventory and General Health Questionnaire-12) were the same for both the surveys. The PCPs participating in COVID2020 survey (n = 145) were mostly the same (70%) who participated in the BURNOUT2016 study (n = 179).

Results: One hundred and forty-five PCPs participated in the study (response rate 73.2%). During the COVID-19 emergency, home PCPs presented a lower burnout frequency (P < .001) and higher level of personal accomplishment than in 2016 (P = .047). Conversely, the risk for psychological morbidity was significantly higher during the pandemic (P < .001).

Conclusions: In the age of COVID-19, the awareness of being at the forefront of containing the pandemic along with the sense of responsibility toward their high-risk patients may arouse PCPs' psychological distress, but, on the other hand, this condition may improve their sense of professional satisfaction and personal accomplishment.
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http://dx.doi.org/10.1016/j.jpainsymman.2020.11.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691143PMC
February 2021

Delirium Rates in Advanced Cancer Patients Admitted to Different Palliative Care Settings: Does It Make the Difference?

J Palliat Med 2020 09 20;23(9):1227-1232. Epub 2019 Dec 20.

ATLANTES Research Programme, Institute for Culture and Society, University of Navarra, Pamplona, Navarra, Spain.

Delirium in advanced cancer inpatient ranges between 13% and 85%. Reasons for this variability on the reported data could be related to the setting where they are admitted. This is an observational, comparative, prospective study on delirium diagnosis and delirium course of advanced cancer inpatients in two different palliative care settings. Hospice (C1) versus palliative care supportive team (C2). Differences between delirium precipitants, delirium treatment, and delirium survival were observed. From 582 consecutive admissions, 494 from C1 and 88 from C2, finally 227 patients met inclusion criteria, were entered in the study. Total population delirium rate at admission, if we add both centers, was 57 patients (25%), 46 (26%) from C1 and 11 (22%) from C2; no statistically significant differences between delirium rate at admission between the two centers were found (). When delirium course between delirious patients admitted in C1 and C2 was analyzed, a significantly higher rate of delirium reversibility was found in C2 [11/14 (78%)] versus [9/65 (14%)] in C1 ( ≤ 0.001). The frequency of delirium at admission and during the hospitalization in advanced cancer patients does not seem to be related to the setting, what seems to be related is the delirium course.
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http://dx.doi.org/10.1089/jpm.2019.0414DOI Listing
September 2020

An online international comparison of thresholds for triggering a negative response to the "Surprise Question": a study protocol.

BMC Palliat Care 2019 Apr 9;18(1):36. Epub 2019 Apr 9.

University College London, London, UK.

Background: The Surprise Question (SQ) "would I be surprised if this patient were to die in the next 12 months?" has been suggested to help clinicians, and especially General Practitioners (GPs), identify people who might benefit from palliative care. The prognostic accuracy of this approach is unclear and little is known about how GPs use this tool in practice. Are GPs consistent, individually and as a group? Are there international differences in the use of the tool? Does including the alternative Surprise Question ("Would I be surprised if the patient were still alive after 12 months?") alter the response? What is the impact on the treatment plan in response to the SQ? This study aims to address these questions.

Methods: An online study will be completed by 600 (100 per country) registered GPs. They will be asked to review 20 hypothetical patient vignettes. For each vignette they will be asked to provide a response to the following four questions: (1) the SQ [Yes/No]; (2) the alternative SQ [Yes/No]; (3) the percentage probability of dying [0% no chance - 100% certain death]; and (4) the proposed treatment plan [multiple choice]. A "surprise threshold" for each participant will be calculated by comparing the responses to the SQ with the probability estimates of death. We will use linear regression to explore any differences in thresholds between countries and other clinician-related factors, such as years of experience. We will describe the actions taken by the clinicians and explore the differences between groups. We will also investigate the relationship between the alternative SQ and the other responses. Participants will receive a certificate of completion and the option to receive feedback on their performance.

Discussion: This study explores the extent to which the SQ is consistently used at an individual, group, and national level. The findings of this study will help to understand the clinical value of using the SQ in routine practice.

Trial Registration: Clinicaltrials.gov NCT03697213 (05/10/2018). Prospectively registered.
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http://dx.doi.org/10.1186/s12904-019-0413-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461816PMC
April 2019

An exploratory study by DMET array identifies a germline signature associated with imatinib response in gastrointestinal stromal tumor.

