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  • 1
    In: Oral Diseases, Wiley, Vol. 26, No. 7 ( 2020-10), p. 1384-1392
    Abstract: To evaluate the role of baseline neutrophil‐to‐lymphocyte ratio (NLR) as prognostic marker in squamous cell carcinoma of the oropharynx (OPC) treated with definitive chemoradiotherapy (CRT) in the era of HPV status. Patients and methods A retrospective analysis of 125 patients (pts) affected with locally advanced OPC was performed. Inclusion criteria were age 〉 18 years, stage III or IV (TNM 7th ed.) and definitive CRT. Haematological marker for their independent role as prognostic biomarkers for progression‐free survival (PFS) and overall survival (OS). Logistic models were used to assess the association with downstage in TNM 8th ed. Results Seventy‐seven (61.6%) pts had HPV/p16 + related OPC. Therapeutic choice consisted in sequential and concurrent CRT. Median follow‐up was 50 months. A value of NLR ≥3 was associated with poorer OS. Two‐year OS was 91% and 81% in pts with NLR 〈 3 and ≥3, respectively. Conclusion A baseline NLR ≥ 3 at treatment initiation represented a negative prognostic marker for OPC treated with definitive CRT. These results are in line with literature data, and prognostic value of NLR has been confirmed restaging our cohort with new TNM staging (8th ed.). Therefore, NLR could be considered a valuable biomarker for risk stratification in pts with OPC.
    Type of Medium: Online Resource
    ISSN: 1354-523X , 1601-0825
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2008428-6
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  • 2
    In: Cancer Epidemiology, Elsevier BV, Vol. 72 ( 2021-06), p. 101925-
    Type of Medium: Online Resource
    ISSN: 1877-7821
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2498032-8
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  • 3
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 27, No. 6_Supplement ( 2021-03-15), p. P16-P16
    Abstract: Introduction: A better understanding of the reality for cancer patients during COVID-19 will help us readapt current predication models. To further inform future clinical guidelines, we need a deep dive into rich data sources from apex Cancer Centres. We report on the outcomes of cancer patients receiving radical surgery between March-September 2020 (as well as 2019) in the European Institute of Oncology (EIO) in Milan and the South East London Cancer Alliance (SELCA). Methods: IEO is one of the largest cancer hospitals in Italy. SELCA includes 3 major hospital trust, treating about 8,000 new cancer patients per annum. Both institutions implemented a COVID-19 minimal pathway, whereby patients were required to shield for 14 days prior to admission and were swabbed for COVID-19 within 3 days of surgery. Positive patients had surgery deferred until a negative swab. Surgical outcomes assessed were: ASA grade, surgery time, theatre time, ICU stay & gt;24h, pneumonia, length of stay (LOS), and admissions. For COVID-19, we focused on infection rate and mortality. Results: At IEO the number of radical surgeries (270 for gynaecological, 339 for head and neck, 377 for thoracic, and 491 for urological cancers) declined by 6% as compared to the same period in 2019 (n=1477 vs 1560). The main decline was observed for thoracic surgery (377 vs 460, i.e. -18%). Age, sex, SES, ethnicity, comorbidities, and performance status were all comparable between both periods (e.g. 58% male, 38% aged 70+, 48% high SES, 15% with existing cardiovascular diseases). Readmissions were required for 39%, and & lt;1% (n=9) developed COVID-19, of which only 1 had severe disease and died. 11 died of other causes during follow-up (1%). At SELCA, the number of radical surgeries (321 for breast, 