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Simple Summary: This position paper aims to address specific clinical questions regarding the use of cyclin-dependent kinase 4/6 inhibitors in elderly patients with early or advanced breast cancer. Its objectives are to delineate the current state of knowledge regarding the efficacy of these treatments in the elderly population and their tolerance profile, including the impact on quality of life, with a particular focus on the frailest subgroups, and to attempt to define the optimal treatment strategy for elderly and fragile patients (dosage and therapeutic sequence). Background: Breast cancer (BC) incidence increases with age, particularly in HR-positive/HER2-negative subtypes. Cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6is) alongside endocrine therapy (ET) have emerged as promising treatments for HR-positive/HER2-negative advanced and early BC. However, their efficacy, safety, and impact on quality of life (QoL) in older and frail patients remain underexplored. Methods: This position paper assesses the existing literature from 2015 to 2024, focusing on CDK4/6is use in patients aged 65 years and older with HR-positive/HER2-negative BC. Results: Our analysis methodically addresses critical questions regarding the utilization of CDK4/6is in the elderly BC patient population, organizing findings from the metastatic and adjuvant settings. In the metastatic setting, CDK4/6is significantly improve progression-free survival (PFS), paralleling benefits observed in younger patients, and suggest potential overall survival (OS) benefits, warranting further investigation. Despite an increased incidence of grade ≥ 3 adverse events (AEs), such as neutropenia and asthenia, CDK4/6is present a markedly lower toxicity profile compared to traditional chemotherapy, with manageable side effects. QoL analysis indicates that integrating CDK4/6is into treatment regimens does not significantly impact elderly BC patients' daily life and symptom management. Special attention is given to frail subgroups, and personalized approaches are recommended to balance efficacy and adverse effects, such as starting with ET alone and introducing CDK4/6is upon progression in patients with a low disease burden. Transitioning to the adjuvant setting, early results, particularly with abemaciclib, indicate positive effects on disease-free survival (DFS), emphasizing the need for continued analysis to validate these findings and assess long-term implications. However, data on older patients are insufficient to conclude whether they truly benefit from this treatment. Conclusion: Overall, CDK4/6is present a favorable benefit-risk profile in older BC patients, at least in advanced BC; however, further research is warranted to optimize treatment strategies and improve outcomes in this population [ABSTRACT FROM AUTHOR]

Simple Summary: Among the various options for urinary diversion following radical cystectomy, the orthotopic neobladder most closely resembles the original bladder both in location and function. However, a significant number of patients with these reservoirs have dysfunctional voiding. Our objective here is to provide the first systematic review focusing on the urodynamic and continence outcomes of ileal orthotopic neobladders. By summarising these important outcomes, the current paper may represent the reference manuscript for outcome comparison in future papers. The manuscript also describes the methodology of the urodynamic evaluation of the neobladders, highlighting the frequent lack of precise indications, accurate guidelines (at the state of the art, the same parameters used for the native bladder are also used for the ileal neobladders), standardised definitions, and standard values for outcome comparison. By underlining these gaps, our systematic review may aid future studies in having more adequate designs and will allow for a more accurate functional evaluation of the patients harbouring an ileal neobladder. Introduction: The orthotopic neobladder is the type of urinary diversion (UD) that most closely resembles the original bladder. However, in the literature the urodynamic aspects are scarcely analysed. Objective: To provide the first systematic review (SR) on the urodynamic (UDS) outcomes of the ileal orthotopic neobladders (ONB). Continence outcomes are also presented. Methods: A PubMed, Embase and Cochrane CENTRAL search for peer-reviewed studies on ONB published between January 2001–December 2022 was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Results and Conclusion: Fifty-nine manuscripts were eligible for inclusion in this SR. A great heterogeneity of data was encountered. Concerning UDS parameters, the pooled mean was 406.2 mL (95% CI: 378.9–433.4 mL) for maximal (entero)cystometric capacity (MCC) and 21.4 cmH2O (95% CI: 17.5–25.4 cmH2O) for Pressure ONB at MCC. Postvoid-residual ranged between 4.9 and 101.6 mL. The 12-mo rates of day and night-time continence were 84.2% (95% CI: 78.7–89.1%) and 61.7% (95% CI: 51.9–71.1%), respectively.Despite data heterogeneity, the ileal ONB seems to guarantee UDS parameters that resemble those of the native bladder. Although acceptable rates of daytime continence are reported the issue of high rates of night-time incontinence remains unsolved. Adequately designed prospective trials adopting standardised postoperative care, terminology and methods of outcome evaluation as well as of conduction of the UDS in the setting of ONB are necessary to obtain homogeneous follow-up data and to establish UDS guidelines for this setting. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer is the second most frequent gynecological cancer in Western countries and the most common cause of death due to gynecological malignancies with an estimated five-year survival rate of 39%. The high aggressiveness and mortality are mainly related to the speed of abdominal spread: 70% of patients are diagnosed at an advanced stage of disease (stage III–IV FIGO) or in the presence of peritoneal carcinomatosis (PC), and about 60% of women will develop a recurrence. In this context, imaging plays an essential role for proper staging and follow-up and in selecting patients eligible for complete cytoreduction (CCR), the most important treatment and prognostic factor for patients. PC represents the most striking picture of the loco-regional spread of ovarian cancer, configuring stage III. In the last few years, many papers have evaluated the role of imaging and therapeutic management in patients with ovarian cancer and PC. This paper summed up the literature on traditional approaches to the imaging of peritoneal carcinomatosis in advanced ovarian cancer, presenting classification systems, most frequent patterns, routes of spread and sites that are difficult to identify. The role of imaging in diagnosis was investigated, with particular attention to the reported sensitivity and specificity data—computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-CT (PET-CT)—and to the peritoneal cancer index (PCI). In addition, we explored the therapeutic possibilities and radiomics applications that can impact management of patients with ovarian cancer. Careful staging is mandatory, and patient selection is one of the most important factors influencing complete cytoreduction (CCR) outcome: an accurate pre-operative imaging may allow selection of patients that may benefit most from primary cytoreductive surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, after conducting a comprehensive review of 1356 papers that evaluated the diagnostic performance of deep learning (DL) methods based on medical images for hepatocellular carcinoma (HCC), the findings showed a pooled sensitivity of 89% (95% CI: 87–91), a specificity of 90% (95% CI: 87–92), and an AUC of 0.95 (95% CI: 0.93–0.97). In addition, both the DL methods and human clinicians demonstrated similar levels of performance in HCC detection, with receiver operating characteristic curve (ROC) values of 0.97 (95% CI: 0.95–0.98) for both groups, indicating no discernible difference. Although the heterogeneity was obvious, the utilization of DL methods for diagnosing HCC through medical images has shown promising outcomes. (1) Background: The aim of our research was to systematically review papers specifically focused on the hepatocellular carcinoma (HCC) diagnostic performance of DL methods based on medical images. (2) Materials: To identify related studies, a comprehensive search was conducted in prominent databases, including Embase, IEEE, PubMed, Web of Science, and the Cochrane Library. The search was limited to studies published before 3 July 2023. The inclusion criteria consisted of studies that either developed or utilized DL methods to diagnose HCC using medical images. To extract data, binary information on diagnostic accuracy was collected to determine the outcomes of interest, namely, the sensitivity, specificity, and area under the curve (AUC). (3) Results: Among the forty-eight initially identified eligible studies, thirty studies were included in the meta-analysis. The pooled sensitivity was 89% (95% CI: 87–91), the specificity was 90% (95% CI: 87–92), and the AUC was 0.95 (95% CI: 0.93–0.97). Analyses of subgroups based on medical image methods (contrast-enhanced and non-contrast-enhanced images), imaging modalities (ultrasound, magnetic resonance imaging, and computed tomography), and comparisons between DL methods and clinicians consistently showed the acceptable diagnostic performance of DL models. The publication bias and high heterogeneity observed between studies and subgroups can potentially result in an overestimation of the diagnostic accuracy of DL methods in medical imaging. (4) Conclusions: To improve future studies, it would be advantageous to establish more rigorous reporting standards that specifically address the challenges associated with DL research in this particular field. [ABSTRACT FROM AUTHOR]

Simple Summary: Downstaging therapies provides a viable alternative approach for expanding the MC limits and selecting a subgroup of patients whose LT candidacy would otherwise be disregarded. However, data on downstaging are still controversial due to a variety of reasons, such as differences in LRT, the wide variability in waiting time before LT and, particularly, the lack of intention-to-treat (ITT) analyses. This article is a systematic review and intends to synthesise the existing evidence about the effectiveness of downstaging therapies, aiming to: (a) assess outcomes from ITT analysis of patients with liver cirrhosis and HCC beyond the listing criteria and selected for downstaging protocol, in comparison with HCC within the listing criteria; (b) evaluate outcomes of patients with liver cirrhosis HCC beyond the listing criteria successfully downstaged and transplanted versus those not transplanted. Background: Locoregional therapies (LRTs) are commonly used to increase the number of potential candidates for liver transplantation (LT). The aim of this paper is to assess the outcomes of LRTs prior to LT in patients with hepatocellular carcinoma (HCC) beyond the listing criteria. Methods: In accordance with the PRISMA guidelines, we searched the Medline and Web of Science databases for reports published before May 2021. We included papers assessing adult patients with HCC considered for LT and reporting intention-to-treat (ITT) survival outcomes. Two reviewers independently identified and extracted the data and evaluated the papers. Outcomes analysed were drop-out rate; time on the waiting list; and 1, 3 and 5 year survival after LT and based on an ITT analysis. Results: The literature search yielded 3,106 records, of which 11 papers (1874 patients) met the inclusion criteria. Patients with HCC beyond the listing criteria and successfully downstaged presented a higher drop-out rate (OR 2.05, 95% CI 1.45–2.88, p < 0.001) and a longer time from the initial assessment to LT than those with HCC within the listing criteria (MD 1.93, 95% CI 0.91–2.94, p < 0.001). The 1, 3 and 5 year survival post-LT and based on an ITT analysis did not show significant differences between the two groups. Patients with HCC beyond the listing criteria, successfully downstaged and then transplanted, presented longer 3 year (OR 3.77, 95% CI 1.26–11.32, p = 0.02) and 5 year overall survival (OS) (OR 3.08, 95% CI 1.15–8.23, p = 0.02) in comparison with those that were not submitted to LT. Conclusions: Patients with HCC beyond the listing criteria undergoing downstaging presented a higher drop-out rate in comparison with those with HCC within the listing criteria. However, the two groups did not present significant differences in 1, 3 and 5 year survival rates based on an ITT analysis. Patients with HCC beyond the listing, when successfully downstaged and transplanted, presented longer 3 and 5-year OS in comparison with those who were not transplanted. [ABSTRACT FROM AUTHOR]

Simple Summary: Completion lobectomy (CL) entails the resection of the remaining pulmonary lobe subsequent to wedge resection or segmentectomy. Indications for CL include reoperations for multiple or relapsed lung cancers and metastatic lung tumors, and the prognostic advantage of these procedures has been widely reported. However, ipsilateral surgical treatments, particularly within the same lobe, present challenges due to the development of intrapleural adhesions, rendering reoperation more difficult and time-consuming. VATS has emerged as the gold standard in the surgical treatment of early-stage NSCLC, offering superior postoperative outcomes when compared to thoracotomy. Its efficacy has been well established, even during complex procedures. However, its application in ipsilateral reoperations remains anecdotal, and to the best of our knowledge, no studies have analyzed the safety and efficacy of uniportal-VATS in this setting. This paper aims to evaluate the role of iniportal-VATS in CL long after wedge resection or anatomical segmentectomy in the same lobe. Background: Completion lobectomy (CL) following a prior resection in the same lobe may be complicated by severe pleural or hilar adhesions. The role of uniportal video-assisted thoracoscopic surgery (U-VATS) has never been evaluated in this setting. Methods: Data were collected from two Italian centers. Between 2015 and 2022, 122 patients (60 men and 62 women, median age 67.7 ± 8.913) underwent U-VATS CL at least 4 weeks after previous lung surgery. Results: Twenty-eight (22.9%) patients were affected by chronic obstructive pulmonary disease (COPD) and twenty-five (20.4%) were active smokers. Among the cohort, the initial surgery was performed using U-VATS in 103 (84.4%) patients, triportal-VATS in 8 (6.6%), and thoracotomy in 11 (9.0%). Anatomical segmentectomy was the initial surgery in 46 (37.7%) patients, while hilar lymphadenectomy was performed in 16 (13.1%) cases. CL was performed on 110 (90.2%) patients, segmentectomy on 10 (8.2%), and completion pneumonectomy on 2 (1.6%). Upon reoperation, moderate pleural adhesions were observed in 38 (31.1%) patients, with 2 (1.6%) exhibiting strong adhesions. Moderate hilar adhesions were found in 18 (14.8%) patients and strong adhesions in 11 (9.0%). The median operative time was 203.93 ± 74.4 min. In four (3.3%) patients, PA taping was performed. One patient experienced intraoperative bleeding that did not require conversion to thoracotomy. Conversion to thoracotomy was necessary in three (2.5%) patients. The median postoperative drainage stay and postoperative hospital stay were 5.67 ± 4.44 and 5.52 ± 2.66 days, respectively. Postoperative complications occurred in 34 (27.9%) patients. Thirty-day mortality was null. Histology was the only factor found to negatively influence intraoperative outcomes (p = 0.000). Factors identified as negatively impacting postoperative outcomes at univariate analyses were male sex (p = 0.003), age > 60 years (p = 0.003), COPD (p = 0.014), previous thoracotomy (p = 0.000), previous S2 segmentectomy (p = 0.001), previous S8 segmentectomy (p = 0.008), and interval between operations > 5 weeks (p= 0.005). In multivariate analysis, only COPD confirmed its role as an independent risk factor for postoperative complications (HR: 5.12, 95% CI (1.07–24.50), p = 0.04). Conclusions: U-VATS CL seems feasible and safe after wedge resection and anatomical segmentectomy. [ABSTRACT FROM AUTHOR]

