Aspirin Colorectal Cancer Prevention in Lynch Syndrome: Recommendations in the Era of Precision Medicine

Cancer prevention in the era of precision medicine has to consider integrated therapeutic approaches. Therapeutic cancer prevention should be offered to selected cohorts with increased cancer risk. Undoubtedly, carriers of hereditary cancer syndromes have a well-defined high cancer risk. Lynch Syndrome is one of the most frequent hereditary syndromes; it is mainly associated with colorectal cancer (CRC). Nonsteroidal anti-inflammatory drugs and, in particular, aspirin use, has been associated with reduced CRC risk in several studies, initially with contradictory results; however, longer follow-up confirmed a reduced CRC incidence and mortality. The CAPP2 study recruited 861 Lynch syndrome participants randomly assigned to 600 mg of aspirin versus placebo. Like sporadic CRCs, a significant CRC risk reduction was seen after an extended follow-up, with a median treatment time that was relatively short (2 years). The ongoing CAPP3 will address whether lower doses are equally effective. Based on pharmacology and clinical data on sporadic CRCs, the preventive effect should also be obtained with low-dose aspirin. The leading international guidelines suggest discussing with Lynch syndrome carriers the possibility of using low-dose aspirin for CRC prevention. We aim systematically promote this intervention with all Lynch syndrome carriers

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

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 1.To help describe the natural history of rare head and neck cancers; 2.To evaluate factors that influence prognosis; 3.To assess treatment effectiveness; 4.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

Wideband 2-D sparse array optimization combined with multiline reception for real-time 3-D medical ultrasound

Three-dimensional (3-D) ultrasound medical imaging provides advantages over a traditional 2-D visualization method. However, the use of a 2-D array to acquire 3-D images may result in a transducer composed of thousands of elements and a large amount of data in the front-end, making it impractical to implement high volume rate imaging and individually control all elements with the scanner. This paper proposes an original approach, valid for wideband operations centered on the design center frequency, to maintain a limited number of active elements and firing events, while preserving high resolution and volume rate. A 7 MHz 2-D array is composed of two circular concentric subparts. In the inner footprint the elements are distributed following a regular grid, while in the outer subpart a sparse non-grid solution is adopted. The inner circular dense array is composed of 256 elements with a pitch of 0.5\u3bb. The overall footprint, delimited by the outer subpart, is equivalent to a 256-element array with a pitch of 1.5\u3bb. All the elements of the inner subpart are activated in transmission. Following an optimization procedure, both subparts, including a subset of the elements placed in the inner footprint (i.e., sparse on-the-grid array) and the elements spread over the outer subpart (i.e., sparse off-the-grid array) are used to receive. A total number of 256 elements, defined by the sum of elements distributed in the inner and outer subparts, is fixed in reception. The proposed approach implies a multiline reception strategy, where for each transmission 3 7 3 firing events occur in reception. The sparse receive array is optimized by using a simulated annealing optimization. An original cost function is designed specifically to achieve successful results in wideband conditions. The receive array is optimized in order to obtain consistent results for different signal bandwidths of the excitation pulse. For all the desired bandwidths, the optimized array will provide the recovery of the lower lateral resolution of the transmission phase and, at the same time, a significant reduction of the undesired side lobe raised in the 3-D two-way beam pattern. The 3-D two-way beam pattern analysis reveals that the proposed solution is able to guarantee a lateral resolution of 1.35 mm at a focus depth of 25 mm for the three fractional signal bandwidths of interest (i.e., 30%, 50% and 70%) considered in the optimization process. The undesired side lobes are successfully suppressed especially when, as a consequence of the multiline strategy, non-coincident steering angles are used in transmission and reception. Moreover, thanks to the firing scheme adopted, a high-volume rate of 63 volumes per second may be achieved at the focus depth. The volume rate decreases to 32 volumes per second at twice the focal depth. Phantom image simulations show that the proposed method maintains a satisfactory and almost uniform image quality in terms of resolution and contrast for all the signal bandwidths of interest