223 results on '"Stefano Cavalieri"'
Search Results
2. MRI radiomics in head and neck cancer from reproducibility to combined approaches
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Anna Corti, Stefano Cavalieri, Giuseppina Calareso, Davide Mattavelli, Marco Ravanelli, Tito Poli, Lisa Licitra, Valentina D. A. Corino, and Luca Mainardi
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Magnetic resonance imaging ,Head and neck squamous cell carcinoma ,Radiomic features ,Prognostic models ,Overall survival ,Cluster analysis ,Medicine ,Science - Abstract
Abstract The clinical applicability of radiomics in oncology depends on its transferability to real-world settings. However, the absence of standardized radiomics pipelines combined with methodological variability and insufficient reporting may hamper the reproducibility of radiomic analyses, impeding its translation to clinics. This study aimed to identify and replicate published, reproducible radiomic signatures based on magnetic resonance imaging (MRI), for prognosis of overall survival in head and neck squamous cell carcinoma (HNSCC) patients. Seven signatures were identified and reproduced on 58 HNSCC patients from the DB2Decide Project. The analysis focused on: assessing the signatures’ reproducibility and replicating them by addressing the insufficient reporting; evaluating their relationship and performances; and proposing a cluster-based approach to combine radiomic signatures, enhancing the prognostic performance. The analysis revealed key insights: (1) despite the signatures were based on different features, high correlations among signatures and features suggested consistency in the description of lesion properties; (2) although the uncertainties in reproducing the signatures, they exhibited a moderate prognostic capability on an external dataset; (3) clustering approaches improved prognostic performance compared to individual signatures. Thus, transparent methodology not only facilitates replication on external datasets but also advances the field, refining prognostic models for potential personalized medicine applications.
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- 2024
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3. Radiation-Induced Oropharyngeal Squamous Cell Carcinoma: Case Report and Review of the Literature
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Lorenzo Giannini, Andrea Alliata, Valentina Cristofaro, Fabiola Incandela, Madia Pompilio, Arianna Ottini, Stefano Cavalieri, Imperia Nuzzolese, Nicola Alessandro Iacovelli, Marzia Franceschini, and Alberto Deganello
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radiotherapy ,radiation-induced cancer ,second primary tumour ,head and neck ,multidisciplinary team ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Radiation therapy (RT) is a mainstay for the treatment of head and neck (HN) cancers, with 80% of patients receiving such treatment. Radiation-induced malignancies represent a life-threatening long-term effect of RT, with an incidence of 0.5% to 15%. Case Description: After 13 years, a 33-year-old woman treated with chemo-radiotherapy for nasopharyngeal carcinoma developed a locally advanced, radiation-induced, p16-negative oropharyngeal squamous cell carcinoma (SCC) at the base of the tongue. Chemo/immunotherapy was administered as a first-line treatment. Given the optimal response and the feasibility of surgery, after three cycles, the patient underwent a total glossectomy, bilateral neck dissection, and reconstruction with a thoraco-dorsal free flap. A histological examination found SCC with a residual cancer burden of 70% and free margins. Discussion: The mechanisms responsible for carcinogenesis after RT are still not completely clear. Diagnosis may be challenging due to the previous treatment; growth patterns are unusual, and lymphotropism is lower. Prognosis is usually poor since surgical resectability is often not achievable. Conclusions: Radiation-induced malignancies are difficult to treat. Patient management should always be discussed at a multidisciplinary level. Future research is needed to assess whether the promising results of clinical studies with pre-operative immunotherapy in locally advanced HN SCC patients may be translated into radiation-induced cancers.
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- 2023
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4. MRI-based radiomic prognostic signature for locally advanced oral cavity squamous cell carcinoma: development, testing and comparison with genomic prognostic signatures
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Anna Corti, Loris De Cecco, Stefano Cavalieri, Deborah Lenoci, Federico Pistore, Giuseppina Calareso, Davide Mattavelli, Pim de Graaf, C. René Leemans, Ruud H. Brakenhoff, Marco Ravanelli, Tito Poli, Lisa Licitra, Valentina Corino, and Luca Mainardi
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Radiomics ,Radiogenomics ,Magnetic resonance imaging ,Head and neck cancer ,Survival models ,Overall survival ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract Background . At present, the prognostic prediction in advanced oral cavity squamous cell carcinoma (OCSCC) is based on the tumor-node-metastasis (TNM) staging system, and the most used imaging modality in these patients is magnetic resonance image (MRI). With the aim to improve the prediction, we developed an MRI-based radiomic signature as a prognostic marker for overall survival (OS) in OCSCC patients and compared it with published gene expression signatures for prognosis of OS in head and neck cancer patients, replicated herein on our OCSCC dataset. Methods For each patient, 1072 radiomic features were extracted from T1 and T2-weighted MRI (T1w and T2w). Features selection was performed, and an optimal set of five of them was used to fit a Cox proportional hazard regression model for OS. The radiomic signature was developed on a multi-centric locally advanced OCSCC retrospective dataset (n = 123) and validated on a prospective cohort (n = 108). Results The performance of the signature was evaluated in terms of C-index (0.68 (IQR 0.66–0.70)), hazard ratio (HR 2.64 (95% CI 1.62–4.31)), and high/low risk group stratification (log-rank p
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- 2023
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5. Editorial: Diagnosis, epidemiology and treatment of salivary gland carcinomas
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Imperia Nuzzolese, Pierluigi Bonomo, Ester Orlandi, Andreas Mock, and Stefano Cavalieri
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salivary gland carcinoma ,multidisciplinarity ,head and neck ,rare cancers ,adenoid cystic carcinoma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2024
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6. Multistep tumor genetic evolution and changes in immunogenicity trigger immune-mediated disease eradication in stage IV melanoma: lessons from a single case
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Adele Busico, Monica Rodolfo, Lorenza Di Guardo, Michele Del Vecchio, Licia Rivoltini, Laura Bergamaschi, Viviana Vallacchi, Mario Santinami, Elisabetta Vergani, Mara Cossa, Chiara Gargiuli, Andrea Devecchi, Matteo Dugo, Loris De Cecco, Stefano Cavalieri, Barbara Valeri, Elena Tamborini, Gianfrancesco Gallino, and Marialuisa Sensi
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Durable remissions are observed in 10%–20% of treated patients with advanced metastatic melanoma but the factors associated with long-term complete clinical responses are largely unknown. Here, we report the molecular characteristics of tumor evolution during disease progression along a 9-year clinical course in a patient with advanced disseminated melanoma who received different treatments, including trametinib, ipilimumab, radiation, vemurafenib, surgical tumor debulking and a second ipilimumab course, ultimately achieving complete long-term disease remission.Longitudinal analyses of therapies-resistant metastatic tumors revealed the effects of different treatments on tumor’s microenvironment and immunogenicity, ultimately creating a milieu favorable to immunotherapy response. Monitoring of the temporal dynamics of T cells by analysis of the T cell receptor (TCR) repertoire in the tumor and peripheral blood during disease evolution indicated that T-cell clones with common TCR rearrangements, present at low levels at baseline, were maintained and expanded after immunotherapy, and that TCR diversity increased. Analysis of genetic, molecular, and cellular components of the tumor depicted a multistep process in which treatment with kinase inhibitors strongly conditioned the immune microenvironment creating an inflamed milieu converting cold into hot tumors, while ipilimumab impacted and increased the TCR repertoire, a requirement for tumor rejection.Since the optimal sequencing of treatment with antibodies targeting immune checkpoints and kinase inhibitors for advanced melanoma is still clinically debated, this case indicates that immunotherapy success is possible even after progression on targeted therapy.
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- 2024
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7. Association of a gene-expression subtype to outcome and treatment response in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab
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Nerina Denaro, Lisa Licitra, Marco Merlano, Francesco Perri, Paolo Bossi, Cristina Gurizzan, Federica Perrone, Athanassios Argiris, Loris De Cecco, Stefano Cavalieri, Mara Serena Serafini, Federico Pistore, Deborah Lenoci, Silvana Canevari, Mario Airoldi, Maria Cossu Rocca, Primoz Strojan, Cvetka Grasic Kuhar, Andrea Vingiani, Maria Grazia Ghi, Alessandra Cassano, and Giacomo Allegrini
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background Immune checkpoint inhibitors have been approved and currently used in the clinical management of recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. The reported benefit in clinical trials is variable and heterogeneous. Our study aims at exploring and comparing the predictive role of gene-expression signatures with classical biomarkers for immunotherapy-treated R/M HNSCC patients in a multicentric phase IIIb trial.Methods Clinical data were prospectively collected in Nivactor tiral (single-arm, open-label, multicenter, phase IIIb clinical trial in platinum-refractory HNSCC treated with nivolumab). Findings were validated in an external independent cohort of immune-treated HNSCC patients, divided in long-term and short-term survivors (overall survival >18 and
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- 2024
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8. Dietary intervention for tertiary prevention in head and neck squamous cell carcinoma survivors: clinical and translational results of a randomized phase II trial
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Stefano Cavalieri, Eleonora Bruno, Mara Serena Serafini, Deborah Lenoci, Silvana Canevari, Laura Lopez-Perez, Liss Hernandez, Luigi Mariani, Rosalba Miceli, Cecilia Gavazzi, Patrizia Pasanisi, Elena Rosso, Francesca Cordero, Paolo Bossi, Wojciech Golusinski, Andreas Dietz, Primož Strojan, Thorsten Fuereder, Loris De Cecco, and Lisa Licitra
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head and neck cancer ,cancer survivors ,diet habits ,tertiary cancer prevention ,translational research ,questionnaires ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundThere is a strong need for preventive approaches to reduce the incidence of recurrence, second cancers, and late toxicities in head and neck squamous cell carcinoma (HNSCC) survivors. We conducted a randomized controlled trial (RCT) to assess a dietary intervention as a non-expensive and non-toxic method of tertiary prevention in HNSCC survivors.MethodsEligible participants were disease-free patients with HNSCC in follow-up after curative treatments. Subjects were randomized 1:1 to receive a highly monitored dietary intervention plus the Word Cancer Research Fund/American Institute for Cancer Research recommendations for cancer prevention (intervention arm) or standard-of-care recommendations (control arm). The planned sample size for the event-free survival evaluation (primary endpoint) was not reached, and the protocol was amended in order to investigate the clinical (nutritional and quality-of-life questionnaires) and translational study [plasma-circulating food-related microRNAs (miRNAs)] as main endpoints, the results of which are reported herein.ResultsOne hundred patients were screened, 94 were randomized, and 89 were eligible for intention-to-treat analysis. Median event-free survival was not reached in both arms. After 18 months, nutritional questionnaires showed a significant increase in Recommended Food Score (p = 0.04) in the intervention arm vs. control arm. The frequency of patients with and without a clinically meaningful deterioration or improvement of the C30 global health status in the two study arms was similar. Food-derived circulating miRNAs were identified in plasma samples at baseline, with a significant difference among countries.ConclusionThis RCT represented the first proof-of-principle study, indicating the feasibility of a clinical study based on nutritional and lifestyle interventions in HNSCC survivors. Subjects receiving specific counseling increased the consumption of the recommended foods, but no relevant changes in quality of life were recorded between the two study arms. Food-derived plasma miRNA might be considered promising circulating dietary biomarkers.