Pharmacogenomics J 2019 08 20;19(4):390-400. Epub 2018 Sep 20.

"Giorgio Prodi" Cancer Research Center, University of Bologna, Bologna, Italy.

Imatinib represents the standard therapy for gastrointestinal stromal tumor (GIST) patients with metastatic/unresectable disease. Despite  the excellent results achieved with its introduction, the majority of patients quite invariably experience disease progression. The aim of this study was to understand the contribution of germline DNA polymorphisms in discriminating between imatinib clinical response [evaluated as progression free survival (PFS)] and toxicity. In particular, a discovery cohort (34 GIST with a KIT exon 11 primary mutation, and no toxicity) was analyzed through DMET array that interrogates 1936 variants in 231 genes of the ADME process. We further confirmed the genotype of selected variants in an extended cohort of 49 patients (the original cohort and 15 new cases, all with exon 11 primary mutation), identifying 6 SNPs- ABCB4 rs1202283, ABCC2 rs2273697, ABCG1 rs1541290, CYP11B1 rs7003319, CYP7B1 rs6987861, and NQO1 rs10517-significantly associated with response to imatinib. Three SNPs, ABCB4 rs1202283, ABCC2 rs2273697, and NQO1 rs10517, which had a significant association after adjusted multivariate analysis, were included in a genetic prediction model. We confirmed that these SNPs could stratify the cohort of 49 patients according to the risk of developing progression under imatinib treatment. In conclusion, we identified a genetic signature of response to imatinib therapy in GIST patients able to stratify patients at low and high risk to progress, according to their genotype.
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http://dx.doi.org/10.1038/s41397-018-0050-4DOI Listing
August 2019

Whole Exome Sequencing Uncovers Germline Variants of Cancer-Related Genes in Sporadic Pheochromocytoma.

Int J Genomics 2018 19;2018:6582014. Epub 2018 Aug 19.

"Giorgio Prodi" Cancer Research Center, University of Bologna, Bologna, Italy.

Background: Pheochromocytomas (PCCs) show the highest degree of heritability in human neoplasms. However, despite the wide number of alterations until now reported in PCCs, it is likely that other susceptibility genes remain still unknown, especially for those PCCs not clearly syndromic.

Methods: Whole exome sequencing of tumor DNA was performed on a set of twelve PCCs clinically defined as sporadic.

Results: About 50% of PCCs examined had somatic mutations on the known susceptibility , , and genes. In addition to these driver events, mutations on , , and genes were also detected. Moreover, extremely rare germline variants were present in half of the sporadic PCC samples analyzed, in particular variants of and were detected in the germline of cases wild-type for mutations in the known susceptibility genes.

Conclusions: Additional somatic passenger mutations can be associated with known susceptibility , , and genes in PCCs, and a wide number of germline variants with still unknown clinical significance can be detected in these patients. Therefore, many efforts should be aimed to better define the pathogenetic role of all these germline variants for discovering novel potential therapeutic targets for this disease still orphan of effective treatments.
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http://dx.doi.org/10.1155/2018/6582014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120303PMC
August 2018

How Do Experienced Professors Teach Palliative Medicine in European Universities? A Cross-Case Analysis of Eight Undergraduate Educational Programs.

J Palliat Med 2018 11 9;21(11):1621-1626. Epub 2018 Jul 9.

1 Faculty of Medicine, University of Navarra , Pamplona (Navarra), Spain .

Background: In Europe in recent decades, university teaching of palliative medicine (PM) has evolved. In some countries it has been introduced as a compulsory subject in all medical schools, but in a majority of countries it remains an isolated subject at few universities.

Objective: To explore how PM has been introduced into the curricula and how it is currently being taught at different European universities.

Method: Case study method using face-to-face semistructured interviews with experienced PM professors, comparing how they have developed PM undergraduate programs at their universities.

