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Simple Summary: Diabetes and cancer are major global health problems that cause significant illness and death. Many cancer patients also have diabetes, which complicates their treatment, especially if surgery is needed. This review highlights the link between diabetes and cancer. It looks into how cancer treatments can worsen blood sugar control, examines the risks that surgery holds for patients with both conditions, and outlines the strategies that can be used to manage diabetes around the time of surgery. More research is needed to provide new strategies that can reduce complications following surgery in patients with diabetes and cancer. Background: Both diabetes and cancer are major global health issues that are among the leading causes of morbidity and mortality. There is a high prevalence of diabetes among cancer patients, many of whom require a surgical procedure. This review focuses on the operative complications in patients with diabetes and cancer, and the perioperative management of diabetes in cancer patients. Methodology: A literature search of articles in English—published between January 2010 and May 2024—was carried out using the databases PubMed, MEDLINE, Google Scholar, and the Cochrane Database of Systematic Reviews. The search primarily focused on the operative complications in patients with diabetes and cancer, and perioperative management strategies. Results: The relationship between cancer and diabetes is complex; cancer patients have a high risk of developing diabetes, while diabetes is a risk factor for certain cancers. In addition, various cancer therapies can induce or worsen diabetes in susceptible patients. Many individuals with cancer and diabetes require surgery, and due to underlying diabetes, they may have elevated risks for operative complications. Optimal perioperative management for these patients includes managing perioperative glycemia and other comorbid illnesses, adjusting diabetic and cancer treatments, optimizing nutrition, minimizing the duration of fasting, supporting early mobilization, and providing patient education to enable self-management. Conclusions: While evidence is limited, optimal perioperative management for patients with both diabetes and cancer is necessary in order to reduce surgical complications. Future studies are needed to develop evidence-informed perioperative strategies and improve outcomes for these patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with metastatic spine disease face significant challenges and limitations with current therapy options. The aim of this study is to explore the existing literature on spinal stereotactic radiosurgery (SRS) to understand its potential and effectiveness in managing this condition. The motivation stems from a desire to contribute to the field of medical science and improve patient care. This study highlights SRS as a safe and effective technique for managing spinal metastases. It offers good pain control and tumor control with minimal complications. This review strengthens the understanding of SRS for managing spinal metastases, emphasizing its efficacy and the need for personalized treatment plans. Overall, the findings highlight the evolving role of SRS in a multidimensional approach to managing spinal metastases. Background: This study investigated the efficacy of stereotactic radiosurgery (SRS) in managing spinal metastasis. Traditionally, surgery was the primary approach, but SRS has emerged as a promising alternative. Objective: The study aims to evaluate the efficacy of stereotactic radiosurgery in the management of spinal metastasis in terms of local tumor control, patient survival, and quality of life, identifying both advantages and limitations of SRS. Methods: Through an extensive literature search in PubMed with cross-referencing, relevant full-text-available papers published between 2012 and 2022 in English or German were included. The search string used was "metastatic spine diseases AND SRS OR stereotactic radiosurgery". Results: There is growing evidence of SRS as a precise and effective treatment. SRS delivers high radiation doses while minimizing exposure to critical neural structures, offering benefits like pain relief, limited tumor growth, and a low complication rate, even for tumors resistant to traditional radiation therapies. SRS can be a primary treatment for certain metastatic cases, particularly those without spinal cord compression. Conclusions: SRS appears to be a preferable option for oligometastasis and radioresistant lesions, assuming there are no contraindications. Further research is necessary to refine treatment protocols, determine optimal radiation dose and fractionation schemes, and assess the long-term effects of SRS on neural structures. [ABSTRACT FROM AUTHOR]

Simple Summary: The mortality of hepatocellular carcinoma (HCC) is rising globally, against the trend of other cancers. People with liver cirrhosis, even after hepatitis C treatment still face a high risk of HCC, requiring ongoing enrolment in HCC surveillance, and new technologies to improve diagnostic sensitivity are being explored. However, their impact on HCC survival remains uncertain relative to improving adherence to existing surveillance methods. This study uses mathematical modeling to assess how different strategies can reduce deaths from liver cancer in people with cirrhosis after being cured of hepatitis C. We compared the impact of improved adherence to ultrasound screening with increased HCC imaging sensitivity on HCC survival. Notably, we found that even modest enhancements in surveillance adherence (5–10 percentage point increases) exhibited significant survival benefits for people with hepatitis C-related cirrhosis, outperforming improvements in diagnostic sensitivity. Background & Aims: Hepatocellular carcinoma (HCC) presents a significant global health challenge, particularly among individuals with liver cirrhosis, with hepatitis C (HCV) a major cause. In people with HCV-related cirrhosis, an increased risk of HCC remains after cure. HCC surveillance with six monthly ultrasounds has been shown to improve survival. However, adherence to biannual screening is currently suboptimal. This study aimed to evaluate the effect of increased HCC surveillance uptake and improved ultrasound sensitivity on mortality among people with HCV-related cirrhosis post HCV cure. Methods: This study utilized mathematical modelling to assess HCC progression, surveillance, diagnosis, and treatment among individuals with cirrhosis who had successfully been treated for HCV. The deterministic compartmental model incorporated Barcelona Clinic Liver Cancer (BCLC) stages to simulate disease progression and diagnosis probabilities in 100 people with cirrhosis who had successfully been treated for hepatitis C over 10 years. Four interventions were modelled to assess their potential for improving life expectancy: realistic improvements to surveillance adherence, optimistic improvements to surveillance adherence, diagnosis sensitivity enhancements, and improved treatment efficacy Results: Realistic adherence improvements resulted in 9.8 (95% CI 7.9, 11.6) life years gained per cohort of 100 over a 10-year intervention period; 17.2 (13.9, 20.3) life years were achieved in optimistic adherence improvements. Diagnosis sensitivity improvements led to a 7.0 (3.6, 13.8) year gain in life years, and treatment improvements improved life years by 9.0 (7.5, 10.3) years. Conclusions: Regular HCC ultrasound surveillance remains crucial to reduce mortality among people with cured hepatitis C and cirrhosis. Our study highlights that even minor enhancements to adherence to ultrasound surveillance can significantly boost life expectancy across populations more effectively than strategies that increase surveillance sensitivity or treatment efficacy. [ABSTRACT FROM AUTHOR]

Simple Summary: MR-Linac is a novel magnetic resonance imaging (MRI)-guided radiotherapy (IGRT) that combines MRI with a linear accelerator (Linac). Although radiation therapy (RT) for lung cancer has traditionally been managed with a computed tomography (CT)-based workflow, an MR-Linac-based workflow would be able to address the many limitations of current practice. This narrative review summarizes the latest developments in MR-Linac lung cancer treatment, as well as its boundaries. Future research directions are also highlighted. Compared with computed tomography (CT), magnetic resonance imaging (MRI) traditionally plays a very limited role in lung cancer management, although there is plenty of room for improvement in the current CT-based workflow, for example, in structures such as the brachial plexus and chest wall invasion, which are difficult to visualize with CT alone. Furthermore, in the treatment of high-risk tumors such as ultracentral lung cancer, treatment-associated toxicity currently still outweighs its benefits. The advent of MR-Linac, an MRI-guided radiotherapy (RT) that combines MRI with a linear accelerator, could potentially address these limitations. Compared with CT-based technologies, MR-Linac could offer superior soft tissue visualization, daily adaptive capability, real-time target tracking, and an early assessment of treatment response. Clinically, it could be especially advantageous in the treatment of central/ultracentral lung cancer, early-stage lung cancer, and locally advanced lung cancer. Increasing demands for stereotactic body radiotherapy (SBRT) for lung cancer have led to MR-Linac adoption in some cancer centers. In this review, a broad overview of the latest research on imaging-guided radiotherapy (IGRT) with MR-Linac for lung cancer management is provided, and development pertaining to artificial intelligence is also highlighted. New avenues of research are also discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with stage IIB and IIC melanoma are considered to have high-risk localized disease and, in some cases, demonstrate worse recurrence-free and overall survival than patients with stage IIIA and even IIIB disease. The mainstay of treatment for patients with high-risk clinical stage II melanoma is surgical resection of the primary tumor and sentinel lymph node biopsy (SLNB), which confers accurate pathologic staging and prognostication for further treatment decisions. Building on the success of adjuvant therapy for stage III melanoma, the KEYNOTE-716 and CheckMate 76K trials found improved recurrence-free survival for patients with high-risk stage II melanoma with adjuvant pembrolizumab and nivolumab, respectively, after complete resection with SLNB. Given these findings, the National Comprehensive Cancer Network now recommends discussing adjuvant pembrolizumab or nivolumab with patients with high-risk stage IIB/C melanoma, weighing the risks of recurrence against the risks of treatment-related adverse events when making the decision regarding adjuvant therapy. Melanoma is the fifth most common cancer in the United States and accounts for the majority of all skin cancer-related deaths, making it the most lethal cutaneous malignancy. Systemic adjuvant therapy for stage IIB-IV melanoma is now approved for patients who have undergone surgical resection, given the appreciable risk of recurrence and mortality in this patient population. Despite the lower stage, high-risk stage II melanoma (stage IIB/IIC) can often exhibit an even more aggressive course when compared to stage IIIA/IIIB disease, thus justifying consideration of adjuvant therapy in these patients. In this review, we highlight the current standard of practice for the treatment of stage IIB/C melanoma, with a focus on adjuvant therapies supported by published landmark clinical trials, including anti-PD-1 therapy. Notably, adjuvant therapies approved thus far in this patient population have demonstrated an improvement in recurrence-free survival, while their impact on overall survival is pending. Finally, this review highlights currently ongoing trials and future directions for research and treatment possibilities for high-risk clinical stage II melanoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain tumors that spread from cancer elsewhere in the body (brain metastases) are becoming more common due to better cancer detection. While historically the outlook for patients with brain metastases was poor, new minimally invasive surgeries and targeted therapies are improving prognoses. Imaging features also depict responses to treatment and help identify the cause of patients' symptoms worsening due to disease or therapy. The development of new MRI techniques, the use of artificial intelligence, and advanced therapeutic delivery systems are creating even more powerful tools that are directly contributing to improving patient care and better survival for patients with brain metastases. This article explores the screening and diagnostic and prognostic roles of various imaging modalities, and recommends standard guidelines in the management of cancer patients to improve the overall survival rate. Brain metastases (BMs) are the most common central nervous system (CNS) neoplasms, with an increasing incidence that is due in part to an overall increase in primary cancers, improved neuroimaging modalities leading to increased detection, better systemic therapies, and longer patient survival. Objective: To identify cancer patients at a higher risk of developing CNS metastases and to evaluate associated prognostic factors. Methods: Review of imaging referral guidelines, response criteria, interval imaging assessment, modality of choice, as well as the association of clinical, serological, and imaging findings as per various cancer societies. Results: Quantitative response assessment of target and non-target brain metastases as well as an interval imaging protocol set up based on primary histological diagnosis and therapy status are discussed as per various cancer societies and imaging programs. Conclusion: Predictive factors in the primary tumor as well as independent variables of brain metastases like size, number, and response to therapy are necessary in management. The location of CNS metastases, symptomatic disease, as well as follow up imaging findings form a skeletal plan to prognosticate the disease, keeping in mind all the available new advanced therapy options of surgery, radiation, and immunotherapy that improve patient outcome significantly. [ABSTRACT FROM AUTHOR]