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- 2024
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9. NUT carcinoma of the submandibular gland: A case report
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Simone Rota, Pasquale Quattrone, Giovanni Centonze, Gianpaolo Dagrada, Arianna Ottini, Elena Colombo, Imperia Nuzzolese, Giuseppina Calareso, Marzia Franceschini, Nicola Alessandro Iacovelli, Federica Perrone, Elena Tamborini, and Stefano Cavalieri
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chromosome 15q14 ,head and neck ,NUT carcinoma ,salivary glands ,submandibular gland ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background NUT carcinoma (NUTc) is a rare and aggressive malignant epithelial tumor characterized by rearrangement of the NUT gene on chromosome 15q14. Methods In this article, we present the fifth case worldwide of a young woman affected by a NUTc arising from a submandibular gland, presenting as a rapidly evolving mass. She underwent a right scialoadenectomy and received the initial diagnosis of high‐grade mucoepidermoid carcinoma. Due to evidence of local recurrence at magnetic resonance imaging 1 month later, a subsequent right radical neck dissection was performed. The patient then sought a second opinion at our cancer center and finally received the correct diagnosis of NUT carcinoma. Given the well‐known aggressive behavior of this neoplasm, as well as clinical and radiological features, she underwent adjuvant chemo‐radiation (intensity‐modulated radiotherapy + concurrent chemotherapy with cisplatin). Results After a disease‐free interval of 2.6 months, a widespread metastatic disease led to rapid deterioration of performance status and patient death in a few weeks after metastatic onset. Conclusions We presented a case of NUTc arising from salivary gland aiming to improve the knowledge of this rare malignancy. First, we pointed out that in the setting of rare tumors like salivary gland cancers, the diagnosis should be obtained by expert pathologists, and patients should be referred to tertiary cancer centers for their clinical management. Second, molecular profiling may help to identify possible druggable targets that may be exploited to treat patients suffering from this aggressive malignancy. Sharing the molecular data provided in this case will be useful for further research.
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- 2023
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10. Multidisciplinary management of pregnancy-associated and early post-partum head and neck cancer patients
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Cristiana Bergamini, Stefano Cavalieri, Carlo Resteghini, Salvatore Alfieri, Imperia Nuzzolese, Elena Colombo, Arianna Ottini, Giuseppina Calareso, Andrea Vingiani, Nicola Alessandro Iacovelli, Marzia Franceschini, Marco Guzzo, Alberto Deganello, and Lisa Licitra
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head and neck cancer ,prognosis ,multidisciplinary management ,pregnancy associated cancer ,diagnosis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundPregnancy-associated cancer (PAC) occurs during pregnancy or within 12 months after the delivery. Head and neck cancer (HNC) during pregnancy is infrequent, therefore diagnosis and personalized therapy are intricate.MethodsWe investigated outcomes of 15 PAC patients (5 salivary, 4 nasopharyngeal, 3 thyroid, 2 oral cavity, one HPV-related carcinoma) diagnosed in the period 2005-2019. A literature review on PAC is provided.ResultsMedian gestational age at PAC diagnosis was 28 weeks (range: 16–40 weeks) in ten cases, at 5 months after delivery (range: 1 week–6 months) in the remaining five. Treatments included surgery (3 during pregnancy, 5 after childbirth), chemoradiation (8), and 3 patients with upfront metastatic disease received chemotherapy. Median survival was 6.6 years (eight women remain with no evidence of disease six years after diagnosis).ConclusionAll patients received state-of-the-art therapy, with encouraging long-term results, highlighting treatment safety in women with HNC during pregnancy.
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- 2023
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11. Head and neck cancers survival in Europe, Taiwan, and Japan: results from RARECAREnet Asia based on a privacy-preserving federated infrastructure
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Laura Botta, Tomohiro Matsuda, Hadrien Charvat, Chun-ju Chiang, Wen-Chung Lee, Anna Jacoba van Gestel, Frank Martin, Gijs Geleijnse, Matteo Cellamare, Simone Bonfarnuzzo, Rafael Marcos-Gragera, Marcela Guevara, Mohsen Mousavi, Stephanie Craig, Jessica Rodrigues, Jordi Rubió-Casadevall, Lisa Licitra, Stefano Cavalieri, Carlo Resteghini, Gemma Gatta, Annalisa Trama, and the RARECAREnet working group
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population-based cancer registry ,survival ,head and neck cancers ,geographical differences ,federated learning approach ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundThe head and neck cancers (HNCs) incidence differs between Europe and East Asia. Our objective was to determine whether survival of HNC also differs between European and Asian countries.MethodsWe used population-based cancer registry data to calculate 5-year relative survival (RS) for the oral cavity, hypopharynx, larynx, nasal cavity, and major salivary gland in Europe, Taiwan, and Japan. We modeled RS with a generalized linear model adjusting for time since diagnosis, sex, age, subsite, and histological grouping. Analyses were performed using federated learning, which enables analyses without sharing sensitive data.FindingsFive-year RS for HNC varied between geographical areas. For each HNC site, Europe had a lower RS than both Japan and Taiwan. HNC subsites and histologies distribution and survival differed between the three areas. Differences between Europe and both Asian countries persisted even after adjustments for all HNC sites but nasal cavity and paranasal sinuses, when comparing Europe and Taiwan.InterpretationSurvival differences can be attributed to different factors including different period of diagnosis, more advanced stage at diagnosis, or different availability/access of treatment. Cancer registries did not have stage and treatment information to further explore the reasons of the observed survival differences. Our analyses have confirmed federated learning as a feasible approach for data analyses that addresses the challenges of data sharing and urge for further collaborative studies including relevant prognostic factors.
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- 2023
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12. On the mean path length invariance property for random walks of animals in open environment
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Federico Tommasi, Lorenzo Fini, Stefano Focardi, Fabrizio Martelli, Giacomo Santini, and Stefano Cavalieri
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Medicine ,Science - Abstract
Abstract Random walks are common in nature and are at the basis of many different phenomena that span from neutrons and light scattering to the behaviour of animals. Despite the evident differences among all these phenomena, theory predicts that they all share a common fascinating feature known as Invariance Property (IP). In a nutshell, IP means that the mean length of the total path of a random walker inside a closed domain is fixed by the geometry and size of the medium. Such a property has been demonstrated to hold not only in optics, but recently also in the field of biology, by studying the movement of bacteria. However, the range of validity of such a universal property, strictly linked to the fulfilment of equilibrium conditions and to the statistical distributions of the steps of the random walkers, is not trivial and needs to be studied in different contexts, such as in the case of biological entities occupied in random foraging in an open environment. Hence, in this paper the IP in a virtual medium inside an open environment has been studied by using actual movements of animals recorded in nature. In particular, we analysed the behaviour of a grazer mollusc, the chiton Acanthopleura granulata. The results depart from those predicted by the IP when the dimension of the medium increases. Such findings are framed in both the condition of nonequilibrium of the walkers, which is typical of animals in nature, and the characteristics of actual animal movements.
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- 2022
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13. Management of patients with skin adnexal carcinomas
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Stefano Cavalieri, Cristiana Bergamini, Salvatore Alfieri, Carlo Resteghini, Imperia Nuzzolese, Elena Colombo, Arianna Ottini, and Lisa Licitra
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Cutaneous adenexal cancers ,Adnexal cancers of the skin ,Appendageal tumors ,Non-melanoma skin cancer ,Sebaceous carcinoma ,Sweat gland carcinoma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Adnexal cancers of the skin constitute a heterogeneous group of malignant tumors with specific pathologic and biological differences. This review aims to provide clinicians with a summary of how to manage the diagnosis, staging, and treatment of cutaneous adnexal cancer patients. In clinical practice, the complexity of this clinical and pathological heterogeneity is partially mitigated by adopting standardized universal classification systems. The WHO classification is used for pathologic diagnosis. Among appendageal skin tumors, it includes four groups of cutaneous adnexal malignancies (apocrine/eccrine differentiation, sebaceous differentiation, follicular differentiation, site-specific appendageal tumors) and seven malignant adnexal tumors of the eyelid. Clinical and pathologic staging should follow the latest AJCC/UICC classification, which includes site-specific systems to be used for these cancers: skin carcinoma of the head and neck, skin carcinoma of the eyelid, anal canal and perianal skin, vulva, penis, breast (for Paget disease), and any other skin carcinoma. The diagnostic hypothesis of genetic syndromes should always be considered for patients diagnosed with an adnexal skin neoplasm, especially when cancers arise in unusual or multiple anatomic sites. The pathologic diagnosis should be performed by expert pathologists, and patients should be referred to high-volume centers. In curative treatments, radical surgery, when feasible, should always be considered the first option for local or regional disease. The opportunity to deliver post-operative treatment should always be discussed at a multidisciplinary level. Patients suffering from advanced disease should be included in clinical studies. Outside trials, the seek for potential druggable targets is advised.
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- 2023
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14. The observational clinical registry (cohort design) of the European Reference Network on Rare Adult Solid Cancers: The protocol for the rare head and neck cancers.