Results: An intentional sample of eight university professors from Spain, France, UK, Italy, Hungary, Sweden, Germany, and Poland was chosen. The introduction of PM in the universities depends on the existence of a favorable social and political context in relation to palliative care and the initiative of pioneers, trusted by students, to push this education forward. A PM curriculum frequently starts as an optional subject and becomes mandatory in a short period. In the reported universities, PM uses a wide variety of teaching methods, such as lectures, workshops, role-plays, and discussions. PM assessment included tests, discussions, reflections, portfolios, and research works. According to respondents' opinions, lack of recognition, funding, and accredited teachers, along with competition from other curricula, are the main barriers for palliative medicine teaching development at universities.

Conclusion: Diverse paths and tools have been identified for PM teaching in Europe. The described cases may shed light on other medical schools to develop PM curricula.
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http://dx.doi.org/10.1089/jpm.2018.0071DOI Listing
November 2018

Mutational burden of resectable pancreatic cancer, as determined by whole transcriptome and whole exome sequencing, predicts a poor prognosis.

Int J Oncol 2018 Jun 29;52(6):1972-1980. Epub 2018 Mar 29.

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Sant' Orsola-Malpighi Hospital, I-40138 Bologna, Italy.

Despite the genomic characterization of pancreatic cancer (PC), marked advances in the development of prognosis classification and novel therapeutic strategies have yet to come. The present study aimed to better understand the genomic alterations associated with the invasive phenotype of PC, in order to improve patient selection for treatment options. A total of 30 PC samples were analysed by either whole transcriptome (9 samples) or exome sequencing (21 samples) on an Illumina platform (75X2 or 100X2 bp), and the results were matched with normal DNA to identify somatic events. Single nucleotide variants and insertions and deletions were annotated using public databases, and the pathogenicity of the identified variants was defined according to prior knowledge and mutation-prediction tools. A total of 43 recurrently altered genes were identified, which were involved in numerous pathways, including chromatin remodelling and DNA damage repair. In addition, an analysis limited to a subgroup of early stage patients (50% of samples) demonstrated that poor prognosis was significantly associated with a higher number of known PC mutations (P=0.047). Samples from patients with a better overall survival (>25 months) harboured an average of 24 events, whereas samples from patients with an overall survival of <25 months presented an average of 40 mutations. These findings indicated that a complex genetic profile in the early stage of disease may be associated with increased aggressiveness, thus suggesting an urgent requirement for an innovative approach to classify this disease.
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http://dx.doi.org/10.3892/ijo.2018.4344DOI Listing
June 2018

Integrated Molecular Characterization of Gastrointestinal Stromal Tumors (GIST) Harboring the Rare D842V Mutation in PDGFRA Gene.

Int J Mol Sci 2018 Mar 4;19(3). Epub 2018 Mar 4.

"Giorgio Prodi" Cancer Research Center, University of Bologna, Bologna 40138 Italy.

Gastrointestinal stromal tumors (GIST) carrying the D842V activating mutation in the platelet-derived growth factor receptor alpha () gene are a very rare subgroup of GIST (about 10%) known to be resistant to conventional tyrosine kinase inhibitors (TKIs) and to show an indolent behavior. In this study, we performed an integrated molecular characterization of D842V mutant GIST by whole-transcriptome and whole-exome sequencing coupled with protein-ligand interaction modelling to identify the molecular signature and any additional recurrent genomic event related to their clinical course. We found a very specific gene expression profile of D842V mutant tumors showing the activation of G-protein-coupled receptor (GPCR) signaling and a relative downregulation of cell cycle processes. Beyond D842V, no recurrently mutated genes were found in our cohort. Nevertheless, many private, clinically relevant alterations were found in each tumor (-complex). Molecular modeling of PDGFRA D842V suggests that the mutant protein binds imatinib with lower affinity with respect to wild-type structure, showing higher stability during the interaction with other type I TKIs (like crenolanib). D842V mutant GIST do not show any actionable recurrent molecular events of therapeutic significance, therefore this study supports the rationale of novel TKIs development that are currently being evaluated in clinical studies for the treatment of D842V mutant GIST.
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http://dx.doi.org/10.3390/ijms19030732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877593PMC
March 2018

Personalization of regorafenib treatment in metastatic gastrointestinal stromal tumours in real-life clinical practice.

Ther Adv Med Oncol 2017 Dec 19;9(12):731-739. Epub 2017 Dec 19.

Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy Giorgio Prodi Cancer Research Center, University of Bologna, Bologna, Italy.

