With the increasing use of immune checkpoint inhibitors (ICIs) in combination regimens and in earlier stages of advanced melanoma, the effective management of immune-related adverse events (irAEs) is key to balancing immunotherapy efficacy and toxicity. Conflicting evidence exists on possible detrimental effects of immunosuppression with corticosteroids for irAEs on ICI effectiveness. We conducted a multicenter, retrospective cohort study of immunotherapy-naïve advanced melanoma patients undergoing treatment with ipilimumab and nivolumab and a small cohort treated with nivolumab/relatlimab. We utilized univariate tests to assess response, PFS, and OS based on presence of irAE, receipt of steroids for irAEs, peak dose, and time-to-steroid, as well as multivariable analysis for response, OS, and PFS in patients receiving steroids for irAEs. Among 226 total ipilimumab/nivolumab patients, those without irAEs had poorer PFS and OS compared to irAE groups regardless of steroid administration. In subgroup analysis of patients receiving steroids for an irAE, increased time-to-steroid was significantly associated with improved response (aOR, 1.026 p = 0.0005), PFS (aHR, 0.986 p = 0.001), and OS (aHR, 0.983 p = 0.0008). Higher peak steroid dose was significantly associated with poorer PFS (aHR, 1.002 p = 0.005), and OS (aHR, 1.002 p = 0.003). Use of additional immunosuppressants was associated with poorer OS (aHR, 1.941 p = 0.018). Cumulative dose was not significantly associated with outcomes. Among 42 additional patients treated with nivolumab/relatlimab, irAEs were significantly associated with improved PFS/OS, which appeared to be slightly mitigated by steroid administration; dosing relationships were limited by small numbers.

Immune checkpoint inhibitors (ICIs) have become an important treatment option for patients with nasopharyngeal carcinoma. With the increasing use of such agents, immune-related adverse events (irAEs) have become a concern. Identifying and managing the toxicity and side effects of ICIs is crucial, since it not only has implications for their safety but also the intensity and efficacy of subsequent use by patients. The present case report documents a 40-year-old male patient with acute erosive hemorrhagic gastritis associated with sintilimab treatment. In particular, the clinical manifestations, treatment, side effects and prognosis of this case was focused upon. The patient was diagnosed with locally advanced nasopharyngeal carcinoma (cT4N3M0 stage IVa) and developed bone metastases after 1 year of standard radiotherapy and adjuvant chemotherapy. After the first- and second-line treatments, pulmonary metastases occurred and sintilimab monotherapy was used as the third-line therapy. During the course of treatment, the optimal outcome for this patient was partial response according to the Response Evaluation Criteria in Solid Tumors (version 1.1). However, after 14 cycles of sintilimab the patient developed melena and epigastric pain and was diagnosed with acute erosive hemorrhagic gastritis, which was treated with methylprednisolone therapy. Progression-free survival with the third-line treatment was 542 days. Sintilimab-associated hemorrhagic gastritis is not fully recognized as an irAE. Therefore, early identification, diagnosis and management of irAEs are critical for subsequent therapy and progression-free survival of patients.

Immune checkpoint inhibitors and targeted therapies (BRAF/MEK inhibitors) have transformed the care of patients with stage IV melanoma, now with 5-year overall survival rates around 50%. Surgeons should be acquainted with these drugs, the multidisciplinary considerations of their use, and the unique immune-related adverse events (irAEs) they can cause. In this review, we discuss systemic therapies for cutaneous melanoma, including the biology of immune checkpoint inhibition, treatment indications, and toxicities. We also explain how these irAEs and other toxicities can impact surgical planning and perioperative management.

To describe presentation, treatment and outcome of immune checkpoint inhibitor (ICI) associated-vasculitis in cancer patients in a multicentre study.

Thanks to the ImmunoCancer International Registry (ICIR), a multidisciplinary network focused on the research of the immune related adverse events related to cancer immunotherapies, patients presenting with a clinical and/or radiological suspicion of vasculitis and histological evidence of vasculitis after being exposed to ICIs were retrospectively identified.

Twenty-eight cases were identified in the ICIR registry. The median interval between starting ICI treatment and vasculitis diagnosis was 4 months. Small vessel vasculitis was predominant (n = 21), followed by large vessel (n = 4) and medium vessel (n = 3). The small vessel vasculitis included 10 unclassified vasculitis either with limited cutaneous involvement (n = 6) or systemic involvement (n = 4), five IgA vasculitis, three cryoglobulinemic vasculitis, and three ANCA+ vasculitis. At presentation or during the evolution, renal and neurologic manifestations were evidenced in seven cases each (25%). Renal biopsies documented immune glomerulopathies in six cases. Only seven patients (25%) fulfilled the 2022 ACR/EULAR classification criteria (four giant cell arteritis, two EGPA and one GPA). Most patients (90%) required systemic corticosteroid and an additional drug was given in 10 patients (36%). Vasculitis outcome was good: 22 patients had vasculitis complete response, no patient died due to vasculitis. Nine patients (32%) were rechallenged with immunotherapy with only one relapse.

ICI-associated vasculitis are rare, heterogeneous, but can be severe requiring urgent multidisciplinary management with aggressive treatment.

Consolidation immunotherapy with immune checkpoint Inhibitor (ICI) Durvalumab is an effective treatment for inoperable stage III non-small cell lung cancer (NSCLC) patients with a PD-L1 expression ≥ 1% after definitive curative concurrent chemoradiotherapy (CCRT). While this approach is widely used as standard therapy, it carries an increased risk of immune-related and radiation-induced pneumonitis. Currently, there is no data on pneumonitis in patients receiving CCRT with an overall dose of 70 Gy (Gy) compared with the standard protocol of 60 Gy ± 10% in this setting.