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Annalisa Trama, Lisa Licitra, Stefano Cavalieri, Simone Bonfarnuzzo, Paolo Baili, Antonio Ciarfella, Pablo Parente, Giovanni Almadori, Mohssen Ansarin, Almalina Bacigalupo, Philipp Baumeister, Bertrand Baujat, Paolo Bossi, Elisa Cavalera, Maria Cecilia Cercato, Francois Dieleman, Nicolas Fakhry, Virginia Ferraresi, Francesca Gaino, Danilo Galizia, Jana Halamkova, Elina Halme, Jose Hardillo, Benedikt Hofauer, Emma Kinloch, Lorenzo Livi, Laura Deborah Locati, Stefan Mattheis, Giuseppe Mercante, Aurora Mirabile, Gabriele Molteni, Ester Orlandi, Roberto Persio, Stefania Sciallero, Ludi Smeele, Marta Tagliabue, Valentino Valentini, Carla Van Harpen, Christoph Benedikt Westphalen, and Laura Botta
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Medicine ,Science - Abstract
IntroductionCare for head and neck cancers is complex in particular for the rare ones. Knowledge is limited and histological heterogeneity adds complexity to the rarity. There is a wide consensus that to support clinical research on rare cancer, clinical registries should be developed within networks specializing in rare cancers. In the EU, a unique opportunity is provided by the European Reference Networks (ERN). The ERN EURACAN is dedicated to rare adults solid cancers, here we present the protocol of the EURACAN registry on rare head and neck cancers (ClinicalTrials.gov Identifier: NCT05483374).Study designRegistry-based cohort study including only people with rare head and neck cancers.Objectivesto help describe the natural history of rare head and neck cancers;to evaluate factors that influence prognosis;to assess treatment effectiveness;to measure indicators of quality of care.MethodsSettings and participants It is an hospital based registry established in hospitals with expertise in head and neck cancers. Only adult patients with epithelial tumours of nasopharynx; nasal cavity and paranasal sinuses; salivary gland cancer in large and small salivary glands; and middle ear will be included in the registry. This registry won't select a sample of patients. Each patient in the facility who meets the above mentioned inclusion criteria will be followed prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for the patient follow-up. Variables Data will be collected on patient characteristics (eg. patient demographics, lifestyle, medical history, health status); exposure data (eg. disease, procedures, treatments of interest) and outcomes (e.g. survival, progression, progression-free survival, etc.). In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will be also collected. Statistical methods The data analyses will include descriptive statistics showing patterns of patients' and cancers' variables and indicators describing the quality of care. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause specific mortality will be used to determine independent predictors of overall survival, recurrence etc. Variables to include in the multivariable regression model will be selected based on the results of univariable analysis. The role of confounding or effect modifiers will be evaluated using stratified analysis or sensitivity analysis. To assess treatment effectiveness, multivariable models with propensity score adjustment and progression-free survival will be performed. Adequate statistical (eg. marginal structural model) methods will be used if time-varying treatments/confounders and confounding by indication (selective prescribing) will be present.ResultsThe registry initiated recruiting in May 2022. The estimated completion date is December 2030 upon agreement on the achievement of all the registry objectives. As of October 2022, the registry is recruiting. There will be a risk of limited representativeness due to the hospital-based nature of the registry and to the fact that hospital contributing to the registry are expert centres for these rare cancers. Clinical Follow-up could also be an issue but active search of the life status of the patients will be guaranteed.
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- 2023
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15. A multicenter randomized trial for quality of life evaluation by non-invasive intelligent tools during post-curative treatment follow-up for head and neck cancer: Clinical study protocol
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Stefano Cavalieri, Claudia Vener, Marissa LeBlanc, Laura Lopez-Perez, Giuseppe Fico, Carlo Resteghini, Dario Monzani, Giulia Marton, Gabriella Pravettoni, Mauricio Moreira-Soares, Despina Elizabeth Filippidou, Aitor Almeida, Aritz Bilbao, Hisham Mehanna, Susanne Singer, Steve Thomas, Luca Lacerenza, Alfonso Manfuso, Chiara Copelli, Franco Mercalli, Arnoldo Frigessi, Elena Martinelli, Lisa Licitra, BD4QoL Consortium, Erlend I. F. Fossen, Katherine Taylor, Paul Nankivell, Mriganke De, Ahmad Abou-Foul, Estefania Estevez-Priego, Maria Fernanda Cabrera-Umpierrez, Itziar Alonso, Sergio Copelli, Andy Ness, Miranda Pring, and Katrina Hurley
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mHealth ,android ,head and neck cancer ,QOL ,BD4QoL ,survivorship ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Patients surviving head and neck cancer (HNC) suffer from high physical, psychological, and socioeconomic burdens. Achieving cancer-free survival with an optimal quality of life (QoL) is the primary goal for HNC patient management. So, maintaining lifelong surveillance is critical. An ambitious goal would be to carry this out through the advanced analysis of environmental, emotional, and behavioral data unobtrusively collected from mobile devices. The aim of this clinical trial is to reduce, with non-invasive tools (i.e., patients’ mobile devices), the proportion of HNC survivors (i.e., having completed their curative treatment from 3 months to 10 years) experiencing a clinically relevant reduction in QoL during follow-up. The Big Data for Quality of Life (BD4QoL) study is an international, multicenter, randomized (2:1), open-label trial. The primary endpoint is a clinically relevant global health-related EORTC QLQ-C30 QoL deterioration (decrease ≥10 points) at any point during 24 months post-treatment follow-up. The target sample size is 420 patients. Patients will be randomized to be followed up using the BD4QoL platform or per standard clinical practice. The BD4QoL platform includes a set of services to allow patients monitoring and empowerment through two main tools: a mobile application installed on participants’ smartphones, that includes a chatbot for e-coaching, and the Point of Care dashboard, to let the investigators manage patients data. In both arms, participants will be asked to complete QoL questionnaires at study entry and once every 6 months, and will undergo post-treatment follow up as per clinical practice. Patients randomized to the intervention arm (n=280) will receive access to the BD4QoL platform, those in the control arm (n=140) will not. Eligibility criteria include completing curative treatments for non-metastatic HNC and the use of an Android-based smartphone. Patients undergoing active treatments or with synchronous cancers are excluded.Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT05315570).
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- 2023
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16. HER2 status in recurrent/metastatic androgen receptor overexpressing salivary gland carcinoma patients
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Stefano Cavalieri, Imperia Nuzzolese, Arianna Ottini, Cristiana Bergamini, Carlo Resteghini, Elena Colombo, Salvatore Alfieri, Pasquale Quattrone, Giuseppina Calareso, Nicola Alessandro Iacovelli, Marzia Franceschini, and Lisa Licitra
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HER2 ,androgen receptor ,SDC ,salivary duct carcinoma ,SGC ,salivary gland carcinoma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundOverexpression of human epidermal growth factor receptor type 2 (HER2) occurs in almost 25-30% of androgen receptor (AR)-positive salivary gland carcinomas (SGCs), notably salivary duct carcinoma (SDC) and adenocarcinoma not otherwise specified (NOS). In the last years, several studies have reported the clinical benefit of HER2 directed therapies in this setting. This work aims at describing the natural history of AR-positive recurrent/metastatic (R/M) SGC patients, based on HER2 amplification status.MethodsConsecutive R/M AR-positive SGC patients accessing our Institution from 2010 to 2021 were analyzed. Descriptive statistics and survival analyses were performed to present the clinical characteristics of the selected patients and the outcomes, based on HER2 status. A specific focus was dedicated to patients developing metastases to the central nervous system (CNS).ResultsSeventy-four R/M AR-positive SGC patients (72 men) were analyzed. Median follow-up was 36.18 months (95% CI 30.19-42.66). HER2 status was available in 62 cases (84%) and in 42% the protein was overexpressed (HER2+). Compared with patients with HER2- SGCs, in patients with HER2+ disease, HR for disease recurrence was 2.97 (95% CI 1.44-6.1, p=0.003), and HR for death from R/M disease was 3.22 (95% CI 1.39-7.49, p=0.007). Moreover, the HER2+ group showed a non-significant trend towards a higher prevalence of CNS metastases (40% vs. 24%, p=0.263). Patients developing CNS metastases had shorter survival than those who did not; at bivariate analysis (covariates: CNS disease and HER2 status), HER2 status demonstrated its independent prognostic significance.DiscussionIn our patient population, HER2 amplification was a negative prognostic factor, and it was associated with a non-statistically significant higher risk of developing CNS metastasis. Further studies are needed to explore the potential clinical benefit of tackling the two biological pathways (AR and HER2) in patients affected by this rare and aggressive malignancy.
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- 2023
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17. Immunotherapy in head and neck squamous cell carcinoma and rare head and neck malignancies
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Stefano Cavalieri, Daria Maria Filippini, Arianna Ottini, Cristiana Bergamini, Carlo Resteghini, Elena Colombo, Roberta Lombardo, Imperia Nuzzolese, Salvatore Alfieri, Lisa Licitra, and Laura D. Locati
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head and neck cancer ,immune checkpoint inhibitors ,rare cancer ,Internal medicine ,RC31-1245 - Abstract
The dismal prognosis of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) prompted recent advances in the field of therapeutic approaches beyond cytotoxic cancer therapy. In recent years, the deeper and increasing knowledge on the genomic landscape and the upcoming new data on immunotherapy enacted by HNSCCs have led to successful therapeutic targeting of the immune system. Immune checkpoint inhibitors (ICIs) have changed state of the art in R/M patients and could have a potential role even in early disease. The purpose of this work is to summarize the role of immunotherapy for R/M HNSCC in clinical practice, with insights about future perspectives. Updated immunotherapy results in other R/M head and neck cancers such as thyroid, salivary glands, nasopharynx, sinonasal cancers, and nuclear protein in testis (NUT) are presented.
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- 2021
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18. Immune-based classification of HPV-associated oropharyngeal cancer with implications for biomarker-driven treatment de-intensificationResearch in context
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Peter Y.F. Zeng, Matthew J. Cecchini, John W. Barrett, Matthew Shammas-Toma, Loris De Cecco, Mara S. Serafini, Stefano Cavalieri, Lisa Licitra, Frank Hoebers, Ruud H. Brakenhoff, C. René Leemans, Kathrin Scheckenbach, Tito Poli, Xiaowei Wang, Xinyi Liu, Francisco Laxague, Eitan Prisman, Catherine Poh, Pinaki Bose, Joseph C. Dort, Mushfiq H. Shaikh, Sarah E.B. Ryan, Alice Dawson, Mohammed I. Khan, Christopher J. Howlett, William Stecho, Paul Plantinga, Sabrina Daniela da Silva, Michael Hier, Halema Khan, Danielle MacNeil, Adrian Mendez, John Yoo, Kevin Fung, Pencilla Lang, Eric Winquist, David A. Palma, Hedyeh Ziai, Antonio L. Amelio, Shawn S-C. Li, Paul C. Boutros, Joe S. Mymryk, and Anthony C. Nichols
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Head and neck squamous cell carcinoma ,Transcriptomics ,Biomarkers ,Cancer immunology ,HPV ,De-escalation ,Medicine ,Medicine (General) ,R5-920 - Abstract
Summary: Background: There is significant interest in treatment de-escalation for human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) patients given the generally favourable prognosis. However, 15–30% of patients recur after primary treatment, reflecting a need for improved risk-stratification tools. We sought to develop a molecular test to risk stratify HPV+ OPSCC patients. Methods: We created an immune score (UWO3) associated with survival outcomes in six independent cohorts comprising 906 patients, including blinded retrospective and prospective external validations. Two aggressive radiation de-escalation cohorts were used to assess the ability of UWO3 to identify patients who recur. Multivariate Cox models were used to assess the associations between the UWO3 immune class and outcomes. Findings: A three-gene immune score classified patients into three immune classes (immune rich, mixed, or immune desert) and was strongly associated with disease-free survival in six datasets, including large retrospective and prospective datasets. Pooled analysis demonstrated that the immune rich group had superior disease-free survival compared to the immune desert (HR = 9.0, 95% CI: 3.2–25.5, P = 3.6 × 10−5) and mixed (HR = 6.4, 95% CI: 2.2–18.7, P = 0.006) groups after adjusting for age, sex, smoking status, and AJCC8 clinical stage. Finally, UWO3 was able to identify patients from two small treatment de-escalation cohorts who remain disease-free after aggressive de-escalation to 30 Gy radiation. Interpretation: With additional prospective validation, the UWO3 score could enable biomarker-driven clinical decision-making for patients with HPV+ OPSCC based on robust outcome prediction across six independent cohorts. Prospective de-escalation and intensification clinical trials are currently being planned. Funding: CIHR, European Union, and the NIH.