Background: Regorafenib (REG) has now been approved as the standard third-line therapy in metastatic gastrointestinal stromal tumour (GIST) patients at the recommended dose and schedule of 160 mg once daily for the first 3 weeks of each 4-week cycle. However, it has a relevant toxicity profile that mainly occurs within the first cycles of therapy, and dose and schedule adjustments are often required to reduce the frequency or severity of adverse events and to avoid early treatment discontinuation. To date, large amounts of data on the use of REG in metastatic GIST patients in daily clinical practice are not available, and we lack information about how this treatment personalization really affects the quality of life (QoL) of patients. The aim of the present retrospective study is to build a comprehensive picture of all alternative REG strategies adopted in daily clinical practice for use in metastatic GIST patients.

Methods: Metastatic GIST patients treated with dose adjustment or alternative schedules of REG at seven reference Italian centres were retrospectively included.

Results: For a total of 62 metastatic GIST patients, we confirmed that REG treatment adjustment is common in clinical practice and that it is very heterogeneous, with approximately 20 different strategies being adopted. Independent of which strategy is chosen, treatment personalization has led to a clinical benefit defined as complete or partial resolution of side effects in almost all patients, affecting the duration of REG treatment.

Conclusions: The personalization of REG, even if it is heterogeneous, seems to be crucial to maximize the overall treatment duration.
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http://dx.doi.org/10.1177/1758834017742627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808843PMC
December 2017

Correlation between MGMT promoter methylation and response to temozolomide-based therapy in neuroendocrine neoplasms: an observational retrospective multicenter study.

Endocrine 2018 06 17;60(3):490-498. Epub 2017 Nov 17.

Department of Experimental, Diagnostic and Specialty Medicine, S.Orsola-Malpighi University Hospital, Bologna, Italy.

Purpose: Temozolomide (TEM) based therapy has been reported being effective in the treatment of metastatic neuroendocrine neoplasms (NEN), with response rates ranging from 30 to 70%. Among patients affected by advanced glioblastoma or melanoma and treated with TEM, loss of tumoral O6-methylguanine DNA methyltransferase (MGMT) is correlated with improved survival. In NEN patients, the role of MGMT deficiency in predicting clinical outcomes of TEM treatment is still under debate.

Methods: In this study we evaluated 95 patients with advanced NENs undergoing treatment with TEM-based therapy. MGMT promoter methylation status was evaluated with two techniques: methylation specific-polymerase chain reaction or pyrosequencing.

Results: Treatment with TEM-based therapy was associated with an overall response rate of 27.4% according to RECIST criteria (51.8% of patients with and 17.7% without MGMT promoter methylation). Response to therapy, progression free survival and overall survival was correlated to MGMT status at univariate and multivariate analysis. Methylation of MGMT promoter could be a strong predictive factor of objective response and an important prognostic factor of a longer PFS and OS.

Conclusion: According to our results, MGMT methylation status, evaluated with methylation specific-polymerase chain reaction or pyrosequencing, should have an important role in patients with metastatic NENs, in order to guide therapeutic options. These results need further confirmation with prospective studies.
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http://dx.doi.org/10.1007/s12020-017-1474-3DOI Listing
June 2018

Occupational exposure to asbestos and risk of cholangiocarcinoma: a population-based case-control study in four Nordic countries.

Occup Environ Med 2018 03 13;75(3):191-198. Epub 2017 Nov 13.

Faculty of Social Sciences, University of Tampere, Tampere, Finland.

Objectives: To assess the association between occupational exposure to asbestos and the risk of cholangiocarcinoma (CC).

Methods: We conducted a case-control study nested in the Nordic Occupational Cancer (NOCCA) cohort. We studied 1458 intrahepatic CC (ICC) and 3972 extrahepatic CC (ECC) cases occurring among subjects born in 1920 or later in Finland, Iceland, Norway and Sweden. Each case was individually matched by birth year, gender and country to five population controls. The cumulative exposure to asbestos (measured in fibres (f)/ml × years) was assessed by applying the NOCCA job-exposure matrix to data on occupations collected during national population censuses (conducted in 1960, 1970, 1980/81 and 1990). Odds ratios (OR) and 95% CI were estimated using conditional logistic regression models adjusted by printing industry work.

