Showing papers by "Laura D. Locati published in 2023"

The association of cemiplimab plus sonidegib for synchronous cutaneous squamous cell carcinoma and basal cell carcinoma of the head and neck: Two case reports

Abstract: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequent cancers in humans, with cumulative ultraviolet radiation exposure, aging, and immunodepression as the main risk factors. In most cases, these malignancies arise in the head and neck area, and they can be treated with locoregional therapies. A minority of cases require systemic therapy. Currently, Sonic Hedgehog inhibitors (i.e., vismodegib and sonidegib) have been approved for advanced BCC, while the PD-1 checkpoint inhibitor cemiplimab has been approved as a first-line treatment for cSCC and as a second-line treatment for BCC. Nevertheless, there is a clinical need for an effective and safe systemic therapies for advanced synchronous (syn) BCC/cSCC not amenable to local treatments. International guidelines do not provide specific recommendations for patients affected by this condition, and no case reports on the full-dose association of these medications have been previously reported. Here, we present the cases of two elderly patients affected by synBCC/cSCC of the head and neck, who received combined therapy with cemiplimab and sonidegib at full dose and standard schedule, achieving remarkable clinical benefit and long-term responses, without major adverse events. The instance of a feasible treatment for patients with advanced synBCC/cSCC will become increasingly frequent with the advancement of life expectancy in the global population, and the synergistic activity of targeted therapies and immunotherapy—administered either in association or sequentially—deserves to be further explored.

The SINTART 2 Study. A phase II non-randomised controlled trial of induction chemotherapy, photon-, proton- and carbon-ion-based radiotherapy integration in patients with locally advanced unresectable sinonasal tumours.

Abstract: Unresectable, locally advanced sinonasal epithelial tumours are rare diseases with poor prognosis. Multimodal approach is widely used, although no standard therapy has been established in prospective trials. This study assessed activity and safety of an innovative integration of multimodality treatment-induction chemotherapy (ICT), surgery and radiotherapy (RT)-modulated by histology and response to ICT.Patients with untreated, unresectable sinonasal epithelial tumours with selected histotypes (squamous cell carcinoma, intestinal-type adenocarcinoma, sinonasal undifferentiated and neuroendocrine carcinoma, olfactory neuroblastoma) were enroled in a single-arm, open-label, phase II, multicentre clinical trial. Patients were treated with up to 5 ICT cycles, whose regimen was selected according to histotype. Photon and/or proton/carbon-ion-based RT was employed according to disease site, stage and ICT response. Primary end-point was 5-years progression-free survival (PFS), secondary end-points were overall survival (OS), ICT objective response rate per RECIST 1.1 and safety.Twenty-five patients were evaluable for primary end-point. Five-year PFS was 26.8% (95% confidence interval [CI]: 12.6-57.1), with a median PFS of 18 months. Five-year OS was 23.8% (95% CI: 9.5-59.3), with a median OS of 27 months. The overall response rate to ICT was 40%. Three-year PFS for patients achieving major volumetric partial response (mPRv) versus non-mPRv was 40% (95% CI: 13.7-100%) versus 23.1% (95% CI: 8.3-64.7%) (P = 0.318) and 3-year OS was 53.3% (95% CI: 21.4-100%) versus 37.7% (95% CI: 20.0-71.0%) (P = 0.114).Multimodal combination of ICT and innovative RT did not provide a significant improvement in survival rates with respect to previous experiences. This finding underscores the need for future research in this rare disease, still characterised by a heavy burden and poor prognosis. We observed longer survival in subjects achieving response to ICT. The overall treatment safety is acceptable.

Use of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer: a multidisciplinary perspective for daily practice.

Abstract: BACKGROUND Most thyroid cancers of follicular origin have a favorable outcome. Only a small percentage of patients will develop metastatic disease, some of which will become radioiodine refractory (RAI-R). Important challenges to ensure the best therapeutic outcomes include proper, timely, and appropriate diagnosis; decisions on local, systemic treatments; management of side effects of therapies; a good relationship between the specialist, patients, and caregivers. METHODS With the aim of providing suggestions that can be useful in everyday practice, a multidisciplinary group of experts organized the following document, based on their shared clinical experience with patients with RAI-R differentiated thyroid cancer (DTC) undergoing treatment with lenvatinib. The main areas covered are patient selection, initiation of therapy, follow-up, and management of adverse events. CONCLUSIONS It is essential to provide guidance for management of RAI-R DTC patients with systemic therapies, and especially lenvatinib, since compliance and adherence to treatment are fundamental to achieve the best outcomes. While the therapeutic landscape in RAI-refractory DTC is evolving, with new targeted therapies, immunotherapy, etc., lenvatinib is expected to remain a first-line treatment and mainstay of therapy for several years in the vast majority of patients and settings. The guidance herein covers baseline work-up and initiation of systemic therapy, relevance of symptoms, multidisciplinary assessment, and patient education. Practical information based on expert experience is also given for the starting dose of lenvatinib, follow-up and monitoring, as well as management of adverse events and discontinuation and reinitiating of therapy. The importance of patient engagement is also stressed.