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- 2022
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19. Verification method of Monte Carlo codes for transport processes with arbitrary accuracy
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Fabrizio Martelli, Federico Tommasi, Angelo Sassaroli, Lorenzo Fini, and Stefano Cavalieri
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Medicine ,Science - Abstract
Abstract In this work, we present a robust and powerful method for the verification, with arbitrary accuracy, of Monte Carlo codes for simulating random walks in complex media. Such random walks are typical of photon propagation in turbid media, scattering of particles, i.e., neutrons in a nuclear reactor or animal/humans’ migration. Among the numerous applications, Monte Carlo method is also considered a gold standard for numerically “solving” the scalar radiative transport equation even in complex geometries and distributions of the optical properties. In this work, we apply the verification method to a Monte Carlo code which is a forward problem solver extensively used for typical applications in the field of tissue optics. The method is based on the well-known law of average path length invariance when the entrance of the entities/particles in a medium obeys to a simple cosine law, i.e., Lambertian entrance, and annihilation of particles inside the medium is absent. By using this law we achieve two important points: (1) the invariance of the average path length guarantees that the expected value is known regardless of the complexity of the medium; (2) the accuracy of a Monte Carlo code can be assessed by simple statistical tests. We will show that we can reach an arbitrary accuracy of the estimated average pathlength as the number of simulated trajectories increases. The method can be applied in complete generality versus the scattering and geometrical properties of the medium, as well as in presence of refractive index mismatches in the optical case. In particular, this verification method is reliable to detect inaccuracies in the treatment of boundaries of finite media. The results presented in this paper, obtained by a standard computer machine, show a verification of our Monte Carlo code up to the sixth decimal digit. We discuss how this method can provide a fundamental tool for the verification of Monte Carlo codes in the geometry of interest, without resorting to simpler geometries and uniform distribution of the scattering properties.
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- 2021
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20. Complete Response to Nivolumab in Recurrent/Metastatic HPV-Positive Head and Neck Squamous Cell Carcinoma Patient After Progressive Multifocal Leukoencephalopathy: A Case Report
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Laura Deborah Locati, Mara Serena Serafini, Andrea Carenzo, Silvana Canevari, Federica Perrone, Ester Orlandi, Serena Delbue, Stefano Cavalieri, Giulia Berzeri, Anna Pichiecchio, Lisa Francesca Licitra, Enrico Marchioni, and Loris De Cecco
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immunotherapy ,HNSCC ,oropharynx ,HPV ,case report ,PML ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
In an immune-competent context nivolumab showed long-term benefit in overall survival in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC); however, in special cancer population such as these patients with immunodeficiency and viral infections, data on checkpoint inhibitors (ICI) activity are scant. Herein, we report a patient with a Human papilloma virus (HPV)-related oropharyngeal cancer (OPC) and CD4 lymphocytopenia. After a first-line treatment complete remission, the patient experienced Human Polyomavirus (JCV) infection in the brain. Consequently, to the recovery from progressive multifocal leukoencephalopathy (PML) the patient metastasized and was enrolled in a single-arm trial with nivolumab (EudraCT number: 2017-000562-30). A complete and durable response (more 3 years) was observed after 10 nivolumab injections Q2wks, interrupted for persistent drug related G2 diarrhea and a syndrome of inappropriate antidiuretic hormone secretion. We describe the circulating immune profile (before-, during-, and after nivolumab), consistent with the clinical history. Moreover, during nivolumab treatment, brain MRI evidenced the presence of small punctuate areas of contrast enhancement, reflecting a mild immune response in perivascular spaces. By cytofluorimetry, we observed that during JCV infection the CD4/CD8 ratio of the patient was under the normal values. After JCV infection recovery and before nivolumab treatment, CD4/CD8 ratio reached the normality threshold, even if the CD4+ T cell count remained largely under the normal values. During ICI, gene expression xCell analyses of circulating immune cells of the patient, showed a progressive normalization of the total immune profile, with significant boost in CD4+ and CD8+ T cells and a reduction in NK T, comparable to the circulating immune profile of reference tumor-free HNSCC patients. The present case supports the activity of ICI in a population of special cancer patients; whether JCV and HPV infections (alone or together) might have a possible role as immune booster(s), require further investigations.
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- 2022
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21. Activity of platinum and cetuximab in cutaneous squamous cell cancer not amenable to curative treatment
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Donata Galbiati, Stefano Cavalieri, Salvatore Alfieri, Carlo Resteghini, Cristiana Bergamini, Ester Orlandi, Francesca Platini, Laura Locati, Luca Giacomelli, Lisa Licitra, and Paolo Bossi
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cetuximab ,combination ,cscc ,platinum-based chemotherapy ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Background: Unresectable or metastatic cutaneous squamous cell cancers (cSCCs) are rare but potentially life-threatening diseases. In this setting, systemic therapy has a palliative intent with limited benefit, but there is no established consensus regarding the proper management of this tumour. This retrospective study aimed to review outcomes in patients with non-curable cSCC treated with platinum-based chemotherapy and cetuximab. Methods: We considered 12 consecutive patients treated between June 2010 and March 2016. All patients had received previous treatment for the local disease. Results: The overall response rate was 50%, and the disease control rate was 67%. Median progression-free survival and overall survival were 6.6 (95% confidence interval [CI]: 1.9–8.4) and 14.6 (95% CI: 9.4–20.1) months, respectively. The median duration of response was 4.8 months (95% CI: 1.2–5.9). The most frequent toxicities were skin reactions (58%; grade 3: 25%) and anaemia (10%). No grade 4 toxicities were observed. Conclusions: Cetuximab and platinum-based chemotherapy were shown to be feasible and active in cSCC, with an acceptable toxicity profile, even if with a limited duration of response.
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- 2019
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22. Biological Rationale and Clinical Evidence of Carbon Ion Radiation Therapy for Adenoid Cystic Carcinoma: A Narrative Review
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Pierre Loap, Barbara Vischioni, Maria Bonora, Rossana Ingargiola, Sara Ronchi, Viviana Vitolo, Amelia Barcellini, Lucia Goanta, Ludovic De Marzi, Remi Dendale, Roberto Pacelli, Laura Locati, Valentin Calugaru, Hamid Mammar, Stefano Cavalieri, Youlia Kirova, and Ester Orlandi
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adenoid cyst carcinoma ,hadrontherapy ,carbon ion radiotherapy (CIRT) ,tumor immunology ,radioresistance ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Adenoid cystic carcinoma (ACC) is a rare, basaloid, epithelial tumor, arising mostly from salivary glands. Radiation therapy can be employed as a single modality for unresectable tumors, in an adjuvant setting after uncomplete resection, in case of high-risk pathological features, or for recurrent tumors. Due to ACC intrinsic radioresistance, high linear energy transfer (LET) radiotherapy techniques have been evaluated for ACC irradiation: while fast neutron therapy has now been abandoned due to toxicity concerns, charged particle beams such as protons and carbon ions are at present the beams used for hadron therapy. Carbon ion radiation therapy (CIRT) is currently increasingly used for ACC irradiation. The aim of this review is to describe the immunological, molecular and clinicopathological bases that support ACC treatment with CIRT, as well as to expose the current clinical evidence that reveal the advantages of using CIRT for treating ACC.
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- 2021
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23. An Inflammatory Signature to Predict the Clinical Benefit of First-Line Cetuximab Plus Platinum-Based Chemotherapy in Recurrent/Metastatic Head and Neck Cancer
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Stefano Cavalieri, Mara Serena Serafini, Andrea Carenzo, Silvana Canevari, Deborah Lenoci, Federico Pistore, Rosalba Miceli, Stefania Vecchio, Daris Ferrari, Cecilia Moro, Andrea Sponghini, Alessia Caldara, Maria Cossu Rocca, Simona Secondino, Gabriella Moretti, Nerina Denaro, Francesco Caponigro, Emanuela Vaccher, Gaetana Rinaldi, Francesco Ferraù, Paolo Bossi, Lisa Licitra, and Loris De Cecco
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HNSCC ,targeted therapy ,cetuximab ,gene-expression ,immune biomarkers ,inflammatory signature ,Cytology ,QH573-671 - Abstract
Epidermal growth factor receptor (EGFR) pathway has been shown to play a crucial role in several inflammatory conditions and host immune-inflammation status is related to tumor prognosis. This study aims to evaluate the prognostic significance of a four-gene inflammatory signature in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients treated with the EGFR inhibitor cetuximab plus chemotherapy. The inflammatory signature was assessed on 123 R/M HNSCC patients, enrolled in the multicenter trial B490 receiving first-line cetuximab plus platinum-based chemotherapy. The primary endpoint of the study was progression free survival (PFS), while secondary endpoints were overall survival (OS) and objective response rate (ORR). The patient population was subdivided into 3 groups according to the signature score groups. The four-genes-signature proved a significant prognostic value, resulting in a median PFS of 9.2 months in patients with high vs. 6.2 months for intermediate vs. 3.9 months for low values (p = 0.0016). The same findings were confirmed for OS, with median time of 18.4, 13.4, and 7.5 months for high, intermediate, and low values of the score, respectively (p = 0.0001). When ORR was considered, the signature was significantly higher in responders than in non-responders (p = 0.0092), reaching an area under the curve (AUC) of 0.65 (95% CI: 0.55–0.75). Our findings highlight the role of inflammation in the response to cetuximab and chemotherapy in R/M-HNSCC and may have translational implications for improving treatment selection.