129 for colorectal, 114 for gynaecological, 152 for head and neck, 92 for liver, 56 for plastics/skin, 305 for thoracic, 72 for upper gastrointestinal, and 312 for urology) declined by 29% (n=1553 vs 2182). Even though a different geographical setting, characteristics were fairly comparable with the IEO: 58% males, 30% aged 70+, 34% high SES, 16% with existing cardiovascular diseases. Readmissions were required for 22%, & lt;1% (n=7) developed COVID-19, and none died from it. 19 died of other causes within 30 days (1%). Conclusion: Milan and London were both at the epicentre of the first COVID-19 wave. Whilst a decline in number of surgeries was observed, the implemented COVID-19 minimal pathways have shown to be safe for cancer patients requiring radical treatment, with limited complications and almost no COVID-19 infections. Citation Format: Marta Tagliabue, Harvey Dickinson, Rita de Berardinis, Graham Roberts, Beth Russell, Charlotte Moss, Sophie Irwin, Jonathon Olsburgh, Jain Urvashi, Hisham Ahmed, Francesca Cocco, Alexis Schizas, Sarah McCrindle, Nath Rahul, Tommy Tomari, Aina Brunet, Ricard Simo, Parthi Srinivasan, Andreas Prachalias, RuJun Ma, Andrew Davies, Jenny Geh, Stephanie Fraser, Tom Routledge, Ella Doerge, Ben Challacombe, Raj Nair, Marios Hadjipavlou, Rosaria Scarpinata, Paolo Sorelli, Saoirse Dolly, Mohssen Ansarin, Alessandro Francesco Mistretta, Gennaro Musi, Ottavio De Cobell, Monica Tessitore, Lorenzo Spaggiar, Aloisi Alessia, Andrea Dell'Acqua, Angelo Maggioni, Fabrizio Mastrilli, Sara Gandini, Kate Haire, Mieke Van Hemelrijck. Continuity of cancer care: The surgical experience of two large Cancer Hubs in London and Milan [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr P16.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 4
    In: BMC Infectious Diseases, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2022-08-06)
    Abstract: The incidence of high-risk human papillomavirus (hrHPV)-driven head and neck squamous cell carcinoma, in particular oropharyngeal cancers (OPC), is increasing in high-resource countries. Patients with HPV-induced cancer respond better to treatment and consequently have lower case-fatality rates than patients with HPV-unrelated OPC. These considerations highlight the importance of reliable and accurate markers to diagnose truly HPV-induced OPC. Methods The accuracy of three possible test strategies, i.e. (a) hrHPV DNA PCR (DNA), (b) p16 (INK4a) immunohistochemistry (IHC) (p16), and (c) the combination of both tests (considering joint DNA and p16 positivity as positivity criterion), was analysed in tissue samples from 99 Belgian OPC patients enrolled in the HPV-AHEAD study. Presence of HPV E6*I mRNA (mRNA) was considered as the reference, indicating HPV etiology. Results Ninety-nine OPC patients were included, for which the positivity rates were 36.4%, 34.0% and 28.9% for DNA, p16 and mRNA, respectively. Ninety-five OPC patients had valid test results for all three tests (DNA, p16 and mRNA). Using mRNA status as the reference, DNA testing showed 100% (28/28) sensitivity, and 92.5% (62/67) specificity for the detection of HPV-driven cancer. p16 was 96.4% (27/28) sensitive and equally specific (92.5%; 62/67). The sensitivity and specificity of combined p16 + DNA testing was 96.4% (27/28) and 97.0% (65/67), respectively. In this series, p16 alone and combined p16 + DNA missed 1 in 28 HPV driven cancers, but p16 alone misclassified 5 in 67 non-HPV driven as positive, whereas combined testing would misclassify only 2 in 67. Conclusions Single hrHPV DNA PCR and p16 (INK4a) IHC are highly sensitive but less specific than using combined testing to diagnose HPV-driven OPC patients. Disease prognostication can be encouraged based on this combined test result.