Simple Summary: Percutaneous cryoablation (PCA) is a minimally invasive procedure that should be considered in comorbid patients with stage T1 renal tumours who are suboptimal candidates for partial nephrectomy (PN). However, there is a scarcity of scientific data regarding the efficacy of PCA. The aim of this meta-analysis was to compare PCA and PN in terms of complications, renal function and survival outcomes. According to this analysis, PCA is associated with fewer complications than PN. Moreover, in tumours up to 4 cm, it provides the same time without local recurrence. Therefore, PCA should be proposed to patients with cT1 renal tumours who are not fit for PN but want to undergo a radical treatment. Percutaneous cryoablation (PCA) can be an alternative to partial nephrectomy (PN) in selected patients with stage T1 renal tumours. Existing meta-analyses regarding ablative techniques compared both laparoscopic and PCA with PN. That is why we decided to perform a meta-analysis that focused solely on PCA. The aim of this study was to compare the complications and functional and oncological outcomes between PCA and PN. A systematic literature search was performed in January 2024. Data for dichotomous and continuous variables were expressed as pooled odds ratios (ORs) and mean differences (MDs), both with 95% confidence intervals (CIs). Effect measures for the local recurrence-free survival (LRFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) were expressed as pooled hazard ratios with 95% CIs. Among 6487 patients included in the 14 selected papers, 1554 (23.9%) and 4924 (76.1%) underwent PCA and PN, respectively. Compared with the PN group, patients undergoing PCA had significantly lower overall and major postoperative complication rates. There was no difference in renal function between PCA and PN groups. When analysing collective data for cT1 renal carcinoma, PCA was associated with worse LRFS compared with PN. However, subgroup analysis revealed that in the case of PCA, LRFS was not decreased in patients with cT1a tumours. Moreover, patients undergoing robotic-assisted PN had improved LRFS compared with those undergoing PCA. No significant differences were observed between PCA and PN in terms of MFS and CSS. Finally, PCA was associated with worse OS than PN in both collective and subgroup analyses. In conclusion, PCA is associated with favourable postoperative complication rates relative to PN. Regarding LRFS, PCA is not worse than PN in cT1a tumours but has a substantially relevant disadvantage in cT1b tumours. Also, RAPN might be the only surgical modality that provides better LRFS than PCA. In cT1 tumours, PCA shows MFS and CSS comparable to PN. Lastly, PCA is associated with a shorter OS than PN. [ABSTRACT FROM AUTHOR]

Simple Summary: The cornerstone of successful treatment of hematologic diseases, including multiple myeloma (MM), is early diagnosis and establishing a prognosis for the patient. Therefore, it is necessary to identify sensitive and specific markers for this disease. Non-coding RNAs including miRNAs are increasingly being recognized as potential diagnostic, predictive, and prognostic markers. These molecules are non-coding, single-stranded RNAs that regulate the expression of many target genes involved in key biological processes, such as cell proliferation, differentiation, and apoptosis. This paper aims to identify the role of non-coding RNAs including miRNAs as potential markers for diagnosis and prognosis in patients with MM. Multiple myeloma (MM) is the second most common hematologic malignancy in the world and accounts for 15% of primary hemocytopathies, with an ever-increasing number of new cases. It is asymptomatic in 30% of instances; hence, the determination of highly sensitive and specific markers is necessary to make a proper diagnosis. In the last 20 years, miRNAs, involved in regulating the expression of genes responsible for cell proliferation and differentiation, including tumor cells, have been identified as potential diagnostic and prognostic markers. The main aim of the following review was to outline the role of miRNAs in the diagnosis and prognosis of MM, considering their role in the pathogenesis of the disease and identifying their target genes and pathways. For this purpose, publications dating from 2013–2023 have been reviewed. Based on the available data, it is concluded that non-coding RNAs including miRNAs could be potential markers in MM. Furthermore, they may serve as therapeutic targets for certain drugs. [ABSTRACT FROM AUTHOR]

Simple Summary: Preoperative mediastinal staging plays a crucial role in determining the appropriate treatment strategy for patients with stage IIIA-N2 disease, but an optimal treatment strategy has yet to be established. Invasive mediastinal staging is indicated in approximately 30% of patients with suspected NSCLC. In general, if proven N2 disease is present, induction therapy is prioritized in order to downstage and achieve a better prognosis. In the absence of N2 disease, surgical resection with mediastinal lymphadenectomy is the most appropriate treatment option. Nevertheless, unforeseen N2 (uN2) disease, also called unexpected or surprise N2, can still be found during or after surgery despite current preoperative mediastinal staging showing N0 or N1 disease. As preoperative mediastinal staging improved over time, the prevalence of uN2 changed. The aim of this study is to determine the prevalence of true uN2 disease and its characteristics. A secondary objective is to identify its significance for long-term outcomes. Patients with unforeseen N2 (uN2) disease are traditionally considered to have an unfavorable prognosis. As preoperative and intraoperative mediastinal staging improved over time, the prevalence of uN2 changed. In this review, the current evidence on uN2 disease and its prevalence will be evaluated. A systematic literature search was performed to identify all studies or completed, published trials that included uN2 disease until 6 April 2023, without language restrictions. The Newcastle-Ottawa Scale (NOS) was used to score the included papers. A total of 512 articles were initially identified, of which a total of 22 studies met the predefined inclusion criteria. Despite adequate mediastinal staging, the pooled prevalence of true unforeseen pN2 (9387 patients) was 7.97% (95% CI 6.67–9.27%), with a pooled OS after five years (892 patients) of 44% (95% CI 31–58%). Substantial heterogeneity regarding the characteristics of uN2 disease limited our meta-analysis considerably. However, it seems patients with uN2 disease represent a subcategory with a similar prognosis to stage IIb if complete surgical resection can be achieved, and the contribution of adjuvant therapy is to be further explored. [ABSTRACT FROM AUTHOR]

Simple Summary: US-MRI fusion biopsy is established as a technique of reference for the detection of clinically significative prostate cancer compared to the ultrasound "template" technique. Several software have been developed to aid clinicians to perform a real-time fusion between MRI and US prostate imaging; however, the images can also be mentally superimposed by the operator performing a cognitive fusion. Many papers in the literature describe the feasibility and efficacy of these two techniques, but few have performed a direct comparison between them. Therefore, we selected all comparative studies with the aim to perform a meta-analysis to find if one technique leads to an improvement in the detection rate of clinically significant prostate cancer (csPCa) for biopsies performed with a transperineal approach. Our findings indicate that csPCa detection is comparable between these techniques. Thus, clinicians can choose to perform a cognitive or software-assisted biopsy in accordance with their personal experience or technologic availability without the potential risk of offering an underperforming methodology. Introduction: We aimed to find potential differences in clinically significant prostate cancer (csPCa) detection rates between transperineal software-assisted fusion biopsy (saFB) and cognitive fusion biopsies (cFB). Methods: A systematic review of the literature was performed to identify comparative studies using PubMed, EMBASE, and Scopus according to the PICOS criteria. Cancer detection and complication rates were pooled using the Cochran–Mantel–Haenszel method with the random effect model and reported as odds ratios (ORs), 95% confidence intervals (CI), and p-values. A meta-analysis was performed using Review Manager (RevMan) 5.4 software by Cochrane Collaboration. The quality assessment of the included studies was performed using the Cochrane Risk of Bias tool, using RoB 2 for randomized studies and ROBINS-I for retrospective and nonrandomized ones. Results: Eight studies were included for the meta-analysis, including 1149 cases in software-based and 963 cases in cognitive fusion biopsy. The detection rates of csPCa were similar between the two groups (OR 1.01, 95% CI 0.74–1.37, p = 0.95). Study heterogeneity was low (I2 55%). Conclusion: There is no actual evidence of the superiority of saFB over cFB in terms of the csPCa detection rate. Operator experience and software availability can drive the choice of one fusion technique over the other. [ABSTRACT FROM AUTHOR]

Simple Summary: There are no effective treatments for patients with cancers that induce airway narrowing via extrinsic pressure to the bronchus (i.e., extrinsic malignant central airway obstruction—MCAO). The effects of these cancerous tumors must be quickly alleviated to allow normal breathing and delay disease progression. Currently, stents are used to keep the airway open, but stents do not halt the progression of the cancerous tumor that can crush the stent. We have shown that interstitial photodynamic therapy (I-PDT) can be a safe and beneficial treatment option for patients with extrinsic MCAO. Image-based pre-treatment planning is critical for patient safety and tumor response in I-PDT. Herein, we present and validate novel image-based computer optimization methods for guiding light administration in I-PDT of extrinsic MCAO, based on a rate-based light dose metric. We demonstrate the benefit of our approach in data from representative patients with extrinsic MCAO who were treated with I-PDT. There are no effective treatments for patients with extrinsic malignant central airway obstruction (MCAO). In a recent clinical study, we demonstrated that interstitial photodynamic therapy (I-PDT) is a safe and potentially effective treatment for patients with extrinsic MCAO. In previous preclinical studies, we reported that a minimum light irradiance and fluence should be maintained within a significant volume of the target tumor to obtain an effective PDT response. In this paper, we present a computational approach to personalized treatment planning of light delivery in I-PDT that simultaneously optimizes the delivered irradiance and fluence using finite element method (FEM) solvers of either Comsol Multiphysics® or Dosie™ for light propagation. The FEM simulations were validated with light dosimetry measurements in a solid phantom with tissue-like optical properties. The agreement between the treatment plans generated by two FEMs was tested using typical imaging data from four patients with extrinsic MCAO treated with I-PDT. The concordance correlation coefficient (CCC) and its 95% confidence interval (95% CI) were used to test the agreement between the simulation results and measurements, and between the two FEMs treatment plans. Dosie with CCC = 0.994 (95% CI, 0.953–0.996) and Comsol with CCC = 0.999 (95% CI, 0.985–0.999) showed excellent agreement with light measurements in the phantom. The CCC analysis showed very good agreement between Comsol and Dosie treatment plans for irradiance (95% CI, CCC: 0.996–0.999) and fluence (95% CI, CCC: 0.916–0.987) in using patients' data. In previous preclinical work, we demonstrated that effective I-PDT is associated with a computed light dose of ≥45 J/cm2 when the irradiance is ≥8.6 mW/cm2 (i.e., the effective rate-based light dose). In this paper, we show how to use Comsol and Dosie packages to optimize rate-based light dose, and we present Dosie's newly developed domination sub-maps method to improve the planning of the delivery of the effective rate-based light dose. We conclude that image-based treatment planning using Comsol or Dosie FEM-solvers is a valid approach to guide the light dosimetry in I-PDT of patients with MCAO. [ABSTRACT FROM AUTHOR]