This study analyzed retrospective data from 39 patients with unresectable NSCLC treated with CCRT. Patients received either 70 Gy (n = 29) or lower than 70 Gy total dose (n = 10) in 2 Gy fractions. Cases of pneumonitis were further classified as RI‑P (Radio-induced Pneumonitis) and ICI‑P (ICI Pneumonitis) based on clinical and radiological findings.

Of the 39 patients, 15 (38.5%) developed pneumonitis, with 10 out of 29 (34.5%) in the 70 Gy group and five out 10 (50%) in the < 70 Gy group. There was no significant difference in pneumonitis and in occurrence of ICI‑P vs. RI‑P (26.7% vs. 73.3%) within both groups. The 70 Gy group showed a significant benefit in mortality (p = < 0.001). Overall survival (OS) differed significantly between groups (p =0.028).

70 Gy radiation dose for CCRT followed by durvalumab is a safe regimen and may provide clinical benefits in NSCLC patients compared to lower doses. Pneumonitis incidence aligns with previous literature. The higher dose is associated with improved overall survival, and reduced disease progression, potentially due to a longer consolidation time.

Immunotherapy has significantly affected cancer treatment and survival rates, accompanied by an increase in immune-related adverse events (irAEs) requiring new management strategies. irAEs can affect various organ systems and have varying severity levels, with higher rates observed when combining immune checkpoint inhibitors. National organizations such as ASCO, the National Comprehensive Cancer Network, the Society for Immunotherapy of Cancer, and the European Society for Medical Oncology have created guidelines for managing irAEs. This chapter expands on these guidelines by discussing practical strategies to improve the multidisciplinary management in irAE care, focusing on the who, what, and how to bridge gaps in care and enhance collaboration between academic and community oncology practices. Effective irAE management involves early recognition and guideline-adherent approaches using a multidisciplinary team, including oncologists, other subspecialists, primary care clinicians, and all care team members. Institutions are developing methods to integrate irAE care into clinical workflows, such as incorporating urgent care clinics and e-consults for efficient irAE management and developing hub-and-spoke models to extend specialized care from academic centers to community hospitals for equitable care delivery. Additionally, effective patient education is critical for improving irAE recognition and health literacy. The new ASCO Community of Practice called the Alliance for Support and Prevention of Immune-Related Adverse Events consortium and patient advocacy group Standing Together to Optimize Research, Interventions, and Education in irAEs initiatives aim to advance irAE clinical care, research, and education through global collaboration, standardized data collection, and improved outreach to patients and caregivers.

Immunotherapy has revolutionized cancer treatment, offering significant survival superiority for advanced malignancies. However, immunotherapy is associated with various immune-related adverse events, one of the most common of them being dermatologic toxicities. Previous studies have reported dermatologic adverse events in almost half of the cancer patients undergoing immunotherapy. The spectrum of dermatologic toxicities ranges from mild, self-limiting reactions to severe, life-threatening conditions, and includes maculopapular rash, pruritus, vitiligo-like depigmentation, psoriasiform eruption, lichenoid eruption, bullae, photosensitivity, hair loss, nail changes, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The management strategies are based on personalized treatment plans, multidisciplinary approaches, and timely therapeutic interventions aimed at addressing dermatologic toxicities while preserving immunotherapy efficacy. Based on the latest findings, this paper offers a novel perspective and provides an evidence-based review of the pathogenesis, manifestations, incidence, grading, clinical management, and prognostic significance of these toxicities, underlining the importance of balancing the efficacy of immunotherapy with timely and proactive management of their dermatological toxicities to enhance patient outcomes and quality of life.

Over the last decade, immune checkpoint inhibitors (ICIs) like PD-1/PD-L1 or CTLA-4, which reinvigorate T cells for tumor control have become standard-of-care treatment options. In response to the increasingly recognized mechanisms of resistance to T cell activation in immunologically cold tumors, immuno-oncology drug development has started to shift beyond T cell approaches. These include tumor-associated macrophages (TAMs), a major pro-tumor immune cell population in the tumor microenvironment known to silence immune responses.

Here we outline anti-TAM therapies in current development, either as monotherapy or in combination with other treatment modalities. We describe emerging drugs targeting TAMs under investigation in phase II and III testing with a focus on their distinguishing mechanism of action which include (1) reprogramming of TAMs toward anti-tumor function and immune surveillance, (2) blockade of recruitment, and (3) reduction and ablation of TAMs.

Several new immuno-oncology agents are under investigation to harness anti-tumor functions of TAMs. While robust anti-tumor efficacy of anti-TAM therapies across advanced solid organ cancers remains elusive to-date, TAM reprogramming therapies have yielded benefits in select cancers. The inherent heterogeneity of the diverse TAM population will require enhanced investments into biomarker-driven approaches to fully leverage its therapeutic potential.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by enabling the immune system to effectively target and destroy cancer cells. While ICIs offer significant survival benefits across various malignancies, their use is associated with a unique profile of immune-related adverse events, including potentially fatal cardiovascular toxicities. Recent studies have highlighted various cardiac complications associated with ICIs, such as myocarditis, arrhythmias, heart failure, pericarditis, atherosclerosis, and hypertension. These complications arise from mechanisms involving T-cell activation and cytokine release. Patient-related factors such as pre-existing cardiovascular disease, diabetes mellitus, age, gender, and genetic predisposition, along with treatment-related factors like specific ICI regimens, contribute to these toxicities. To manage these complications effectively, comprehensive cardiovascular risk assessment and monitoring before, during, and after ICI therapy are crucial. Adhering to guidelines from the European Society of Cardiology (ESC) and other international organizations allows for early recognition of cardiovascular toxicities and tailored interventions. This review emphasizes the importance of cardioprotective measures, regular monitoring, and multidisciplinary collaboration between oncologists and cardiologists to mitigate cardiovascular risk and optimize patient outcomes. Ongoing research is essential to better understand the mechanisms of ICI-induced cardiovascular toxicities and to develop effective management strategies for affected patients. As we continue to expand the use of ICIs in oncology, balancing oncologic efficacy with cardiovascular safety remains critical.