Results: We observed an increasing risk of ICC with cumulative exposure to asbestos: never exposed, OR 1.0 (reference category); 0.1-4.9 f/mL × years, OR 1.1 (95% CI 0.9 to 1.3); 5.0-9.9 f/mL × years, OR 1.3 (95% CI 0.9 to 2.1); 10.0-14.9 f/mL × years, OR 1.6 (95% CI 1.0 to 2.5); ≥15.0 f/mL × years, OR 1.7 (95% CI 1.1 to 2.6). We did not observe an association between cumulative asbestos exposure and ECC.

Conclusions: Our study provides evidence that exposure to asbestos might be a risk factor for ICC. Our findings also suggest that the association between ECC and asbestos is null or weaker than that observed for ICC. Further studies based on large industrial cohorts of asbestos workers and possibly accounting for personal characteristics and clinical history are needed.
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http://dx.doi.org/10.1136/oemed-2017-104603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869450PMC
March 2018

Brain Metastases from Biliary Tract Cancer: A Monocentric Retrospective Analysis of 450 Patients.

Oncology 2018 13;94(1):7-11. Epub 2017 Oct 13.

Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.

Objective: Brain metastases (BMs) from biliary tract cancer (BTC) are extremely rare. The aim of our study was to report the incidence of BMs in patients with BTC.

Methods: We retrospectively analyzed a series of 450 patients with BTC. Presence of brain lesions was investigated only when symptoms were evident. Cumulative incidence, median overall survival (OS) from detection of BMs, median OS from cancer diagnosis, and median time from cancer diagnosis to detection of BMs were evaluated.

Results: In our series, 6 patients developed BMs with an incidence of about 1.4%. Median OS from detection of BMs and from cancer diagnosis was, respectively, 3.7 (0.9-17.8) and 23 (9.9-57.6) months. Median time between cancer diagnosis and detection of BMs was 13.6 (7.3-52.8) months. Moreover, we observed a significant association between BMs and bone metastases (particularly vertebral lesions).

Discussion: Despite the retrospective design, this is the first study evaluating the incidence of BMs among patients with BTC in Western countries. BMs from BTC remain atypical, although their incidence is probably a little higher than previously assumed. Patients with BMs had poor prognosis. Unpredictably, bone involvement occurred in 5 out of 6 patients.
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http://dx.doi.org/10.1159/000479929DOI Listing
March 2018

Identification of SRF-E2F1 fusion transcript in EWSR-negative myoepithelioma of the soft tissue.

Oncotarget 2017 Sep 17;8(36):60036-60045. Epub 2017 May 17.

"Giorgio Prodi" Cancer Research Center, University of Bologna, Bologna, Italy.

Myoepithelial neoplasms (MN) are rare and not well-circumstanced entities displaying a heterogeneous spectrum of genetic abnormalities, including EWSR1, FUS and PLAG1 rearrangements. However, in the remaining MN no other fusion gene has been described and knowledge concerning secondary acquired molecular alterations is still poor. Therefore, we screened 5 cases of MN of the soft tissue by RNA sequencing with the aim of identifying novel fusion transcripts. A novel SRF-E2F1 fusion was detected in two cases: one was negative for other fusions while the other showed also the presence of FUS-KLF17. The fusion was validated through independent techniques and, in both cases, SRF-E2F1 was detected only in a subclone of the tumoral mass. SRF-E2F1 maintained the coding frame, thus leading to the translation of a chimeric protein containing the DNA-binding domain of SRF and the trans-activation domain of E2F1. Moreover, ectopical expression of SRF-E2F1 demonstrated that the chimeric transcript is functionally active and could affect tumor growth. Occurrence in two cases and biological relevance of the two genes involved suggest that the SRF-E2F1 fusion might become a helpful diagnostic tool. Further biologic studies are needed to better assess its role in MN biology.
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http://dx.doi.org/10.18632/oncotarget.17958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601120PMC
September 2017

Non-Coding RNAs as Predictive Biomarkers to Current Treatment in Metastatic Colorectal Cancer.

Int J Mol Sci 2017 Jul 17;18(7). Epub 2017 Jul 17.

Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Sant'Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy.