Simple Summary: Peritoneal sarcomatosis has traditionally been characterized by a poor prognosis and few effective treatment options. Improving radical surgery procedures with high percentages of complete cytoreduction and limited morbidity in centers with considerable experience, together with new systemic treatments associated with evolutionary development in oncology, may modify this concept. The wide histological variability of soft tissue sarcomas that can cause peritoneal sarcomatosis prompts its evaluation and treatment by expert multidisciplinary teams. An updated review of the scientific evidence in this regard and the consensus regarding recommendations for the adequate management of this condition represent the main objective of this study. Peritoneal sarcomatosis is a rare malignant disease with a poor prognosis, secondary to peritoneal dissemination of abdominopelvic soft tissue sarcomas. Its rarity, together with the characteristic histological heterogeneity and the historically poor response to systemic treatments, has prevented the establishment of widely accepted treatment criteria with curative intent. In this sense, radical cytoreductive surgery (CRS) with peritonectomy procedures and hyperthermic intraperitoneal chemotherapy (HIPEC), widely used in peritoneal carcinomatosis with excellent results, have not had the same evolutionary development in patients with peritoneal sarcomatosis. A multidisciplinary working group of experts in sarcomas and peritoneal oncological surgery established a series of recommendations based on current scientific evidence for the management of peritoneal sarcomatosis, taking into account the different histological subgroups of abdominopelvic sarcomas that can cause it depending on their origin: retroperitoneal sarcomas, uterine sarcomas, and visceral/peritoneal sarcomas of GIST (gastrointestinal stromal tumor) and non-GIST origin. This article shows the results of sarcoma experts' voting on the recommendations presented during the I Ibero-American Consensus on the Management of Peritoneal Sarcomatosis, which took place during the recent celebration of the III Hispanic-Portuguese Meeting for Updates on the Treatment of Sarcomas. [ABSTRACT FROM AUTHOR]

Simple Summary: Epithelioid vascular tumors are rare bone vascular lesions with a spectrum of overlapping cancer entities with varying degrees of malignant potential that remain controversial because of their rarity, unusual morphologic features, and unpredictable biologic behavior. The classification of vascular tumors of bone proposed by the World Health Organization in 2020 incorporated morphologic findings with available genetic evidence, including mainly angiosarcoma, epithelioid hemangioma, pseudomyogenic hemangioendothelioma, and epithelioid hemangioendothelioma. Here, we report our experience with eleven patients suffering from epithelioid hemangioma (EH) of the spine. As very few cases of EH of the spine have been reported in the literature, the evidence-based decision-making process for these patients can be very difficult. Thus, we propose a treatment flowchart based on our single center's experience. Epithelioid hemangioma is recognized by the World Health Organization as a distinct benign neoplasm; however, it is characterized by locally aggressive and rarely metastasizing behavior. Epithelioid vascular tumors are rare bony vascular lesions with varying degrees of malignant potential that remain controversial because of their rarity, unusual morphological features, and unpredictable biological behavior. The application of new molecular tools, such as massive parallel sequencing technologies, have provided new diagnostic markers and an opportunity to further refine the classification of bone vascular neoplasms. Very few cases of EH of the spine have been reported in the literature; therefore, it is difficult to make evidence-based therapeutic decisions for these patients. We report herein our experience with eleven patients suffering from EH of the spine. The study population included three males and eight females treated in our center from 2016 to the present; the average age was 44.8 years (range 14–75 years). The surgical, clinical, and radiographic data were retrospectively analyzed. The mean follow-up was 34.8 months. All patients presented lytic vertebral body lesions, six of them with pathological fracture. The majority of patients (80%) presented myelo-radicular compression. All patients were surgically treated, and preoperative embolization was performed in all cases. In light of the literature review and the clinical experience of our center, we can consider EH a locally aggressive tumor that requires surgical treatment in case of symptoms. Here, we propose a treatment algorithm that could be useful in the management of patients with this rare disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Cervical cancer, a very aggressive gynecological malignancy that also affects young women, remains significantly prevalent despite worldwide efforts in HPV vaccination campaigns. Cervical cancer research is experiencing a period of significant change, with intense ongoing debates on issues that could potentially transform current guidelines. Therefore, in light of these changes, guidelines and protocols will soon need significant updates. Hence, this paper aims to summarize and compare the most recent recommendations published by international gynecological oncology societies for patients with cervical cancer. A comparative analysis of American, Asian, and European guidelines was conducted to evaluate the different recommendations for diagnostic, surgical, medical, and follow-up management. Cervical cancer continues to have a significant incidence, despite global efforts in HPV vaccination campaigns. Managing this condition involves a diverse team of healthcare professionals. Research in this field is undergoing a period of great revolution in multiple areas, and international guidelines will soon have to adapt to new scientific evidence. This could be true mainly in locally advanced stages, and it could also be true for minimal invasive surgery. This paper aims to summarize and compare the most recent recommendations published by international gynecological oncological societies for patients with cervical cancer. From their comparison, common aspects and disagreements emerged, especially in the diagnostic pathway and follow-up strategies. Several issues that remain to be debated in the literature were addressed and compared, highlighting similarities and differences, from the role of the sentinel lymph node in early stages to that of the adjuvant hysterectomy in locally advanced tumors. On the surgical side, for this last subset of patients, currently, a laparotomic approach is recommended. At the same time, the advent of immunotherapy has just opened up new and promising scenarios in systemic treatment for locally advanced cervical cancer, and international guidelines will soon introduce it into their algorithms. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic neuroendocrine tumors are rare, but their incidence is rising. Several grades exist, and distinguishing between these is pivotal for clinical management. Currently, the grades can only be differentiated by histological analysis requiring invasive sampling. MicroRNAs are short non-protein coding RNA molecules that were shown to be differentially expressed in a wide variety of tumors. Here, we examined whether microRNAs could be exploited to differentiate grade 1 and 2 pancreatic neuroendocrine tumors and established significantly differentially expressed microRNAs. Pancreatic neuroendocrine neoplasms pose a growing clinical challenge due to their rising incidence and variable prognosis. The current study aims to investigate microRNAs (miRNA; miR) as potential biomarkers for distinguishing between grade 1 (G1) and grade 2 (G2) pancreatic neuroendocrine tumors (PanNET). A total of 33 formalin-fixed, paraffin-embedded samples were analyzed, comprising 17 G1 and 16 G2 tumors. Initially, literature-based miRNAs were validated via real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), confirming significant downregulation of miR-130b-3p and miR-106b in G2 samples. Through next-generation sequencing, we have identified and selected the top six miRNAs showing the highest difference between G1 and G2 tumors, which were further validated. RT-qPCR validation confirmed the downregulation of miR-30d-5p in G2 tumors. miRNA combinations were created to distinguish between the two PanNET grades. The highest diagnostic performance in distinguishing between G1 and G2 PanNETs by a machine learning algorithm was achieved when using the combination miR-106b + miR-130b-3p + miR-127-3p + miR-129-5p + miR-30d-5p. The ROC analysis resulted in a sensitivity of 83.33% and a specificity of 87.5%. The findings underscore the potential use of miRNAs as biomarkers for stratifying PanNET grades, though further research is warranted to enhance diagnostic accuracy and clinical utility. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper addresses the complex diagnostic challenges of pigmented lesions in the oral mucosa, ranging from benign to potentially malignant conditions. Our study provides a narrative review with a clinical case overview to guide clinicians in differentiating these lesions. By classifying pigmented lesions based on clinical and histological features, we emphasize the need for a structured approach to diagnosis. The study incorporates a retrospective analysis of cases from our oral medicine experience, utilizing clinical pictures and relevant histology. Our findings aim to enhance early and precise diagnosis, improving patient management and outcomes in dental and medical practice. This paper examines the clinical differentiation of pigmented lesions in the oral mucosa, which poses significant diagnostic challenges across dental and medical disciplines due to their spectrum from benign to potentially malignant conditions. Through a literature review and analysis of clinical cases, this study clarifies current diagnostic methodologies, with an emphasis on differential diagnosis, to provide a practical guide for clinicians. The classification of pigmented lesions, such as endogenous, focal melanocytic, and multifocal pigmentation, based on clinical and histological features, highlights the necessity for a structured and informed approach. A retrospective examination of cases from our oral medicine and pathology clinic, coupled with analysis of photographic and histological records, aids in classifying these lesions. This fosters a better understanding and promotes informed discussions among clinicians, ultimately aiming to enhance early and precise diagnosis, thus improving patient management and outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Bladder cancer (BC) possesses distinct molecular profiles that influence progression depending on its biological nature and delivered treatment intensity. Muscle-invasive BC (MIBC) and non-MIBC (NMIBC) demonstrate great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. Transurethral resection of bladder tumor (TURBT) is the standard treatment for NMIBC. The high risks of disease recurrence from residual tumor and progression after TURBT in NMIBC are well known. A new-generation photosensitizer, 5-Aminolevulinic acid (5-ALA), with a high tumor specificity, has been studied for detecting precise tumor areas. Moreover, it has been applied for treatment by producing its cytotoxic reactive oxygen species, as well as screening for urological carcinomas by excreting porphyrin in the blood and urine. Thus, 5-ALA may contribute to the inclusive treatment of NMIBC. Bladder cancer (BC) possesses distinct molecular profiles that influence progression depending on its biological nature and delivered treatment intensity. Muscle-invasive BC (MIBC) and non-MIBC (NMIBC) demonstrate great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. Transurethral resection of bladder tumor (TURBT) is the standard of care in treating NMIBC and serves both diagnostic and therapeutic purposes despite the prevalent recurrence and progression among many patients. In particular, flat urothelial carcinoma in situ and urothelial carcinoma with lamina propria invasion are the major precursors of MIBC. A new-generation photosensitizer, 5-Aminolevulinic acid (5-ALA), demonstrates high tumor specificity by illuminating the tumor lesion with a specific wavelength of light to produce fluorescence and has been studied for photodynamic diagnosis to detect precise tumor areas by TURBT. Additionally, it has been applied for treatment by producing its cytotoxic reactive oxygen species, as well as screening for urological carcinomas by excreting porphyrin in the blood and urine. Moreover, 5-ALA may contribute to screening before and after TURBT in NMIBC. Here, we summarize the updated evidence and ongoing research on photodynamic technology for NMIBC, providing insight into the potential for improving patient outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper investigates the expression of miR-101-3p, miR-106a-5p, and miR-326 in colon cancer tissues compared to adjacent healthy tissues. This study involves 40 colon cancer patients, whose tissue samples were analyzed using qRT-PCR. Results indicate that these miRNAs are overexpressed in adjacent healthy tissues but decrease in advanced cancer stages. This study suggests a strong correlation between miR-106a-5p and miR-326 with colon cancer severity. The findings propose that miRNA profiling could be useful for early diagnosis and prognosis in colon cancer management. Early diagnosis and prognosis of cancer progression through biomarker profiling are crucial in managing colon cancer patients. Our research aimed to investigate the expression of miR-101-3p, miR-106a-5p, and miR-326 in tumor and adjacent healthy tissues of colon cancer patients and determine their potential diagnostic utility. This study included 40 patients divided into four groups according to the TNM staging classification. MiRNA expression was analyzed using qRT-PCR. The results showed that miR-101-3p, miR-106a-5p, and miR-326 are overexpressed in adjacent healthy tissues but decrease in advanced cancer stages. MiR-106a-5p and miR-326 are strongly correlated with colon cancer severity. These findings suggest that miRNA profiling could be useful for early diagnosis and prognosis in colon cancer management. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer treatment options vary depending on the type and stage of the cancer. For non-small cell lung cancer (NSCLC), treatments may include surgery, chemotherapy, radiation therapy, targeted therapy, or a combination of these methods. Targeted therapies have demonstrated efficacy as adjuvant treatment in early-stage NSCLC when used alongside primary interventions such as surgery. In advanced stages of NSCLC, targeted therapies serve as a means of palliative care, enhancing quality of life and extending survival time. Our review article focuses on recent evidence of various treatment approaches and their impact on overall and progression-free survival in NSCLC patients, particularly targeting specific molecular and genetic alterations associated with NSCLC. Non-small cell lung cancer (NSCLC) presents a complex and diverse disease, exhibiting variations at individuals' cellular and histological levels. This complexity gives rise to different subtypes and genetic mutations, posing challenges for accurate diagnosis and effective treatment. Nevertheless, continuous progress in medical research and therapies is continually shaping the landscape of NSCLC diagnosis and management. The treatment of NSCLC has undergone significant advancements in recent years, especially with the emergence of targeted therapies that have shown remarkable efficacy in patients with actionable mutations. This has ushered in the era of personalized medicine in NSCLC treatment, with improvements in molecular and immunohistochemical techniques contributing to enhanced progression-free survival. This review focuses on the latest progress, challenges, and future directions in developing targeted therapies for NSCLC, including tyrosine kinase inhibitors (TKIs), DNA-damaging agents, immunotherapy regimens, natural drug therapy, and nanobodies. Furthermore, recent randomized studies have demonstrated enhanced overall survival in patients receiving different targeted and natural drug therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, scientists investigated how pathologists test for a protein called HER2 in a type of cancer called endometrial cancer (EC). They checked samples from 180 patients tested over the first two years following approval of the test in the clinic. They found that 28% of the samples had HER2 overexpression, which makes them eligible for HER2-targeted therapies. They also noticed that in some cases, the test results were different depending on the method used. This study shows that there are challenges in testing for HER2 in endometrial cancer and suggests that we need standardized guidelines to help doctors make better decisions about endometrial cancer treatment. HER2-targeted therapies have transformed the management of advanced or recurrent serous endometrial cancer (EC), leading to an increased clinical demand for HER2 testing. Despite its adoption in select academic centers, the global extent of such tumor testing is unclear. In this study, we report on the initial two-year experience of HER2 testing at a major academic center with a reference gynecologic oncology service and biomarker reference laboratory. All patients who underwent HER2 testing based on physician discretion, reflex HER2 testing, and reference laboratory requests were included. From February 2021 to October 2023, HER2 testing was performed on 192 tumor tissue samples from 180 EC patients. Serous carcinoma constituted 52% of samples, reflecting diagnostic challenges and limited therapeutic options for advanced EC. HER2 positivity was found in 28% of all cases and 30% of p53-aberrant cases. An immunohistochemistry (IHC) score of 3+ was found in 15% of samples, while IHC 2+ was found in 45% (13% IHC 2+/ISH+ and 32% IHC 2+/ISH−). The newly identified 'HER2-low' category comprised 46% of the samples. Heterogeneity was noted in 42% of HER2-positive cases, with complex patterns in 3%. NGS and HER2 IHC-FISH showed a 24% discordance, attributed to intratumoral heterogeneity, tumor cellularity, a small number of amplified cells, and the HER2/CEP17 ratio near the cut-off. This study offers real-world insights into HER2 testing in EC, highlighting the challenges and underscoring the need for standardized guidelines in specimen handling, proficiency testing, and scoring criteria to enhance patient management and therapeutic decision-making. [ABSTRACT FROM AUTHOR]