This bibliometric study aimed to map the global research landscape of programmed cell death (PCD) in renal cancer, delineating publication trends, influential authors, contributing regions, and thematic shifts between 1998 and 2023 year.

We retrieved 5, 134 records from the Web of Science Core Collection (1998-2023) using comprehensive keywords encompassing "renal cancer," "programmed cell death," and related synonyms. After applying inclusion and exclusion criteria, we conducted co-citation, keyword, and cluster analyses with CiteSpace (v.6.3.R2) and VOSviewer (v.1.6.20) to identify major research fronts, collaboration networks, and thematic clusters.

Findings revealed a progressive increase in publications, notably accelerating after 2010 in tandem with the rise of immunotherapeutic strategies and targeted molecular interventions. China and the United States emerged as leading contributors, while journals such as Cancer Research and Clinical Cancer Research dominated in both publication frequency and citation impact. Authors including Kwon Taeg Kyu and Dahiya Rajvir significantly shaped foundational apoptosis research. Keyword and cluster analyses demonstrated a shift from earlier apoptosis- and angiogenesis-focused studies toward intersections of metabolic reprogramming, immune infiltration, and newer cell death modalities (e.g., ferroptosis, pyroptosis). High-impact papers underscored immunotherapy's pivotal role in modulating cell death pathways and informing novel combination regimens.

PCD research in renal cancer has evolved into a dynamic, interdisciplinary domain integrating immunology, molecular targeting, and multi-omic profiling. Future development of the field aimed at refining precision therapies that exploit diverse cell death mechanisms and thereby improve clinical outcomes.

More promising, effective, and less-invasive biomarkers for PD(L)-1 targeted responses, immune-related adverse events (irAEs), and prognosis are being explored. We conducted a single-center retrospective study in pan-cancer patients with anti-PD(L)-1 monotherapy. Observational endpoints included treatment response, prognosis, and irAEs. Peripheral blood immunophenotypes were analyzed by Flow Cytometry. 104 patients were enrolled. Higher pretreatment percentages of CD3+CD4+ Th cells were associated with both responses (HR: 6.170, P = 0.034) and prognosis (HR: 1.930, P = 0.022). The higher baseline percentage of CD16+CD56+ NK cells was positively correlated with response (HR: 3.730, P = 0.050) and negatively related to irAEs (HR: 0.460, P = 0.012). Decreased pretreatment CD3+ T cell counts were related to more irAEs (HR: 0.970, P = 0.026), while the percentage of CD3+ T cells was negatively associated with prognosis (HR: 1.930, P = 0.022). The higher baseline cell counts of CD3+CD8+ CTL, CD19+ B, and the percentage of CD19+ B cells might be related to more irAEs (P < 0.05). Significant correlation between duration of treatment (DOT) and prognosis, irAE and outcome was also confirmed (P < 0.0001). Our findings confirmed multiple baseline circulating immunophenotype characteristics were related to PD(L)-1 targeted response, irAE onset, and prognosis.

To illustrate the diagnostic challenges, as well as the importance of early recognition of rare immunotherapy-induced complications, presenting a case and literature of sarcoid-like granulomatous reaction.

This report presents a case of asymptomatic hypercalcemia, revealing a sarcoid-like granulomatosis in a patient with metastatic melanoma, treated with an immune checkpoint inhibitor (ICI). In the discussion, an overview of the existing literature is provided through a PubMed search.

Thorough investigations are essential to rule out disease progression and other possible explanations. Ultimately, biopsy with extensive staining led to the diagnosis of sarcoid-like granulomatosis. As there is no consensus in treatment, we suggest a case-by-case assessment, if possible by discussion within the multidisciplinary treatment team, to decide discontinuation of the causal ICI-therapy or the use of systemic steroids as supportive therapy.

This case demonstrates the importance of a broad differential diagnosis when identifying an asymptomatic hypercalcemia as well as new CT-graphic lesions, since the diagnosis of sarcoid-like granulomatosis can avoid not only unnecessary changes in treatment plans, avoiding toxicity, but also be a sign of good prognosis.

Nowadays immune-based combinations are the standard first-line treatment for metastatic renal cell carcinoma and involve the use of either two immunotherapy agents or an immunotherapeutic drug associated with a tyrosine kinase inhibitor. Treatment-related toxicity is the primary cause of drug discontinuation or dose reduction. A thorough understanding of the prevention and management of adverse events of the immune-based combinations is critical to ensure the success of treatment. Endocrinological toxicities during treatment with immune-based combinations are frequent and often manageable. However, in some cases, diagnosis can be complex, and the treatment requires multidisciplinary discussion. In addition, it is often challenging to determine which agent in the combination is responsible for a specific toxicity. In this review, we analyze the evidence regarding treatment-related endocrinopathies in renal cell carcinoma first-line therapy. We also discuss monitoring strategies to diagnose endocrinological adverse events and provide some practical tools for their daily management.