Simple Summary: According to cancer research statistics, there are 7500 new ovarian cancer diagnoses in the UK each year. An earlier detection of ovarian cancer leads to a better prognosis; however, there is currently no screening programme for ovarian cancer, and detection using ultrasound examinations remains challenging. The use of artificial intelligence in gynaecological ultrasound examinations aims to improve the diagnostic accuracy of ultrasound for ovarian cancer and improve outcomes for patients. This review aims to collate current research on AI in the ultrasound diagnosis of ovarian cancer and suggests the usefulness of incorporating this into clinical care. Ovarian cancer is the sixth most common malignancy, with a 35% survival rate across all stages at 10 years. Ultrasound is widely used for ovarian tumour diagnosis, and accurate pre-operative diagnosis is essential for appropriate patient management. Artificial intelligence is an emerging field within gynaecology and has been shown to aid in the ultrasound diagnosis of ovarian cancers. For this study, Embase and MEDLINE databases were searched, and all original clinical studies that used artificial intelligence in ultrasound examinations for the diagnosis of ovarian malignancies were screened. Studies using histopathological findings as the standard were included. The diagnostic performance of each study was analysed, and all the diagnostic performances were pooled and assessed. The initial search identified 3726 papers, of which 63 were suitable for abstract screening. Fourteen studies that used artificial intelligence in ultrasound diagnoses of ovarian malignancies and had histopathological findings as a standard were included in the final analysis, each of which had different sample sizes and used different methods; these studies examined a combined total of 15,358 ultrasound images. The overall sensitivity was 81% (95% CI, 0.80–0.82), and specificity was 92% (95% CI, 0.92–0.93), indicating that artificial intelligence demonstrates good performance in ultrasound diagnoses of ovarian cancer. Further prospective work is required to further validate AI for its use in clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Vacuum-assisted breast biopsy (VABB) represents one of the best instruments for radiologists to obtain a histological diagnosis of suspicious lesions on imaging. The advent of digital breast tomosynthesis (DBT)-guided VABB has increased the accuracy of diagnosis in the most complex lesions, particularly those without ultrasound correlation or those visible only on DBT. In this paper, we retrospectively analyzed our experience with VABB. Starting from a review of the literature, we evaluated the challenges arising from clinical practice to provide useful indications for the implementation of this technique. We identified 37 breast cancers at an early stage with a low complication rate and high histopathological concordance between VABB and surgery. Compared to the literature, our results confirmed the fundamental role of DBT-VABB in achieving a timely diagnosis for nonpalpable lesions, offering a safe and minimally invasive approach when the technique is executed correctly. Vacuum-assisted breast biopsy (VABB) guided by digital breast tomosynthesis (DBT) represents one of the best instruments to obtain a histological diagnosis of suspicious lesions with no ultrasound correlation or those which are visible only on DBT. After a review of the literature, we retrospectively analyzed the DBT-guided VABBs performed from 2019 to 2022 at our department. Descriptive statistics, Pearson's correlation and χ2 test were used to compare distributions of age, breast density (BD) and early performance measures including histopathology. We used kappa statistics to evaluate the agreement between histological assessment and diagnosis. Finally, we compared our experience to the literature to provide indications for clinical practice. We included 85 women aged 41–84 years old. We identified 37 breast cancers (BC), 26 stage 0 and 11 stage IA. 67.5% of BC was diagnosed in women with high BD. The agreement between VABB and surgery was 0.92 (k value, 95% CI: 0.76–1.08). We found a statistically significant inverse correlation between age and BD. The post-procedural clip was correctly positioned in 88.2%. The post-procedural hematoma rate was 14.1%. No infection or hemorrhage were recorded. When executed correctly, DBT-guided VABB represents a safe and minimally invasive technique with high histopathological concordance, for detecting nonpalpable lesions without ultrasound correlation. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor gene (EGFR) Exon 20 insertion mutations (Exon20ins) used to have poor outcomes after the failure of platinum-based therapies. Amivantamab, a drug that targets two proteins involved in NSCLC (EGFR/MET), was developed and studied in the CHRYSALIS clinical trial. This paper summarizes an analysis comparing outcomes for amivantamab from CHRYSALIS to the outcomes for a mix of treatments that were used in real-world clinical practice (real-world physician's choice [RWPC]). RWPC data were collected from hospitals across Europe in the CATERPILLAR real-world evidence (RWE) study. The outcomes of 114 patients from CHRYSALIS were compared to 55 lines of treatment (LOTs) from CATERPILLAR-RWE, accounting for differences in patient characteristics between the two populations. Overall, the results show that amivantamab was at least twice as good as RWPC for platinum pre-treated patients in terms of tumor response and survival rates. Patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor gene (EGFR) Exon 20 insertions (Exon20ins) at the second line and beyond (2L+) have an unmet need for new treatment. Amivantamab, a bispecific EGFR- and MET-targeted antibody, demonstrated efficacy in this setting in the phase 1b, open-label CHRYSALIS trial (NCT02609776). The primary objective was to compare the efficacy of amivantamab to the choices made by real-world physicians (RWPC) using an external control cohort from the real-world evidence (RWE) chart review study, CATERPILLAR-RWE. Adjustment was conducted to address differences in prognostic variables between cohorts using inverse probability weighting (IPW) and covariate adjustments based on multivariable regression. In total, 114 patients from CHRYSALIS were compared for 55 lines of therapy from CATERPILLAR-RWE. Baseline characteristics were comparable between the amivantamab and IPW-weighted RWPC cohorts. For amivantamab versus RWPC using IPW adjustment, the response rate ratio for the overall response was 2.14 (p = 0.0181), and the progression-free survival (PFS), time-to-next-treatment (TTNT) and overall survival (OS) hazard ratios (HRs) were 0.42 (p < 0.0001), 0.47 (p = 0.0063) and 0.48 (p = 0.0207), respectively. These analyses provide evidence of clinical and statistical benefits across multiple outcomes and adjustment methods, of amivantamab in platinum pre-treated patients with advanced NSCLC harboring EGFR Exon20ins. These results confirm earlier comparisons versus pooled national registry data. [ABSTRACT FROM AUTHOR]

Simple Summary: The association between HPV and cancer has been the focus of research, but there has been a lack of a comprehensive high-level evidence studies to systematically examine the relationship between them. Using Mendelian randomization, this paper provided an extensive analysis of the causal effect of HPV in cancer development. Our study conclusively identified HPV16 as a risk factor implicated in the development of bladder cancer, colorectal cancer, and breast cancer, while HPV18 was identified as a risk factor for prostate cancer, ovarian cancer, lung cancer and breast cancer. The results of Mendelian randomization also showed that HPV16 may be a protective factor for prostate cancer, anal cancer, lung cancer and oropharyngeal cancer, while HPV18 may be a protective factor for vaginal cancer. Introduction: More and more studies have focused on the associations between human papillomavirus (HPV) infection and pan-cancers. However, current evidence is largely based on retrospective studies, which are susceptible to confounding factors and do not enable the establishment of causal relationships. Methods: A bidirectional two-sample Mendelian randomization (MR) design was employed to thoroughly evaluate the causal relationships between HPV and 12 site-specific cancers except cervical cancer. Single nucleoside polymers (SNPs) with strong evidence from genome-wide association studies (GWAS) were selected from HPV exposure datasets and used as instrumental variables (IVs) in this study. For the MR analysis results, MR-Egger's intercept P test, MR-PRESSO global test, Cochran's Q test and a leave-one-out test were applied for sensitivity analysis. Using HPVTIMER, we also performed immune infiltration analyses in head and neck squamous cell carcinoma (HNSCC), oropharyngeal squamous cell carcinoma (OPSCC) and vulval squamous cell carcinoma (VSCC) to evaluate the tumor-immune microenvironment. Results: Based on the evidence of MR analysis, our study conclusively identified HPV16 as a risk factor implicated in the development of bladder cancer, colorectal cancer, and breast cancer, while HPV18 was identified as a risk factor for prostate cancer, ovarian cancer, lung cancer and breast cancer. The MR results also showed that HPV16 may be a protective factor for prostate cancer, anal cancer, lung cancer and oropharyngeal cancer, while HPV18 may be a protective factor for vaginal cancer. Conclusion: An HPV infection may modulate the immune microenvironment and therefore has a potential inhibitory effect on the development of certain cancers. These conclusions provided new insights into the potential mechanisms of carcinogenesis and needed further research for validation. [ABSTRACT FROM AUTHOR]

Simple Summary: We provide an extensive review of the fundamental principles of statistical science that are needed to accurately interpret randomized controlled trials (RCTs). We use these principles to explain how RCTs are motivated by the powerful but strange idea that flipping a coin to choose each patient's treatment is the most statistically reliable way to compare treatments. Random treatment assignment ensures fair comparisons between treatments because it does away with bias and confounding from variables other than treatment. If the goal is to estimate treatment effects in a patient population, rather than compare two or more treatments, then random sampling, not random treatment assignment, is required. However, random sampling is virtually impossible to carry out in a clinical trial because patients are accrued over time as they arrive in the clinic, subject to a trial's entry criteria. Consequently, in practice, a trial provides a nonrepresentative convenience sample. Valid treatment comparisons provided by RCT data subsequently require additional causal assumptions of transportability of between-treatment effects from the sample to the patient population of interest. This may be used as a basis for choosing treatments for future patients. The present paper discusses what this means for practicing physicians who encounter RCT data in the literature. This article describes rationales and limitations for making inferences based on data from randomized controlled trials (RCTs). We argue that obtaining a representative random sample from a patient population is impossible for a clinical trial because patients are accrued sequentially over time and thus comprise a convenience sample, subject only to protocol entry criteria. Consequently, the trial's sample is unlikely to represent a definable patient population. We use causal diagrams to illustrate the difference between random allocation of interventions within a clinical trial sample and true simple or stratified random sampling, as executed in surveys. We argue that group-specific statistics, such as a median survival time estimate for a treatment arm in an RCT, have limited meaning as estimates of larger patient population parameters. In contrast, random allocation between interventions facilitates comparative causal inferences about between-treatment effects, such as hazard ratios or differences between probabilities of response. Comparative inferences also require the assumption of transportability from a clinical trial's convenience sample to a targeted patient population. We focus on the consequences and limitations of randomization procedures in order to clarify the distinctions between pairs of complementary concepts of fundamental importance to data science and RCT interpretation. These include internal and external validity, generalizability and transportability, uncertainty and variability, representativeness and inclusiveness, blocking and stratification, relevance and robustness, forward and reverse causal inference, intention to treat and per protocol analyses, and potential outcomes and counterfactuals. [ABSTRACT FROM AUTHOR]

Simple Summary: Large intestinal cancer is one of the most common lifestyle-related types of cancer. However, the exact mechanism in the relation between adipose tissue, systemic inflammation and intestinal cancer remains unknown. Furthermore, there are many hypotheses regarding the pathways in which alcohol consumption, smoking, malnutrition and physical inactivity cause low-grade systemic inflammation. In this paper, we discuss the relation of lifestyle with inflammation, in terms of inflammatory markers at the time of diagnosis in intestinal cancer patients. Our findings suggest that an overall unhealthier lifestyle and a higher risk of malnutrition at the time of diagnosis were associated with elevated levels of inflammatory markers. These findings could contribute to formulating lifestyle advice in the future. Colorectal cancer is one of the most common lifestyle-related types of cancer. The exact pathophysiologic mechanism in the relation between (visceral) adipose tissue, systemic inflammation and colorectal cancer remains unknown. This study aimed to assess the association of lifestyle with markers of systemic inflammation at the time of diagnosis in stage I-III colorectal cancer patients. Patients (n = 298) with stage I-III colorectal cancer from three Dutch hospitals were included at diagnosis. Several lifestyle-related variables (MUST nutritional status score, WCRF/AICR healthy lifestyle score, active smoking, alcohol consumption and BMI) and inflammatory markers (plasma levels of IL-6, IL-8, IL-10, TNFα and 'high sensitive' hsCRP) were measured at the time of diagnosis. Confounder-adjusted multivariable linear regression models were used to analyse how the lifestyle variables were associated with the inflammatory markers. Statistically significant associations were found between a better WCRF/AICR lifestyle score and lower levels of IL-6 and hsCRP. A medium and high risk of malnutrition according to the MUST score was associated with elevated levels of both IL-8 and hsCRP. An overall unhealthier lifestyle indicated by a lower WCRF/AICR lifestyle score and a higher risk of malnutrition according to the MUST score at the time of diagnosis was associated with elevated levels of inflammatory markers. These findings can contribute to formulating lifestyle advice to improve treatment outcomes and prognosis in patients having CRC in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Various genomic variants that are statistically associated with breast cancer (BC) have been discovered and robustly replicated as a result of different genome-wide association studies. Such findings have led to the development of a different risk classification with the Polygenic Risk Score (PRS). In this paper, we have calculated the PRS of the Norwegian samples using various PRS models, compared their performances, and then evaluated the PRS-based lifetime risk of developing BC. The best performing PRS model includes 3820 SNPs (AUC = 0.625 and OR = 1.567), and the other studied models also provide closer performances. The results show that the PRS can be a useful instrument for lifetime risk stratification of developing BC in the Norwegian population, and can thus be utilized in the BC screening program. Background: Statistical associations of numerous single nucleotide polymorphisms with breast cancer (BC) have been identified in genome-wide association studies (GWAS). Recent evidence suggests that a Polygenic Risk Score (PRS) can be a useful risk stratification instrument for a BC screening strategy, and a PRS test has been developed for clinical use. The performance of the PRS is yet unknown in the Norwegian population. Aim: To evaluate the performance of PRS models for BC in a Norwegian dataset. Methods: We investigated a sample of 1053 BC cases and 7094 controls from different regions of Norway. PRS values were calculated using four PRS models, and their performance was evaluated by the area under the curve (AUC) and the odds ratio (OR). The effect of the PRS on the age of onset of BC was determined by a Cox regression model, and the lifetime absolute risk of developing BC was calculated using the iCare tool. Results: The best performing PRS model included 3820 SNPs, which yielded an AUC = 0.625 and an OR = 1.567 per one standard deviation increase. The PRS values of the samples correlate with an increased risk of BC, with a hazard ratio of 1.494 per one standard deviation increase (95% confidence interval of 1.406–1.588). The individuals in the highest decile of the PRS have at least twice the risk of developing BC compared to the individuals with a median PRS. The results in this study with Norwegian samples are coherent with the findings in the study conducted using Estonian and UK Biobank samples. Conclusion: The previously validated PRS models have a similar observed accuracy in the Norwegian data as in the UK and Estonian populations. A PRS provides a meaningful association with the age of onset of BC and lifetime risk. Therefore, as suggested in Estonia, a PRS may also be integrated into the screening strategy for BC in Norway. [ABSTRACT FROM AUTHOR]