Simple Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)(COVID-19) has been reported in China since December 2019, and the global outbreak began in early 2020, with the first lockdowns in Europe implemented in February 2020. Restrictions taken to limit the exposure of patients to virus contagion had a notable impact for non-COVID-19 pathologies, including eye cancers. Despite the fact that uveal melanoma is the most common primary intraocular cancer in adults, the number of publications on the impact of the COVID-19 pandemic on the characteristics and treatment of uveal melanoma is limited, and most of them have included small patient samples. We studied the impact of the COVID-19 pandemic on the characteristics and management of uveal melanoma (UM) in a group of 1336 patients from the National Referral Center in Poland. (1) Background: to analyze the impact of the COVID-19 pandemic on the characteristics and management of uveal melanoma (UM) in the National Referral Center in Poland. (2) Materials and Methods: the retrospective analysis of 1336 patients who were newly diagnosed with UM at the Department of Ophthalmology and Ophthalmic Oncology, Jagiellonian University Collegium Medicum Krakow, Poland between 1 January 2018 and 31 December 2021. The demographic and clinical data were compiled, including localization, size, and treatment methods of tumors. (3) Results: In total, 728 patients with UM were included before the COVID-19 pandemic, in the years 2018–2019, and 608 were included during the COVID-19 pandemic, in the years 2020–2021. Fixed-base dynamics indicators for the incidence of uveal melanoma (base year 2018) in the National Referral Center in Poland were 80.22% and 86.81% in the years 2020 and 2021, respectively. UMs were statistically significantly larger and more frequently localized anterior to the equator of the eye globe in the year 2021 than in the year 2018 (Chi-square Pearson test p = 0.0001 and p = 0.0077, respectively). The rate of patients treated with enucleation increased from 15.94% in the year 2018 to 26.90% in the year 2021 (Chi-square Pearson test p = 0.0005). (4) Conclusions: Statistically significant differences were found in the management of uveal melanoma in the National Referral Center in Poland during the COVID-19 pandemic with tumors being larger, more frequently localized anterior to the equator of the eye globe, and more often enucleated. [ABSTRACT FROM AUTHOR]

Simple Summary: The introduction of trastuzumab deruxtecan is significantly changing the therapeutic landscape of advanced HER2-mutated non-small cell lung cancer (NSCLC). The results of the DESTINY-Lung04 trial are highly anticipated for their potential to redefine the first-line therapeutic standard for HER2-mutant disease. Furthermore, several studies evaluating combination therapy regimes are currently ongoing. This review outlines the current state of the art in the clinical management of HER2-altered NSCLC and explores potential future perspectives in the field of HER2 targeted strategies. For patients diagnosed with advanced HER2-altered non-small cell lung cancer (NSCLC), the current standard of care is represented by a platinum-pemetrexed-based chemotherapy, eventually in combination with immunotherapy. Different pan-HER tyrosine kinase inhibitors have been evaluated in limited phase II trials, yielding generally unsatisfactory outcomes, although certain genotypes demonstrated some clinical benefit. Conversely, antibody-drug conjugates (ADCs) targeting HER2, particularly trastuzumab-deruxtecan, have shown promising results against HER2-mutant disease, including a great intracranial activity in patients with brain metastasis. Based on the results obtained from DESTINY-Lung01 and DESTINY-Lung02 trials, trastuzumab deruxtecan received regulatory approval as the first targeted therapy for pre-treated, HER2-mutant, advanced NSCLC patients. More recently, the Food and Drug Administration (FDA) granted the accelerated approval of trastuzumab deruxtecan for advanced, pre-treated HER2-positive solid tumours with no other treatment options. In this scenario, emerging evidence is increasingly pointing towards the exploration of combination regimens with synergistic effects in the advanced disease. In this review, we provide a detailed summary of current approaches and emerging strategies in the management of HER2-altered NSCLC, also focusing on unmet needs, including the treatment of patients with brain metastases. [ABSTRACT FROM AUTHOR]

Simple Summary: The treatment of chronic lymphocytic leukemia is constantly evolving. Within the past few years, the treatment algorithm of patients with CLL has been radically transformed by the introduction of BTK and BCL2 inhibitors. This change has raised the need to optimize their use to ensure the greatest possible efficacy by personalizing therapies as much as possible. This review aims to clarify how to tailor the sequence of different treatments in CLL, and illustrate what resources are currently available to patients previously treated with the different molecules. As treatments with BTK inhibitors and BCL2 inhibitors have replaced the use of chemoimmunotherapy in CLL in both first-line and relapsed patients, it becomes critical to rationalize their use and exploit the full potential of each drug. Despite their proven, robust, and manifest efficacy, BTKis and BCL2is fail to provide long-term disease control in some categories of patients, and to date this is an unmet clinical need that is critical to recognize and address. Ongoing clinical trials are evaluating new treatment algorithms and new molecules to progressively thin this population. In this review for each category of patients we explicate the different possible patterns of treatment sequencing based on currently available evidence, starting from the frontline to currently ongoing trials, in order to optimize therapies as much as possible. [ABSTRACT FROM AUTHOR]