Immune checkpoint inhibitors (ICIs) have demonstrated favorable outcomes in various cancers. However, it has been observed that ICIs may induce life-threatening cardiovascular toxicity. In this study, a meta-analysis was conducted to determine the risk of cardiovascular toxicities in patients exposed to ICIs or in combination with chemotherapy. PubMed, Cochrane Library, and Embase databases were searched from inception to September 24, 2023. This study was conducted in accordance with the PRISMA guidelines. A meta-analysis was conducted on the risk of cardiotoxicity in cancer patients. Data were pooled with a random-effect model. This protocol was registered prospectively in PROSPERO (CRD42023467319). The primary outcome was cardiotoxicity risk in observational studies with ICIs or combined with chemotherapy. The risk factors that affected the occurrence of cardiovascular toxicities were also examined. ICIs or combined with chemotherapy increased the cardiotoxicity risk compared with mono-chemotherapy (OR 1.47; 95% CI 1.05-2.06, p = 0.024). The risk of pericardial disease in cardiotoxic events (OR 1.99; 95% CI 1.23-3.22, p = 0.005) and thromboembolic events (OR 1.34; 95% CI 1.04-1.72, p = 0.025) was significantly increased. Smoking (OR 1.25; 95% CI 1.12-1.39, p < 0.001), previous heart disease (OR 2.01; 95% CI 1.64-2.46, p < 0.001), and lung cancer (OR 1.46; 95% CI 1.26-1.69, p < 0.001) were risk factors worthy of attention. ICIs or combined with chemotherapy show an elevated risk of cardiovascular toxicities. Patients who are smoking, diagnosed lung cancer, and having prior medical history of heart diseases need more attention.

Immune-related adverse events (irAEs), including endocrine irAEs, can occur in response to cancer immunotherapy using immune checkpoint inhibitors (ICIs). Of the endocrine irAEs, pituitary and thyroid irAEs are most frequently observed, followed by primary adrenal insufficiency, type 1 diabetes mellitus and hypoparathyroidism. Notably, pituitary irAEs and type 1 diabetes mellitus can be lethal if overlooked, potentially leading to adrenal crisis and diabetic ketoacidosis, respectively. On the other hand, pituitary and thyroid irAEs are reported to be associated with more favourable prognoses in some cancers if treated appropriately with hormone-replacement therapies. It would be useful to identify those people who are likely to develop endocrine irAEs before initiating therapy with ICIs. Anti-pituitary antibodies and thyroid autoantibodies have been identified as potential biomarkers for the development of pituitary and thyroid irAEs, respectively. This Review elaborates on the clinical characteristics and management strategies of several endocrine irAEs, using the latest research findings and guidelines published by several academic societies.

Immune checkpoint inhibitor-associated myocarditis (ICI myocarditis) is a rare but highly fatal immune-related adverse reaction. This study aimed to develop nomogram prognostic models for both short-term and long-term survival outcomes in patients with ICI myocarditis based on key biomarkers in peripheral blood.

In this single-center retrospective study, we included 90 patients with ICI myocarditis at the Fourth Hospital of Hebei Medical University. Critical peripheral biomarkers associated with 40-day and 1-year overall survival (OS) were identified. Two prognostic models were developed and evaluation of the models were performed with receiver operating characteristic (ROC) curves, C-index, calibration curves, and decision curve analysis (DCA).

A total of 24 patients (26.7%) succumbed within 40 days, while 40 patients (44.4%) died within one year. Cardiac troponin-I (cTnI), N-terminal pro-brain natriuretic peptide (NTBNP) and lactic dehydrogenase-to-albumin ratio (LAR) were identified as critical prognostic factors for 40-day OS in patients with ICI myocarditis and utilized to develop a nomogram model. The model demonstrates an area under the curve (AUC) of 0.867 [95% confidence interval (CI): 0.774-0.960] and a C-index of 0.824. Another predictive model for the 1-year OS was developed based on cTnI, NTBNP, LAR and systemic inflammatory response index (SIRI) with an AUC of 0.765 (95% CI: 0.664-0.866) and a C index of 0.742. The calibration curve demonstrates that both models exhibit strong consistency. The results of the DCA further indicate that both nomograms possess substantial clinical utility.

These two prediction models will enable clinicians to more effectively utilize readily available peripheral blood biomarkers for the convenient and efficient identification of high-risk patients with poor prognoses, thereby facilitating early intervention.

Tumor displays various forms of tumor heterogeneity including immune heterogeneity that allow cancer cells to survive during conventional anticancer drug interventions. Thus, there is a strong rationale for overcoming anticancer drug resistance by employing the components of immune cells. Using the immune system to target tumor cells has revolutionized treatment. Recently, significant progress has been achieved at preclinical and clinical levels to benefit cancer patients.

A review of literature from the past ten years across PubMed, Scopus, and Web of Science focused on immunotherapy strategies. These include immune checkpoint inhibitors (ICIs), tumor-infiltrating lymphocyte therapy, antibody-drug conjugates (ADCs), cancer vaccines, CAR T-cell therapy, and the role of the gut microbiome.

While immunotherapy outcomes have improved, particularly for tumor types such as melanoma and non-small cell lung cancer (NSCLC), challenges persist regarding predictive biomarker identification and better management. Ongoing research on modifiers of immune function like gut microbiome-derived metabolites, next-generation ADCs, and new classes of biologics is warranted. Overall, continued investigation toward optimizing synergistic immunotherapeutic combinations through strategic drug delivery systems is imperative for preclinical and clinical success in cancer patients.

Lynch syndrome is the most common hereditary colorectal cancer (CRC) syndrome, accounting for 3-5% of all CRC cases. Situs inversus totalis (SIT) is a rare congenital malformation with an incidence of 1 in 8,000 to 1 in 25,000. The co-occurrence of Lynch syndrome and SIT is extremely uncommon. Immune checkpoint inhibitors (ICIs) have demonstrated significant efficacy in treating microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) CRC. Tumors associated with Lynch syndrome frequently exhibit MSI-H, providing a theoretical basis for ICI use.

We report a case of bifocal colon cancer associated with Lynch syndrome and SIT. After seven cycles of sintilimab, the patient developed gastrointestinal perforation due to tumor regression, necessitating emergency surgery. The anatomical variations associated with SIT required the surgical team to adopt an alternative approach. Postoperatively, the patient continued sintilimab treatment for 2 years. In June 2024, he underwent a colostomy reversal and proximal colectomy. Pathological examination revealed a tumor regression grade (TRG) of 0, indicating complete pathological remission (pCR), with no recurrence or metastasis detected upon follow-up.