The onset and selection of resistant clones during cancer treatment with chemotherapy or targeted therapy is a major issue in the clinical management of metastatic colorectal cancer patients. It is possible that a more personalized treatment selection, using reliable response-to-therapy predictive biomarkers, could lead to an improvement in the success rate of the proposed therapies. Although the process of biomarker selection and validation could be a long one, requiring solid statistics, large cohorts and multicentric validations, non-coding RNAs (ncRNAs) and in particular microRNAs, proved to be extremely promising in this field. Here we summarize some of the main studies correlating specific ncRNAs with sensitivity/resistance to chemotherapy, anti-VEGF therapy, anti-EGFR therapy and immunotherapy in colorectal cancer (CRC).
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http://dx.doi.org/10.3390/ijms18071547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536035PMC
July 2017

Palliative medicine in Mediterranean countries: different approaches, same philosophy.

BMJ Support Palliat Care 2018 09 14;8(3):356-358. Epub 2017 Jul 14.

University of Navarra Clinic, University of Navarra, Pamplona, Spain.

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http://dx.doi.org/10.1136/bmjspcare-2017-001311DOI Listing
September 2018

Postsorafenib systemic treatments for hepatocellular carcinoma: questions and opportunities after the regorafenib trial.

Future Oncol 2017 Sep 11;13(21):1893-1905. Epub 2017 Jul 11.

'G. Prodi' Interdepartmental Center for Cancer Research (C.I.R.C.), University of Bologna, Italy.

The search for systemic therapies for hepatocellular carcinoma has been characterized by difficulties and failures. Despite recent progresses, many issues are still to be settled. In particular, the development of drugs inhibiting different neoplastic pathways remains a priority for patients intolerant or resistant to antiangiogenic drugs. This task may be daunting, as previous failures extensively demonstrated. We aimed to identify the future perspective of postsorafenib trials analyzing the strengths and the critical points of past and currently undergoing studies, in the light of the most recent evidences in the field. We identified various points (including stratification, biomarkers, end points, radiologic criteria of response, treatment beyond radiologic progression) that should be considered by future trials to reduce the risks of failure.
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http://dx.doi.org/10.2217/fon-2017-0166DOI Listing
September 2017

Good performance of platinum-based chemotherapy for high-grade gastroenteropancreatic and unknown primary neuroendocrine neoplasms.

J Chemother 2018 Feb 22;30(1):53-58. Epub 2017 Jun 22.

a Department of Experimental, Diagnostic and Speciality Medicine , 'L. & A. Seragnoli' Institute of Hematology and Medical Oncology, Sant'Orsola-Malpighi Hospital , Bologna , Italy.

To evaluate efficacy and safety of platinum and etoposide combination in the treatment of advanced gastroenteropancreatic (GEP) and unknown primary (CUP) neuroendocrine carcinomas (NEC), we analysed the records of 21 consecutive patients treated with this regimen from 1999 to 2012. Objective responses were obtained in 11 patients (52%) and disease stability (DS) in 5 (24%). Median progression-free survival (PFS) was 7 months (95% CI, 5.33-8.66). Median overall survival (OS) was 16 months (95% CI, 14.97-17.03). Patients with limited liver disease had a significantly (p = 0.002) better PFS than patients with extrahepatic disease at diagnosis with 9 months (95% CI, 7.14-10.85) vs. 4 months (95% CI, 1.60-6.40). Two patients experienced durable complete response (30 and 90 months). The most common grade 3-4 toxicities were neutropenia (61%), anaemia (50%), nausea and vomiting (27%) and fatigue (22%). The platinum plus etoposide regimen has an acceptable toxicity profile and is effective in patients with GEP and CUP-NECs.
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http://dx.doi.org/10.1080/1120009X.2017.1340127DOI Listing
February 2018

Erratum to: The progressive fragmentation of the KIT/PDGFRA wild-type (WT) gastrointestinal stromal tumors (GIST).

J Transl Med 2017 06 2;15(1):125. Epub 2017 Jun 2.

Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy.

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http://dx.doi.org/10.1186/s12967-017-1228-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455107PMC
June 2017

The progressive fragmentation of the KIT/PDGFRA wild-type (WT) gastrointestinal stromal tumors (GIST).