Simple Summary: Targeted agents, such as Bruton's Tyrosine Kinase inhibitors and BCL-2 inhibitors, have transformed the treatment landscape for Chronic Lymphocytic Leukemia (CLL). While these therapies offer a more precise approach compared to traditional chemotherapy, they also bring a spectrum of adverse events that can impact patient health and treatment efficacy. This review aims to provide a comprehensive overview of the management strategies for these AEs, encompassing cardiac complications, Tumor Lysis Syndrome, bleeding risks, and other organ-specific challenges. Our goal is to equip healthcare professionals with the knowledge to effectively manage these adverse events, enhancing patient safety and optimizing therapeutic outcomes. The insights from this review will contribute to better clinical decision-making and patient care in CLL treatment, highlighting the significance of personalized management in the era of targeted therapy. The treatment landscape for CLL has undergone a profound transformation with the advent of targeted agents (TAs) like Bruton's Tyrosine Kinase inhibitors (BTKis) and BCL-2 inhibitors (BCL-2is). These agents target crucial cellular pathways in CLL, offering superior efficacy over traditional chemo-immunotherapy, which has led to improved progression-free and overall survival rates. This advancement promises enhanced disease control and potentially normal life expectancy for many patients. However, the journey is not without challenges, as these TAs are associated with a range of adverse events (AEs) that can impact treatment efficacy and patient quality of life. This review focuses on detailing the various AEs related to TA management in CLL, evaluating their frequency and clinical impact. The aim is to present a comprehensive guide to the effective management of these AEs, ensuring optimal tolerability and efficacy of TAs. By reviewing the existing literature and consolidating findings, we provide insights into AE management, which is crucial for maximizing patient outcomes in CLL therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma (GBM) is the most aggressive primary brain tumor. Despite intensive management with surgery, radio-, and chemotherapy, prognosis remains bleak, with a median survival of 15 months. Recently, microglia, the resident immune cells of the brain, have emerged as a potential therapeutic target for treatment of GBM. However, precisely how microglia interact with GBM cells and may be exploited for novel immunotherapies is not well understood. Here, we discuss the role of microglia in the GBM tumor microenvironment (TME), focusing particularly on the pro- and anti-tumorigenic pathways involved. We first introduce microglia and their role in the normal brain environment. Next, we discuss the microglia-GBM crosstalk, delving into specific factors that mediate these interactions. Finally, we present a comprehensive discussion of suitable microglial pathways that can be targeted to modulate the immune response in the TME to halt tumor progression. We discuss this in the context of current and past clinical trials targeting microglia, summarizing both successes and failures, and highlight promising pathways that are yet to be explored, suggesting future directions for study. Glioblastoma (GBM) is one of the most aggressive and devastating primary brain tumors, with a median survival of 15 months following diagnosis. Despite the intense treatment regimen which routinely includes maximal safe neurosurgical resection followed by adjuvant radio- and chemotherapy, the disease remains uniformly fatal. The poor prognosis associated with GBM is multifactorial owing to factors such as increased proliferation, angiogenesis, and metabolic switching to glycolytic pathways. Critically, GBM-mediated local and systemic immunosuppression result in inadequate immune surveillance and ultimately, tumor-immune escape. Microglia—the resident macrophages of the central nervous system (CNS)—play crucial roles in mediating the local immune response in the brain. Depending on the specific pathological cues, microglia are activated into either a pro-inflammatory, neurotoxic phenotype, known as M1, or an anti-inflammatory, regenerative phenotype, known as M2. In either case, microglia secrete corresponding pro- or anti-inflammatory cytokines and chemokines that either promote or hinder tumor growth. Herein, we review the interplay between GBM cells and resident microglia with a focus on contemporary studies highlighting the effect of GBM on the subtypes of microglia expressed, the associated cytokines/chemokines secreted, and ultimately, their impact on tumor pathogenesis. Finally, we explore how understanding the intricacies of the tumor-immune landscape can inform novel immunotherapeutic strategies against this devastating disease. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the adverse effects of selective intra-arterial chemotherapy (SIAC) on the eyes and optic nerves of retinoblastoma patients using magnetic resonance imaging (MRI). We aim to understand the post-SIAC changes in orbital and ocular structures and evaluate their impact on eye and optic nerve growth. Experienced radiologists analyzed MR images of retinoblastoma eyes treated with SIAC, comparing them to eyes treated with other eye-saving methods and healthy eyes. Results reveal common adverse effects like inflammation and vascular changes, along with significant ocular growth arrest and optic nerve atrophy in eyes treated with SIAC, especially in children treated ≤ 12 months of age. This study underscores the importance of careful consideration when utilizing SIAC, particularly in young patients, due to its potential negative effects on eye and optic nerve development. This retrospective multicenter study examines therapy-induced orbital and ocular MRI findings in retinoblastoma patients following selective intra-arterial chemotherapy (SIAC) and quantifies the impact of SIAC on ocular and optic nerve growth. Patients were selected based on medical chart review, with inclusion criteria requiring the availability of posttreatment MR imaging encompassing T2-weighted and T1-weighted images (pre- and post-intravenous gadolinium administration). Qualitative features and quantitative measurements were independently scored by experienced radiologists, with deep learning segmentation aiding total eye volume assessment. Eyes were categorized into three groups: eyes receiving SIAC (Rb-SIAC), eyes treated with other eye-saving methods (Rb-control), and healthy eyes. The most prevalent adverse effects post-SIAC were inflammatory and vascular features, with therapy-induced contrast enhancement observed in the intraorbital optic nerve segment in 6% of patients. Quantitative analysis revealed significant growth arrest in Rb-SIAC eyes, particularly when treatment commenced ≤ 12 months of age. Optic nerve atrophy was a significant complication in Rb-SIAC eyes. In conclusion, this study highlights the vascular and inflammatory adverse effects observed post-SIAC in retinoblastoma patients and demonstrates a negative impact on eye and optic nerve growth, particularly in children treated ≤ 12 months of age, providing crucial insights for clinical management and future research. [ABSTRACT FROM AUTHOR]

Simple Summary: This is a contemporary overview of how cardiology issues arise in the breast cancer population from anti-cancer agents (e.g., chemotherapy, targeted therapy, endocrine therapy, and radiotherapy). The overview demonstrates how we identify these cardiac issues and what we can do about them. Breast cancer is amongst the most common invasive cancers in adults. There are established relationships between anti-cancer treatments for breast cancer and cardiovascular side effects. In recent years, novel anti-cancer treatments have been established, as well as the availability of multi-modal cardiac imaging and the sophistication of treatment for cardiac disease. This review provides an in-depth overview regarding the interface of breast cancer and cancer therapy-related cardiovascular toxicity. Specifically, it reviews the pathophysiology of breast cancer, the method of action in therapy-related cardiovascular toxicity from anti-cancer treatment, the use of echocardiography, cardiac CT, MRI, or nuclear medicine as diagnostics, and the current evidence-based treatments available. It is intended to be an all-encompassing review for clinicians caring for patients in this situation. [ABSTRACT FROM AUTHOR]

Simple Summary: In this paper, we look at the role of artificial intelligence (AI) advancements in prostate cancer diagnosis and management. Specifically, we focus on magnetic resonance prostate reconstruction, prostate cancer detection/stratification/reconstruction, positron emission tomography/computed tomography, androgen deprivation therapy, and prostate biopsy. A total of 64 studies were included. Our results showed that deep learning AI models in prostate cancer diagnosis show promise but are not yet ready for clinical use due to variability in methods, labels, and evaluation criteria. Conducting additional research while acknowledging the limitations is crucial for reinforcing the utility and effectiveness of AI-based models in clinical settings. Background: The aim was to analyze the current state of deep learning (DL)-based prostate cancer (PCa) diagnosis with a focus on magnetic resonance (MR) prostate reconstruction; PCa detection/stratification/reconstruction; positron emission tomography/computed tomography (PET/CT); androgen deprivation therapy (ADT); prostate biopsy; associated challenges and their clinical implications. Methods: A search of the PubMed database was conducted based on the inclusion and exclusion criteria for the use of DL methods within the abovementioned areas. Results: A total of 784 articles were found, of which, 64 were included. Reconstruction of the prostate, the detection and stratification of prostate cancer, the reconstruction of prostate cancer, and diagnosis on PET/CT, ADT, and biopsy were analyzed in 21, 22, 6, 7, 2, and 6 studies, respectively. Among studies describing DL use for MR-based purposes, datasets with magnetic field power of 3 T, 1.5 T, and 3/1.5 T were used in 18/19/5, 0/1/0, and 3/2/1 studies, respectively, of 6/7 studies analyzing DL for PET/CT diagnosis which used data from a single institution. Among the radiotracers, [68Ga]Ga-PSMA-11, [18F]DCFPyl, and [18F]PSMA-1007 were used in 5, 1, and 1 study, respectively. Only two studies that analyzed DL in the context of DT met the inclusion criteria. Both were performed with a single-institution dataset with only manual labeling of training data. Three studies, each analyzing DL for prostate biopsy, were performed with single- and multi-institutional datasets. TeUS, TRUS, and MRI were used as input modalities in two, three, and one study, respectively. Conclusion: DL models in prostate cancer diagnosis show promise but are not yet ready for clinical use due to variability in methods, labels, and evaluation criteria. Conducting additional research while acknowledging all the limitations outlined is crucial for reinforcing the utility and effectiveness of DL-based models in clinical settings. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer cachexia (CC) is a complex syndrome requiring a multimodal approach. Although a universally accepted definition and staging criteria for cancer cachexia remains elusive, there is general consensus regarding the importance of elements such as weight loss, muscle wasting, and poor appetite. Epidemic trends of obesity and overlapping conditions such as sarcopenia and frailty further complicate CC definition, staging, and relevant outcome measures. Despite progress in understanding the molecular mechanisms of CC, there is no single, consistently effective pharmacotherapy for CC and, unsurprisingly, there are variations among guidelines regarding management. Current pharmacologic research is focused on promising targeted treatments; however, a multimodal approach is likely to be more effective than any single therapeutic agent. This narrative review provides an update on non-pharmacologic and pharmacologic treatment and proposes a theoretical model for management of CC, which includes a multimodal therapeutic approach directed at the various mechanisms contributing to CC. Despite a better understanding of the mechanisms causing cancer cachexia (CC) and development of promising pharmacologic and supportive care interventions, CC persists as an underdiagnosed and undertreated condition. CC contributes to fatigue, poor quality of life, functional impairment, increases treatment related toxicity, and reduces survival. The core elements of CC such as weight loss and poor appetite should be identified early. Currently, addressing contributing conditions (hypothyroidism, hypogonadism, and adrenal insufficiency), managing nutrition impact symptoms leading to decreased oral intake (nausea, constipation, dysgeusia, stomatitis, mucositis, pain, fatigue, depressed mood, or anxiety), and the addition of pharmacologic agents when appropriate (progesterone analog, corticosteroids, and olanzapine) is recommended. In Japan, the clinical practice has changed based on the availability of Anamorelin, a ghrelin receptor agonist that improved lean body mass, weight, and appetite-related quality of life (QoL) compared to a placebo, in phase III trials. Other promising therapeutic agents currently in trials include Espindolol, a non-selective β blocker and a monoclonal antibody to GDF-15. In the future, a single therapeutic agent or perhaps multiple medications targeting the various mechanisms of CC may prove to be an effective strategy. Ideally, these medications should be incorporated into a multimodal interdisciplinary approach that includes exercise and nutrition. [ABSTRACT FROM AUTHOR]