The anatomical variations associated with SIT increase the complexity of surgical procedures. Advanced imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) are essential for assessing fine anatomical details and facilitating surgery. ICIs are an effective treatment option for Lynch syndrome-associated CRC, as demonstrated in this case. Future studies should investigate the optimal timing of immunotherapy, combination treatment strategies, and methods to mitigate immune-related toxicities. Such research will help develop comprehensive and personalized treatment plans for Lynch syndrome-associated CRC.

Immune checkpoint inhibitors (ICIs) have dramatically changed the landscape of cancer treatment and are increasingly used either as monotherapy or in combination with other ICIs, chemotherapy, and molecularly targeted agents. ICI myocarditis is a rare but potentially fatal irAE associated with the use of ICI characterized by T-cell mediated cardiomyocyte death. Diagnosing ICI myocarditis can be intricate as its atypical presentations. Multimodal imaging plays a crucial role in the diagnosis and risk stratification of ICI myocarditis. Current management strategies for ICI myocarditis include corticosteroids and immunosuppressants. Multidisciplinary collaboration is vital in these cases-combining oncology expertise with cardiology insights.

This review discusses the epidemiology, pathophysiology, and factors associated with refractory immune-mediated diarrhea and colitis (r-IMDC), emphasizing tailored treatment strategies.

The current literature on r-IMDC was reviewed using PubMed (2015-2025), focusing on clinical trials, meta-analyses, and case reports relevant to its management.

Effectively managing r-IMDC is crucial for balancing toxicities and antitumor response. Available second and third-line management options for r-IMDC cases must be carefully evaluated. Future perspectives include development of standardized protocols beyond second-line therapies and predictive biomarkers to enable personalized treatment.

This review highlights the critical role of radiologists in personalized cancer treatment, focusing on the evaluation of treatment outcomes using imaging tools like Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Ultrasound. Radiologists assess the effectiveness and complications of therapies such as chemotherapy, immunotherapy, and ablative treatments. Understanding treatment mechanisms and consistent imaging protocols are essential for accurate evaluation, especially in managing complex cases like liver cancer. Collaboration between radiologists and oncologists is key to optimizing patient outcomes through precise imaging assessments.

Immune-checkpoint inhibitors (ICIs) can cause inflammation and immune-related adverse events (irAEs). Although irAEs may be caused by dysregulation of cytokines, the impact of various COVID- 19-related factors on expression of ICI-related AEs remains unclear. Assessment of AEs following ICI administration during the COVID- 19 pandemic may provide valuable insights that enable optimization of patient selection, thereby maximizing the benefits of ICI therapy. The aim of this study was to investigate the actual occurrence of severe AEs after ICI administration during the COVID- 19 pandemic. The medical records of patients who received ICI at Saga University Hospital were examined retrospectively. The primary endpoint was the incidence of all AEs ≥ Grade 3 that occurred after ICI administration. The survey period, from Jan 2020 to Dec 2022, was divided into an earlier (Jan 2020-March 2021) and a later (April 2021-Dec 2022) period. AEs with a clear cause other than ICI were excluded from the analysis. A total of 527 patients were included in the analysis, with a median follow-up of 422 days. During the COVID- 19 pandemic, the incidence of AEs ≥ Grade 3 after ICI administration was 52.8%. The incidence of AEs ≥ Grade 3 AEs after ICI administration was significantly higher during the later period [23.4% (57/244) in the earlier period and 49.8% (236/474) in the later period; mixed effect model p < 0.0001, odds ratio, 3.37 (95% CI: 2.32-4.89)]. Overall survival was significantly worse in the group with AEs ≥ Grade 3 than in the group without AEs ≥ Grade 3 [HR (95% CI) = 0.48 (0.36-0.65), p = 0.0001]. During the COVID- 19 pandemic, it became clear that the incidence of severe AEs (including irAEs) increased after ICI administration, particularly during the later period of the disease. Various factors may be associated with occurrence of severe AEs after ICI administration, and long-term careful observation and prospective multicenter clinical studies are required.

Gestational trophoblastic neoplasia (GTN) is a rare but aggressive malignancy that follows normal or aberrant pregnancies. Until the advent of immunotherapy in 2017, surgery and chemotherapy were the standard treatment modalities, with chemotherapy remaining the cornerstone. However, chemoresistance and high-risk disease present significant challenges in managing GTN. Recent advancements in immunotherapy, particularly immune checkpoint inhibitors (ICIs), have offered new hope for managing these difficult cases. This review provides the comprehensive overview of the mechanisms underlying ICIs in GTN, and explores the potential synergy of combining ICIs with targeted therapies, such as vascular endothelial growth factor and epidermal growth factor receptor inhibitors. We also provide an overview of the latest evidence on the use of ICIs in treating GTN, focusing on their effectiveness in both low- and high-risk cases, as well as in chemorefractory settings. In addition, we discuss ongoing clinical trials, immune-related adverse events associated with ICIs, biomarker-driven approaches, immunosuppressive tumor microenvironments, and the challenges posed with ICIs resistance. The review also explores future directions, including the integration of ICIs into standard regimens, the potential for personalized treatment based on tumor biology, and the importance of fertility preservation in young patients with GTN. In conclusion, while challenges remain, immunotherapy represents a promising frontier in GTN treatment, with the potential to improve outcomes and provide a more personalized approach to care.

Onco-rheumatology, the intersection of oncology and rheumatology, is an emerging field requiring further definition. This study aimed to identify the knowledge and skills essential for rheumatologists in clinical oncology.