Simple Summary: Testicular cancer is a prevalent malignancy in young men aged 15 to 35 years. Sonoelastography is an emerging technique for distinguishing between non-neoplasms, benignities, and malignancies by characterizing the tissue stiffness of testes. This review provides a summary of studies on the diagnostic accuracy of sonoelastography for identifying benign and malignant lesions, as well as tumors and non-tumors. The objective of this review was to summarize the applications of sonoelastography in testicular tumor identification and inquire about their test performances. Two authors independently searched English journal articles and full conference papers from CINAHL, Embase, IEEE Xplore®, PubMed, Scopus, and Web of Science from inception and organized them into a PIRO (patient, index test, reference test, outcome) framework. Eleven studies (n = 11) were eligible for data synthesis, nine of which (n = 9) utilized strain elastography and two (n = 2) employed shear-wave elastography. Meta-analyses were performed on the distinction between neoplasm (tumor) and non-neoplasm (non-tumor) from four study arms and between malignancy and benignity from seven study arms. The pooled sensitivity of classifying malignancy and benignity was 86.0% (95%CI, 79.7% to 90.6%). There was substantial heterogeneity in the classification of neoplasm and non-neoplasm and in the specificity of classifying malignancy and benignity, which could not be addressed by the subgroup analysis of sonoelastography techniques. Heterogeneity might be associated with the high risk of bias and applicability concern, including a wide spectrum of testicular pathologies and verification bias in the reference tests. Key technical obstacles in the index test were manual compression in strain elastography, qualitative observation of non-standardized color codes, and locating the Regions of Interest (ROI), in addition to decisions in feature extractions. Future research may focus on multiparametric sonoelastography using deep learning models and ensemble learning. A decision model on the benefits–risks of surgical exploration (reference test) could also be developed to direct the test-and-treat strategy for testicular tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with multiple myeloma (MM) who become refractory to three or more lines of therapy (RRMM patients) have few valid therapeutic alternatives. Among them, drugs directed against the BCMA antigen expressed in plasma cells are very appealing. Belantamab-mafodotin (belamaf) is the first antibody-drug conjugate against BCMA ready for clinical use. In this paper, we report the Spanish experience of belamaf monotherapy in 156 patients with RRMM. The overall response rate was 41.8%, with 39.8% of patients achieving a partial response or better. Median progression-free survival was 3.61 months, but interestingly, it increased to 14.47 months in patients achieving a minimal response or better. Treatment was well tolerated, ocular events being the most reported toxicity (87.9%; grade ≥ 3, 33.7%), but only two patients discontinued treatment due to side effects. Overall, our results confirm the safety and efficacy of belamaf in this poor prognosis subset of patients. Belantamab-mafodotin (belamaf) is a novel antibody-drug conjugate targeting B-cell maturation antigen that showed anti-myeloma activity in patients with relapsed and refractory multiple myeloma (RRMM). We performed an observational, retrospective, and multicenter study aimed to assess the efficacy and safety of single-agent belamaf in 156 Spanish patients with RRMM. The median number of prior therapy lines was 5 (range, 1–10), and 88% of patients were triple-class refractory. Median follow-up was 10.9 months (range, 1–28.6). The overall response rate was 41.8% (≥CR 13.5%, VGPR 9%, PR 17.3%, MR 2%). The median progression-free survival was 3.61 months (95% CI, 2.1–5.1) and 14.47 months (95% CI, 7.91–21.04) in patients achieving at least MR (p < 0.001). Median overall survival in the entire cohort and in patients with MR or better was 11.05 months (95% CI, 8.7–13.3) and 23.35 (NA-NA) months, respectively (p < 0.001). Corneal events (87.9%; grade ≥ 3, 33.7%) were the most commonly adverse events, while thrombocytopenia and infections occurred in 15.4% and 15% of patients, respectively. Two (1.3%) patients discontinued treatment permanently due to ocular toxicity. Belamaf showed a noticeably anti-myeloma activity in this real-life series of patients, particularly among those achieving MR or better. The safety profile was manageable and consistent with prior studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Since the introduction of effective systemic therapies (ESTs) (in the form of both targeted and immuno-based therapies) in the treatment of malignant melanoma, the prognosis of metastatic patients has dramatically changed. The role of metastasectomy in oligometastatic patients has rarely been addressed in this new pharmacological era. Even though lungs represent the most frequent site of melanoma metastases, only limited data are available on the role of surgery in isolated pulmonary metastases from malignant melanoma (PmMM). In this study, we describe the outcomes of patients who underwent metastasectomy of PmMM in the era of ESTs, and identified prognostic factors affecting survival in our multicentric experience. To the best of our knowledge, this is the first paper analyzing in detail the impact of metastasectomy of PmMM in the era of ESTs. In the last decade, the emergence of effective systemic therapies (ESTs) in the form of both targeted and immuno-based therapies has revolutionized the treatment of patients with advanced stage III and stage IV melanoma. Even though lungs represent the most frequent site of melanoma metastases, only limited data are available on the role of surgery in isolated pulmonary metastases from malignant melanoma (PmMM) in the era of ESTs. The aim of this study is to describe the outcomes of patients who underwent metastasectomy of PmMM in the era of ESTs, in order to identify prognostic factors affecting survival and to provide a framework for more informed patient selection of treatmeant with lung surgery in the future. Clinical data of 183 patients who underwent metastasectomy of PmMM between June 2008 and June 2021 were collected among four Italian Thoracic Centers. The main clinical, surgical and oncological variables reviewed were: sex, comorbidities, previous oncological history, melanoma histotypes and primary site, date of primary cancer surgical treatment, melanoma growth phase, Breslow thickness, mutation pattern disease, stage at diagnosis, metastatic sites, DFI (Disease Free Interval), characteristics of lung metastases (number, side, dimension, type of resection), adjuvant therapy after lung metastasectomy, site of recurrence, disease-free survival (DFS) and cancer-specific survival (CSS; defined as the time interval between the first melanoma resection or lung metastasectomy and death from cancer). All patients underwent surgical resection of the primary melanoma before lung metastasectomy. Twenty-six (14.2%) patients already had a synchronous lung metastasis at the time of primary melanoma diagnosis. A wedge resection was performed in 95.6% of cases to radically remove the pulmonary localizations, while an anatomical resection was necessary in the remaining cases. The incidence of major post-operative complications was null, while only 21 patients (11.5%) developed minor complications (mainly air leakage followed by atrial fibrillation). The mean in-hospital stay was 4.46 ± 2.8 days. Thirty- and sixty-day mortality were null. After lung surgery, 89.6% of the population underwent adjuvant treatments (47.0% immunotherapy, 42.6% targeted therapy). During a mean FUP of 107.2 ± 82.3 months, 69 (37.7%) patients died from melanoma disease, 11 (6.0%) from other causes. Seventy-three patients (39.9%) developed a recurrence of disease. Twenty-four (13.1%) patients developed extrapulmonary metastases after pulmonary metastasectomy. The CSS from melanoma resection was: 85% at 5 years, 71% at 10 years, 54% at 15 years, 42% at 20 years and 2% at 25 years. The 5- and 10-year CSS from lung metastasectomy were 71% and 26%, respectively. Prognostic factors negatively affecting CSS from lung metastasectomy at multivariable analysis were: melanoma vertical growth (p = 0.018), previous metastatic sites other than lung (p < 0.001) and DFI < 24 months (p = 0.007). Our results support the evidence that surgical indication confirms its important role in stage IV melanoma with resectable pulmonary metastases, and selected patients can still benefit from pulmonary metastasectomy in terms of overall cancer specific survival. Furthermore, the novel systemic therapies may contribute to prolonged survival after systemic recurrence following pulmonary metastasectomy. Patients with long DFI, radial growth melanoma phase and no site of metastatization other than lung seem to be the best candidate cases for lung metastasectomy; however, to drive stronger conclusions, further studies evaluating the role of metastasectomy in patients with iPmMM are needed. [ABSTRACT FROM AUTHOR]

Simple Summary: The initiation of non-small-cell lung cancer (NSCLC) causes significant changes in a patient's blood plasma metabolomic profile. Locally and early-advanced NSCLC patients receive a complete surgical resection of the lung tumor, but the level of metabolic changes after this surgical treatment is currently unknown. By collecting multiple blood plasma samples before and after complete NSCLC removal, metabolic changes can be detected by analyzing the patient's plasma using proton nuclear magnetic resonance (NMR) spectroscopy. Detection of significant changes in the plasma metabolism, a so-called metabolic shift in the patient's blood plasma after surgical tumor resection, indicates the absence of disease recurrence and thus can provide an indication of a good prognosis. Background: Lung cancer can be detected by measuring the patient's plasma metabolomic profile using nuclear magnetic resonance (NMR) spectroscopy. This NMR-based plasma metabolomic profile is patient-specific and represents a snapshot of the patient's metabolite concentrations. The onset of non-small cell lung cancer (NSCLC) causes a change in the metabolite profile. However, the level of metabolic changes after complete NSCLC removal is currently unknown. Patients and methods: Fasted pre- and postoperative plasma samples of 74 patients diagnosed with resectable stage I-IIIA NSCLC were analyzed using 1H-NMR spectroscopy. NMR spectra (s = 222) representing two preoperative and one postoperative plasma metabolite profile at three months after surgical resection were obtained for all patients. In total, 228 predictors, i.e., 228 variables representing plasma metabolite concentrations, were extracted from each NMR spectrum. Two types of supervised multivariate discriminant analyses were used to train classifiers presenting a strong differentiation between the pre- and postoperative plasma metabolite profiles. The validation of these trained classification models was obtained by using an independent dataset. Results: A trained multivariate discriminant classification model shows a strong differentiation between the pre- and postoperative NSCLC profiles with a specificity of 96% (95% CI [86–100]) and a sensitivity of 92% (95% CI [81–98]). Validation of this model results in an excellent predictive accuracy of 90% (95% CI [77–97]) and an AUC value of 0.97 (95% CI [0.93–1]). The validation of a second trained model using an additional preoperative control sample dataset confirms the separation of the pre- and postoperative profiles with a predictive accuracy of 93% (95% CI [82–99]) and an AUC value of 0.97 (95% CI [0.93–1]). Metabolite analysis reveals significantly increased lactate, cysteine, asparagine and decreased acetate levels in the postoperative plasma metabolite profile. Conclusions: The results of this paper demonstrate that surgical removal of NSCLC generates a detectable metabolic shift in blood plasma. The observed metabolic shift indicates that the NSCLC metabolite profile is determined by the tumor's presence rather than donor-specific features. Furthermore, the ability to detect the metabolic difference before and after surgical tumor resection strongly supports the prospect that NMR-generated metabolite profiles via blood samples advance towards early detection of NSCLC recurrence. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer antigen 125 (CA-125) is a protein found at a high concentration in the blood of patients with specific types of cancer, mainly ovarian cancer. In 2004, the Gynecologic Cancer Intergroup (GCIG) proposed criteria defining response to treatment, as well as disease progression, based on the CA-125 concentration. Ever since, for the follow-up of ovarian cancer patients, the CA-125 concentration and/or CT-scans are used. This paper aims to compare different summaries of CA-125 evolution in the 3 to 6 months following treatment initiation in newly diagnosed advanced ovarian cancer and explore their prognostic capacity to predict overall survival. Based on individual patient data from the GCIG meta-analysis, we propose the most appropriate timeframe between follow-up and the prediction horizon in order to obtain robust, dynamic, individual predictions. (1) Background: Cancer antigen 125 (CA-125) is a protein produced by ovarian cancer cells that is used for patients' monitoring. However, the best ways to analyze its decline and prognostic role are poorly quantified. (2) Methods: We leveraged individual patient data from the Gynecologic Cancer Intergroup (GCIG) meta-analysis (N = 5573) to compare different approaches summarizing the early trajectory of CA-125 before the prediction time (called the landmark time) at 3 or 6 months after treatment initiation in order to predict overall survival. These summaries included observed and estimated measures obtained by a linear mixed model (LMM). Their performances were evaluated by 10-fold cross-validation with the Brier score and the area under the ROC (AUC). (3) Results: The estimated value and the last observed value at 3 months were the best measures used to predict overall survival, with an AUC of 0.75 CI 95% [0.70; 0.80] at 24 and 36 months and 0.74 [0.69; 0.80] and 0.75 [0.69; 0.80] at 48 months, respectively, considering that CA-125 over 6 months did not improve the AUC, with 0.74 [0.68; 0.78] at 24 months and 0.71 [0.65; 0.76] at 36 and 48 months. (4) Conclusions: A 3-month surveillance provided reliable individual information on overall survival until 48 months for patients receiving first-line chemotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Papillary thyroid cancer is not an aggressive cancer, even when metastasis are present; therefore, treatment has been downgraded in recent years. However rare, mortality exists and finding the factors associated with mortality is essential and has not yet been fully accomplished; the answer probably lies in molecular factors. This study aimed to find MicroRNAs related to death in metastatic patients and found that patients who died due to progression of PTC had higher expression levels of miR-101-3p, miR-17-5p, and miR-191-5p compared with those of patients with stable metastatic disease. These findings are new in the literature and may open new doors in differentiating the patients who need more aggressive treatment from those who do not. Papillary thyroid carcinoma (PTC) is the most common neoplasm of the endocrine system and has an excellent long-term prognosis, with low rates of distant metastatic disease. Although infrequent, there are cases of deaths directly related to PTC, especially in patients with metastatic disease, and the factors that could be associated with this unfavorable outcome remain a major challenge in clinical practice. Recently, research into genetic factors associated with PTC has gained ground, especially mutations in the TERT promoter and BRAF gene. However, the role of microRNAs remains poorly studied, especially in those patients who have an unfavorable outcome at follow-up. This paper aims to evaluate molecular markers related to the different pathological processes of PTC, as well as the histological characteristics of the neoplasm, and to compare this profile with prognosis and death from the disease using an analysis of patients treated for metastatic disease in a single tertiary cancer center. Evaluation of microRNA expression in paraffin-embedded tumor specimens was carried out by quantitative PCR using the TaqMan® Low Density Array (TLDA) system. Metastatic patients who died from progression of PTC had higher expressions of miR-101-3p, miR-17-5p, and miR-191-5p when compared to patients with stable metastatic disease. These findings are of great importance but should be considered as preliminary because of the small sample. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune-checkpoint inhibitors have been proven to aid in tumor regression. We performed a meta-analysis and systematic review to investigate the relationship between hospital volume and patient outcomes. We found that centers performing ≥ 33 annual cases had fewer cardiac-related adverse events (AEs). The pooled estimated rates of grade 5 AEs were 2.75% (95%CI: 2.18–3.47), with higher annual cases associated with reduced grade 5 AEs at meta-regression. Ultimately, patients should be referred to high-volume centers when severe immune-related AEs occur. Immune-checkpoint inhibitors (ICIs) were proven effective in inducing tumor regression. However, its toxicity tends to be fatal. We sought to investigate the hospital volume/outcomes relationship. Databases were searched for studies reporting immune-checkpoint inhibitors adverse events (AEs) in patients with solid-organ malignancies. The outcomes were A) the pooled events rate (PER) of grade 5, grade 3–4, cardiac-related, and pulmonary-related AEs, and B) the assessment of the volume/outcomes relationship. One hundred and forty-seven studies met our inclusion criteria. The PER of grade 5, grade 3–4, and any-grade AEs was 2.75% (95%CI: 2.18–3.47), 26.69% (95%CI: 21.60–32.48), and 77.80% (95%CI: 70.91–83.44), respectively. The PER of pulmonary-related AEs was 4.56% (95%CI: 3.76–5.53). A higher number of annual cases per center was significantly associated with reduced grade 5 (p = 0.019), grade 3–4 (p = 0.004), and cardiac-related AEs (p = 0.035) in the meta-regression. In the current era of cancer immunotherapy, knowledge regarding the early diagnosis and management of immunotherapy-related AEs is essential. Our meta-analysis demonstrates the importance of center volume in improving outcomes and reducing the incidence of severe AEs. [ABSTRACT FROM AUTHOR]