Simple Summary: Patient awareness of postoperative lymphedema has been poorly explored in gynecologic oncology. While current research has extensively focused on the impact of pelvic and paraortic lymphadenectomy on patient survival, it remains relatively unknown how much of this information is actually discussed with patients that undergo surgery or radiation therapy for the treatment of their disease. In the present study we present information relevant to lymphedema awareness provided by 386 gynecological cancer patients that were treated for gynecologic malignancy. A significant lack of appropriate counseling was noted that seems to be driven by lack of appropriate physician training. This information calls for further research that will help improve patient counseling and pre-treatment decision making. Introduction: Patient awareness of postoperative lymphedema in the field of gynecologic oncology has been poorly documented in the international literature. We wished to capture and document the awareness among gynecological cancer survivors about postoperative lymphedema, including aspects such as the adequacy of perioperative counseling, management, and quality of life. Methods: A web-based survey comprising 25 multiple-choice questions was distributed to gynecological cancer advocacy groups within the European Network of Gynecological Cancer Advocacy Groups (ENGAGe) group. The survey was validated in a pilot group of gynecological patients prior to distribution. Results: Overall, 386 women from 20 countries completed the questionnaire. Only half of the patients (n = 211) knew what lymphedema is, whereas 52% of the respondents stated that they were never informed at their pre-operative assessment about the potential risk of developing lymphedema. Fifty-three percent of those women who were informed about the risk and management of lymphedema received information through self-initiative, connecting mainly with patient groups or online. Approximately 84% of patients with lymphedema reported that they informed their doctor about their symptoms. Ninety-four patients (55.3%, which is not 55% of the 386) were treated for lymphedema. Forty-five women out of 136 reported that lymphedema significantly affected their everyday lives. Discussion: We report a large lack of awareness and a significant gap of knowledge about the risks and treatment options related to postoperative lymphedema among gynecological cancer survivors. Institutional practice routines and awareness among professionals need to be urgently recalled and adapted to adequately inform and support gynecological cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck paragangliomas (HNPGLs) are rare and have high rates of genetic mutations. SDHx mutations currently account for the vast majority of mutations identified in HNPGLs, and SDHB and SDHD are the two most common types. Surgery remains the definitive treatment, while radiation therapy is being increasingly used as an adjuvant or primary treatment for surgically challenging or inoperable cases. Our study provided clinical and outcome data on a large cohort of patients with HNPGLs and the results can help provide guidance on improving the care and outcomes of patients with HNPGL. Head and neck paragangliomas (HNPGLs) are rare and have high rates of genetic mutations. We conducted a retrospective review of 187 patients with 296 PGLs diagnosed between 1974 and 2023. The mean age of diagnosis was 48.8 years (range 10 to 82) with 69.0% female and 26.5% patients with multiple PGLs. Among 119 patients undergoing genetic testing, 70 (58.8%) patients had mutations, with SDHB (30) and SDHD (26) being the most common. The rates of metastasis and recurrence were higher among patients with SDHB mutations or SDHD mutations associated with multiple PGLs. Metabolic evaluation showed elevated plasma dopamine levels were the most common derangements in HNPGL. MRI and CT were the most common anatomic imaging modalities and DOTATATE was the most common functional scan used in this cohort. Most patients (81.5%) received surgery as the primary definitive treatment, while 22.5% patients received radiation treatment, mostly as an adjuvant therapy or for surgically challenging or inoperable cases. Systemic treatment was rarely used in our cohort. Our single-center experience highlights the need for referral for genetic testing and metabolic evaluation and for a team-based approach to improve the clinical outcomes of patients with HNPGLs. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic neuroendocrine tumors (PNETs) represent a small portion of pancreatic neoplasms and can manifest as either functional or non-functional. Managing these tumors presents a challenge due to their rarity and heterogenous tumor biology. This manuscript offers a comprehensive review of PNET types, classification, and management strategies, with a focus on the evolving landscape of pancreatic surgery. It aims to assist clinicians in facilitating the management of these increasingly common tumors and optimizing patient outcomes. The incidence of pancreatic neuroendocrine tumors (PNETs) is on the rise primarily due to the increasing use of cross-sectional imaging. Most of these incidentally detected lesions are non-functional PNETs with a small proportion of lesions being hormone-secreting, functional neoplasms. With recent advances in surgical approaches and systemic therapies, the management of PNETs have undergone a paradigm shift towards a more individualized approach. In this manuscript, we review the histologic classification and diagnostic approaches to both functional and non-functional PNETs. Additionally, we detail multidisciplinary approaches and surgical considerations tailored to the tumor's biology, location, and functionality based on recent evidence. We also discuss the complexities of metastatic disease, exploring liver-directed therapies and the evolving landscape of minimally invasive surgical techniques. [ABSTRACT FROM AUTHOR]

Simple Summary: This review discusses new radiotracers for diagnosing and treating thyroid cancer. It focuses on PSMA-based tracers, FAPI-based tracers, RGD-based tracers, and 18F-TFB. These tracers show promise in detecting thyroid cancer, especially in challenging cases. They offer better accuracy and help in choosing the right treatment. Further research is needed, especially on the promising 18F-TFB and FAP-targeting tracers, to improve thyroid cancer staging and treatment outcomes. Thyroid cancer poses a significant challenge in clinical management, necessitating precise diagnostic tools and treatment strategies for optimal patient outcomes. This review explores the evolving field of radiotracers in the diagnosis and management of thyroid cancer, focusing on prostate-specific membrane antigen (PSMA)-based radiotracers, fibroblast activation protein inhibitor (FAPI)-based radiotracers, Arg-Gly-Asp (RGD)-based radiotracers, and 18F-tetrafluoroborate (18F-TFB). PSMA-based radiotracers, initially developed for prostate cancer imaging, have shown promise in detecting thyroid cancer lesions; however, their detection rate is lower than 18F-FDG PET/CT. FAPI-based radiotracers, targeting fibroblast activation protein highly expressed in tumors, offer potential in the detection of lymph nodes and radioiodine-resistant metastases. RGD-based radiotracers, binding to integrin αvβ3 found on tumor cells and angiogenic blood vessels, demonstrate diagnostic accuracy in detecting radioiodine-resistant thyroid cancer metastases. 18F-TFB emerges as a promising PET tracer for imaging of lymph node metastases and recurrent DTC, offering advantages over traditional methods. Overall, these radiotracers show promise in enhancing diagnostic accuracy, patient stratification, and treatment selection in differentiated thyroid cancer, warranting further research and clinical validation. Given the promising staging capabilities of 18F-TFB and the efficacy of FAP-targeting tracers in advanced, potentially dedifferentiated cases, continued investigation in these domains is justified. [ABSTRACT FROM AUTHOR]

Simple Summary: Our research demonstrates that genetic factors may play a significant role in the development of non-small cell lung cancer (NSCLC). We focused on the Hispanic/Latinx community in South Florida to determine if certain germline (or inherited) variants in DNA were expressed in patients diagnosed with NSCLC. We found that certain germline variants were present at a higher rate in the Hispanic/Latinx community. Identification of these variants may change the management of their cancer. Pathogenic germline variants (PGVs) may be under-detected as causative etiologies in patients with non-small cell lung cancer (NSCLC). The prevalence of PGVs has been reported between 1 and 15% of patients, depending on the patient population. The rate within Hispanic/Latinx populations remains unknown. We retrospectively analyzed the genomic results (Guardant360, Redwood City, CA, USA) of 878 patients with advanced or metastatic NSCLC at five centers in South Florida, USA, from 2019 to 2022 to analyze the rate of incidental PGVs (iPGVs) identified via circulating cell-free tumor DNA (ctDNA). We then stratified the results by tumor histology, age, gender, race, ethnicity, genetic pathway, and co-mutations. Twenty-one iPGVs were identified (21/878 = 2.4%). Among the 21 iPGVs identified, 14 patients were female (66.7%) and 7 were male (33.3%), with a median age of 67 years and tobacco history of 2.5 pack-years. In total, 52.4% of patients identified as Hispanic/Latinx (n = 11) of any race; 19.0% as Ashkenazi Jewish (n = 4), 9.5% as non-Hispanic/Latinx black (n = 2), and 19.0% as non-Hispanic/Latinx white (n = 4). iPGVs in the homologous recombination repair pathway were solely expressed in this cohort (10 ATM, 8 BRCA2, and 3 BRCA1). In total, 76% (16/21) of patients with iPGVs co-expressed somatic alterations, with 56% (9/16) demonstrating alterations in targetable genes. Overall, our real-world findings offer a point prevalence of iPGVs in patients with NSCLC of diverse populations, such as patients who report Hispanic/Latinx ethnicity. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer is the fourth most common female malignancy in high socioeconomic index nations and the sixth most common cancer in women worldwide. The disease incidence has increased globally by 132% in the last 30 years, and this trend is set to continue in light of an ageing population and increasing levels of obesity and diabetes. Although more women than ever before are dying of endometrial cancer, the mortality rates are falling due to recent advances in early diagnosis and treatment. Our understanding of the molecular drivers of endometrial cancer has increased substantially, and doctors are now, for the first time, starting to translate this knowledge into the true personalisation of care. This review summarises the recent advances in the field and identifies avenues for future exploration. Endometrial cancer is the sixth commonest cancer in women worldwide, with over 417,000 diagnoses in 2020. The disease incidence has increased by 132% over the last 30 years and is set to continue to rise in response to an ageing population and increasing global rates of obesity and diabetes. A greater understanding of the mechanisms driving endometrial carcinogenesis has led to the identification of potential strategies for primary disease prevention, although prospective evaluation of their efficacy within clinical trials is still awaited. The early diagnosis of endometrial cancer is associated with improved survival, but has historically relied on invasive endometrial sampling. New, minimally invasive tests using protein and DNA biomarkers and cytology have the potential to transform diagnostic pathways and to allow for the surveillance of high-risk populations. The molecular classification of endometrial cancers has been shown to not only have a prognostic impact, but also to have therapeutic value and is increasingly used to guide adjuvant treatment decisions. Advanced and recurrent disease management has also been revolutionised by increasing the use of debulking surgery and targeted treatments, particularly immunotherapy. This review summarises the recent advances in the prevention, diagnosis and treatment of endometrial cancer and seeks to identify areas for future research. [ABSTRACT FROM AUTHOR]

