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Simple Summary: Oral cancer is among the twenty most common cancers worldwide. Finding and treating this cancer early improves survival rates. Screening the whole population to check for oral cancer is unlikely to be an efficient use of resources; however, screening only individuals at higher risk has been shown to reduce oral cancer deaths and be cost-effective for healthcare services. Mathematical models have previously been developed to identify these high-risk groups; however, it is not known whether any of these would be suitable for use in clinical practice. In this study, we identified and compared previously published models. We found several that had potential, but only two had been tested outside the original study population. We suggest that future research should focus on (a) testing how well the models identify those at high risk within potential screening populations and (b) assessing how the models might be included within the healthcare systems. In the last 30 years, there has been an increasing incidence of oral cancer worldwide. Earlier detection of oral cancer has been shown to improve survival rates. However, given the relatively low prevalence of this disease, population-wide screening is likely to be inefficient. Risk prediction models could be used to target screening to those at highest risk or to select individuals for preventative interventions. This review (a) systematically identified published models that predict the development of oral cancer and are suitable for use in the general population and (b) described and compared the identified models, focusing on their development, including risk factors, performance and applicability to risk-stratified screening. A search was carried out in November 2022 in the Medline, Embase and Cochrane Library databases to identify primary research papers that report the development or validation of models predicting the risk of developing oral cancer (cancers of the oral cavity or oropharynx). The PROBAST tool was used to evaluate the risk of bias in the identified studies and the applicability of the models they describe. The search identified 11,222 articles, of which 14 studies (describing 23 models), satisfied the eligibility criteria of this review. The most commonly included risk factors were age (n = 20), alcohol consumption (n = 18) and smoking (n = 17). Six of the included models incorporated genetic information and three used biomarkers as predictors. Including information on human papillomavirus status was shown to improve model performance; however, this was only included in a small number of models. Most of the identified models (n = 13) showed good or excellent discrimination (AUROC > 0.7). Only fourteen models had been validated and only two of these validations were carried out in populations distinct from the model development population (external validation). Conclusions: Several risk prediction models have been identified that could be used to identify individuals at the highest risk of oral cancer within the context of screening programmes. However, external validation of these models in the target population is required, and, subsequently, an assessment of the feasibility of implementation with a risk-stratified screening programme for oral cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic neuroendocrine tumors (PanNETs) and lung NETs (LNETs) have garnered increased attention in recent years due to their diverse clinical manifestations and challenging management. Although the vast majority of both PanNETs and LNETs are sporadic, they can also occur in the context of inherited syndromes that necessitate a high index of suspicion as the course of the disease is different and there are additional clinical implications for other family members. Our systematic review encompasses studies conducted over the past decade, focusing on the incidence, diagnosis, and treatment of PanNETs and/or LNETs encountered in hereditary syndromes such as Multiple Endocrine Neoplasia type 1 (MEN1), MEN4, von Hippel–Lindau (VHL), Tuberous Sclerosis Complex (TSC), and Neurofibromatosis type 1 (NF1). We discuss the importance of early detection and tailored management strategies, emphasizing the need for multidisciplinary collaboration among relevant healthcare professionals to optimize patients' outcomes. Moreover, we highlight the importance of active surveillance strategies for early tumor detection in high-risk individuals and the evolving landscape of personalized medicine for targeted intervention. Pancreatic neuroendocrine tumors (PanNETs) and lung NETs (LNETs) represent a rare but clinically significant subgroup of neoplasms. While the majority is sporadic, approximately 17% of PanNETs and a subset of LNETs develop in the context of monogenic familial tumor syndromes, especially multiple endocrine neoplasia type 1 (MEN1) syndrome. Other inherited syndromes associated with PanNETs include MEN4, von Hippel–Lindau (VHL) syndrome, neurofibromatosis type 1 (NF1), and tuberous sclerosis complex (TSC). These syndromes are highly penetrant and their clinical manifestations may vary even among members of the same family. They are attributed to genetic mutations involving key molecular pathways regulating cell growth, differentiation, and angiogenesis. Pancreatic NETs in hereditary syndromes are often multiple, develop at a younger age compared to sporadic tumors, and are associated with endocrine and nonendocrine tumors derived from multiple organs. Lung NETs are not as common as PanNETs and are mostly encountered in MEN1 syndrome and include typical and atypical lung carcinoids. Early detection of PanNETs and LNETs related to inherited syndromes is crucial, and specific follow-up protocols need to be employed to optimize diagnosis and management. Genetic screening is recommended in childhood, and diagnostic screening starts often in adolescence, even in asymptomatic mutation carriers. Optimal management and therapeutic decisions should be made in the context of a multidisciplinary team in specialized centers, whereas specific biomarkers aiming to identify patients denoted to follow a more aggressive course need to be developed. [ABSTRACT FROM AUTHOR]

