Exploring RAS mutation incidence and temporal heterogeneity in metastatic colorectal cancer patients - a single-institution experience utilising circulating tumour DNA.

Introduction: Colorectal cancer (CRC) remains a significant global health challenge, ranking among the leading causes of neoplastic mortality. Despite transformative therapeutic advances, a considerable proportion of patients are diagnosed with metastatic disease, and 15-30% of those initially presenting with early-stage CRC eventually experience recurrence. Comprehensive molecular testing, especially the evaluation of microsatellite instability and mutations in KRAS/NRAS or BRAF genes, is essential upon diagnosis of stage IV disease, guiding treatment decisions. Material and methods: This manuscript explores the mutational landscape of KRAS and NRAS in patients with CRC, employing digital polymerase chain reaction (PCR) BEAMing for the detection of mutations in liquid biopsy. Our study enrolled patients with histologically confirmed CRC and stage IV disease, focusing on identifying mutations in KRAS and NRAS genes during various stages of therapy. Results: Evaluating baseline, midline, and progression samples, we found that 66.6% maintained consistent mutational status post-disease progression, while 33.3% exhibited a shift in mutational status. The application of techniques with high sensitivity, such as BEAMing Digital PCR, is pivotal for accurate circulating tumour DNA (ctDNA) mutation detection. The study underscores the significance of continuous molecular monitoring in guiding therapeutic decisions for patients with metastatic CRC. Conclusions: Our findings contribute to our understanding of the evolving mutational landscape and the potential clinical implications of ctDNA ana- lysis in the era of personalised cancer medicine.

Global coverage and consistency of guideline recommendations for cancer cachexia on the Web in 2011 and 2018.

INTRODUCTION: Cancer cachexia is a common associate of cancer and has a negative impact on both patients' quality of life and overall survival. Nonetheless its management remains suboptimal in clinical practice. Provision of medical recommendations in websites is of extreme importance for medical decision making and translating evidence into clinical practice. AIM OF THE STUDY: To scrutinize the magnitude, consistency and changes over time of cancer-cachexia recommendations for physicians on the Web among oncology related societies. Intercontinental, continental, national and socioeconomic variations were further analyzed. MATERIAL AND METHODS: Web identification of oncology related societies and prospective analyses of relative Web guideline recommendations for physicians on cancer-cachexia at different time-points. RESULTS: In June 2011, we scrutinized 144,000 Web pages. We identified 275 societies, of which 270 were eligible for analyses: 67 were international (African, American, Asian, European, Oceania and Intercontinental), 109 belonged to the top 10 countries with the highest development index and 94 pertained to 10 countries with a long lasting tradition in medical oncology. CONCLUSIONS: The magnitude of cancer cachexia recommendations for physicians on the Web at a global level was scant both for coverage and consistency, and at any time-point considered: 3.7% (10/270) in 2011 and 8.1% (22/270) in 2018. The proportion of societies giving evidence-based and updated recommendations for cancer cachexia for physicians was only 1.1% (3/270) in 2011 and 2.96% (8/270) in 2018. Continent, national highest developmental index, oncology tradition and economic-geographic areas were not found to influence Web guideline provision.

Exploring Immune-Related Adverse Events: A Case of Febrile Neutropenia in a Melanoma Patient Receiving Immunotherapy.

Introduction: The introduction of immune checkpoint inhibitors (ICIs) has opened a new chapter in cancer treatment. Nevertheless, their use may result in immune-related adverse events (irAEs) with multifactorial determinants, complex mechanisms, and varying clinical implications. In specific cancer types, like melanoma, irAEs exhibit a complex relationship with patient outcomes. Case Presentation: We present a case of febrile neutropenia following ICI therapy in a patient with metastatic melanoma, underscoring the intricate clinical landscape associated with irAEs in the context of cancer immunotherapy. More specifically, a 68-year-old man was diagnosed with metastatic malignant melanoma and administered a combination of nivolumab and ipilimumab. However, after a single dose, the patient was hospitalized due to febrile neutropenia. The patient eventually recovered, but a diagnosis of myelosuppression related to prior immunotherapy led to treatment discontinuation. Subsequently, the patient transitioned to a second-line therapy. Conclusion: This case contributes to our comprehension of rare yet potentially severe hematological irAEs and their influence on immunotherapy outcomes. Such insights will guide future diagnostic and therapeutic strategies in the field of immunotherapy.

TAMs and PD-1 Networking in Gastric Cancer: A Review of the Literature.