Simple Summary: Pituitary tumours are slowly growing tumours of the pituitary gland, and they can cause damage due to the invasion or compression of surrounding tissues, such as the nerves responsible for vision, and/or due to altered hormone production. The treatment of pituitary tumours is complex and requires a wide range of medical specialists, including neurosurgeons, endocrinologists, neuropathologists, neuroradiologists, neuro-ophthalmologists, and otorhinolaryngologists, among others. Thus, optimal management of patients with pituitary tumours is best provided in the context of a dedicated multidisciplinary team with expertise in treating such conditions. The optimal care for patients with pituitary tumours is best provided in a multidisciplinary and collaborative environment, which requires the contribution of multiple medical specialties working together. The benefits and advantages of the pituitary multidisciplinary team (MDT) are broad, and all relevant international consensus and guidelines in the field recommend that patients with pituitary tumours should always be managed in a MDT. Endocrinologists and neurosurgeons are normally the leading specialties within the pituitary MDT, supported by many other specialties with significant contributions to the diagnosis and management of pituitary tumours, including neuropathology, neuroradiology, neuro-ophthalmology, and otorhinolaryngology, among others. Here, we review the literature concerning the concepts of Pituitary MDT/Pituitary Tumour Centre of Excellence (PTCOE) in terms of their mission, goals, benefits, structure, proposed models of function, and barriers, and we also provide the views of different specialists involved in our Pituitary MDT. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer patients with a specific gene mutation often undergo tissue biopsies to guide treatment. But what if a simple blood test could do the same? This review explores "liquid biopsies", which detect circulating tumor DNA (ctDNA) in the blood, offering several advantages. For early-stage disease, it could help decide on treatment after surgery. In advanced stages, it can identify genetic changes in the tumor that might affect treatment response. Additionally, tracking ctDNA levels can monitor treatment progress and detect resistance early. While tissue biopsies remain standard, liquid biopsies are becoming a recommended alternative. Ongoing research aims to improve test sensitivity for early detection, refine treatment approaches based on ctDNA results, and explore other bodily fluids for even better detection. Making liquid biopsies more accessible and integrated into routine care could significantly improve lung cancer management. Circulating tumor DNA (ctDNA) offers a new paradigm in optimizing treatment strategies for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). Its potential spans early-stage disease, influencing adjuvant therapy, to advanced disease, where it aids in identifying genomic markers and resistance mechanisms. This review explores the evolving landscape of utilizing liquid biopsies, specifically circulating tumor DNA (ctDNA), in the management of NSCLC with EGFR mutations. While tissue-based genomic testing remains the cornerstone for clinical decision-making, liquid biopsies offer a well-validated, guideline-recommended alternative approach. Ongoing trials integrating ctDNA for EGFR-mutant NSCLC management are also discussed, shedding light on the potential of ctDNA in early-stage disease, including its applications in prognostication, risk stratification, and minimal residual disease detection post-curative intent treatment. For advanced disease, the role of ctDNA in identifying resistance mechanisms to EGFR tyrosine kinase inhibitors (TKIs) is explored, providing insights into disease progression and guiding treatment decisions. This review also addresses the challenges, including the limitations in sensitivity of current assays for disease recurrence detection, and calls for future studies to refine treatment approaches, standardize reporting, and explore alternative biofluids for enhanced sensitivity. A systematic approach is crucial to address barriers to ctDNA deployment, ensuring equitable access, and facilitating its integration into routine clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer is a common cancer diagnosis, with many patients suffering from metastatic disease. Unfortunately, the prognosis for these patients remains grim, but there is a cohort in whom surgery remains a viable option, with the potential for a cure. The management of this cohort of patients is complex and requires the guidance of a dedicated hepatobiliary surgeon. There also remains a deep interplay between perioperative and operative decisions, which ultimately need tailoring to each individual patient. In this review, we aim to define these key perioperative and operative considerations in the contemporary management of colorectal liver metastasis. Colorectal cancer is the third most common cancer in the United States and the second most common cause of cancer-related death. Approximately 20–30% of patients will develop hepatic metastasis in the form of synchronous or metachronous disease. The treatment of colorectal liver metastasis (CRLM) has evolved into a multidisciplinary approach, with chemotherapy and a variety of locoregional treatments, such as ablation and portal vein embolization, playing a crucial role. However, resection remains a core tenet of management, serving as the gold standard for a curative-intent therapy. As such, the input of a dedicated hepatobiliary surgeon is paramount for appropriate patient selection and choice of surgical approach, as significant advances in the field have made management decisions extremely nuanced and complex. We herein aim to review the contemporary surgical management of colorectal liver metastasis with respect to both perioperative and operative considerations. [ABSTRACT FROM AUTHOR]

Simple Summary: In this retrospective study conducted at a tertiary cancer center, real-world outcomes from advanced melanoma patients were analyzed approximately a decade after the introduction of immune checkpoint inhibitors and BRAF/MEK-inhibitors into clinical use. The study included patients in the resectable/adjuvant (n = 331) and unresectable/metastatic setting (n = 375). Adjuvant anti-PD1 or BRAF/MEK inhibitors demonstrated 3-year relapse-free survival rates of 53% and 67.6%, respectively. Toxicity led to treatment cessation in 10.9% of cases, with no impact on relapse-free or overall survival rates unless treatment duration was <3 months. First-line treatment in the unresectable setting showed 5-year overall survival rates of 46.5% for anti-PD1, 52.4% for anti-CTLA4/PD1, and 49.2% for BRAF/MEK inhibitors. Brain metastases and elevated LDH levels substantially affected overall survival. For patients with progressive disease, the median overall survival rate dropped below two years. The study highlights real-world clinical management and outcomes of advanced melanoma patients, emphasizing the efficacy of approved treatments while addressing ongoing challenges. Background: Immune checkpoint inhibitors (ICIs) and BRAF/MEK inhibitors (BRAF/MEKi) have drastically changed the outcomes of advanced melanoma patients in both the resectable/adjuvant and unresectable/metastatic setting. In this follow-up analysis of real-world data, we aimed to investigate the clinical management and outcomes of advanced melanoma patients in a tertiary referral center in Switzerland approximately a decade after the introduction of ICIs and BRAF/MEKi into clinical use. Moreover, we aimed to compare the results with seminal phase 3 trials and to identify areas of high unmet clinical need. Methods: This single-center retrospective cohort study analyzed the melanoma registry of the University Hospital Zurich, a tertiary cancer center in Switzerland, and included patients treated in the resectable/adjuvant (n = 331) or unresectable/metastatic setting (n = 375). Results: In the resectable setting, adjuvant anti-PD1 or BRAF/MEKi showed a 3-year relapse-free survival (RFS) of 53% and 67.6%, respectively, and the overall median RFS was 50 months. Patients with lymph node plus in-transit metastases or with distant metastases prior to commencing adjuvant treatment had a significantly reduced overall survival (OS). In 10.9% of patients, the treatment was stopped due to toxicity, which did not affect RFS/OS, unless the duration of the treatment was <3 months. Following a relapse of the disease during the first adjuvant treatment, the median progression-free survival (PFS2) was only 6.6 months; outcomes were particularly poor for relapses that were unresectable (median PFS2 3.9 months) or occurred within the first 2 months (median PFS2 2.7 months). A second adjuvant treatment for patients with resectable relapses still showed efficacy (median RFS2 43.7 months). Elevated LDH levels in patients with an unresectable relapse was correlated with a strong reduction in OS2 (HR 9.84, p = 0.018). In the unresectable setting, first-line anti-PD1, anti-CTLA4/PD1 combination, or BRAF/MEKi showed a 5-year OS of 46.5%, 52.4%, and 49.2%, respectively. In a multivariate analysis, elevated LDH levels or the presence of brain metastases substantially shortened OS (HR > 1.78, p < 0.035). There was a non-significant trend for the improved survival of patients treated with anti-CTLA4/PD1 compared to anti-PD1 (HR 0.64, p = 0.15). After a progression on first-line therapy, the median OS2 was reduced to below two years. Elevated LDH (HR 4.65, p < 0.001) levels and widespread disease with at least three metastatic sites, particularly bone metastases (HR 2.62, p = 0.026), affected OS2. Conclusion: Our study offers real-world insights into the clinical management, treatment patterns, and outcomes of advanced melanoma patients in both the adjuvant and unresectable setting. Early relapses in patients undergoing adjuvant treatment pose a particular challenge but these patients are generally excluded from first-line trials. The approved first-line metastatic treatments are highly effective in the real-world setting with 5-year OS rates around 50%. However, outcomes remain poor for patients with brain metastases or who fail first-line treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Constant technological development of modern imaging has led to substantial improvement in management and decision-making in the diagnostic and prognostic process of many different neoplasms. This also applies to cervical cancer. The main evidence, providing the base of recently updated ESGO-ESTRO-ESP recommendations (2023) on the management and treatment of cervical cancer, has been evaluated and reviewed in this paper. Ultrasound has been suggested as a valid alternative to MRI in primary diagnostic workup of cervical cancer if performed by an expert sonographer. Additionally, CT or PET/CT exhibits a substantial role in assessing the extrapelvic spread of the disease in locally advanced cases or when suspicious lymph nodes are detected. The purpose of this article is to provide a comprehensive review of the role of different imaging techniques in staging settings, displaying a focused interest in the use of ultrasound. Following the European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) joint guidelines (2018) for the management of patients with cervical cancer, treatment decisions should be guided by modern imaging techniques. After five years (2023), an update of the ESGO-ESTRO-ESP recommendations was performed, further confirming this statement. Transvaginal/transrectal ultrasound (TRS/TVS) or pelvic magnetic resonance (MRI) enables tumor delineation and precise assessment of its local extent, including the evaluation of the depth of infiltration in the bladder- or rectal wall. Additionally, both techniques have very high specificity to confirm the presence of metastatic pelvic lymph nodes but fail to exclude them due to insufficient sensitivity to detect small-volume metastases, as in any other currently available imaging modality. In early-stage disease (T1a to T2a1, except T1b3) with negative lymph nodes on TVS/TRS or MRI, surgicopathological staging should be performed. In all other situations, contrast-enhanced computed tomography (CECT) or 18F-fluorodeoxyglucose positron emission tomography combined with CT (PET-CT) is recommended to assess extrapelvic spread. This paper aims to review the evidence supporting the implementation of diagnostic imaging with a focus on ultrasound at primary diagnostic workup of cervical cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Intrahepatic cholangiocarcinoma is a rare primary liver tumor with a poor prognosis and a 5-year survival rate of 9%. While surgical resection offers the best chance of long-term survival, only a subset of patients will present with resectable disease at presentation, and upwards of 70% of patients experience recurrence following resection. Consequently, systemic therapies play an important role in the management of resectable disease. This review summarizes the approach to resectable intrahepatic cholangiocarcinoma and reviews current evidence from clinical trials regarding systemic and targeted therapies. The management of resectable intrahepatic cholangiocarcinoma remains a challenge due to the high risk of recurrence. Numerous clinical trials have identified effective systemic therapies for advanced biliary tract cancer; however, fewer trials have evaluated systemic therapies in the perioperative period. The objective of this review is to summarize the current recommendations regarding the diagnosis, surgical resection, and systemic therapy for anatomically resectable intrahepatic cholangiocarcinoma. Our review demonstrates that surgical resection with microscopic negative margins and lymphadenectomy remains the cornerstone of treatment. High-level evidence regarding specific systemic therapies for use in resectable intrahepatic cholangiocarcinoma remains sparse, as most of the evidence is extrapolated from trials involving heterogeneous tumor populations. Targeted therapies are an evolving practice for intrahepatic cholangiocarcinoma with most evidence coming from phase II trials. Future research is required to evaluate the use of neoadjuvant therapy for patients with resectable and borderline resectable disease. [ABSTRACT FROM AUTHOR]