We retrospectively reviewed consultations with the onco-rheumatology department of a high-volume tertiary cancer centre in Japan from January 2020 to December 2023.

We analysed 417 consultations. The most common consultation (229, 55%) was related to immune checkpoint inhibitor-induced immune-related adverse events (irAEs). Of the 238 irAEs in 185 patients, 15% were rheumatic and 85% were nonrheumatic (e.g. hepatobiliary toxicities, colitis). Approximately 25% of nonendocrine irAEs were refractory/relapsing, requiring second-line therapy (e.g. mycophenolate mofetil, biologics, immunoglobulin). In addition to irAE consultations, 137 (33%) consultations were about possible rheumatic diseases. The final diagnosis often related to cancer treatment, such as granulocyte colony-stimulating factor-related aortitis (15 patients, 11%), olaparib-related erythema nodosum (10 patients, 7.3%), and surgical menopause-related arthralgia (10 patients, 7.3%). Five patients (3.6%) were diagnosed with autoinflammatory bone disease mimicking bone tumours.

Onco-rheumatologists are expected to play a central role in the management of a wide range of irAEs, not limited to rheumatic irAEs. They must also manage rheumatologic manifestations during cancer treatment and rheumatic diseases that mimic tumours.

Ophthalmic immune-related adverse events (Eye-irAEs) from immune checkpoint inhibitors can cause visual morbidity. The absence of standardized definitions for Eye-irAEs not only impedes the development of evidence-based treatments but also progress in translational research. The objective of this study was to develop consensus guidance for an approach to Eye-irAEs.Four ophthalmic physicians (uveitis specialists and neuro-ophthalmologists) drafted Eye-irAE consensus guidance and definitions, which were reviewed by the multidisciplinary Eye-irAE definition panel. The panel was divided into Group A (Neuro-ophthalmology/Orbital Disease) and Group B (Uveitis/Ocular Surface Disease). A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two meetings to discuss areas of controversy. For each disorder, five diagnostic components were evaluated: symptoms, examination findings, laboratory studies/imaging findings, diagnostic criteria, and treatment. Panelists rated content for usability, appropriateness and accuracy on 9-point scales in electronic surveys and provided free-text comments. Aggregated survey responses were incorporated into revised definitions. Consensus was based on numeric ratings using the RAND Corporation/ University of California Los Angeles Health Services Utilization Study (RAND/UCLA) Appropriateness Method with prespecified definitions.29 panelists from 25 academic medical centers voted on 114 rating scales (66 neuro-ophthalmic/orbital disease components, 48 uveitis/ocular surface disease components); of these, 86.3% (57/66) in Group A and 89.6% (43/48) in Group B reached first-round consensus. After revisions, all items except 6.1% (4/66) in Group A and 1.6% (1/60) in Group B received second-round consensus. Consensus definitions were achieved for 10/11 neuro-ophthalmic/orbital disorders: optic neuritis, inflammatory optic disc edema, arteritic ischemic optic neuropathy, optic perineuritis, orbital inflammation, thyroid eye disease-like orbital inflammation, cavernous sinus syndrome, oculomotor mononeuritis, trochlear mononeuritis, and abducens mononeuritis. Consensus definitions were achieved for 9/10 uveitis/ocular surface disorders: anterior uveitis, intermediate uveitis, posterior uveitis, panuveitis, Vogt-Koyanagi-Harada-like syndrome, sarcoidosis-like syndrome, acute macular neuroretinopathy, dry eye disease, and scleritis.These disease definitions establish a standardized classification for Eye-irAE, highlighting differences between irAEs and other inflammatory disorders. Importantly, diagnostic certainty does not always align directly with the need to treat as an Eye-irAE. Given the consensus from this representative panel group, it is anticipated the definitions will be used broadly across clinical and research settings.

Immunotherapy is revolutionizing oncological treatment, but its unique toxicity profile emphasizes the need for multidisciplinary teams involving nurses. In the absence of guidelines tailored for nurses, a comprehensive guide focusing on patient history and care is presented.

To outline the methodology for creating a practical guide for nurses, aimed at improving care for patients undergoing oncologic immunotherapy by focusing on comprehensive support and complementing pharmacological treatment.

A guide was developed following Evidence-Based Nursing principles, with the involvement of experts from Spanish oncology scientific societies. Through evidence searches, external review, and editing, robust and applicable recommendations were ensured.

The guide focuses on toxicity management, incorporating an algorithm for its handling, along with detailed descriptions and recommendations for early symptom identification from the nursing perspective.

The guide emphasizes the essential role of oncology nurses in immunotherapy, highlighting their contribution from advanced roles. Endorsed by scientific societies, it serves as an evidence-based resource.

To provide an update on the literature regarding diagnosis and management of immune checkpoint inhibitor myocarditis.

The diagnosis of immune checkpoint inhibitor myocarditis has evolved to include more reliance on performing endomyocardial biopsy to clarify the diagnosis in selected cases. Additionally, there is recognition of a spectrum of disease both clinically and on endomyocardial biopsy suggesting that there is a range of severity from mild to fulminant. The treatment of immune checkpoint inhibitor myocarditis is shifting towards increased use of additional immunosuppressive medications as steroid sparing agents. There are increased studies including two randomized controlled trials evaluating abatacept in the treatment of immune checkpoint inhibitor myocarditis. This review summarizes the latest literature regarding diagnosis and management of immune checkpoint inhibitor myocarditis and provides our experience and approach to this rare but potentially fatal condition.

The impact of incorporating immune checkpoint inhibitors (ICIs) into standard chemotherapy on the severity and risk of myelosuppression in advanced non-small cell lung cancer (NSCLC) patients remains uncertain.