Simple Summary: In the modern era, characterized by parenchymal-sparing procedures, in some cases pneumonectomy remains the only therapeutic approach to achieving oncological radicality. One of the most feared complications is undoubtedly respiratory failure and ARDS. Its cause after pneumonectomy is still unclear, and the study of risk factors is a subject of debate. In this paper, we evaluate the main risk factors for ARDS of a large cohort of patients and we classify them in four classes of growing risk in order to quantify their postoperative risk of ARDS and facilitate their global management. (1) Background: The cause of ARDS after pneumonectomy is still unclear, and the study of risk factors is a subject of debate. (2) Methods: We reviewed a large panel of pre-, peri- and postoperative data of 211 patients who underwent pneumonectomy during the period 2014–2021. Univariable and multivariable logistic regression was used to quantify the association between preoperative parameters and the risk of developing ARDS, in addition to odds ratios and their respective 95% confidence intervals. A backward stepwise selection approach was used to limit the number of variables in the final multivariable model to significant independent predictors of ARDS. A nomogram was constructed based on the results of the final multivariable model, making it possible to estimate the probability of developing ARDS. Statistical significance was defined by a two-tailed p-value < 0.05. (3) Results: Out of 211 patients (13.3%), 28 developed ARDS. In the univariate analysis, increasing age, Charlson Comorbidity Index and ASA scores, DLCO < 75% predicted, preoperative C-reactive protein (CRP), lung perfusion and duration of surgery were associated with ARDS; a significant increase in ARDS was also observed with decreasing VO2max level. Multivariable analysis confirmed the role of ASA score, DLCO < 75% predicted, preoperative C-reactive protein and lung perfusion. Using the nomogram, we classified patients into four classes with rates of ARDS ranking from 2.0% to 34.0%. (4) Conclusions: Classification in four classes of growing risk allows a correct preoperative stratification of these patients in order to quantify the postoperative risk of ARDS and facilitate their global management. [ABSTRACT FROM AUTHOR]

Simple Summary: This is a systematic and meta-analysis of proportions study that investigated the distribution of head and neck cutaneous squamous cell carcinoma between men and women. Males were disproportionally affected by HNcSCC overall, and this was most evident in the ear subtype, while this disparity was less obvious for the eyelid subtype. This paper underscores the risk of metastatic progression of HNcSCC and denotes further research is warranted to elucidate the mechanisms for these sex differences. Improving our understanding of this will better inform clinical practices, and eventually improve patient outcomes for all—males and females. The incidence of head and neck cutaneous squamous cell carcinoma (HNcSCC) is unevenly distributed between men and women. At present, the mechanism behind this disparity remains elusive. This study conducted a systematic review and meta-analysis of proportions to investigate the disparity between sexes for patients with HNcSCC. PubMed, Scopus, EMBASE, MEDLINE, Emcare and CINAHL were searched in November 2021 and June 2022 (N > 50, English, human), and studies which examined the association between sex and HNcSCC were included. Analysis was conducted using RStudio with data and forest plots displaying males as a proportion of total patients with HNcSCC. Two independent researchers performed study selection, data extraction, data analysis and risk of bias. Eighty-two studies (1948 to 2018) comprising approximately 186,000 participants (67% male, 33% female) from 29 countries were included. Significantly more males had HNcSCC overall (71%; CI: 67–74). Males were also significantly more affected by cSCC of the ear (92%; CI: 89–94), lip (74%; CI: 66–81), and eyelid (56%; CI: 51–62). This study found HNcSCC disproportionately affected males overall and across all subtypes. Improving our understanding of sex-specific mechanisms in HNcSCC will better inform our preventive, therapeutic and prognostic practices. [ABSTRACT FROM AUTHOR]

Simple Summary: Recently, nivolumab, pembrolizumab, both immune-checkpoint inhibitors (ICIs) and the combination of dabrafenib plus trametinib (D + T) were registered as adjuvant melanoma treatments, to prevent recurrence. The aim of this paper was to retrospectively review the benefits and risks of these treatments in clinical practice, by extracting data from electronic health records with a text-mining tool. In a population of 122 patients, 55 used nivolumab, 48 used pembrolizumab and 20 used D + T, and we found that the ICIs were better tolerated than D + T. However, the frequent adverse events of D + T are reversible and include pyrexia and fatigue. ICIs show immune-related chronic adverse events, and chronic thyroid-related adverse events occurred frequently. The efficacy results, including the recurrence-free survival, are promising; however, the follow-up was too short for conclusions. This study furthermore showed that the application of text-mining is a valuable method to collect data for the evaluation of adjuvant melanoma treatments. Introduction: Nivolumab (N), pembrolizumab (P), and dabrafenib plus trametinib (D + T) have been registered as adjuvant treatments for resected stage III and IV melanoma since 2018. Electronic health records (EHRs) are a real-world data source that can be used to review treatments in clinical practice. In this study, we applied EHR text-mining software to evaluate the real-world tolerability, safety, and efficacy of adjuvant melanoma treatments. Methods: Adult melanoma patients receiving adjuvant treatment between January 2019 and October 2021 at the Leiden University Medical Center, the Netherlands, were included. CTcue text-mining software (v3.1.0, CTcue B.V., Amsterdam, The Netherlands) was used to construct rule-based queries and perform context analysis for patient inclusion and data collection from structured and unstructured EHR data. Results: In total, 122 patients were included: 54 patients treated with nivolumab, 48 with pembrolizumab, and 20 with D + T. Significantly more patients discontinued treatment due to toxicity on D + T (N: 16%, P: 6%, D + T: 40%), and X2 (6, n = 122) = 14.6 and p = 0.024. Immune checkpoint inhibitors (ICIs) mainly showed immune-related treatment-limiting adverse events (AEs), and chronic thyroid-related AE occurred frequently (hyperthyroidism: N: 15%, P: 13%, hypothyroidism: N: 20%, P: 19%). Treatment-limiting toxicity from D + T was primarily a combination of reversible AEs, including pyrexia and fatigue. The 1-year recurrence-free survival was 70.3% after nivolumab, 72.4% after pembrolizumab, and 83.0% after D + T. Conclusions: Text-mining EHR is a valuable method to collect real-world data to evaluate adjuvant melanoma treatments. ICIs were better tolerated than D + T, in line with RCT results. For BRAF+ patients, physicians must weigh the higher risk of reversible treatment-limiting AEs of D + T against the risk of long-term immune-related AEs. [ABSTRACT FROM AUTHOR]

Simple Summary: There is a growing need to clarify the effect of modifiable lifestyle factors such as obesity on outcomes of multiple myeloma (MM). In this paper, we examined the associations between body mass index (BMI) at different periods of life up to the time of diagnosis and overall survival among patients newly diagnosed with multiple myeloma. The key findings are that BMIs before and at the time of diagnosis were not associated with overall survival in MM, except that a higher BMI at diagnosis was associated with a better overall survival for females, irrespective of race/ethnicity. This is the first evidence that the BMI-survival association may differ by sex. Obesity is associated with survival in several solid tumors and non-Hodgkin lymphoma, but its impact on multiple myeloma (MM) survival is unclear. We examined the associations between body mass index (BMI) at different periods of life up to the time of diagnosis and overall survival (OS) among 563 patients newly diagnosed with MM in 2010–2019. BMI at diagnosis was calculated using measured height and weight from electronic medical records (EMR). BMIs at age 20, maximum during adulthood, and 5 years before diagnosis were calculated using self-reported weights and measured height from EMR. Over a median follow-up of 49.3 months, 191 (33.93%) deaths were identified. We used multivariable Cox proportional-hazards models to examine the associations between BMIs and OS. Height as well as BMI before and at diagnosis was not associated with OS, but there is a U-shape association between weight and OS. Higher BMIs at diagnosis were associated with better OS among females (HR = 0.39 [0.22–0.71]), irrespective of race. In conclusion, our results suggest that BMI at different periods of life up to the time of diagnosis may not be associated with OS in MM, except that a higher BMI at diagnosis was associated with superior OS for females. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer and its treatment are associated with energy balance-related problems, such as overweight, malnourishment, compromised muscle mass and quality, and physical inactivity. This may impact the quality of life and treatment outcome. These factors may be modifiable, and women with ovarian cancer have indicated that they want to do something themselves to help improve their treatment outcome. In order to better understand the role of energy-balance-related problems in patients treated for ovarian cancer, this study synthesized the available research on (i) the association of body weight, body composition, diet, and physical activity or exercise with survival or treatment-related complications and (ii) the evidence from exercise- and/or dietary interventions. The results indicate that body mass index has a limited prognostic value, while other measures of body composition may have more prognostic potential. Additionally, the findings provide important leads for future research directions. Background: This systematic review and meta-analysis synthesized evidence in patients with ovarian cancer at diagnosis and/or during first-line treatment on; (i) the association of body weight, body composition, diet, exercise, sedentary behavior, or physical fitness with clinical outcomes; and (ii) the effect of exercise and/or dietary interventions. Methods: Risk of bias assessments and best-evidence syntheses were completed. Meta-analyses were performed when ≥3 papers presented point estimates and variability measures of associations or effects. Results: Body mass index (BMI) at diagnosis was not significantly associated with survival. Although the following trends were not supported by the best-evidence syntheses, the meta-analyses revealed that a higher BMI was associated with a higher risk of post-surgical complications (n = 5, HR: 1.63, 95% CI: 1.06–2.51, p = 0.030), a higher muscle mass was associated with a better progression-free survival (n = 3, HR: 1.41, 95% CI: 1.04–1.91, p = 0.030) and a higher muscle density was associated with a better overall survival (n = 3, HR: 2.12, 95% CI: 1.62–2.79, p < 0.001). Muscle measures were not significantly associated with surgical or chemotherapy-related outcomes. Conclusions: The prognostic value of baseline BMI for clinical outcomes is limited, but muscle mass and density may have more prognostic potential. High-quality studies with comprehensive reporting of results are required to improve our understanding of the prognostic value of body composition measures for clinical outcomes. Systematic review registration number: PROSPERO identifier CRD42020163058. [ABSTRACT FROM AUTHOR]

Simple Summary: Although the deep inferior epigastric perforator flap (DIEP) has become the most frequent autologous flap in breast reconstruction, it remains unclear whether reconstruction should be performed at the same time as the mastectomy or delayed. Therefore, we conducted a meta-analysis to offer an overview of recipient site postoperative complications and help guide practicians toward the ideal timing for breast reconstruction. A pooled analysis using the Mantel and Haenszel methods with a fixed effect model provided results as an odd ratio with a 95% confidence interval. Among most complications including hematoma, infection, fat necrosis, and flap loss, no significant differences were observed. However, delayed wound healing was significantly higher for patients who underwent delayed breast reconstruction. This paper offers evidence that both surgical timings offer similar outcomes and are, therefore, valid surgical strategies. Purpose: The setting regarding the ideal timing for deep inferior epigastric perforator flap (DIEP) reconstruction remains unclear. Immediate breast reconstruction (IBR) is performed at the same time as mastectomy, while delayed breast reconstruction (DBR) is performed at any time after mastectomy except immediately. We compared both strategies to assess whether IBR or DBR should be performed to reduce postoperative adverse events. Methods: A systematic review of PubMed, Embase, Medline, Cochrane, and Web of Science was conducted, aiming at articles comparing the recipient site outcomes of IBR versus DBR with DIEP. We used the Mantel–Haenszel method with a fixed effects model. Results were expressed as the OR with a 95% CI. Results: Two retrospective and two prospective studies were identified involving 5784 DIEPs (1744 immediate and 4040 delayed). We showed a significant difference in favor of IBR for wound healing issues (OR = 0.57, 95% CI 0.41, 0.77; p = 0.0003). However, no significant differences for hematoma, infection, fat necrosis, partial flap loss, and total flap loss rate were seen. Conclusions: Despite variability in the choice of the ideal time for breast reconstruction and outcomes reported among studies, immediate DIEP surgery appears to be a reliable setting with less delayed healing issues. [ABSTRACT FROM AUTHOR]