Simple Summary: We describe the clinicopathologic features of eight patients with atypical presentation of NPM1-mutated myeloid neoplasms (MN) and review the literature. Initially, we extensively describe the rarest case, a patient diagnosed with chronic eosinophilic leukemia (CEL) with less than 1% bone marrow blasts associated with an NPM1 mutation who progressed to an acute myeloid leukemia (AML). Secondly, we summarize the clinicopathologic features of seven additional cases with infrequent presentation of NPM1-mutated MN, five of them corresponding to CMML and the other two to MDS. Thirdly, we review the literature. Non-acute myeloid neoplasms (MNs) with NPM1 mutations (NPM1mut-MNs) pose a diagnostic and therapeutic dilemma, primarily manifesting as chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS). The classification and treatment approach for these conditions as acute myeloid leukemia (AML) are debated. We describe eight cases of atypical NPM1mut-MNs from our institution and review the literature. We include a rare case of concurrent prostate carcinoma and MN consistent with chronic eosinophilic leukemia, progressing to myeloid sarcoma of the skin. Of the remaining seven cases, five were CMML and two were MDS. NPM1 mutations occur in 3–5% of CMML and 1–6% of MDS, with an increased likelihood of rapid evolution to AML. Their influence on disease progression varies, and their prognostic significance in non-acute MNs is less established than in AML. Non-acute MNs with NPM1 mutations may display an aggressive clinical course, emphasizing the need for a comprehensive diagnosis integrating clinical and biological data. Tailoring patient management on an individualized basis, favoring intensive treatment aligned with AML protocols, is crucial, regardless of blast percentage. Research on the impact of NPM1 mutations in non-acute myeloid neoplasms is ongoing, requiring challenging prospective studies with substantial patient cohorts and extended follow-up periods for validation. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous squamous cell carcinoma is the second most common subtype of skin cancer. The scalp is one of the most frequently affected locations and is associated with a higher risk of complications, compared to other locations. In addition, it has a characteristic thickness and anatomical structure that may influence both growth pattern and treatment of primary cutaneous squamous cell carcinoma; while clinical peripheral margins may be easily achieved during surgery, vertical excision of the tumor is limited by the skull. Despite having a unique anatomy, current guidelines do not offer specific recommendations for cutaneous squamous cell carcinoma of the scalp, which may lead to inconsistent decision-making in multidisciplinary committees when discussing tumors with some risk factors or with close histological margins. Thus, more data are needed to improve its management and assist multidisciplinary teams in shared decisions. Cutaneous squamous cell carcinoma (cSCC) is the second most common subtype of skin cancer. The scalp is one of the most frequently affected locations and is associated with a higher rate of complications, compared to other locations. In addition, it has a characteristic thickness and anatomical structure that may influence both growth pattern and treatment of primary cSCC; while clinical peripheral margins may be easily achieved during the surgery, vertical excision of the tumor is limited by the skull. Despite having a unique anatomy, current guidelines do not contemplate specific recommendations for scalp cSCC, which leads to inconsistent decision-making in multidisciplinary committees when discussing tumors with high risk factors or with close margins. This article provides specific recommendations for the management of patients with scalp cSCC, based on current evidence, as well as those aspects in which evidence is lacking, pointing out possible future lines of research. Topics addressed include epidemiology, clinical presentation and diagnosis, imaging techniques, surgical and radiation treatments, systemic therapy for advanced cases, and follow-up. The primary focus of this review is on management of primary cSCC of the scalp with localized disease, although where relevant, some points about recurrent cSCCs or advanced disease cases are also discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with global impact, especially in the context of the rising epidemic of metabolic-dysfunction-associated steatotic liver disease and alcohol-related liver disease. The treatment landscape for HCC is evolving and has changed significantly in the last few years with new treatment options for patients, while the multidisciplinary team model of care remains critical. This review aims to summarize the various treatment options for patients at all stages of HCC, highlighting the growing array of systemic therapies with multi-modal options, including the potential of combining locoregional therapies with immunotherapy across different stages of the disease. With the increasing recognition of the importance of patient-centered care, the future paradigm of HCC care includes the incorporation of non-hospice palliative care in the multidisciplinary team care model to improve patient quality of care, quality of life, and overall outcomes. Liver cancer is the third most common cause of cancer-related deaths worldwide, and hepatocellular carcinoma (HCC) makes up the majority of liver cancer cases. Despite the stabilization of incidence rates in recent years due to effective viral hepatitis treatments, as well as improved outcomes from early detection and treatment advances, the burden of HCC is anticipated to rise again due to increasing rates of metabolic dysfunction-associated steatotic liver disease and alcohol-related liver disease. The treatment landscape is evolving and requires a multidisciplinary approach, often involving multi-modal treatments that include surgical resection, transplantation, local regional therapies, and systemic treatments. The optimal approach to the care of the HCC patient requires a multidisciplinary team involving hepatology, medical oncology, diagnostic and interventional radiology, radiation oncology, and surgery. In order to determine which approach is best, an individualized treatment plan should consider the patient's liver function, functional status, comorbidities, cancer stage, and preferences. In this review, we provide an overview of the current treatment options and key trials that have revolutionized the management of HCC. We also discuss evolving treatment paradigms for the future. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper delves into the latest developments in the emerging therapies for cholangiocarcinoma, with a focus on precision medicine, immunotherapy, and targeted therapies. We explore the potential of genomic profiling to tailor treatments to individual patients, as well as the promising results of immunotherapeutic agents in clinical trials. Furthermore, we examine the role of specific molecular targets and their inhibitors in slowing disease progression. The findings discussed in this paper offer hope for improved outcomes and prolonged survival in cholangiocarcinoma patients using more effective and personalized treatment strategies. Cholangiocarcinoma is a heterogeneous group of biliary tract cancers that has a poor prognosis and globally increasing incidence and mortality. While surgical resection remains the only curative option for the treatment of cholangiocarcinoma, the majority of cancers are unresectable at the time of diagnosis. Additionally, the prognosis of cholangiocarcinoma remains poor even with the current first-line systemic therapy regimens, highlighting the difficulty of treating locally advanced, metastatic, or unresectable cholangiocarcinoma. Through recent developments, targetable oncogenic driver mutations have been identified in the pathogenesis of cholangiocarcinoma, leading to the utilization of molecular targeted therapeutics. In this review, we comprehensively discuss the latest molecular therapeutics for the treatment of cholangiocarcinoma, including emerging immunotherapies, highlighting promising developments and strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgical candidacy in the treatment of pancreatic cancer is complex. There are multiple factors influencing if a patient is a good candidate for surgery with or without preceding treatment with chemotherapy. This review summarizes the importance of both anatomical (tumor size and its relation to important blood vessels to the liver and bowel) and biological (aggressiveness of the tumor) considerations. Pancreatic ductal adenocarcinoma (PDAC) remains associated with poor outcomes with a 5-year survival of 12% across all stages of the disease. These poor outcomes are driven by a delay in diagnosis and an early propensity for systemic dissemination of the disease. Recently, aggressive surgical approaches involving complex vascular resections and reconstructions have become more common, thus allowing more locally advanced tumors to be resected. Unfortunately, however, even after the completion of surgery and systemic therapy, approximately 40% of patients experience early recurrence of disease. To determine resectability, many institutions utilize anatomical staging systems based on the presence and extent of vascular involvement of major abdominal vessels around the pancreas. However, these classification systems are based on anatomical considerations only and do not factor in the burden of systemic disease. By integrating the biological criteria, we possibly could avoid futile resections often associated with significant morbidity. Especially patients with anatomically resectable disease who have a heavy burden of radiologically undetected systemic disease most likely do not derive a survival benefit from resection. On the contrary, we could offer complex resections to those who have locally advanced or oligometastatic disease but have favorable systemic biology and are most likely to benefit from resection. This review summarizes the current literature on defining anatomical and biological resectability in patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Although considerable advances have been made in the understanding of the pathogenesis of Merkel cell carcinoma (MCC), many questions remain unanswered, particularly regarding the clinical characteristics and behavior of the less frequent, combined MCC and squamous cell carcinoma (SCC) tumors, as well as the origin of each element of these combined tumors. The main objective of this systematic review was to assess whether combined MCC and SCC tumors are associated with a worse prognosis than pure MCC. The results of this study showed similarly aggressive behavior and equivalent prognosis for combined MCC and SCC and pure, Merkel cell polyomavirus (MCPyV)-negative MCC. Moreover, preliminary data strongly suggest that all MCPyV-negative MCC tumors, whether combined or pure, are part of a common spectrum. Combined Merkel cell carcinoma (MCC) and squamous cell carcinoma (SCC) have classically been regarded as more aggressive than conventional, pure, Merkel cell polyomavirus (MCPyV)-positive MCC. It is still unknown whether combined MCC and SCC are more aggressive than pure, MCPyV-negative MCC, and the origin of both the SCC and MCC elements of these combined tumors has not been elucidated. The main objective of this systematic review was to assess whether combined MCC and SCC tumors are associated with a worse prognosis than pure MCC; the secondary goals were the characterization of the clinical and histopathological features of these combined neoplasms. A total of 38 studies, including 152 patients, were selected for review. In total, 76% of the cases were MCPyV-negative, whereas 4% were MCPyV-positive. The most frequent histopathological pattern was that of an SCC in situ combined with a dermal MCC (36%), followed by both an in situ and invasive SCC combined with a dermal MCC (20%). Forty-seven percent of all cases fitted in the morphology of the so-called "collision tumors". Three combined MCC cases that would fit in the morphological category of collision tumors presented both squamous and neuroendocrine elements in their respective nodal metastases. The mean overall survival was 36 months, comparable to that of pure, MCPyV-negative MCC. This review found similarly aggressive behavior for combined MCC and SCC and pure, MCPyV-negative MCC. Preliminary data strongly suggest that all MCPyV-negative MCC tumors, whether combined or pure, are part of a common spectrum. [ABSTRACT FROM AUTHOR]

Simple Summary: Intramedullary spinal cord tumors (IMSCTs), a rare category of neoplastic growth, comprise around two to five percent of tumors. Genetic analysis and sequencing to identify mutations can affect prognostication and management of these tumors. The aim of our retrospective analysis was to discern genetic alterations and describe the potential utility of genetic markers in the characterization of these tumors, thereby facilitating individualized therapy. In our cohort of eight patients undergoing whole-genomic sequencing, we suggest that loss of heterozygosity (LOH) is a genetic predictor of shorter progression-free survival in ependymomas and glioblastomas. Intramedullary spinal cord tumors (IMSCTs) harbor unique genetic mutations which may play a role in prognostication and management. To this end, we present the largest cohort of IMSCTs with genetic characterization in the literature from our multi-site institutional registry. A total of 93 IMSCT patient records were reviewed from the years 1999 to 2020. Out of these, 61 complied with all inclusion criteria, 14 of these patients had undergone genetic studies with 8 undergoing whole-genomic sequencing. Univariate analyses were used to assess any factors associated with progression-free survival (PFS) using the Cox proportional hazards model. Firth's penalized likelihood approach was used to account for the low event rates. Fisher's exact test was performed to compare whole-genome analyses and specific gene mutations with progression. PFS (months) was given as a hazard ratio. Only the absence of copy neutral loss of heterozygosity (LOH) was shown to be significant (0.05, p = 0.008). Additionally, higher risk of recurrence/progression was associated with LOH (p = 0.0179). Our results suggest LOH as a genetic predictor of shorter progression-free survival, particularly within ependymoma and glioblastoma tumor types. Further genomic research with larger multi-institutional datasets should focus on these mutations as possible prognostic factors. [ABSTRACT FROM AUTHOR]