J Transl Med 2017 05 23;15(1):113. Epub 2017 May 23.

Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy.

Recent advances in molecular biology have revolutionized the concept of KIT/PDGFRA wild type (WT) gastrointestinal stromal tumors (GIST) than the past. Indeed, from being defined as GIST without KIT or PDGFRA mutations, we are now faced with the opposite scenario, where KIT/PDGFRA WT GIST are "positively" defined according to their specific molecular alterations. In particular, if until recently KIT/PDGFRA GIST without abnormalities of KIT, PDGFRA, SDH, and the RAS signaling pathway were referred as quadruple WT GIST, today also this small subset of GIST is emerging out as a group of heterogeneous distinct entities with multiple different molecular alterations. Therefore, given this still growing and rapidly evolving scenario, the progressive molecular fragmentation may inevitably lead over the time to the disappearance of KIT/PDGFRA WT GIST, destined to be singularly defined by their molecular fingerprint.
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http://dx.doi.org/10.1186/s12967-017-1212-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442859PMC
May 2017

Microbiota, NASH, HCC and the potential role of probiotics.

Carcinogenesis 2017 03;38(3):231-240

Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi Hospital, Bologna University, 40138 Bologna, Italy.

Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Clearly identifiable risk factors are lacking in up to 30% of HCC patients and most of these cases are attributed to non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Beyond the known risk factors for NAFLD, the intestinal microbiota, in particular dysbiosis (defined as any change in the composition of the microbiota commonly found in healthy conditions) is emerging as a new factor promoting the development of chronic liver diseases and HCC. Intestinal microbes produce a large array of bioactive molecules from mainly dietary compounds, establishing an intense microbiota-host transgenomic metabolism with a major impact on physiological and pathological conditions. A better knowledge of these 'new' pathways could help unravel the pathogenesis of HCC in NAFLD to devise new prevention strategies. Currently unsettled issues include the relative role of a 'negative microbiota' (in addition to the other known risk factors for NASH) and the putative prevention of NAFLD through modulation of the gut microbiota.
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http://dx.doi.org/10.1093/carcin/bgx007DOI Listing
March 2017

HSPA8 as a novel fusion partner of NR4A3 in extraskeletal myxoid chondrosarcoma.

Genes Chromosomes Cancer 2017 07 4;56(7):582-586. Epub 2017 May 4.

Adult Mesenchymal Tumour and Rare Cancer Medical Oncology Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori Milan, Italy.

Extraskeletal myxoid chondrosarcoma (EMC) is a very rare sarcoma most often arising in the soft tissue. Rare EMC of the bone have been reported. EMC exhibits distinctive clinico-pathological and genetic features; however, despite the name, it lacks any feature of cartilaginous differentiation. EMC is characterized by the rearrangement of the NR4A3, which, in most cases (about 62-75%), is fused with EWSR1 and less frequently with other partners, including TAF15 (27%), TCF12 (4%), TFG, and FUS. We herein report the identification by whole-transcriptome sequencing of HSPA8 as a novel fusion partner of NR4A3 in a case of EMC. FISH analysis confirmed the presence of a genomic HSPA8-NR4A3 translocation in the vast majority of tumor cells. Our findings expand the spectrum of NR4A3 fusion partners involved in EMC pathobiology.
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http://dx.doi.org/10.1002/gcc.22462DOI Listing
July 2017

Genome-Wide Analysis Identifies MEN1 and MAX Mutations and a Neuroendocrine-Like Molecular Heterogeneity in Quadruple WT GIST.

Mol Cancer Res 2017 05 27;15(5):553-562. Epub 2017 Jan 27.

Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.