Simple Summary: HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) is unique amongst oropharyngeal cancers in its high responsiveness to treatment and its lower mortality rate. As a result, numerous clinical trials have been conducted to identify treatment modalities and protocols. In order for these trials to have meaningful impact on HPV-associated OPSCC patients, proper demographic representation by trial participants is essential. The aim of our systematic review and meta-analysis was to assess the demographics of trial participants for HPV-associated OPSCC clinical trials and compare them with those reported by national databases. We determined that clinical-trial participants were predominately non-smoking white men, with tonsils as the primary tumor site. These findings reflect the demographics reported by the National Cancer Database. Our results imply that HPV-associated OPSCC clinical trials appropriately represent the target population and offer immense benefit. The objective of our paper was to answer the following question: how do patients with HPV-related oropharyngeal squamous cell carcinoma OPSCC (Population) enrolled in clinical trials (Intervention), compared with national database reports of HPV-associated OPSCC patients (Comparison), present demographically (Outcome)? We conducted a systematic review and meta-analysis of studies pertaining to clinical trials of HPV-associated OPSCC and participant demographics in the United States. PubMed, Scopus, CINAHL, and the Cochrane Library were searched from inception to 2 February 2022. Studies of overlapping participant cohorts and/or studies conducted outside of the United States were excluded. Primary outcomes were patient age, sex, and race. Secondary outcomes were smoking history, alcohol history, history of prior cancer, and tumor origin site. Meta-analysis of single means (mean, N for each study, and standard deviation) for age, pack years, and smoking years was performed. Pooled prevalence rates of gender, race, alcohol history, tobacco history, and tumor origin site were expressed as a percentage, with 95% confidence intervals. Meta-analysis found patients to be predominately non-smoking white males, with tumors originating from the tonsil. Our findings reflected the demographics reported by the National Cancer Database (NCDB) for HPV-associated OPSCC. This indicates that HPV-associated OPSCC patients are appropriately represented in clinical trial demographics. [ABSTRACT FROM AUTHOR]

Simple Summary: Cigarette smoking increases the risk of developing bladder cancer; many of these patients are active smokers at diagnosis. There is evidence that smokers with cancer at other sites (e.g., lung) may improve their chance of surviving if they stop smoking upon diagnosis. However, similar evidence is still lacking for bladder cancer. Here, we reviewed the scientific literature up to January 2022 but found a mere nine articles focusing on this topic, which provided insufficient evidence to draw firm conclusions. While more research is urgently needed, bladder cancer patients who are still smoking at diagnosis should receive information on the multiple health benefits of smoking cessation and all the support they need to stop successfully. We reviewed the studies examining whether quitting smoking at or around diagnosis favourably affects the prognosis of bladder cancer (BC) patients, who are often active smokers at diagnosis. We found only nine eligible articles published until 31 January 2022, which encompassed around 5500 BC in total, the majority of which were nonmuscle invasive BC (only one paper included muscle-invasive BC). We used random effects meta-analysis to obtain a summary hazard ratio (SHR) and 95% confidence intervals (CI). The median proportion of smokers who quit at or around diagnosis was 29.8% (range 8.4–43.1%). For the overall, BC-specific, and progression-free survival, the studies were limited in number (n = 3) and provided conflicting results. At the same time, quitters did not appear to have a lower risk of recurrence than continued smokers (SHR 0.99, 95% CI 0.61–1.61). In conclusion, while the evidence is currently not sufficient to draw firm conclusions (especially for patients with muscle-invasive BC), physicians should not refrain from educating smoking BC patients about the benefits of smoking cessation and provide the necessary support. [ABSTRACT FROM AUTHOR]

Simple Summary: Primary liver transplantation (PLT) for HCC represents the ideal treatment. However, since organ shortage increases the risk of drop-out from the waiting list for tumor progression, a new surgical strategy has been developed: Salvage Liver Transplantation (SLT) can be offered as an additional curative strategy for HCC recurrence after liver resection. The aim of this updated meta-analysis is to compare surgical and long-term outcomes of SLT versus PLT for HCC. The findings of our analysis reveal that SLT offers comparable surgical outcomes but slightly poorer oncological long-term outcomes with respect to PLT. (1) Background: Primary liver transplantation (PLT) for HCC represents the ideal treatment. However, since organ shortage increases the risk of drop-out from the waiting list for tumor progression, a new surgical strategy has been developed: Salvage Liver Transplantation (SLT) can be offered as an additional curative strategy for HCC recurrence after liver resection. The aim of this updated meta-analysis is to compare surgical and long-term outcomes of SLT versus PLT for HCC. (2) Materials and Methods: A systematic review and meta-analysis was conducted using the published papers comparing SLT and PLT up to January 2022. (3) Results: 25 studies describing 11,275 patients met the inclusion criteria. The meta-analysis revealed no statistical difference in intraoperative blood loss, overall vascular complications, retransplantation rate, and hospital stay in the SLT group compared with the PLT group. However, the SLT group showed a slightly significant lower 5-year OS rate and 5-year disease-free survival rate. (4) Conclusion: meta-analysis advocates the relative safety and feasibility of both Salvage LT and Primary LT strategies. Specifically, SLT seems to have comparable surgical outcomes but slightly poorer long-term survival than PLT. [ABSTRACT FROM AUTHOR]

Simple Summary: High local failure and treatment-related morbidity represent a great challenge for postcricoid carcinoma which appears to be more aggressive and requires more morbid oncologic surgery with reconstruction of the larynx and hypopharynx. This paper presents a retrospective analysis focusing on the evaluation of clinical characteristics, therapeutic approaches, quality of swallowing, voice rehabilitation, and verbal communication after a long-term follow-up. To date, this is the first and largest cohort published to reveal a deep understanding of clinical routines in postcricoid carcinoma. Background: Postcricoid carcinoma is a rare but aggressive type of hypopharyngeal carcinoma with poor prognosis and high mortality; thus, it is indispensable to investigate the surgical efficacy and multimodal strategies. Methods: This retrospective study included postcricoid carcinoma patients undergoing surgical resection from 2008 to 2022. Treatment methods and clinical characteristics were analyzed to evaluate prognostic factors for oncological outcomes. Results: Of 72 patients, 13 cases were in the I–II stage and 59 in the III–IV stage. The overall survival (OS) was 50.0%; the laryngeal function preservation rate was 69.4%. Univariate analysis found that high mortality was associated with low tumor differentiation, lymph node metastasis, neck recurrence, and smoke history via log-rank test (p < 0.05); postoperative radiotherapy (RT) remained positive in OS (p = 0.04). The multivariable model further revealed that lymph node metastasis was a dominant determinant after accounting for covariates (HR 1.75; 95% CI 0.85–3.59). The data also indicated that neoadjuvant chemotherapy (NAC) and tumor diameter ≤ 2 cm were causing lower rates of pharyngeal fistula and locoregional relapse. Conclusions: Surgeons should emphasize high-risk features and optimize individualized surgical procedures for postcricoid carcinoma patients. Combined with multimodal treatments, it is feasible to reconstruct laryngeal function and lessen postoperative morbidities in advanced patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Currently, around 30% of vulvar cancer cases at first diagnosis are spread to the inguinal lymph nodes. Preoperative staging of patients affected by vulvar carcinoma is still a hot topic. To date, MRI has shown a great diagnostic accuracy on defining disease extension to soft tissue and deep organs. At present, regarding the study of inguinal nodes, the PET/CT scan has shown a high negative predictive value, although in the presence of a suspicious/positive report it should be taken with caution. We report the results of a study aimed to investigate the role of groin ultrasound in the assessment of lymph nodal status in vulvar cancer. Furthermore, this review represents the most accurate collection of papers available in the literature. This work demonstrates that groin ultrasound can be considered a valuable tool for risk assessment of the presence of groin lymph node metastases. Achieving a high diagnostic accuracy would allow tailored surgical planning with access to minimally invasive surgery techniques for an increasing number of patients. Objective. To determine the efficacy of ultrasound in assessing the inguinal lymph nodes in patients with vulvar cancer. Methods. A systematic review of published research up to October 2020 that compares the results of ultrasound to determine groin node status with histology was conducted. All study types that reported primary data on the role of ultrasound in the evaluation of groin lymph nodes in vulvar cancer were included in the systematic review. Data retrieved from the included studies were pooled in random-effects meta-analyses. Results. After the screening and selection process, eight articles were deemed pertinent for inclusion in the systematic review and meta-analysis. The random-effects model showed a pooled Se of 0.85 (95% CI: 0.81–0.89), Sp of 0.86 (95% CI: 0.81–0.91), PPV of 0.65 (95% CI: 0.54–0.79) and NPV of 0.92 (95% CI: 0.91–0.94). There was a pooled LR+ and LR− of 6.44 (95% CI: 3.72–11.4) and 0.20 (95% CI: 0.14–0.27), respectively. The pooled accuracy was 0.85 (95% CI: 0.80–0.91). Conclusions. Although the studies had small sample sizes, this review represents the best summary of the data so far. Ultrasound has revealed high sensitivity and high negative predictive value in the assessment of nodal status in vulvar cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Growing evidence indicates that blood-count-based compound scores could be used as prognostic biomarkers in cancer as reflectors of uncontrolled inflammation in the tumor microenvironment. Several markers have been developed in this regard, including the recent pan-immune-inflammation value (PIV) that incorporates the levels of blood neutrophil, monocyte, platelet, and lymphocytes. In this paper, we reviewed the association between PIV and overall survival or progression-free survival in cancer from the published studies to date. We observed that higher PIV levels were an adverse prognostic factor consistently across several clinical scenarios, including non-metastatic or metastatic disease and treatment with targeted therapy or immunotherapy. In contrast, the data were limited in patients treated with chemotherapy or patients with non-metastatic disease. The available evidence demonstrates that PIV could be a readily available biomarker for prognosis prediction in cancer. However, further research is needed to explore the promise of PIV as a prognostic biomarker in cancer. Background: Prognostic scores derived from the blood count have garnered significant interest as an indirect measure of the inflammatory pressure in cancer. The recently developed pan-immune-inflammation value (PIV), an equation including the neutrophil, platelet, monocyte, and lymphocyte levels, has been evaluated in several cohorts, although with variations in the tumor types, disease stages, cut-offs, and treatments. Therefore, we evaluated the association between survival and PIV in cancer, performing a systematic review and meta-analysis. Methods: We conducted a systematic review from the Pubmed, Medline, and Embase databases to filter the published studies until 17 May 2022. The meta-analyses were performed with the generic inverse-variance method with a random-effects model. Results: Fifteen studies encompassing 4942 patients were included. In the pooled analysis of fifteen studies, the patients with higher PIV levels had significantly increased risk of death than those with lower PIV levels (HR: 2.00, 95% CI: 1.51–2.64, p < 0.001) and increased risk of progression or death (HR: 1.80, 95% CI: 1.39–2.32, p < 0.001). Analyses were consistent across several clinical scenarios, including non-metastatic or metastatic disease, different cut-offs (500, 400, and 300), and treatment with targeted therapy or immunotherapy (p < 0.001 for each). Conclusion: The available evidence demonstrates that PIV could be a prognostic biomarker in cancer. However, further research is needed to explore the promise of PIV as a prognostic biomarker in patients with non-metastatic disease or patients treated without immunotherapy or targeted therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Anticancer treatments commonly cause adverse events (AE). Among others, pneumatosis intestinalis (PI) is reported to be infrequent, though it can lead to severe consequences. The aim of our systematic review was to investigate the concurrency of PI and oncological therapy exposure; moreover, we defined the characteristics of patients and the primarily involved tumor types. We analyzed 88 different episodes of PI. The median time of onset was 6 weeks and oncological patients with respiratory system cancers and those treated with targeted therapies appeared be at higher risk. Symptoms were frequently mild to absent; nevertheless, life-threatening complications were reported. Therefore, this AE, although uncommon, should be considered in the case of specific symptoms. Potential pharmacological mechanisms of anticancer drugs in inducing PI are also discussed. Pneumatosis intestinalis (PI) is a rare condition due to the presence of gas within the bowel wall; it is mainly caused by endoscopic procedures, infections and other gastrointestinal diseases. Oncological therapies have been reported to be a cause of PI as well, but their role is not clearly defined. This systematic review investigates the concurrency of PI and antitumor therapy in cancer patients, considering both solid tumors and onco-hematological ones. We performed a literature review of PubMed, Embase and the Web of Science up to September 2021 according to the PRISMA guidelines. A total of 62 papers reporting 88 different episodes were included. PI was mainly reported with targeted therapies (sunitinib and bevacizumab above all) within the first 12 weeks of treatment. This adverse event mostly occurred in the metastatic setting, but in 10 cases, it also occurred also in the neoadjuvant and adjuvant setting. PI was mostly localized in the large intestine, being fatal in 11 cases, while in the remaining cases, symptoms were usually mild, or even absent. A significant risk of PI reoccurrence after drug reintroduction was also reported (6/18 patients), with no fatal outcomes. Potential pharmacological mechanisms underlying PI pathogenesis are also discussed. In conclusion, although uncommonly, PI can occur during oncological therapies and may lead to life-threatening complications; therefore, consideration of its occurrence among other adverse events is warranted in the presence of clinical suspicion. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs) are commonly used for acid reduction in patients with peptic ulcer disease or esophageal reflux. Previous studies have shown that acid-reducing agents (ARAs) might affect bevacizumab treatment. This study found that PPI use worsened the oncological outcomes in patients with metastatic colorectal cancer (mCRC) undergoing bevacizumab treatment. There was a negative dose–response relationship when compared to H2RA use. Physicians should consider the benefits and risks of long-term use of ARAs, especially PPIs, in mCRC patients treated with bevacizumab. Background: Approximately one-third of patients with advanced colorectal cancer (CRC) and treated with bevacizumab are prescribed proton pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs). However, there is limited data on the effects of PPIs and H2RAs in these patients. To investigate the oncological outcomes of PPI and H2RA use in CRC patients treated with bevacizumab, we performed a retrospective cohort study using the Taiwan National Health Insurance Research Database and Taiwan Cancer Registry Database from 2005 to 2020. Methods: In CRC patients treated with bevacizumab, the PPI users and H2RA users were matched with patients without acid-reducing agents (ARAs) by 1:4 propensity score matching. PPI users and H2RA users were matched with propensity scoring in a 1:1 ratio. We divided patients into 4 cumulative PPI dosage levels to assess the dose–response relationship. The primary endpoints were 5-year overall survival and cancer-specific survival. Results: Compared with ARA non-users, both H2RA users and PPI users were associated with reduced overall survival. PPI users were associated with more significant negative effects on overall survival. Compared with H2RA users, PPI users were associated with lower 5-year overall survival (aHR: 1.19, 95% CI: 1.09–1.31) and cancer-specific survival (aHR: 1.20, 95% CI: 1.09–1.31). A similar dose–response relationship was observed for PPI users in terms of 5-year overall survival and cancer-specific overall survival. Conclusions: Compared to H2AR use, PPI use was associated with dose-dependent poorer oncological outcomes in metastatic CRC patients treated with bevacizumab. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to develop and validate a radiomic model for predicting overall survival (OS) in glioblastoma multiforme (GBM) patients using pre-treatment MRI images. A retrospective dataset of 289 patients from multiple institutions was used to extract 660 radiomic features (RFs) from each patient's tumor volume. The initial model was enhanced by incorporating clinical variables and validated through repeated three-fold cross-validation. The final clinical–radiomic model utilized primary gross tumor volume (GTV) and T2-FLAIR MRI modality and includes the age variable and two robust RFs. The model achieved a moderately good discriminatory performance (C-Index: 0.69) and significant patient stratification (p = 7 × 10−5) on the validation cohort. Notably, the trained model exhibited the highest integrated area under curve (iAUC) at 11 months (0.81) in the literature. The study concluded that the validated clinical–radiomic model can effectively stratify GBM patients into low and high-risk groups based on OS. Future work will focus on integrating deep learning-based features and standardized convolutional filters to improve OS predictions. Purpose: To develop and validate an MRI-based radiomic model for predicting overall survival (OS) in patients diagnosed with glioblastoma multiforme (GBM), utilizing a retrospective dataset from multiple institutions. Materials and Methods: Pre-treatment MRI images of 289 GBM patients were collected. From each patient's tumor volume, 660 radiomic features (RFs) were extracted and subjected to robustness analysis. The initial prognostic model with minimum RFs was subsequently enhanced by including clinical variables. The final clinical–radiomic model was derived through repeated three-fold cross-validation on the training dataset. Performance evaluation included assessment of concordance index (C-Index), integrated area under curve (iAUC) alongside patient stratification into low and high-risk groups for overall survival (OS). Results: The final prognostic model, which has the highest level of interpretability, utilized primary gross tumor volume (GTV) and one MRI modality (T2-FLAIR) as a predictor and integrated the age variable with two independent, robust RFs, achieving moderately good discriminatory performance (C-Index [95% confidence interval]: 0.69 [0.62–0.75]) with significant patient stratification (p = 7 × 10−5) on the validation cohort. Furthermore, the trained model exhibited the highest iAUC at 11 months (0.81) in the literature. Conclusion: We identified and validated a clinical–radiomic model for stratification of patients into low and high-risk groups based on OS in patients with GBM using a multicenter retrospective dataset. Future work will focus on the use of deep learning-based features, with recently standardized convolutional filters on OS tasks. [ABSTRACT FROM AUTHOR]