We conducted a systematic review and meta-analysis of phase 3 randomized controlled trials (RCTs) that evaluated ICIs in people with NSCLC. A comprehensive search of four databases, PubMed, Web of Science, Embase, and the Cochrane Library, was carried out from inception to 30 October 2023. Pooled analyses assessed the risk ratios (RR) for treatment-related hematological adverse events greater than or equal to grade 3. The protocol is registered with PROSPERO and has the CRD42024500056 registration number.

Twenty-three phase 3 RCTs were contained, involving 15,844 people with NSCLC receiving ICIs with or without chemotherapy. Compared with chemotherapy alone, ICI monotherapy or dual immunotherapy reduced treatment-associated leukopenia (relative risk (RR) 0.03, 95% CI 0.01-0.08), neutropenia (RR 0.02, 95% CI 0.01-0.03), thrombocytopenia (RR 0.05, 95% CI 0.02-0.14), and anemia (RR 0.09, 95% CI 0.05-0.15), with a pooled incidence of 0.07%, 0.08%, 0.14%, and 9.07%. Compared with chemotherapy alone, ICIs in combination with chemotherapy increased the risk of developing treatment-related thrombocytopenia (RR 1.35, 95% CI 1.04-1.77), with a pooled incidence rate of 6.83%; it did not increase leukopenia (RR 0.97, 95% CI 0.70-1.35), neutropenia (RR 1.05, 95% CI 0.90-1.23), and anemia (RR 1.10, 95% CI 0.85-1.43), with pooled incidence rates of 4.47%, 14.67%, and 13.36%, respectively.

For patients with advanced or metastatic NSCLC, severe hematological adverse events are uncommon when ICIs are used alone, as opposed to chemotherapy. However, when used in conjunction with chemotherapy, these side effects may be intensified, particularly in the form of an elevated incidence of thrombocytopenia of grade 3 or higher.

The immune checkpoint inhibitors (ICIs)-induced anti-Hu antibody-associated gastrointestinal pseudo-obstruction (GIPO) is a paraneoplastic neurological syndrome related to autoantibodies. It has a very low incidence but a high mortality rate. This report presents the case of a patient with extensive-stage small-cell lung cancer who developed recurrent bowel obstruction symptoms following ICI therapy. Colonoscopy and abdominal CT tomography failed to identify the underlying cause. A definitive diagnosis of GIPO was made based on the histological findings from an exploratory laparotomy and serum levels of paraneoplastic antibodies. Despite treatment with corticosteroids, no significant improvement was detected in the symptoms, and the patient ultimately died. This case highlights the challenges of managing this rare complication. When unexplained bowel obstruction occurs during ICI therapy, antineuronal antibody testing should be performed to exclude GIPO, as early identification and intervention can reduce mortality.

Background/Objectives: Worldwide, colon cancer is a major cause of cancer-related mortality, with an increasing incidence influenced by genetic, environmental, and lifestyle factors. Despite advances in diagnosis and personalized treatments, challenges remain in improving patient prognosis, particularly in metastatic colorectal cancer (mCRC). Bevacizumab (BEV), a monoclonal antibody, is widely used in colorectal cancer treatment. This study aimed to analyze adverse events associated with BEV compared with other therapies based on data from the EudraVigilance (EV) database. Methods: A descriptive and disproportionality analysis was conducted on signals reported in the EV database related to BEV. The study included comparisons with other antineoplastic treatments, such as chemotherapy, targeted therapy, and immunotherapy. Patient demographics, severity of adverse drug reactions (ADRs), and distribution patterns were analyzed to assess the safety profile of BEV in colorectal cancer treatment. Results: The majority of the signals for BEV were from patients aged 18-64 years (39.42%) and 65-85 years (34.08%). Hypertension, thromboembolism, proteinuria, and gastrointestinal disorders have been the most frequently reported. Serious ADRs, including gastrointestinal perforations, hemorrhage, and arterial thromboembolism, were observed in 93.74% of Individual Case Safety Reports. BEV was associated with a higher likelihood of vascular and endocrine disorders compared with chemotherapy and other targeted therapies. Immunotherapy was linked to increased immunological ADRs, while BEV demonstrated fewer immune-related toxicities. Conclusions: Continuous monitoring is necessary to optimize patient management, particularly in elderly patients or those with cardiovascular comorbidities. Understanding BEV's safety profile allows for better personalization of treatment strategies, minimizing risks while enhancing therapeutic outcomes.

Oral cancer, a prevalent form of head and neck malignancy, accounts for 4% of global cancer cases. The most common type, oral squamous cell carcinoma (OSCC), has a survival rate of about 50%. Even though emerging molecular therapies show promise for managing oral cancer, current treatments like surgery, radiotherapy, and chemotherapy have significant side effects. In addition, the complex tumor microenvironment (TME), involving the extracellular matrix (ECM) and cells like fibroblasts and stromal cells like immune cells, promotes tumor growth and inhibits immune responses, complicating treatment. Nonetheless, immunotherapy is crucial in cancer treatment, especially in oral cancers. Indeed, its effectiveness lies in targeting immune checkpoints such as PD-1 and CTLA-4 inhibitors, as well as monoclonal antibodies like pembrolizumab and cetuximab, adoptive cell transfer methods (including CAR-T cell therapy), cytokine therapy such as IL-2, and tumor vaccines. Thus, these interventions collectively regulate tumor proliferation and metastasis by targeting the TME through autocrine-paracrine signaling pathways. Immunotherapy indeed aims to stimulate the immune system, leveraging both innate and adaptive immunity to counteract cancer cell signals and promote tumor destruction. This review will explore how the TME controls tumor proliferation and metastasis via autocrine-paracrine signaling pathways. It will then detail the effectiveness of immunotherapy in oral cancers, focusing on immune checkpoints, targeted monoclonal antibodies, adoptive cell transfer, cytokine therapy, and tumor vaccines.