BACKGROUND: Gastric cancer (GC) is one of the most common and aggressive types of cancer. Immune checkpoint inhibitors (ICIs) have proven effective in treating various types of cancer. The use of ICIs in GC patients is currently an area of ongoing research. The tumor microenvironment (TME) also seems to play a crucial role in cancer progression. Tumor-associated macrophages (TAMs) are the most abundant population in the TME. TAMs are capable of displaying programmed cell death protein 1 (PD-1) on their surface and can form a ligand with programmed death ligand 1 (PD-L1), which is found on the surface of cancer cells. Therefore, it is expected that TAMs may significantly influence the immune response related to immune checkpoint inhibitors (ICIs). AIM OF THE STUDY: Understanding the role of TAMs and PD-1/PD-L1 networking in GC. METHODS: A systematic review of published data was performed using MEDLINE (PubMed), Embase, and Cochrane databases. We retrieved articles investigating the co-existence of TAMs and PD-1 in GC and the prognosis of patients expressing high levels of PD-1+ TAMs. RESULTS: Ten articles with a total of 2277 patients were included in the systematic review. The examined data suggest that the expression of PD-L1 has a positive correlation with the infiltration of TAMs and that patients who express high levels of PD-1+ TAMs may have a worse prognosis than those who express low levels of PD-1+ TAMs. CONCLUSIONS: TAMs play a pivotal role in the regulation of PD-1/PD-L1 networking and the progression of GC cells. Nevertheless, additional studies are needed to better define the role of TAMs and PD-1/PD-L1 networking in GC.

Exploring a Rarity: Incidence of and Therapeutic Approaches for Neurological Complications and Hypophysitis in Cancer Patients on Immune Checkpoint Inhibitors-A Single-Center Study.

Immune checkpoint inhibitors, such as anti-PD-1 and anti-CTLA-4 inhibitors, have become the standard of care for many cancer types. However, they induce immune-related adverse events (irAEs), including neurotoxicity and hypophysitis. The incidence and outcomes of neurotoxicity and hypophysitis in patients treated with immune checkpoint inhibitors are not well established. We conducted a retrospective study of 812 patients with solid cancers who received immune checkpoint inhibitors at the University General Hospital of Ioannina between January 2018 and January 2023. We assessed demographic and clinical data, including the severity of symptoms, treatment regimen, other irAEs, resolution type and time, and death. Two patients experienced neurotoxicity and two hypophysitis. All four patients required inpatient administration and received corticosteroids or/and hormone replacement. Three patients responded to the initial therapy, experiencing full recovery, while one patient was corticosteroid-resistant, and immunoglobin G was administered. Two patients never received immunotherapy after their toxicity due to the severity of symptoms; one patient continued monotherapy with nivolumab, changing from combination therapy with ipilimumab-nivolumab, while the fourth patient continued his initial treatment with nivolumab. Our study suggests that the incidence of neurotoxicity and hypophysitis in patients treated with immune checkpoint inhibitors is low, but careful monitoring and prompt treatment with corticosteroids are necessary for effective management.

Cancer pain who cares? International and national patterns of evidence-based global guidelines recommendations for physicians on the Web (2011 vs. 2018).

PURPOSE: Although pain is a common event during treatment of cancer, its assessment and management remains suboptimal in everyday clinical practice at global level. METHODS: Considering both the important role of internet in daily life and that clinical guidelines are important for translating evidence in clinical practice, we performed a prospective study to scrutinize the magnitude of updated evidence-based cancer-pain guideline recommendation for physicians on the web. Changes over-time at a global level were scrutinized at two time points: 2011 for baseline and 2018 at first follow-up. Both anesthesiology and oncology societies were analyzed. RESULTS: In 2011 we scrutinized 181,00 WebPages and 370 eligible societies were identified; 364 of these were eligible for analyses both in 2011 and 2018. The magnitude of cancer pain updated and evidence-based guideline recommendations on the web for health care providers was extremely low at global level and at any time point considered: 1.1% (4/364) in 2011 and 4.7% (17/364) in 2018. Continental and intercontinental patterns, National's highest developmental index, oncology tradition and economic-geographic areas were not found to influence cancer pain web-guideline provision. In 2018, pain & supportive care societies provided the highest rate of updated evidence-based cancer-pain guidelines for clinicians. Only 3/25 medical oncology societies and 1/34 radiation oncology societies, provided own or e-link (to other societies') evidence-based guidelines in their websites. CONCLUSIONS: Major medical oncology and radiation oncology societies - at global level - fail to produce updated cancer pain recommendations for their physicians, with most of these providing no or inconsistent or outdated guidelines.

Facing internet fake-medicine and web para-pharmacy in the total absence of official recommendations from medical societies.

PURPOSE: Internet fake information, parapharmacy and counterfeit drugs are a market of hundreds of billion dollars. Misleading internet data decrease patients' compliance to medical care, promote use of questionable and detrimental practices, and jeopardize patient outcome. This is particularly harmful among cancer patients, especially when pain and nutritional aspects are considered. Provision of Web recommendations for the general audience (patients, relatives, general population) from official medical-providers might be useful to outweigh the detrimental internet information produced by non-medical providers. METHODS: 370 oncology and anesthesiology related societies were analyzed. Our objective was to evaluate the magnitude of web-recommendation for cancer cachexia and cancer pain for the general audience provided by official medical organizations' web sites at global level. RESULTS: Magnitude of web-recommendations at global level was surprisingly scant both for coverage and consistency. Seven official medical societies provided updated web-recommendation for cancer cachexia to their patients/family members, and 15 for cancer pain. Scantiness was unrelated by continent, developmental index, oncology tradition, economic-geographic area and society type scrutinized. CONCLUSIONS: Patients need expert advice when exposed to fake internet information largely dominated by paramedical market profits. In this era of "new media" the patients' net-education represents a new major educational challenge for medical societies.