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- 2022
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24. Role of IMRT/VMAT-Based Dose and Volume Parameters in Predicting 5-Year Local Control and Survival in Nasopharyngeal Cancer Patients
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Nicola Alessandro Iacovelli, Alessandro Cicchetti, Anna Cavallo, Salvatore Alfieri, Laura Locati, Eliana Ivaldi, Rossana Ingargiola, Domenico A. Romanello, Paolo Bossi, Stefano Cavalieri, Chiara Tenconi, Silvia Meroni, Giuseppina Calareso, Marco Guzzo, Cesare Piazza, Lisa Licitra, Emanuele Pignoli, Fallai Carlo, and Ester Orlandi
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nasopharyngeal carcinoma (NPC) ,intensity-modulated radiation therapy (IMRT) ,gross tumor volume (GTV) ,dose-volume parameters ,outcomes ,nomogram ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Objective: This study aimed to look into the relationship between intensity-modulated-radiotherapy (IMRT)- or volumetric-modulated-arc-therapy (VMAT)-based dose–volume parameters and 5-year outcome for a consecutive series of non-metastatic nasopharyngeal cancer (NPC) patients (pts) treated in a single institution in a non-endemic area in order to identify potential prognostic factors.Materials and methods: A retrospective analysis of consecutive non-metastatic NPC pts treated curatively with IMRT or VMAT and chemotherapy (CHT) between 2004 and 2014 was conducted. One patient was in stage I (0.7%), and 24 pts (17.5%) were in stage II, 38 pts (27.7%) in stage III, 29 pts (21.2%) in stage IVA, and 45 pts (32.8%) in stage IVB. Five pts (3.6%) received radiotherapy (RT) alone. Of the remaining 132 pts (96.4%), 30 pts (21.9%) received CHT concomitant to RT, and 102 pts (74.4%) were treated with induction CHT followed by RT-CHT. IMRT was given with standard fractionation at a total dose of 70 Gy. Clinical outcomes investigated in the study were local control (LC), disease-free survival (DFS), and overall survival (OS). Kaplan–Meier (KM) analysis was performed for the outcomes considering dose and coverage parameters, staging, and RT technique.Results: Overall, 137 pts were eligible for this retrospective analysis. With a median follow-up of 70 months (range 12–143), actuarial rates at 5 years were LC 90.4, DFS 77.2, and OS 82.8%. For this preliminary study, T stage was dichotomized as T1, T2, T3 vs. T4. At 5 years, the group T1–T2–T3 reported an LC of 93%, a DFS of 79%, and an OS of 88%, whereas T4 pts reported LC, DFS, and OS, respectively, of 56, 50, and 78%. Pts with V95% > 95.5% had better LC (p = 0.006). Pts with D99% > 63.8 Gy had better LC (p = 0.034) and OS (p = 0.005). The threshold value of 43.2 cm3 of GTVT was prognostic for LC (p = 0.016). To predict the risk of local recurrence at 5 years, we constructed a nomogram which combined GTVT with D99% relative to HRPTV.Conclusions: We demonstrated the prognostic value of some dose–volume parameters, although in a retrospective series, this is potentially useful to improve planning procedure. In addition, for the first time in a non-endemic area, a threshold value of GTVT, prognostic for LC, has been confirmed.
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- 2020
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25. Computed tomography-derived radiomic signature of head and neck squamous cell carcinoma (peri)tumoral tissue for the prediction of locoregional recurrence and distant metastasis after concurrent chemo-radiotherapy.
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Simon Keek, Sebastian Sanduleanu, Frederik Wesseling, Reinout de Roest, Michiel van den Brekel, Martijn van der Heijden, Conchita Vens, Calareso Giuseppina, Lisa Licitra, Kathrin Scheckenbach, Marije Vergeer, C René Leemans, Ruud H Brakenhoff, Irene Nauta, Stefano Cavalieri, Henry C Woodruff, Tito Poli, Ralph Leijenaar, Frank Hoebers, and Philippe Lambin
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Medicine ,Science - Abstract
INTRODUCTION:In this study, we investigate the role of radiomics for prediction of overall survival (OS), locoregional recurrence (LRR) and distant metastases (DM) in stage III and IV HNSCC patients treated by chemoradiotherapy. We hypothesize that radiomic analysis of (peri-)tumoral tissue may detect invasion of surrounding tissues indicating a higher chance of locoregional recurrence and distant metastasis. METHODS:Two comprehensive data sources were used: the Dutch Cancer Society Database (Alp 7072, DESIGN) and "Big Data To Decide" (BD2Decide). The gross tumor volumes (GTV) were delineated on contrast-enhanced CT. Radiomic features were extracted using the RadiomiX Discovery Toolbox (OncoRadiomics, Liege, Belgium). Clinical patient features such as age, gender, performance status etc. were collected. Two machine learning methods were chosen for their ability to handle censored data: Cox proportional hazards regression and random survival forest (RSF). Multivariable clinical and radiomic Cox/ RSF models were generated based on significance in univariable cox regression/ RSF analyses on the held out data in the training dataset. Features were selected according to a decreasing hazard ratio for Cox and relative importance for RSF. RESULTS:A total of 444 patients with radiotherapy planning CT-scans were included in this study: 301 head and neck squamous cell carcinoma (HNSCC) patients in the training cohort (DESIGN) and 143 patients in the validation cohort (BD2DECIDE). We found that the highest performing model was a clinical model that was able to predict distant metastasis in oropharyngeal cancer cases with an external validation C-index of 0.74 and 0.65 with the RSF and Cox models respectively. Peritumoral radiomics based prediction models performed poorly in the external validation, with C-index values ranging from 0.32 to 0.61 utilizing both feature selection and model generation methods. CONCLUSION:Our results suggest that radiomic features from the peritumoral regions are not useful for the prediction of time to OS, LR and DM.
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- 2020
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26. Correction: Computed tomography-derived radiomic signature of head and neck squamous cell carcinoma (peri)tumoral tissue for the prediction of locoregional recurrence and distant metastasis after concurrent chemo-radiotherapy.
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Simon Keek, Sebastian Sanduleanu, Frederik Wesseling, Reinout de Roest, Michiel van den Brekel, Martijn van der Heijden, Conchita Vens, Calareso Giuseppina, Lisa Licitra, Kathrin Scheckenbach, Marije Vergeer, C René Leemans, Ruud H Brakenhoff, Irene Nauta, Stefano Cavalieri, Henry C Woodruff, Tito Poli, Ralph Leijenaar, Frank Hoebers, and Philippe Lambin
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Medicine ,Science - Abstract
[This corrects the article DOI: 10.1371/journal.pone.0232639.].
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- 2020
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27. Direct Measurement of the Reduced Scattering Coefficient by a Calibrated Random Laser Sensor
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Federico Tommasi, Baptiste Auvity, Lorenzo Fini, Fabrizio Martelli, and Stefano Cavalieri
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sensor ,random laser ,scattering ,Chemical technology ,TP1-1185 - Abstract
The research in optical sensors has been largely encouraged by the demand for low-cost and less or non-invasive new detection strategies. The invention of the random laser has opened a new frontier in optics, providing also the opportunity to explore new possibilities in the field of sensing, besides several different and peculiar phenomena. The main advantage in exploiting the physical principle of the random laser in optical sensors is due to the presence of the stimulated emission mechanism, which allows amplification and spectral modification of the signal. Here, we present a step forward in the exploitation of this optical phenomenon by a revisitation of a previous experimental setup, as well as the measurement method, in particular to mitigate the instability of the results due to shot-to-shot pump energy fluctuations. In particular, the main novelties of the setup are the use of optical fibers, a reference sensor, and a peristaltic pump. These improvements are devoted to: eliminating optical beam alignment issues; improving portability; mitigating the variation in pump energy and gain medium performances over time; realizing an easy and rapid change of the sensed medium. The results showed that such a setup can be considered a prototype for a portable device for directly measuring the scattering of liquid samples, without resorting to complicated numerical or analytic inversion procedures of the measured data, once the suitable calibration of the system is performed.
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- 2022
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28. Quality Assessment in Supportive Care in Head and Neck Cancer
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Pierluigi Bonomo, Alberto Paderno, Davide Mattavelli, Sadamoto Zenda, Stefano Cavalieri, and Paolo Bossi
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supportive care ,head and neck cancer ,quality assessment ,multimodal treatment ,surgery ,chemotherapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Quality assessment is a key issue in every clinical intervention, to be periodically performed so to measure the adherence to standard and to possibly implement strategies to improve its performance. This topic is rarely discussed for what concerns supportive care; however, it is necessary to verify the quality of the supportive measures; “supportive care makes excellent cancer care possible,” as stated by the Multinational Association of Supportive Care in Cancer (MASCC). In this regard, the quality of supportive care in head and neck cancer patients is a crucial topic, both to allow administration of treatments according to planned dose intensity or surgical indications and to maintain or improve patients' quality of life. This paper aims to provide insight on state of the art supportive care and its future developments for locally advanced and recurrent/metastatic head and neck cancer, with a focus on quality assessment in relation to surgery, radiotherapy, and systemic therapy.
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- 2019
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29. Unusual Skin Carcinomas Induced by BRAF Inhibitor for Metastatic Melanoma: A Case Report
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Stefano Cavalieri, Lorenza Di Guardo, Mara Cossa, Carolina Cimminiello, and Michele Del Vecchio
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basal cell carcinoma ,dabrafenib ,trametinib ,vemurafenib ,Medicine - Abstract
The most frequently reported skin tumours during treatment with targeted therapies for BRAF (B type Rapidly Accelerated Fibrosarcoma kinase) mutated metastatic melanoma are squamous cell carcinomas (SCCs). Basal cell carcinomas (BCCs) have been described in such setting, but no cases of multiple and recurring tumours have been reported so far. A patient with a history of chronic sun exposure and more than 10 BCCs removed since 1998 started treatment with vemurafenib for BRAF mutated metastatic melanoma. Therapy was complicated by sporadic episodes of atrial fibrillation and by the development of recurrent, multiple and diffuse BCCs. So, vemurafenib was discontinued and dabrafenib and trametinib were started. Since then, only four BCCs occurred in the patient. Histopathological re-examination showed that most BCCs occurred under vemurafenib presented with squamous features. Such characteristic was significantly less evident before therapy start and in lesions removed under treatment with dabrafenib and trametinib. BRAF inhibition (BRAFi) without MEK inhibition induces mitogen activated kinases overactivation, with consequent skin toxicity and acquired drug resistance. The BCCs removed from our patient showed squamous features, more evident during vemurafenib monotherapy. Both the switch from vemurafenib to dabrafenib and the addition of MEK inhibitor (MEKi) might have reduced the incidence of BCCs and their squamous differentiation.
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- 2017
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30. Smartphone-Based Strategy for Quality-of-Life Monitoring in Head and Neck Cancer Survivors.
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Laura Lopez-Perez, Itziar Alonso, Despina Elisabeth Filippidis, Franco Mercalli, Stefano Cavalieri, Elena Martinelli, Lisa Licitra, Anastassios Manos, María Fernanda Cabrera-Umpiérrez, and Giuseppe Fico
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- 2022
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31. Methodology and technology for the development of a prognostic MRI-based radiomic model for the outcome of head and neck cancer patients.