Simple Summary: In a comprehensive analysis of phase 3 clinical trials, including the two FLAIR sub-studies, ECOG1912, and the CLL13 trials, we assessed the impact of first-line treatments with targeted agents (TAs), or fludarabine, cyclophosphamide, and rituximab (FCR)-based chemo-immunotherapy (CIT), on overall survival (OS) compared to age- and sex-matched individuals in the general population. TAs demonstrated a higher 5-year restricted mean survival time (RMST) (58.1 months; 95% CI: 57.4 to 58.8) compared to CIT (5-year RMST, 56.9 months; 95% CI: 56.7–58.2). Moreover, the comparison with age- and gender-matched general populations (AGMGP) suggested that TAs may mitigate CLL's impact on OS during the first five years post-treatment initiation. In contrast, CLL patients treated with FCR exhibited sustained OS differences compared to both the Italian and US AGMGP cohorts. These results support TAs as the preferred first-line treatment for younger/fit CLL patients but imply the need for a careful interpretation due to variations in patient selection criteria and clinical profiles across trials. Longer follow-up is essential to assess the survival improvement of younger CLL patients treated with TAs relative to the AGMGP. To assess the impact of first-line treatment with targeted agents (TAs) or fludarabine, cyclophosphamide, and rituximab (FCR)-based chemo-immunotherapy (CIT) on overall survival (OS) compared to age- and sex-matched individuals in the general population, we conducted an aggregated analysis of phase 3 clinical trials, including the two FLAIR sub-studies, ECOG1912, and CLL13 trials. The restricted mean survival time (RMST), an alternative measure in outcome analyses capturing OS changes over the entire history of the disease, was used to minimize biases associated with the short follow-up time of trials. Patients treated with TAs demonstrated a higher 5-year RMST (58.1 months; 95% CI: 57.4 to 58.8) compared to those treated with CIT (5-year RMST, 56.9 months; 95% CI: 56.7–58.2). Furthermore, the OS comparison of treatment groups with the AGMGP suggests that TAs may mitigate the impact of CLL on OS during the first five years post-treatment initiation. In summary, the 5-year RMST difference was −0.4 months (95% CI: −0.8 to 0.2; p = 0.10) when comparing CLL patients treated with TAs to the Italian age- and gender-matched general population (AGMGP). A similar trend was observed when CLL patients treated with TAs were compared to the US AGMGP (5-year RMST difference, 0.3 months; 95% CI: −0.1 to 0.9; p = 0.12). In contrast, CLL patients treated with FCR exhibited sustained OS differences when compared to both the Italian cohort (5-year RMST difference: −1.6 months; 95% CI: −2.4 to −0.9; p < 0.0001) and the US AGMGP cohort (5-year RMST difference: −0.9 months; 95% CI: −1.7 to −0.2; p = 0.015). Although these results support TAs as the preferred first-line treatment for younger CLL patients, it is crucial to acknowledge that variations in patient selection criteria and clinical profiles across clinical trials necessitate a cautious interpretation of these findings that should be viewed as directional and hypothesis-generating. A longer follow-up is needed to assess the survival improvement of younger CLL patients treated with TAs relative to the AGMGP. [ABSTRACT FROM AUTHOR]

Simple Summary: With ageing, the number of pancreaticoduodenectomies (PD) for benign or malignant disease is expected to increase in elderly patients. The aim of the present meta-analysis is to compare the surgical outcomes of MIPD in elderly versus younger patients. The results of our analysis disclose no considerable differences in terms of technical and post-operative outcomes between the two groups. However, slightly higher, but acceptable, major complication and mortality rates were recorded in the elderly cohort. Although the real additional value of minimally invasive surgery in this frailty subset of patients needs to be further investigated, our findings reveal that MIPD seems to be relatively safe and feasible in elderly patients. (1) Background: With ageing, the number of pancreaticoduodenectomies (PD) for benign or malignant disease is expected to increase in elderly patients. However, whether minimally invasive pancreaticoduodenectomy (MIPD) should be performed in the elderly is not clear yet and it is still debated. (2) Materials and Methods: A systematic review and meta-analysis was conducted including seven published articles comparing the technical and post-operative outcomes of MIPD in elderly versus younger patients up to December 2022. (3) Results: In total, 1378 patients were included in the meta-analysis. In term of overall and Clavien–Dindo I/II complication rates, post-operative pancreatic fistula (POPF) grade > A rates and biliary leakage, abdominal collection, post-operative bleeding and delayed gastric emptying rates, no differences emerged between the two groups. However, this study showed slightly higher intraoperative blood loss [MD 43.41, (95%CI 14.45, 72.38) p = 0.003], Clavien–Dindo ≥ III complication rates [OR 1.87, (95%CI 1.13, 3.11) p = 0.02] and mortality rates [OR 2.61, (95%CI 1.20, 5.68) p = 0.02] in the elderly compared with the younger group. Interestingly, as a minor endpoint, no differences in terms of the mean number of harvested lymphnode and of R0 resection rates were found. (4) Conclusion: MIPD seems to be relatively safe; however, there are slightly higher major morbidity, lung complication and mortality rates in elderly patients, who potentially represent the individuals that may benefit the most from the minimally invasive approach. [ABSTRACT FROM AUTHOR]