    Type of Medium: Online Resource
    ISSN: 1471-2334
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2041550-3
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  • 5
    Online Resource
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    Springer Science and Business Media LLC ; 2022
    In:  Journal of Experimental & Clinical Cancer Research Vol. 41, No. 1 ( 2022-12)
    In: Journal of Experimental & Clinical Cancer Research, Springer Science and Business Media LLC, Vol. 41, No. 1 ( 2022-12)
    Abstract: Head and Neck cancer (HNC) is a fatal malignancy with poor prognosis. Human Papillomavirus (HPV) infection is becoming the prominent cause of HNC in the western world, and studying the molecular mechanisms underlying its action in cancers is key towards targeted therapy. To replicate, HPV regulates the host DNA damage repair (DDR) pathway. SMAD4 is also involved in the regulation of the DDR machinery and likely plays important role in maintaining cell viability upon genotoxic stress. In this study, we investigated the role of HPV in the upregulation of SMAD4 to control the DDR response and facilitate its lifecycle. Methods SMAD4, Rad51 and CHK1 expression was assessed in HPV-positive and HPV-negative HNC using TCGA data, a panel of 14 HNC cell lines and 8 fresh tumour tissue samples from HNC patients. HPV16 expression was modulated by E6/E7 siRNA knock-down or transduction in HPV-positive HNC cell lines and Human Primary keratinocytes respectively. SMAD4 half-life was assessed by cycloheximide treatment in HNC cell lines, together with βTRCP1-dependent SMAD4 ubiquitination. SMAD4 siRNA knock-down was used to determine its role in HPV-mediated regulation of DDR machinery and to assess cisplatin sensitivity in HPV-positive HNC cell lines. Results We found that HPV increases SMAD4 expression is both HPV-positive HNC tumours and cell lines, impairing its degradation which is mediated by the E3 ubiquitin ligase βTRCP1. SMAD4 expression highly correlates with the expression of two main players of the DDR pathway, CHK1 and Rad51, which expression is also upregulated by the presence of HPV. In particular, we demonstrate that HPV stabilizes SMAD4 to increase CHK1 and Rad51 expression. In addition, SMAD4-deficient HPV-positive cells have increased sensitivity to cisplatin treatment. Conclusions Our results give a clear molecular mechanism at the basis of HPV regulation of the DDR pathway. In particular, we show how HPV stabilizes SMAD4 to promote DDR protein expression, which may be used to facilitate viral replication and HNC onset. Moreover, we found that SMAD4 silencing in HPV-positive HNC cell lines increases sensitivity to cisplatin treatment, suggesting that HPV-positive HNC with low SMAD4 expression may be preferentially susceptible to similar treatments.
    Type of Medium: Online Resource
    ISSN: 1756-9966
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2430698-8
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  • 6
    In: Cancers, MDPI AG, Vol. 13, No. 7 ( 2021-03-30), p. 1597-
    Abstract: The SARS-CoV-2 (COVID-19) pandemic is having a large effect on the management of cancer patients. This study reports on the approach and outcomes of cancer patients receiving radical surgery with curative intent between March and September 2020 (in comparison to 2019) in the European Institute of Oncology, IRCCS (IEO) in Milan and the South East London Cancer Alliance (SELCA). Both institutions implemented a COVID-19 minimal pathway where patients were required to self-isolate prior to admission and were swabbed for COVID-19 within 72 h of surgery. Positive patients had surgery deferred until a negative swab. At IEO, radical surgeries declined by 6% as compared to the same period in 2019 (n = 1477 vs. 1560, respectively). Readmissions were required for 3% (n = 41), and 〈 1% (n = 9) developed COVID-19, of which only one had severe disease and died. At SELCA, radical surgeries declined by 34% (n = 1553 vs. 2336). Readmissions were required for 11% (n = 36), 〈 1% (n = 7) developed COVID-19, and none died from it. Whilst a decline in number of surgeries was observed in both centres, the implemented COVID-19 minimal pathways have shown to be safe for cancer patients requiring radical treatment, with limited complications and almost no COVID-19 infections.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 7
    In: Oral Diseases, Wiley, Vol. 29, No. 1 ( 2023-01), p. 128-137
    Abstract: The space comprised between tumor and neck lymph nodes (T‐N tract) is one of the main routes of tumor spread in oral cavity tumors. Aim of the study was to investigate the impact of T‐N tract involvement on the postoperative radiotherapy (PORT) outcomes. Materials and Methods Patients (pts) treated between 2000 and 2016 with indication to PORT were retrospectively retrieved. Inclusion criteria were: (a) locally advanced tumors of the oral cavity, (b) who received with indication to PORT (c) with a minimum follow‐up of six months. Results One hundred and fifty‐seven pts met the inclusion criteria (136 pts treated with PORT and 21 pts not treated with PORT). In the PORT cohort, the T‐N tract involvement had no impact on both OS ( p  = .09) and LRFS ( p  = .2). Among the non‐PORT cohort, both OS ( p  = .007) and LRFS ( p  = .017) were worse for pts with positive T‐N tract compared to those with negative T‐N tract. PORT improved both OS ( p  = .008) and LRFS ( p  = .003) in pts with positive T‐N tract but not in those with negative T‐N tract ( p  = .36 and p  = .37, respectively). Conclusions Our results suggest that involvement of T‐N tract should be considered as prognostic factors informing the indication to PORT.
    Type of Medium: Online Resource
    ISSN: 1354-523X , 1601-0825
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2008428-6
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