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Marco Bologna, Valentina D. A. Corino, Chiara Tenconi, Nadia Facchinetti, Giuseppina Calareso, Nicola Iacovelli, Anna Cavallo, Salvatore Alfieri, Stefano Cavalieri, Carlo Fallai, Riccardo Valdagni, Tiziana Rancati, Annalisa Trama, Lisa Licitra, Ester Orlandi, and Luca T. Mainardi
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- 2020
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32. Integrating population data in a computerized Decision Support System for Head and Neck Cancer.
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Laura Lopez-Perez, Liss Hernández, Laura Pfaff, Annalisa Trama, Gemma Gatta, Silvia Francisci, Sandra Mallone, Elena Martinelli, Ana M. Ugena, Stefano Cavalieri, Lisa Licitra, María Teresa Arredondo, and Giuseppe Fico
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- 2019
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33. Verification test of Monte Carlo codes for biomedical optics applications with arbitrary accuracy
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Fabrizio Martelli, Federico Tommasi, Angelo Sassaroli, Lorenzo Fini, and Stefano Cavalieri
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- 2023
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34. Relation between fluence rate and mean photons pathlengths: an interesting option for Monte Carlo-based fluence calculations in biomedical optics
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Fabrizio Martelli, Angelo Sassaroli, Federico Tommasi, Lorenzo Fini, and Stefano Cavalieri
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- 2023
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35. Prognostic radiomic signature for head and neck cancer: Development and validation on a multi-centric MRI dataset
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Marco Bologna, Valentina Corino, Stefano Cavalieri, Giuseppina Calareso, Silvia Eleonora Gazzani, Tito Poli, Marco Ravanelli, Davide Mattavelli, Pim de Graaf, Irene Nauta, Kathrin Scheckenbach, Lisa Licitra, Luca Mainardi, Radiology and nuclear medicine, AII - Cancer immunology, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, and Otolaryngology / Head & Neck Surgery
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Radiomics ,Settore MED/36 - Diagnostica per Immagini e Radioterapia ,Oncology ,Settore MED/06 - Oncologia Medica ,Head and neck cancer ,MRI ,Machine learning ,Survival analysis ,Radiology, Nuclear Medicine and imaging ,Hematology - Abstract
BACKGROUND AND PURPOSE: Prognosis in locally advanced head and neck cancer (HNC) is currently based on TNM staging system and tumor subsite. However, quantitative imaging features (i.e., radiomic features) from magnetic resonance imaging (MRI) may provide additional prognostic info. The aim of this work is to develop and validate an MRI-based prognostic radiomic signature for locally advanced HNC.MATERIALS AND METHODS: Radiomic features were extracted from T1- and T2-weighted MRI (T1w and T2w) using the segmentation of the primary tumor as mask. In total 1072 features (536 per image type) were extracted for each tumor. A retrospective multi-centric dataset (n = 285) was used for features selection and model training. The selected features were used to fit a Cox proportional hazard regression model for overall survival (OS) that outputs the radiomic signature. The signature was then validated on a prospective multi-centric dataset (n = 234). Prognostic performance for OS and disease-free survival (DFS) was evaluated using C-index. Additional prognostic value of the radiomic signature was explored.RESULTS: The radiomic signature had C-index = 0.64 for OS and C-index = 0.60 for DFS in the validation set. The addition of the radiomic signature to other clinical features (TNM staging and tumor subsite) increased prognostic ability for both OS (HPV- C-index 0.63 to 0.65; HPV+ C-index 0.75 to 0.80) and DFS (HPV- C-index 0.58 to 0.61; HPV+ C-index 0.64 to 0.65).CONCLUSION: An MRI-based prognostic radiomic signature was developed and prospectively validated. Such signature can successfully integrate clinical factors in both HPV+ and HPV- tumors.
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- 2023
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36. Abiraterone Acetate in Patients With Castration-Resistant, Androgen Receptor–Expressing Salivary Gland Cancer: A Phase II Trial
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Pasquale Quattrone, Laura D. Locati, Salvatore Alfieri, Luigi Mariani, Paolo Bossi, Lisa Licitra, Cristiana Bergamini, Francesca Platini, Carlo Resteghini, Elena Colombo, Giuseppina Calareso, Iolanda Capone, and Stefano Cavalieri
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Adult ,Male ,Cancer Research ,medicine.drug_class ,Abiraterone Acetate ,Antineoplastic Agents ,Castration resistant ,chemistry.chemical_compound ,medicine ,Humans ,In patient ,Aged ,Salivary gland ,business.industry ,Abiraterone acetate ,Middle Aged ,Salivary Gland Neoplasms ,Androgen ,medicine.disease ,Androgen receptor ,medicine.anatomical_structure ,Oncology ,chemistry ,Salivary gland cancer ,Cancer research ,Female ,business - Abstract
PURPOSE The activity of androgen-deprivation therapy (ADT) in androgen receptor–positive (AR+) salivary gland carcinomas (SGCs) has been established in the past few years. Second-line treatment in castration-resistant patients is still unknown. We investigated the activity of abiraterone acetate as second-line treatment in ADT-resistant, AR+ patients with SGC. METHODS This was a single-institution phase II trial. A two-stage Simon's design was applied. The primary end point was confirmed objective response rate. Secondary end points were disease control rate, safety, progression-free survival, and overall survival. Patients were eligible when the following criteria were met: histologic diagnosis of AR-overexpressing SGC, measurable disease according to RECIST 1.1, clinical and/or radiologic progression on ADT, suppressed serum testosterone, and no limits for the number of previous chemotherapy lines. All patients received abiraterone 1 g daily plus prednisone 10 mg and luteinizing hormone-releasing hormone agonist until progression or unacceptable toxicities. RESULTS From 2015 to 2019, 24 AR+ patients with SGC (23 men; median age 65.8 years) were treated within the study. The overall response rate was 21% (5 partial responses), with a disease control rate of 62.5%. The median duration of response was 5.82 months. Median progression-free survival was 3.65 months (95% CI, 1.94 to 5.89), and median overall survival was 22.47 months (95% CI, 6.74 to not reached). Objective response to previous ADT did not correlate with the activity of abiraterone. Adverse events (AEs) were recorded in 22 cases (92%) with grade 3 AEs in six patients (25%): fatigue (two), flushing (one), supraventricular tachycardia (one), and two non–drug-related AEs. No drug-related grade 4 or 5 AEs were recorded. CONCLUSION Abiraterone plus luteinizing hormone-releasing hormone agonist is active and safe as a second-line option in AR-expressing, castration-resistant SGC.
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- 2021
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37. Fluence rate directly derived from photon pathlengths: a tool for Monte Carlo simulations in biomedical optics
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Angelo Sassaroli, Federico Tommasi, Stefano Cavalieri, and Fabrizio Martelli
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Atomic and Molecular Physics, and Optics ,Article ,Biotechnology - Abstract
In biomedical optics, the mean fluence rate of photons, assessed in a sub-volume of a propagating medium, is classically obtained in Monte Carlo simulations by taking into account the power deposited by the absorbed photons in the sub-volume. In the present contribution, we propose and analytically demonstrate an alternative method based on the assessment of the mean pathlength traveled by all the photons inside the sub-volume. Few practical examples of its applications are given. This method has the advantage of improving, in many cases, the statistics and the convergence of the Monte Carlo simulations. Further, it also works when the absorption coefficient is nil and for a non-constant spatial distribution of the absorption coefficient inside the sub-volume. The proposed approach is a re-visitation of a well-known method applied in radiation and nuclear physics in the context of radiative transfer, where it can be derived in a more natural manner.
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- 2022
38. Toxicity of carbon ion radiotherapy and immune checkpoint inhibitors in advanced melanoma
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Michele Del Vecchio, Maria Bonora, Viviana Vitolo, Sara Ronchi, Barbara Vischioni, Amelia Barcellini, Riccardo Villa, Stefano Cavalieri, Ester Orlandi, and Lisa Licitra
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business.industry ,Immune checkpoint inhibitors ,Mucosal melanoma ,Heavy Ion Radiotherapy ,Hematology ,medicine.disease ,Oncology ,Toxicity ,Cancer research ,Humans ,Medicine ,Carbon Ion Radiotherapy ,Radiology, Nuclear Medicine and imaging ,business ,Adverse effect ,Immune Checkpoint Inhibitors ,Melanoma ,Advanced melanoma - Abstract
We analyzed CTCAE adverse events of sequential Carbon Ion radiotherapy (CIRT) and immune checkpoint inhibitors (ICIs) in advanced melanoma patients. The frequencies of early and late adverse events (AEs) were 100% and 82% of patients, respectively. The frequency of G3+ AEs was in line with the literature.
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- 2021
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39. Bleeding complications in patients with squamous cell carcinoma of the head and neck
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Jing Xie, Muzammil Ali, Kevin J. Harrington, Robert L. Ferris, Amanda Psyrri, Lisa Licitra, William C. Holmes, Stefano Cavalieri, Cristiana Bergamini, and Gabriella Mariani
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Oncology ,Vascular Endothelial Growth Factor A ,medicine.medical_specialty ,Clinical Review ,Immune checkpoint inhibitors ,medicine.medical_treatment ,head and neck squamous cell carcinoma ,Clinical Reviews ,immune checkpoint inhibitors ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Epidemiology ,Medicine ,Humans ,030212 general & internal medicine ,Epidermal growth factor receptor ,antiangiogenic drugs ,Head and neck ,Chemotherapy ,biology ,business.industry ,Squamous Cell Carcinoma of Head and Neck ,medicine.disease ,Head and neck squamous-cell carcinoma ,Clinical trial ,Vascular endothelial growth factor ,stomatognathic diseases ,Otorhinolaryngology ,chemistry ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,biology.protein ,Carcinoma, Squamous Cell ,molecular targeted therapies ,hemorrhage ,Neoplasm Recurrence, Local ,business - Abstract
Hemorrhage in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) may be attributed to chemotherapy and local tumor irradiation. Evidence of the relationship between hemorrhage in R/M HNSCC and targeted therapies, including epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) inhibitors, or immune checkpoint inhibitors, is limited. We aimed to identify epidemiological and clinical data related to the occurrence of hemorrhage in R/M HNSCC and to explore its relationship with various therapies. We describe information obtained from literature searches as well as data extracted from a commercial database and a database from the author's institution (Istituto Nazionale dei Tumori of Milan). Evidence suggests that most bleeding events in R/M HNSCC are minor. Clinical trial safety data do not identify a causal association between hemorrhage and anti‐EGFR agents or immune checkpoint inhibitors. In contrast, anti‐VEGF agents are associated with increased, and often severe/fatal, hemorrhagic complications.