Survival rates after a diagnosis of cancer are improving. Poorly managed gastrointestinal (GI) side effects can interfere with delivery of curative cancer treatment. Long-term physical side effects of cancer therapy impinge on quality of life in up to 25% of those treated for cancer, and GI side effects are the most common and troublesome.

To provide comprehensive, practical guidance on the management of acute and chronic luminal gastrointestinal symptoms arising during and after treatment for cancer METHODS: A multidisciplinary expert group including patients treated for cancer, divided into working parties to identify, and synthesise recommendations for the optimal assessment, diagnosis and appropriate interventions for luminal GI side effects of systemic and local cancer therapies. Recommendations were developed using the principles of the BMJ AGREE II reporting.

103 recommendations were agreed. The importance of the patient perspective and what can be done to support patients are emphasised. Key physiological principles underlying the development of GI toxicity arising from cancer therapy are outlined. Individual symptoms or symptom clusters are poor at distinguishing the underlying cause(s), and investigations are required if empirical therapy does not lead rapidly to significant benefits. Patients frequently have multiple GI causes for symptoms; all need to be diagnosed and optimally treated to achieve resolution. Investigations and management approaches now known to be ineffective or of questionable benefit are highlighted.

The physical, emotional and financial costs to individuals, their families and society from cancer therapy can be considerable. Identifying and signposting affected patients who require specialist services is the role of all clinicians. Progress in the treatment of cancer increasingly means that patients require expert, multidisciplinary supportive care providing effective and safe treatment at every stage of the cancer journey. Development of such expertise should be prioritised as should the education of health professionals and the public in what, when and how acute and chronic gastrointestinal symptoms and complications should be managed.

Gastric adenocarcinoma (GAC) remains a significant global public health challenge, characterized by high incidence and mortality rates. Progress in tumor immunology has introduced immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) pathways, demonstrating substantial potential in GAC therapy. Clinical research indicates that ICIs, particularly when combined with chemotherapy or targeted therapies, significantly enhance treatment efficacy in advanced GAC and specific molecular subtypes, including microsatellite instability-high (MSI-H) and human epidermal growth factor receptor 2 (HER2)-positive patients. However, immunotherapy is also associated with a range of immune-related adverse events (irAEs), necessitating effective management strategies to ensure treatment safety and maintain patients' quality of life. Future studies should focus on identifying new therapeutic targets, optimizing patient selection, and developing personalized treatment approaches to further improve the efficacy and safety of immunotherapy in GAC.

Immune checkpoint inhibitors-induced pancreatitis (ICIs-P) is an uncommon immune-related adverse event. The available evidence consists mostly of case reports, case series, and narrative reviews. This research focuses on the clinical characteristics and management options for ICIs-P to provide a practice-based global perspective on this disease.

Five electronic databases were systematically reviewed to identify the relevant studies. Furthermore, we performed a disproportionality analysis utilizing OpenVigil 2.1 to interrogate the United States Food and Drug Administration's Adverse Event Reporting System (FAERS) database.

A total of 61 patients from 58 studies were included in this study. Most patients with ICIs-P were males (60.7%). Most patients received anti-PD-1/PD-L1 monotherapy (78.7%) or anti-PD-1/PD-L1 monotherapy in conjunction with CTLA-4 blockade (19.7%). The median time from the initiation of immune checkpoint inhibitors treatment to pancreatitis was 108 days (range 52-278). Most cases were severe or life-threatening (G3-G4; 64.0%). Corticosteroids were administered to 73.8% of the patients during the treatment of pancreatitis. Regarding treatment outcomes, ICIs-P was reversible in most cases (83.6%), despite the 8.2% relapse and 8.2% deaths. We identified 606 reports of pancreatitis associated with ICIs in the FAERS database, with the greatest proportion of males (50.7%), 62.0% of PD-1 inhibitors, and 22.1% of all reports of death or life-threatening outcomes. Signals indicating pancreatitis were observed across all ICIs, with particular emphasis on Cemiplimab, Pembrolizumab and Nivolumab.

By using a pharmacovigilance database, we discovered an elevated risk of pancreatitis following ICIs therapy, especially with PD-1 inhibitors. Meanwhile, risk factors for ICIs-P remain poorly understood, and diagnosis is challenging. Which may manifest as asymptomatic elevated pancreatic enzyme levels or clinical pancreatitis. Patients with pancreatitis symptoms should have their lipase and amylase levels and radiology evaluated. Diagnosis should be made by excluding other causes. Steroids are the cornerstone of ICIs-P treatment and slow dose reduction is recommended to reduce recurrence.

Significant gaps remain in our understanding of immunotherapy-related neurotoxicity in pediatric patients, largely because much of our knowledge comes from studies in adults. Accurately identifying the adverse effects of immunotherapy in children is also challenging, owing to variations in terminology and grading systems. Moreover, the manifestation of immunotherapy-related neurotoxicity differs greatly across different diseases, various modalities, dosages, and delivery methods. Combining immunotherapy with other treatments might improve outcomes but introduces new complexities and potential for increased toxicities. Additionally, pediatric patients with intracranial malignancy have unique responses to immunotherapies and distinct neurotoxicity compared to those with extracranial malignancy. Consequently, we must enhance our understanding of the pathophysiology, prevalence, severity, and management of immunotherapy's neurotoxic effects in this vulnerable group. This review consolidates the current knowledge of immunotherapy-related neurotoxicity in pediatric oncology, highlighting various types of neurotoxicity including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and tumor inflammation-associated neurotoxicity (TIAN), among others. Furthermore, we examine the unique features of neurotoxicity associated with adoptive cellular therapy (ACT), antibody-based therapies, immune checkpoint inhibitors (ICIs), oncolytic viruses (OV), and cancer vaccines.