Simple Summary: This review explores the role of physiotherapy in early and traditional palliative care (PC) for cancer patients, focusing on its effects on patient-reported outcomes (PROMs) such as fatigue, pain, and quality of life (QoL). The findings suggest that certain physiotherapy interventions, like cognitive behavioral therapy (CBT) and massage, can improve these outcomes, while others show limited or no significant benefits. However, the overall quality of the studies reviewed was low, highlighting the need for more rigorous research in this area to better understand how physiotherapy can support patients in PC. Background: This review aims to explore the role of physiotherapy in early and traditional palliative care (PC) for oncology patients, focusing on its impact on six patient-reported outcomes (PROMs), namely fatigue, pain, cachexia, quality of life (QoL), physical functioning (PHF), and psychosocial functioning (PSF). The purpose is to assess the effectiveness of various physiotherapy interventions and identify gaps in the current research to understand their potential benefits in PC better. Methods: A systematic literature search was conducted across PubMed, Embase, and Web of Science, concluding on 21 December 2023. Two independent reviewers screened the articles for inclusion. The Cochrane Risk of Bias Tool 2 was employed to assess the risk of bias, while the GRADE approach was used to evaluate the certainty of the evidence. Results: Nine randomized controlled trials (RCTs) were included, with most showing a high risk of bias, particularly in outcome measurement and missing data. Cognitive behavioral therapy (CBT) was the only intervention that significantly reduced fatigue, enhanced PHF, and improved QoL and emotional functioning. Graded exercise therapy (GET) did not yield significant results. Combined interventions, such as education with problem-solving or nutritional counseling with physical activity, showed no significant effects. Massage significantly improved QoL and reduced pain, while physical application therapies were effective in pain reduction. Mindful breathing exercises (MBE) improved QoL but had a non-significant impact on appetite. The overall certainty of the evidence was low. Conclusions: Physiotherapy can positively influence PROMs in oncology PC; however, the low quality and high risk of bias in existing studies highlight the need for more rigorous research to confirm these findings and guide clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Inclusion of Black patients and other racial minorities has been limited (<2%) in urothelial carcinoma clinical trials. On meta-analysis of all recent ICIs, ADCs and targeted therapy phase III trials in UC (n = 17), women had inferior OS to men (RR 0.89; p = 0.04) on investigational agents. No OS differences by race or age were observed on meta-analysis. Background: Urothelial carcinoma (UC) is one of the most common cancers diagnosed worldwide. However, minority populations, such as female, elder, and Black patients, may have disparate outcomes and are commonly neglected in randomized prospective trials. This review aims to study the relationship between age, sex, and race on urothelial cancer prognosis, particularly focusing on contemporary therapy and its effect on overall survival. Methods: Phase III prospective trials since 2016 of immune checkpoint inhibitors, antibody-drug conjugates, or targeted therapies in urothelial carcinoma were identified from PubMed. Trials that did not report on survival by race, sex, or age distribution were excluded, and remaining trials (n = 17) were compared by subgroup. Results: Women were reported to have inferior OS on investigational agents compared to men in 9/17 trials. In a meta-analysis, women had inferior OS to men (OR 0.89 [95% CI: 0.78–0.99]; p = 0.04). Asian/Pacific Islander patients had inferior outcomes to White patients on investigational agents in 3/5 trials. In a meta-analysis, OS was not significant by race (OR 1.18 [0.90–1.46], p = 0.38). Black patients composed <2% of all trial patients, and no subgroup data were reported. Both 65 (n = 7) and 75 (n = 2) were reported as age cut-offs in trial subgroups, and survival data were mixed. Conclusions: Women in UC trials may have inferior survival outcomes to men. Racial diversity was poor and thus limited any conclusions on survival disparities. [ABSTRACT FROM AUTHOR]

Simple Summary: Solitary fibrous tumors represent a rare mesenchymal malignancy that can occur anywhere in the body. Due to the low prevalence of the disease, there is a lack of contemporary data regarding patient demographics and cancer-control outcomes. We validated the importance of stage and surgical resection as independent predictors of cancer-specific mortality in malignant solitary fibrous tumors. Moreover, we provide novel observations regarding the independent importance of tumor size, regardless of the site of origin, stage and/or surgical resection status. Background/Objectives: Solitary fibrous tumors (SFTs) represent a rare mesenchymal malignancy that can occur anywhere in the body. Due to the low prevalence of the disease, there is a lack of contemporary data regarding patient demographics and cancer-control outcomes. Methods: Within the SEER database (2000–2019), we identified 1134 patients diagnosed with malignant SFTs. The distributions of patient demographics and tumor characteristics were tabulated. Cumulative incidence plots and competing risks analyses were used to estimate cancer-specific mortality (CSM) after adjustment for other-cause mortality. Results: Of 1134 SFT patients, 87% underwent surgical resection. Most of the tumors were in the chest (28%), central nervous system (22%), head and neck (11%), pelvis (11%), extremities (10%), abdomen (10%) and retroperitoneum (6%), in that order. Stage was distributed as follows: localized (42%) vs. locally advanced (35%) vs. metastatic (13%). In multivariable competing risks models, independent predictors of higher CSM were stage (locally advanced HR: 1.6; metastatic HR: 2.9), non-surgical management (HR: 3.6) and tumor size (9–15.9 cm HR: 1.6; ≥16 cm HR: 1.9). Conclusions: We validated the importance of stage and surgical resection as independent predictors of CSM in malignant SFTs. Moreover, we provide novel observations regarding the independent importance of tumor size, regardless of the site of origin, stage and/or surgical resection status. [ABSTRACT FROM AUTHOR]

Simple Summary: This research was inspired by a desire to understand how adverse childhood experiences (ACEs) impact depression among cancer survivors. The study's findings revealed that cancer survivors with three or more ACEs had a depression rate of 40.8%, compared to 18.7% among those with one to two ACEs and 10.9% among those with no ACEs. Survivors with three or more ACEs were significantly more likely to report experiencing depression. Among the three ACE subtypes—sexual abuse, physical abuse, and having family members with mental illnesses—cancer survivors with family members suffering from mental illnesses had the highest odds of depression, followed by those who experienced physical abuse. These findings provide a crucial basis for health providers to screen cancer survivors for ACEs and depression, guiding proactive screening and treatment of depression in this vulnerable population. Objectives: Adverse childhood experiences (ACEs) are linked to a heightened risk of depression. We explored the relationship between ACEs and both depression and mental distress among cancer survivors. Methods: This was a cross-sectional analysis using the 2022 Behavioral Risk Factor Surveillance System database of cancer survivors aged ≥18 (n = 14,132). The primary outcome was self-reported history of depression, and the secondary outcome was mental distress. The exposure variable was the number of ACEs, classified as 0, 1–2, and ≥3. Weighted multivariable logistic regression models assessed the association between the number of ACEs and depression and mental distress while adjusting for covariates. Results: Approximately 22% of respondents reported experiencing ≥3 ACEs. The prevalence of depression was 21.8%, and mental distress was 15.4%. Compared with cancer survivors who had experienced 0 ACEs, those who had experienced ≥3 (aOR = 3.94; 95% CI, 3.04–5.10) or 1–2 (aOR = 1.85; 95% CI, 1.47–2.32) ACEs had a higher likelihood of reporting depression. Compared with cancer survivors who had experienced 0 ACEs, those who had experienced ≥3 (aOR = 0.67; 95% CI, 0.48–0.93) had a lower likelihood of reporting mental distress. Conclusions: This study highlights the impact of ACEs on depression in adulthood among cancer survivors. [ABSTRACT FROM AUTHOR]