Simple Summary: With around 15 kD molecular weight, VHHs are considered the smallest antigen-binding fragments. Based on their unique properties, VHHs have broad application prospects such as bio-sensing, molecular imaging, drug delivery, disease treatments, and diagnosis. In this review, we discuss VHH applications for cancer treatments and diagnosis. Meanwhile, an overview of VHH-based agents in clinical trials is provided. The discovery of the distinctive structure of heavy chain-only antibodies in species belonging to the Camelidae family has elicited significant interest in their variable antigen binding domain (VHH) and gained attention for various applications, such as cancer diagnosis and treatment. This article presents an overview of the characteristics, advantages, and disadvantages of VHHs as compared to conventional antibodies, and their usage in diverse applications. The singular properties of VHHs are explained, and several strategies that can augment their utility are outlined. The preclinical studies illustrating the diagnostic and therapeutic efficacy of distinct VHHs in diverse formats against solid cancers are summarized, and an overview of the clinical trials assessing VHH-based agents in oncology is provided. These investigations demonstrate the enormous potential of VHHs for medical research and healthcare. [ABSTRACT FROM AUTHOR]

Simple Summary: The management of locally advanced esophageal cancer poses considerable challenges and current strategies have significant risks. Moreover, despite various treatment regimens, response rates are inconsistent. In recent years, a new class of targeted therapy classified as 'immunotherapy' has changed the landscape of cancer management. The immune system is naturally designed to destroy malignant and aberrant cells; however, cancer cells have developed mechanisms to escape recognition. Immunotherapy, stimulates and enhances the patient's own immune system, improving its ability to detect and eliminate cancerous cells more effectively. A thorough comprehension of how immunotherapy yields clinical benefit is intricately tied to the tumor microenvironment and its complex interactions across various pathways. Clinical trials have been conducted to determine the efficacy of immunotherapy in the management of esophageal cancer. This manuscript is aimed at understanding the evolving role of immunotherapy and esophageal cancer in both neoadjuvant and adjuvant settings to assist in the clinical decision making process. Locally advanced esophageal cancer (LAEC) poses a significant and persistent challenge in terms of effective treatment. Traditionally, the primary strategy for managing LAEC has involved concurrent neoadjuvant chemoradiation followed by surgery. However, achieving a pathologic complete response (pCR) has proven to be inconsistent, and despite treatment, roughly half of patients experience locoregional recurrence or metastasis. Consequently, there has been a paradigm shift towards exploring the potential of immunotherapy in reshaping the landscape of LAEC management. Recent research has particularly focused on immune checkpoint inhibitors, investigating their application in both neoadjuvant and adjuvant settings. These inhibitors, designed to block specific proteins in immune cells, are meant to enhance the immune system's ability to target and combat cancer cells. Emerging evidence from these studies suggests the possibility of a mortality benefit, indicating that immunotherapy may contribute to improved overall survival rates for individuals grappling with esophageal cancer. This manuscript aims to meticulously review the existing literature surrounding neoadjuvant and adjuvant immunotherapy in the context of LAEC management. The intention is to thoroughly examine the methodologies and findings of relevant studies, providing a comprehensive synthesis of the current understanding of the impact of immunotherapy on esophageal cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Rare diseases represent a major health problem, since patients face difficulties in obtaining a rapid diagnosis and appropriate treatments. Vulvar dermatofibrosarcoma protuberans is one of these rare entities, in which reaching a correct pathological diagnosis is intricate and surgical techniques are not standardised. The aim of our paper is to review the available literature on vulvar dermatofibrosarcoma protuberans to summarise previous experiences and main issues, in an attempt to improve the management of this rare disease. Dermatofibrosarcoma protuberans of the vulva needs to be diagnosed early and managed by a referral centre, where the patient can receive appropriate management: surgical treatment should aim to obtain free margins, lowering the probability of recurrence. Long-term follow up is needed, since recurrences are documented even after several years. Background: Vulvar dermatofibrosarcoma protuberans is an extremely rare disease. Its rarity can hamper the quality of treatment; deeper knowledge is necessary to plan appropriate management. The purpose of this review is to analyse the data reported in the literature to obtain evidence regarding appropriate disease management. Methods: We made a systematic search of the literature, including the terms "dermatofibrosarcoma protuberans", "vulva", and "vulvar", alone or in combination. We selected articles published in English from two electronic databases, PubMed and MEDLINE, and we analysed their reference lists to include other potentially relevant studies. Results: We selected 39 articles, with a total of 68 cases reported; they were retrospective case reports and case series. Dermatofibrosarcoma protuberans of the vulva tends towards local recurrence; an early and timely pathological diagnosis, together with an appropriate surgical approach, are of utmost importance to ensure free margins and maximise the curative potential. Conclusions: Even if this is an indolent disease and it generally shows a good prognosis, appropriate management may help in reducing the rate of local recurrences that may hamper patients' quality of life. Management by a multidisciplinary team is highly recommended. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer is a prevalent disease, often progressing to metastatic stages. A subgroup of patients displaying oligometastases presents a unique opportunity for extended survival due to the advances in multidisciplinary treatment. The imperative goal is complete metastatic eradication, with surgical resection serving as the standard of care. For patients ineligible for surgery, percutaneous ablation or stereotactic body radiotherapy are viable options. Although clinical trial evidence supports perioperative systemic therapy in improving progression-free survival, consistent enhancement in overall survival is not observed. Consequently, tailored treatment strategies, considering various oncological factors, are essential for patients with oligometastatic colorectal cancer. Further prospective trials are crucial to establish a comprehensive framework for defining and optimizing the treatment strategy for oligometastatic colorectal cancer. Colorectal cancer (CRC) is the third most common cancer, and nearly half of CRC patients experience metastases. Oligometastatic CRC represents a distinct clinical state characterized by limited metastatic involvement, demonstrating a less aggressive nature and potentially improved survival with multidisciplinary treatment. However, the varied clinical scenarios giving rise to oligometastases necessitate a precise definition, considering primary tumor status and oncological factors, to optimize treatment strategies. This review delineates the concepts of oligometastatic CRC, encompassing oligo-recurrence, where the primary tumor is under control, resulting in a more favorable prognosis. A comprehensive examination of multidisciplinary treatment with local treatments and systemic therapy is provided. The overarching objective in managing oligometastatic CRC is the complete eradication of metastases, offering prospects of a cure. Essential to this management approach are local treatments, with surgical resection serving as the standard of care. Percutaneous ablation and stereotactic body radiotherapy present less invasive alternatives for lesions unsuitable for surgery, demonstrating efficacy in select cases. Perioperative systemic therapy, aiming to control micrometastatic disease and enhance local treatment effectiveness, has shown improvements in progression-free survival through clinical trials. However, the extension of overall survival remains variable. The review emphasizes the need for further prospective trials to establish a cohesive definition and an optimized treatment strategy for oligometastatic CRC. [ABSTRACT FROM AUTHOR]

Simple Summary: This study addresses the global healthcare challenge of cancer by investigating hereditary cancer syndromes (HCS) and their genetic underpinnings. Using a multigene hereditary cancer panel, we examined Russian patients with suspected HCS, revealing that 21.6% had pathogenic or likely pathogenic genetic variants. Predominant mutations were found in BRCA1/BRCA2, CHEK2, and ATM genes, and we identified 16 previously undescribed variants in MUTYH, GALNT12, MSH2, MLH1, MLH3, EPCAM, and POLE genes. Our findings underscore the importance of comprehensive genetic testing for personalized cancer prevention and treatment. This research contributes essential genetic insights, particularly in regions like Russia where epidemiological data are limited, establishing the way for improved understanding and management of hereditary cancer syndromes. Cancer is a major global public health challenge, affecting both quality of life and mortality. Recent advances in genetic research have uncovered hereditary cancer syndromes (HCS) that predispose individuals to malignant neoplasms. While traditional single-gene testing has focused on high-penetrance genes, the past decade has seen a shift toward multigene panels, which facilitate the analysis of multiple genes associated with specific HCS. This approach reveals variants in less-studied gene regions and improves our understanding of cancer predisposition. In a study composed of Russian patients with clinical signs of HCS, we used a multigene hereditary cancer panel and revealed 21.6% individuals with pathogenic or likely pathogenic genetic variants. BRCA1/BRCA2 mutations predominated, followed by the CHEK2 and ATM variants. Of note, 16 previously undescribed variants were identified in the MUTYH, GALNT12, MSH2, MLH1, MLH3, EPCAM, and POLE genes. The implications of the study extend to personalized cancer prevention and treatment strategies, especially in populations lacking extensive epidemiological data, such as Russia. Overall, our research provides valuable genetic insights that give the way for further investigation and advances in the understanding and management of hereditary cancer syndromes. [ABSTRACT FROM AUTHOR]

Simple Summary: Compared to the resounding success demonstrated in the field of B-cell leukemia, lymphoma, and multiple myeloma, in the field of acute myeloid leukemia, CAR-T-cell-therapy slows down its application in clinical practice. Yet, immunotherapy and/or cell therapy could be curative in certain high-risk AML subtypes refractory to classical chemotherapy approaches. Several CAR-T constructs targeting different antigens have been tested and have shown promising results. This review illustrates the main results obtained with the use of CAR-T in AML. Chimeric antigen receptors (CAR)-T-cell therapy represents the most important innovation in onco-hematology in recent years. The progress achieved in the management of complications and the latest generations of CAR-T-cells have made it possible to anticipate in second-line the indication of this type of treatment in large B-cell lymphoma. While some types of B-cell lymphomas and B-cell acute lymphoid leukemia have shown extremely promising results, the same cannot be said for myeloid leukemias—in particular, acute myeloid leukemia (AML), which would require innovative therapies more than any other blood disease. The heterogeneities of AML cells and the immunological complexity of the interactions between the bone marrow microenvironment and leukemia cells have been found to be major obstacles to the clinical development of CAR-T in AML. In this review, we report on the main results obtained in AML clinical trials, the preclinical studies testing potential CAR-T constructs, and future perspectives. [ABSTRACT FROM AUTHOR]