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- 2021
40. Spondylodiscitis in Pediatric Age: A Retrospective Cohort Study
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Stefano Cavalieri, Benedetta Pessina, Giuseppe Indolfi, Luisa Galli, and Sandra Trapani
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Microbiology (medical) ,Male ,Delayed Diagnosis ,Discitis ,Infant ,Staphylococcal Infections ,Anti-Bacterial Agents ,Infectious Diseases ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Humans ,Female ,Child ,Retrospective Studies - Abstract
Pediatric spondylodiscitis is rare, hardly diagnosed and treated due to the nonspecificity of clinical presentation and laboratory investigations, difficulty of etiologic identification and lack of management guidelines.A retrospective study was conducted on 29 children with spondylodiscitis. Clinical, hematic and radiologic data were collected and compared between 2 age-subgroups (below and from 4 years old on) to investigate age-related differences. Epidemiologic, management and follow-up data were also described.Slight male predominance and a peak of incidence2 years were observed. Symptoms were significantly differently distributed in the 2 age-subgroups: children4 years showed mainly refusal/inability to sit or bear weight, irritability, limping and poor general conditions; children ≥4 years most frequently had back pain and fever, and pain upon palpation of the spine. The lumbar spine and more than 1 vertebra were most frequently involved. Median diagnostic delay of 12 days was observed, without significant difference between age-subgroups, and delay2 months was always associated with multivertebral involvement and complications. All children were treated with broad-spectrum antibiotics for a median of 12 weeks. Only in 1 complicated case, surgical treatment was also required.The clinical presentation of spondylodiscitis may be age-specific, with younger children often exhibiting subtle signs and symptoms. Broad-spectrum antibiotics covering for Staphylococcus aureus should be initiated as soon as possible and performed many weeks, being effective in treating the infection without clinical sequelae, even in patients with comorbidities. Surgical treatment should be reserved for complicated cases with neurologic involvement.
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- 2022
41. Monitoring patients with head and neck cancer for flu-like symptoms during the COVID-19 pandemic
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Francesca Platini, Emma Zattarin, A. Bottiglieri, Salvatore Alfieri, Laura D. Locati, Lisa Licitra, Vito Di Martino, Giacomo Massa, Valentina Tiraferri, Cristiana Bergamini, Carlo Resteghini, Arianna Ottini, Daria Maria Filippini, Elena Colombo, and Stefano Cavalieri
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Flu-like symptoms ,Cancer Research ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Medical Oncology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Pandemic ,Humans ,Medicine ,030212 general & internal medicine ,Large head ,Pandemics ,SARS-CoV-2 ,business.industry ,Head and neck cancer ,COVID-19 ,Cancer ,General Medicine ,Middle Aged ,medicine.disease ,Triage ,Oncology ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Cohort ,business - Abstract
Objective: To capture and monitor flu-like symptoms in relation to the clinical characteristics and the oncologic treatment of a large head and neck cancer (HNC) patient cohort during the Coronavirus disease 2019 (COVID-19) pandemic. Methods: Patients were monitored through by 2 rounds of interviews. Clinical characteristics of patients with no symptoms (group 0) and of those reporting ⩾1 (group A), ⩾3 (group B), or ⩾5 symptoms (group C) were analyzed. Patients with ⩾1 symptom at both interviews were defined as group A2. Results: Five hundred patients with HNC were analyzed. A higher frequency of patients with the following characteristics was observed in group A vs group 0: active treatment (40% vs 24%, p = 0.0002), gastrostomy (6% vs 2%, p = 0.027), recent active treatment (48% vs 29%, p < 0.0001), and higher number of concomitant medications ( p = 0.01). A lower median age was observed in group B vs group no-B (patients with fewer than three symptoms) (59 vs 63.55 years, p = 0.016) and in group A2 vs group no-A2 (patients without at least one symptom at both interviews) (56 vs 63 years, p = 0.021); patients in group B received more recent active treatment than those in group no-B and in group A2 vs those in group no-A2 ( p = 0.024 and 0.043, respectively); patients in group B had a lower body mass index than those in group no-B (22.4 vs 23.93 kg/m2, p = 0.0066). Conclusions: This work is based on patient-reported symptoms and signs independently of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. In the future, these results might serve as a a benchmark for clinicians triaging and managing patients with HNC during infectious outbreaks involving flu-like symptoms.
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- 2021
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42. Late toxicities burden in patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib
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Lisa Licitra, Francesca Platini, E Seregni, Stefano Cavalieri, Laura D. Locati, Salvatore Alfieri, Carlo Resteghini, Biagio Paolini, L Mazzeo, Cristiana Bergamini, Elena Colombo, and A. Bottiglieri
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medicine.medical_specialty ,Side effect ,Endocrinology, Diabetes and Metabolism ,Antineoplastic Agents ,030209 endocrinology & metabolism ,Iodine Radioisotopes ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Refractory ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Thyroid Neoplasms ,Adverse effect ,Protein Kinase Inhibitors ,Thyroid cancer ,Survival analysis ,Retrospective Studies ,business.industry ,Phenylurea Compounds ,Incidence (epidemiology) ,medicine.disease ,chemistry ,030220 oncology & carcinogenesis ,Quinolines ,Female ,business ,Lenvatinib - Abstract
Radioactive-iodine (RAI)-resistant differentiated thyroid cancer (DTC) patients benefit from multi-kinase inhibitors (MKIs), such as lenvatinib. Incidence of treatment-related (TR) late toxicities has been not yet described. From January 2015 to June 2019 we retrospectively reviewed clinical records of patients with RAI-resistant DTC treated with lenvatinib at Istituto Nazionale dei Tumori (Milan, Italy). New side effect of any grade, appeared after 12 months of lenvatinib, was defined as late adverse event (AE). Descriptive analyses were performed. Survival curves were estimated with Kaplan–Meier method and compared with log-rank test. Thirty-seven patients were included, 65% had ≥65 years and 68% were female. Thirty patients received lenvatinib for >12 months. Lenvatinib was started at ≤20 mg/daily in 59% of patients, 64% were ≥65 years. The frequency of late AEs was 80% and cardiovascular toxicity was the most common (57%). There was no difference in the incidence of late AEs between younger/older population (77% and 82%, respectively). Median lenvatinib treatment duration (TD) was 39.96 months (95% CI 21.64-NR): 39.96 months for patients
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- 2021
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43. Abstract 4529: The tumor molecular landscape of nasopharyngeal carcinoma (NPC) in endemic and non endemic areas
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Deborah Lenoci, Carlo Resteghini, Mara Serena Serafini, Federico Pistore, Silvana Canevari, Brigette B.Y. Ma, Stefano Cavalieri, Annalisa Trama, Lisa Licitra, and Loris De Cecco
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Cancer Research ,Oncology - Abstract
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with a higher incidence in Asian endemic areas (EA) than in non endemic areas (NEA). Epstein-Barr virus infection is associated with most NPCs in both areas. We dissected the gene expression (GE) and microenvironment of NPC, leading to the identification of molecular subtypes that might explain the differences between EA and NEA NPCs. We retrieved data from NPC-EA transcriptomic repositories: 6 GE datasets, including tumor and normal samples (GSE12452, GSE34573, GSE132112, GSE53819, GSE68799, GSE102349); one validation dataset with both EA and NEA(https://doi.org/10.5281/zenodo.5347891); 4 GE signatures associated with prognosis and treatment prediction (PMID: 24297049, 35262435, 32596151, 33096113); and NPC EBV related genes/pathways and gene sets (PMID: 35846746, 35394843, 35105963; Liu NPC, Wood EBV EBNA1 Down, Sengupta NPC LMP1 UP, REACTOME DNA Repair; Hallmarks). The 6 datasets were integrated using a bioinformatic meta-analysis approach, and the classifier method was applied to the validation dataset in order to identify the subtype with worst prognosis. Furthermore, RNA sequencing was performed on 50 Italian NEA NPC samples (INT188/19; GSE208281). Biological and functional profiling of EA and NEA were performed using xCell, Gene set enrichment analyses, and treatment prediction methods (PMID: 16103067, pRRophetic R, PMID: 28052254). Four clusters (Cl) were identified through a meta-analysis of EA-NPC. Prognostic analyses revealed that Cl3 had the worst prognosis (P=0.0476), confirmed by three of the four prognostic signatures and in the validation dataset (P=0.0368). Based on the biological and functional characterization of these clusters, we arrived at the following GE subtypes: Cl1, Immune-active; Cl2, Defense-response; Cl3, Proliferation; Cl4, Perineural-interaction/EBV-exhaustion. According to the treatment prediction methods, the sensitivity of each cluster was radiotherapy and immunotherapy for immune-active, radiochemotherapy and immunotherapy for defense-response, chemotherapy for proliferation, and cisplatin treatment for perineural-interaction/EBV-exhaustion. In our NEA cohort, only three clusters were expressed (excluding perineural-interaction/EBV-exhaustion). Immune/biological characterization and treatment prediction analyses of NEA partially replicated the EA results. Our study provides a relevant biological overview of EBV-related NPC in both EA and NEA. The immune microenvironment plays a critical role in NPC owing to the viral etiology of this malignancy. The presence of a perineural-interaction/EBV-exhaustion cluster in EA suggests an inactive EBV infection according to the viral related “hit and run theory”; however, further analyses are needed. The immune/biological characterization of EA and NEA may help predict the response to different therapeutic strategies. Citation Format: Deborah Lenoci, Carlo Resteghini, Mara Serena Serafini, Federico Pistore, Silvana Canevari, Brigette B.Y. Ma, Stefano Cavalieri, Annalisa Trama, Lisa Licitra, Loris De Cecco. The tumor molecular landscape of nasopharyngeal carcinoma (NPC) in endemic and non endemic areas. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4529.
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- 2023
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44. Which future for de-intensified treatments in HPV-related oropharyngeal carcinoma?
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Stefano Cavalieri, Imperia Nuzzolese, and Lisa Licitra
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HPV ,De-escalation ,deintensification ,head and neck cancer ,oropharyngeal cancer ,Settore MED/06 - Oncologia Medica ,Papillomavirus Infections ,Carcinoma ,Hematology ,Chemoradiotherapy ,Combined Modality Therapy ,Oropharyngeal Neoplasms ,Oncology ,Humans - Abstract
The development of deintensified therapies aiming at reducing the treatment-related toxicity while not impairing the outcome is an unmet need in HPV+ oropharyngeal carcinoma patients. Several deintensification approaches have been explored in this setting, including induction chemotherapy with reduced chemoradiation dose in responding pts. The findings of the studies conducted so far show that the available deescalated therapy should be based on the disease risk profile. At present, we still lack robust high level data to infer that the cited interventions are equivalent or superior to standard of care treatments. However, literature data suggest that approximately 70% of low-risk patients might receive a deintensified approach by including either surgery or induction chemotherapy. In the context of high-risk disease, more than 80% of patients may undergo a deintensified loco-regional treatment by neoadjuvant systemic therapy. Epidemiological data suggest that in the next decades, most of the HPV-related OPSCC patients will be made of old and possibly frail individuals. However, this patient population was excluded from most of the studies conducted so far. Therefore, there is a strong need for clinical trials to define risk-based deescalation strategies in this population and in younger patients as well.