Implementing a virtual multidisciplinary clinical case discussion to manage rare and complex head and neck cancers: an expert-defined protocol proposal from the Italian Association of Head and Neck Oncology (AIOCC)

Abstract: Discussione multidisciplinare virtuale per la gestione di casi clinici rari e complessi dei tumori della testa e collo: una proposta di protocollo da parte degli esperti dell’Associazione Italiana di Oncologia Cervico-Cefalica (AIOCC).

International phase IV field study for the reliability and validity of the European Organisation for Research and Treatment of Cancer Thyroid Cancer Module EORTC QLQ-THY34.

Abstract: Purpose The aim of this study was to validate the new European Organisation for Research and Treatment of Cancer Quality of Life Thyroid Cancer Module (EORTC QLQ-THY34). Methods We enrolled 437 thyroid cancer patients from 17 countries. One group (n=303), undergoing treatment or best supportive care, completed the questionnaires at three time points (before therapy (t1), 6 weeks later (t2) and 6 months after t2 (t3). A second group (survivors ≥ 2y after diagnosis, n=134) completed it at a random baseline time point and a second time 1 week later. We determined internal consistency (using Cronbach's Alpha), the scale structure (with confirmatory factor analysis), and discriminant validity (using known-group comparisons). Group 1 data was used to assess responsiveness and group 2 data to determine test-retest reliability using intra-class correlations (ICC). Results All 34 items fulfilled the criteria to be kept in the questionnaire. Cronbach's Alpha was >0.70 in 8 of the 9 multi-item scales. All standardised factor loadings exceeded 0.40, confirming the proposed scale structure. The ICC was >0.70 in all scales expressing good test-retest reliability. Differences in scale scores between patients with different histology were >5 points in all scales. In all but one of the pre-specified scales (Dry Mouth), changes over time were ≥|4| points between at least two time-points. Conclusion The EORTC QLQ-THY34 with its 9 multi-item and 8 single-item scales is a reliable and valid tool to measure quality of life in thyroid cancer patients and can be used in future trials and studies.

A data-driven approach to refine predictions of differentiated thyroid cancer outcomes: a prospective multicenter study.

Abstract: BACKGROUND The risk stratification of patients with differentiated thyroid cancer (DTC) is crucial in clinical decision making. The most widely accepted method to assess risk of recurrent/persistent disease is described in the 2015 American Thyroid Association (ATA) guidelines. However, recent research has focused on the inclusion of novel features or questioned the relevance of currently included features. OBJECTIVE To develop a comprehensive data-driven model to predict persistent/recurrent disease that is able to capture all available features and determine the weight of predictors. DESIGN Prospective cohort study using the Italian Thyroid Cancer Observatory (ITCO) database (NCT04031339). SETTING Forty Italian clinical centers. METHODS We selected consecutive cases with DTC and at least early follow-up data (n=4773; median follow-up 26 months, interquartile range 12-46 months). A decision tree was built to assign a risk index to each patient. The model allowed us to investigate the impact of different variables in risk prediction. RESULTS 2492 patients (52.2%) were classified as low, 1873 (39.2%) as intermediate, and 408 as high risk, according to ATA risk estimation. The decision-tree model outperformed the ATA risk stratification system: the sensitivity of high-risk classification for structural disease increased from 37% to 49%, and the negative predictive value for low-risk patients increased by 3%. Feature importance was estimated. Several variables not included in the ATA system significantly impacted the prediction of disease persistence/recurrence: age, body mass index, tumor size, sex, family history of thyroid cancer, surgical approach, pre-surgical cytology, and circumstances of the diagnosis. CONCLUSIONS Current risk stratification systems may be complemented by the inclusion of other variables in order to improve the prediction of treatment response. A complete dataset allows for more precise patient clustering.

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

Abstract: Introduction Care 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 design Registry-based cohort study including only people with rare head and neck cancers. Objectives to 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. Methods Settings 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. Results The 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.