Simple Summary: Renal cancer is the eighth most frequent cancer in Europe, and its prevalence is increasing. Surgery is the treatment of choice for localised renal cell carcinoma requiring interventional management, but less invasive treatment methods are emerging. Stereotactic body radiotherapy (SBRT) utilises precise delivery of high doses of radiation to ablate the primary cancer. In our systematic review and meta-analysis, we pooled data from available prospective trials, including 13 studies involving 308 patients. The results of the meta-analysis show that SBRT for localised renal cell carcinoma is highly effective in controlling local diseases and has low complication rates. In the second year, 97% of patients were free from local recurrence. Only 3% experienced severe adverse events, which included abdominal pain and fatigue. SBRT presents a valuable treatment for patients who require treatment but cannot undergo surgery; however, it has not been yet confirmed to be equieffective to surgery as trials directly comparing these methods are missing. Context: Surgery is the gold standard for the local treatment of primary renal cell carcinoma (RCC), but alternatives are emerging. We conducted a systematic review and meta-analysis to assess the results of prospective studies using definitive stereotactic body radiotherapy (SBRT) to treat primary localised RCC. Evidence acquisition: This review was prospectively registered in PROSPERO (CRD42023447274). We searched PubMed, Embase, Scopus, and Google Scholar for reports of prospective studies published since 2003, describing the outcomes of SBRT for localised RCC. Meta-analyses were performed for local control (LC), overall survival (OS), and rates of adverse events (AEs) using generalised linear mixed models (GLMMs). Outcomes were presented as rates with corresponding 95% confidence intervals (95% CIs). Risk-of-bias was assessed using the ROBINS-I tool. Evidence synthesis: Of the 2983 records, 13 prospective studies (n = 308) were included in the meta-analysis. The median diameter of the irradiated tumours ranged between 1.9 and 5.5 cm in individual studies. Grade ≥ 3 AEs were reported in 15 patients, and their estimated rate was 0.03 (95%CI: 0.01–0.11; n = 291). One- and two-year LC rates were 0.98 (95%CI: 0.95–0.99; n = 293) and 0.97 (95%CI: 0.93–0.99; n = 253), while one- and two-year OS rates were 0.95 (95%CI: 0.88–0.98; n = 294) and 0.86 (95%CI: 0.77–0.91; n = 224). There was no statistically significant heterogeneity, and the estimations were consistent after excluding studies at a high risk of bias in a sensitivity analysis. Major limitations include a relatively short follow-up, inhomogeneous reporting of renal function deterioration, and a lack of prospective comparative evidence. Conclusions: The short-term results suggest that SBRT is a valuable treatment method for selected inoperable patients (or those who refuse surgery) with localised RCC associated with low rates of high-grade AEs and excellent LC. However, until the long-term data from randomised controlled trials are available, surgical management remains a standard of care in operable patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous melanoma (CM) is an aggressive skin cancer that develops from melanocytic cells. The most important prognostic factor is still the vertical tumour thickness according to Breslow. Liver function is associated with better overall patient outcomes and is currently under increasing investigation in cancer patients. Current findings show that liver function is an important factor in different tumour entities and represents a potential biomarker. Therefore, we aimed to evaluate liver metabolism by using liver scores in CM. High tumour thickness (≥1.66 mm) and aspartate transaminase-to-platelet ratio index (APRI ≥ 0.2241) at the initial diagnosis were associated with a worse prognosis in stage I and II melanoma. Background: Neoadjuvant and adjuvant therapies are currently getting increasingly important in cutaneous melanoma (CM) management. However, there is still a lack of prognostic tools to identify which patients have a poor prognosis. There is increasing evidence that the liver score may be a potential prognostic parameter in different tumour types. The aim was to investigate whether established liver scores can establish the prognosis of CM. Methods: According to established methods, the APRI, the MELD score, the MELD-Na score and the De Ritis ratio were calculated from the laboratory values at the time of the initial diagnosis. Survival was compared with the Kaplan–Meier curve and tested with log-rank tests. Risk factors associated with cutaneous melanoma-specific survival (CMSS) and progression-free survival (PFS) were assessed by using the Cox proportional hazards regression model. To determine the diagnostic accuracy, we performed a time-dependent ROC analysis. Results: A total of 423 patients were included, including 141 patients in AJCC stage (2017) I (33.3%), 82 in stage II (19.4%), 128 in stage III (30.3%) and 72 in stage IV (17%). Median time until melanoma-specific death was 99 months (IQR: 37–126). In addition, 37.6% of patients relapsed with a median time to relapse of 88 months (IQR: 17.5–126). In all stages, tumour thickness and ulceration were independent markers for predicting CMSS and PFS (p < 0.05). The multivariable analysis with all stages showed no significant association with CM outcome for liver scores (p > 0.05). The subgroup analysis revealed that the APRI (≥0.2241) was associated with CMSS and PFS in melanoma stages I and II, independently of tumour thickness, age and ulceration (HR 2.57, 95% CI 1.14–5.75; HR 2.94, 95% CI 1.42–6.09, respectively). Conclusions: The 20-year prognosis of AJCC stage I and II CM was dependent on tumour thickness and the APRI. High tumour thickness and an APRI ≥ 0.2241 at the initial diagnosis were associated with a worse prognosis. Future studies should investigate the independent prognostic value of the APRI in low-stage CM. Furthermore, the APRI score could be a potential biomarker for nomograms. [ABSTRACT FROM AUTHOR]

Simple Summary: A systematic review was carried out to provide evidence regarding the role of stereotactic body radiation therapy (SBRT) for oligometastatic urothelial cancer (omUC). The present work aims to summarize and critically analyze the available data, with a focus on controversial areas and future directions in this emerging field. Eight studies were identified. Heterogeneous SBRT dose/fractionation and metastatic setting did not allow for a meta-analysis. SBRT showed a good toxicity profile, and the better outcomes for both local control and survival were associated with a biologically effective dose (BED10) ≥ 78 Gy. Background: Stereotactic body radiation therapy (SBRT) is the most commonly used metastasis-directed therapy (MDT) for oligometastatic urothelial carcinoma (omUC). Despite efforts in defining this disease entity, open questions remain concerning the role of MDT and the use of biomarkers, imaging, and its combination with systemic therapies. The aim of the present systematic review is to provide an updated overview of the current clinical evidence on SBRT for omUC in terms of survival and local control benefits. We also aim to provide updates on controversial areas and future directions in this emerging field. Methods: With a systematic approach, following PRISMA recommendations, we searched two databases to identify and select articles published up until March 2024 reporting the use of SBRT for omUC with or without concomitant systemic therapies. Prospective randomized or non-randomized studies as well as retrospective studies were included. Results: Eight studies were selected for data extraction and 293 omUC patients treated with SBRT were collectively analyzed. In metachronous omUC patients, SBRT delivered with ablative doses (BED10 ≥ 78 Gy) was associated with a 2-year overall survival (OS) rate of 50.7% (95% CI 35.1–64.4%). The use of sub-ablative SBRT doses (BED10 = 43.2 Gy) in combination with immunotherapy did not demonstrate significant clinical outcome improvement in two prospective studies. The overall tolerance was good, with only one study reporting toxicity of grade 3 in up to 18% of the patients treated with SBRT in combination with immunotherapy. Conclusions: SBRT is an effective and widely available MDT option in omUC, although this is based on a limited number of studies. Despite the attempt to use SBRT as an immune response trigger in combination with immunotherapy, no significant improvement in survival outcomes has been observed. The integration of new systemic agents with MDT will likely define a new scenario for the treatment of omUC. The review protocol was registered in PROSPERO, ID: CRD42024522381. [ABSTRACT FROM AUTHOR]

Simple Summary: The primary treatment for operable pancreatic cancer involves surgery followed by adjuvant therapy, with an increasing use of perioperative or neoadjuvant chemotherapy. We performed a network meta-analysis to assess the comparative efficacy of various treatment approaches for resectable pancreatic cancer. A total of 24 studies were incorporated, comparing 21 treatments with surgery in isolation. Eleven treatments showed superior efficacy compared to surgery alone. Excluding Asian studies, the perioperative regimen of gemcitabine combined with nab-paclitaxel was the most effective regimen. The findings endorse the utilization of perioperative and multi-agent chemotherapy as the favored intervention for operable PC in Western nations. The primary treatment for operable pancreatic cancer (PC) involves surgery followed by adjuvant therapy. Nevertheless, perioperative or neoadjuvant chemotherapy (CT) may be used to mitigate the likelihood of recurrence and mortality. This network meta-analysis (NMA) assesses the comparative efficacy of various treatment approaches for resectable PC. A thorough search was carried out on January 31, 2023, encompassing PubMed/MEDLINE, Cochrane Library, and Embase databases. We incorporated randomized clinical trials (RCTs) that compared surgical interventions with or without (neo)adjuvant or perioperative therapies for operable PC. We conducted a fixed-effects Bayesian NMA. We presented the effect sizes in terms of hazard ratios (HRs) for overall survival (OS) along with 95% credible intervals (95% CrIs). The treatment was deemed statistically superior when the 95% credible interval (CrI) did not encompass a null value (hazard ratio < 1). Treatment rankings were established based on the surface under the cumulative ranking curve (SUCRA). A total of 24 studies were incorporated, comparing 21 treatments with surgery in isolation. Eleven treatments showed superior efficacy compared to surgery alone, with HRs ranging from 0.38 for perioperative treatments to 0.73 for adjuvant 5-fluorouracil. After the exclusion of studies conducted in Asia, it was found that the perioperative regimen of gemcitabine combined with nab-paclitaxel was the most effective regimen (SUCRA, p = 0.99). The findings endorse the utilization of perioperative CT, especially multi-agent CT, as the favored intervention for operable PC in Western nations. [ABSTRACT FROM AUTHOR]

Simple Summary: Pulmonary neuroendocrine neoplasms (NENs) are a challenging type of lung cancer due to their varied clinical features and aggressive behavior. This study aimed to find specific metabolomic profiles in the blood of patients with different subtypes of lung NENs, which could help in early diagnosis. By analyzing 153 metabolites in the plasma of 120 NEN patients and comparing them with healthy individuals and patients with other lung cancers, we identified specific metabolic changes. These findings could lead to new biomarkers for early detection and better management of lung NENs, ultimately improving patient outcomes. Background/Objectives: Pulmonary neuroendocrine neoplasms (NENs) account for 20% of malignant lung tumors. Their management is challenging due to their diverse clinical features and aggressive nature. Currently, metabolomics offers a range of potential cancer biomarkers for diagnosis, monitoring tumor progression, and assessing therapeutic response. However, a specific metabolomic profile for early diagnosis of lung NENs has yet to be identified. This study aims to identify specific metabolomic profiles that can serve as biomarkers for early diagnosis of lung NENs. Methods: We measured 153 metabolites using liquid chromatography combined with mass spectrometry (LC-MS) in the plasma of 120 NEN patients and compared them with those of 71 healthy individuals. Additionally, we compared these profiles with those of 466 patients with non-small-cell lung cancers (NSCLCs) to ensure clinical relevance. Results: We identified 21 metabolites with consistently altered plasma concentrations in NENs. Compared to healthy controls, 18 metabolites were specific to carcinoid tumors, 5 to small-cell lung carcinomas (SCLCs), and 10 to large-cell neuroendocrine carcinomas (LCNECs). These findings revealed alterations in various metabolic pathways, such as fatty acid biosynthesis and beta-oxidation, the Warburg effect, and the citric acid cycle. Conclusions: Our study identified biomarker metabolites in the plasma of patients with each subtype of lung NENs and demonstrated significant alterations in several metabolic pathways. These metabolomic profiles could potentially serve as biomarkers for early diagnosis and better management of lung NENs. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aims to evaluate how radiotherapy treatment for cervical cancer affects the patient's short-term clinical status. In total, 69 cervical cancer patients were included in the study. The authors analyzed the impact of radiation on the short-term clinical adverse events and changes in blood cell counts. The results showed that factors such as age, body mass index, type of radiation therapy, and total radiation dose can predict the likelihood of a decrease in hemoglobin levels and the onset of other hematological adverse reactions. The findings of this study can help healthcare providers monitor and better care for cervical cancer patients who are at risk for these adverse reactions during treatment. Background: Cervical cancer ranks third in frequency among female cancers globally and causes high mortality worldwide. Concurrent chemoradiotherapy improves the overall survival in cervical cancer patients by 6% but it can cause significant acute and late toxicities affecting patient quality of life. Whole pelvis radiotherapy doses of 10–20 Gy can lead to myelosuppression and to subsequent hematological toxicities since pelvic bones contain half of bone marrow tissue. Methods: A total of 69 patients with IB-IVB-staged cervical cancer have been included in this retrospective cohort study. We analyzed clinical adverse events and changes in blood cell counts (hemoglobin, neutrophils, leukocytes, and platelets) during radiation or chemoradiotherapy received at the Oncological Institute of Bucharest from 2018 to 2021. Results: Decreases in hemoglobin levels of over 2.30 g/dL during treatment were associated with BMI > 23.2 kg/m2 (OR = 8.68, 95%CI = [1.01, 75.01]), age over 53 years (OR = 4.60 95%CI = [1.10, 19.22]), with conformational 3D irradiation (OR = 4.78, 95%CI = [1.31, 17.40]) and with total EQD2 of over 66.1 Gy (OR = 3.67, 95%CI = [1.02, 13.14]). The hemoglobin decrease rate of 0.07 g/dL/day was related to 95% isodose volume (OR = 18.00). Neutropenia is associated frequently with gastrointestinal side effects and with the bowel and rectal V45 isodoses (OR = 16.5 and OR = 18.0, respectively). Associations of total external and internal radiation dose with the time durations calculated from the initiation of treatment to the onset of hematological adverse reactions were also obtained. The maximum drop in leukocytes was observed before day 35 from the RT initiation in patients who underwent treatment with 3D conformal radiotherapy (OR = 4.44, 95%CI = [1.25, 15.82]). Neutrophil levels under 2.2 × 103/μL and thrombocyte levels under 131 × 103/μL during the follow-up period were associated with a total planned dose of 54 Gy to the pelvic region volume (OR = 6.82 and OR = 6.67, respectively). Conclusions: This study shows the existence of clinical and blood predictors of hematological adverse reactions in cervical cancer patients. Thus, patients who are in a precarious clinical situation, with low hematological values (but not yet abnormal), should be monitored during days 29–35 after the initiation of RT, especially if they are obese or over 53 years of age. [ABSTRACT FROM AUTHOR]