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- 2022
45. Patients with adenoid cystic carcinomas of the salivary glands treated with lenvatinib: Activity and quality of life
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Roberta Granata, Salvatore Lo Vullo, Carlo Resteghini, Donata Galbiati, Pasquale Quattrone, Salvatore Alfieri, Luigi Mariani, Cristiana Bergamini, Francesca Platini, Susanne Singer, Lisa Licitra, Ester Orlandi, Laura D. Locati, Giuseppina Calareso, Moela Mancinelli, Stefano Cavalieri, and Paolo Bossi
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Adult ,Male ,adenoid cystic carcinoma ,lenvatinib ,quality of life ,toxicity ,Cancer Research ,medicine.medical_specialty ,Adenoid cystic carcinoma ,Antineoplastic Agents ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Swallowing ,Quality of life ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Prospective Studies ,030212 general & internal medicine ,Neoplasm Metastasis ,Protein Kinase Inhibitors ,Dose-Response Relationship, Drug ,business.industry ,Phenylurea Compounds ,Cancer ,Common Terminology Criteria for Adverse Events ,Middle Aged ,Salivary Gland Neoplasms ,medicine.disease ,Carcinoma, Adenoid Cystic ,Survival Analysis ,Salivary Gland Adenoid Cystic Carcinoma ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Quinolines ,Female ,Neoplasm Recurrence, Local ,business ,Lenvatinib - Abstract
The treatment of patients with recurrent and/or metastatic (R/M) salivary gland adenoid cystic carcinoma (ACC) remains an unmet need.Patients with R/M disease with a history of clinical or symptomatic disease progression within 6 months and a maximum of 1 previous line of chemotherapy or a multiple kinase inhibitor received oral lenvatinib at a dose of 24 mg/day. The primary endpoint was the objective response rate; secondary endpoints included quality of life (QOL) (according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Items [EORTC QLQ-C30] and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Module Head and Neck Module [EORTC QLQ-HN35]), progression-free survival and overall survival, duration of response, and toxicities.Twenty-eight patients with R/M ACC were enrolled. Among 26 evaluable patients, 3 partial responses (11.5%) were reported. Target lesion reductions between 23% to 28% were observed in 4 of 20 patients with stable disease. Treatment-related adverse events were frequent (all grades, 96%; grade≥3 in 50% of cases according to version 4.03 of the National Cancer Institute Common Terminology Criteria for Adverse Events). The dose of lenvatinib was reduced in 24 patients, whereas in 21 patients the dose was reduced within the first 12 weeks and 4 patients maintained the full dose throughout treatment. The QOL deteriorated between baseline and 6 months with regard to Fatigue and Dry Mouth. There was no evidence of changes in Swallowing and Physical Functioning. At a median follow-up of 29 months, 2 patients remained on treatment, 10 patients were off protocol for disease progression and were alive with disease, and 14 patients had died of disease progression. The median overall survival, progression-free survival, and duration of response were 27 months, 9.1 months, and 3.1 months, respectively.Lenvatinib appears to have modest activity in ACC. Toxicities are common but manageable and QOL was found to deteriorate in some domains.
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- 2020
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46. A Clinically Translatable Immune-based Classification of HPV-associated Head and Neck Cancer with Implications for Biomarker-Driven Treatment Deintensification and Immunotherapy
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Peter YF. Zeng, Matthew J. Cecchini, John W. Barrett, Matthew Shammas-Toma, Loris De Cecco, Mara S. Serafini, Stefano Cavalieri, Lisa Licitra, Frank Hoebers, Ruud H. Brakenhoff, C René Leemans, Kathrin Scheckenbach, Tito Poli, Xiaowei Wang, Xinyi Liu, Francisco Laxague, Eitan Prisman, Catherine Poh, Pinaki Bose, Joseph C. Dort, Mushfiq H. Shaikh, Sarah EB. Ryan, Allie Dawson, Mohammed I. Khan, Christopher J. Howlett, William Stecho, Paul Plantinga, Sabrina Daniela da Silva, Michael Hier, Halema Khan, Danielle MacNeil, Adrian Mendez, John Yoo, Kevin Fung, Pencilla Lang, Eric Winquist, David A. Palma, Hedyeh Ziai, Antonio L. Amelio, Shawn S-C. Li, Paul C. Boutros, Joe S. Mymryk, and Anthony C. Nichols
- Abstract
PurposeHuman papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) is the fastest rising cancer in North America. There is significant interest in treatment de-escalation for these patients given the generally favourable prognosis. However, 15-30% of patients recur after primary treatment, reflecting a need for improved risk-stratification tools. We sought to develop a molecular test to predict the survival of patients with newly diagnosed HPV+ HNSCC.MethodsWe created a prognostic score (UWO3) that was successfully validated in six independent cohorts comprising 906 patients, including blinded retrospective and prospective external validations. Transcriptomic data from two aggressive radiation de-escalation cohorts were used to assess the ability of UWO3 to identify patients who recur. Multivariate Cox models were used to assess the associations between the UWO3 immune class and outcomes.ResultsA three-gene immune score classified patients into three immune classes (immune rich, mixed, or immune desert) and was strongly associated with disease-free survival in six datasets, including large retrospective and prospective datasets. Pooled analysis demonstrated that the immune rich group had superior disease-free survival at 5 years to the immune desert (HR= 9.0, 95% CI 3.2–25.5, P=3.6×10−5) and mixed (HR=6.4, 95%CI 2.2–18.7, P=0.006) groups after adjusting for age, sex, smoking status, and AJCC8 clinical stage. Finally, UWO3 was able to identify patients from two treatment de-escalation cohorts who remain disease-free after aggressive de-escalation to 30 Gy radiation.ConclusionsThe UWO3 immune score could enable biomarker-driven clinical decision-making for patients with HPV+ HNSCC based on robust outcome prediction across six independent cohorts. The superior survival of immune rich patients supports de-intensification strategies, while the inferior outcomes of the immune desert patients suggest the potential for intensification and/or immunotherapy. Prospective de-escalation and intensification clinical trials are currently being planned.
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- 2022
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47. The Role of Immune Checkpoint Inhibitors in the Treatment of Less Common Head and Neck Cancers
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Stefano Cavalieri, Paolo Bossi, and Lisa Licitra
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- 2022
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48. The Interplay between Age and Viral Status in EBV-Related Nasopharyngeal and HPV-Related Oropharyngeal Carcinoma Patients
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Stefano Cavalieri, Paolo Bossi, Gabriele Infante, Rosalba Miceli, Nicola Alessandro Iacovelli, Eliana Ivaldi, Laura Deborah Locati, Cristiana Bergamini, Carlo Resteghini, Imperia Nuzzolese, Salvatore Alfieri, Elena Colombo, Rossana Ingargiola, Marzia Franceschini, Giuseppina Calareso, Lisa Licitra, and Ester Orlandi
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Cancer Research ,HPV ,Oncology ,EBV ,Settore MED/06 - Oncologia Medica ,elderly ,nasopharyngeal carcinoma ,oropharyngeal carcinoma ,prognosis - Abstract
Background. The aim of this work was to analyze the interplay between age and viral status on the outcomes in loco-regionally advanced oropharyngeal and nasopharyngeal cancer patients treated with radiotherapy and different chemotherapy combinations. Methods. A retrospective (2006–2017) analysis was performed on non-metastatic loco-regionally advanced oropharyngeal (both HPV+ and HPV−) and EBV+ nasopharyngeal cancer patients (young
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- 2022
49. Biological properties of hypoxia-related gene expression models/signatures on clinical benefit of anti-EGFR treatment in two head and neck cancer window-of-opportunity trials
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Deborah Lenoci, Andrea Carenzo, Stefano Cavalieri, Federico Pistore, Mara Serena Serafini, Paolo Bossi, Sandra Schmitz, Jean-Pascal Machiels, Lisa Francesca Licitra, Loris De Cecco, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Unité d'oncologie médicale, and UCL - (SLuc) Service d'oto-rhino-laryngologie
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Cancer Research ,Oncology ,Squamous Cell ,Settore MED/06 - Oncologia Medica ,Head and Neck Neoplasms ,Carcinoma ,Carcinoma, Squamous Cell ,Gene Expression ,Humans ,Hypoxia ,Oral Surgery - Abstract
Not applicable (letter)
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- 2022
50. Verification method of Monte Carlo codes for transport processes with arbitrary accuracy
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Angelo Sassaroli, Lorenzo Fini, Stefano Cavalieri, Fabrizio Martelli, and Federico Tommasi
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Multidisciplinary ,Uniform distribution (continuous) ,Scattering ,Computer science ,Mathematics and computing ,Science ,Physics ,Monte Carlo method ,Scalar (physics) ,Expected value ,Models, Theoretical ,Random walk ,Average path length ,Article ,Path length ,Optics and photonics ,Medicine ,Humans ,Statistical physics ,Monte Carlo Method ,Algorithms - Abstract
In this work, we present a robust and powerful method for the verification, with arbitrary accuracy, of Monte Carlo codes for simulating random walks in complex media. Such random walks are typical of photon propagation in turbid media, scattering of particles, i.e., neutrons in a nuclear reactor or animal/humans’ migration. Among the numerous applications, Monte Carlo method is also considered a gold standard for numerically “solving” the scalar radiative transport equation even in complex geometries and distributions of the optical properties. In this work, we apply the verification method to a Monte Carlo code which is a forward problem solver extensively used for typical applications in the field of tissue optics. The method is based on the well-known law of average path length invariance when the entrance of the entities/particles in a medium obeys to a simple cosine law, i.e., Lambertian entrance, and annihilation of particles inside the medium is absent. By using this law we achieve two important points: (1) the invariance of the average path length guarantees that the expected value is known regardless of the complexity of the medium; (2) the accuracy of a Monte Carlo code can be assessed by simple statistical tests. We will show that we can reach an arbitrary accuracy of the estimated average pathlength as the number of simulated trajectories increases. The method can be applied in complete generality versus the scattering and geometrical properties of the medium, as well as in presence of refractive index mismatches in the optical case. In particular, this verification method is reliable to detect inaccuracies in the treatment of boundaries of finite media. The results presented in this paper, obtained by a standard computer machine, show a verification of our Monte Carlo code up to the sixth decimal digit. We discuss how this method can provide a fundamental tool for the verification of Monte Carlo codes in the geometry of interest, without resorting to simpler geometries and uniform distribution of the scattering properties.
- Published
- 2021
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