Quadruple wild-type (WT) gastrointestinal stromal tumor (GIST) is a genomic subgroup lacking KIT/PDGFRA/RAS pathway mutations, with an intact succinate dehydrogenase (SDH) complex. The aim of this work is to perform a wide comprehensive genomic study on quadruple WT GIST to improve the characterization of these patients. We selected 14 clinical cases of quadruple WT GIST, of which nine cases showed sufficient DNA quality for whole exome sequencing (WES). NF1 alterations were identified directly by WES. Gene expression from whole transcriptome sequencing (WTS) and miRNA profiling were performed using fresh-frozen, quadruple WT GIST tissue specimens and compared with SDH and KIT/PDGFRA-mutant GIST. WES identified an average of 18 somatic mutations per sample. The most relevant somatic oncogenic mutations identified were in TP53, MEN1, MAX, FGF1R, CHD4, and CTDNN2. No somatic alterations in NF1 were identified in the analyzed cohort. A total of 247 mRNA transcripts and 66 miRNAs were differentially expressed specifically in quadruple WT GIST. Overexpression of specific molecular markers (COL22A1 and CALCRL) and genes involved in neural and neuroendocrine lineage (ASCL1, Family B GPCRs) were detected and further supported by predicted miRNA target analysis. Quadruple WT GIST show a specific genetic signature that deviates significantly from that of KIT/PDGFRA-mutant and SDH-mutant GIST. Mutations in MEN1 and MAX genes, a neural-committed phenotype and upregulation of the master neuroendocrine regulator ASCL1, support a genetic similarity with neuroendocrine tumors, with whom they also share the great variability in oncogenic driver genes. This study provides novel insights into the biology of quadruple WT GIST that potentially resembles neuroendocrine tumors and should promote the development of specific therapeutic approaches. .
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http://dx.doi.org/10.1158/1541-7786.MCR-16-0376DOI Listing
May 2017

Gastrointestinal stromal tumors (GIST): Facing cell death between autophagy and apoptosis.

Autophagy 2017 Mar 5;13(3):452-463. Epub 2017 Jan 5.

a Department of Pharmacy and Biotechnology , University of Bologna , Bologna Italy.

Autophagy and apoptosis are 2 fundamental biological mechanisms that may cooperate or be antagonistic, although both are involved in deciding the fate of cells in physiological or pathological conditions. These 2 mechanisms coexist simultaneously in cells and share common upstream signals and stimuli. Autophagy and apoptosis play pivotal roles in cancer development. Autophagy plays a key function in maintaining tumor cell survival by providing energy during unfavorable metabolic conditions through its recycling mechanism, and supporting the high energy requirement for metabolism and growth. This review focuses on gastrointestinal stromal tumors and cell death through autophagy and apoptosis, taking into account the involvement of both of these processes in tumor development and growth and as mechanisms of drug resistance. We also focus on the crosstalk between autophagy and apoptosis as an emerging field with major implications for the development of novel therapeutic options.
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http://dx.doi.org/10.1080/15548627.2016.1256522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5361605PMC
March 2017

Aspirin for cholangiocarcinoma prevention: New targets to shift the dogma from ascertained risk to possible prevention.

Hepatology 2017 03 3;65(3):1075-1076. Epub 2017 Feb 3.

Department of Experimental, Diagnostic, and Specialty Medicine, Universita degli Studi di Bologna Azienda Ospedaliera Sant'Orsola-Malpighi, Bologna, Italy.

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http://dx.doi.org/10.1002/hep.28999DOI Listing
March 2017

Position paper of the Italian Association of Medical Oncology on early palliative care in oncology practice (Simultaneous Care).

Tumori 2017 Jan 19;103(1):9-14. Epub 2016 Dec 19.

Oncology Department, Sacro Cuore-Don Calabria Hospital, Negrar (Verona) - Italy.

One of the priorities of personalized medicine regards the role of early integration of palliative care with cancer-directed treatments, called simultaneous care. This article, written by the Italian Association of Medical Oncology (AIOM) Simultaneous and Continuous Care Task Force, represents the position of Italian medical oncologists about simultaneous care, and is the result of a 2-step project: a Web-based survey among medical oncologists and a consensus conference. We present the opinion of more than 600 oncologists who helped formulate these recommendations. This document covers 4 main aspects of simultaneous care: 1) ethical, cultural, and relational aspects of cancer and implications for patient communication; 2) training of medical oncologists in palliative medicine; 3) research on the integration between cancer treatments and palliative care; and 4) organizational and management models for the realization of simultaneous care. The resulting recommendations highlight the role of skills and competence in palliative care along with implementation of adequate organizational models to accomplish simultaneous care, which is considered a high priority of AIOM in order to grant the best quality of life for cancer patients and their families.
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http://dx.doi.org/10.5301/tj.5000593DOI Listing
January 2017