UNASSIGNED: The outcome of patients with metastatic tumors who discontinued immune checkpoint inhibitors (ICIs) not for progressive disease (PD) has been poorly explored. We performed a meta-analysis of all studies reporting the clinical outcome of patients who discontinued ICIs for reasons other than PD.
UNASSIGNED: We searched PubMed, Embase and Scopus databases, from the inception of each database to December 2023, for clinical trials (randomized or not) and observational studies assessing PD-(L)1 and CTLA-4 inhibitors in patients with metastatic solid tumors who discontinued treatment for reasons other than PD. Each study had to provide swimmer plots or Kaplan-Meier survival curves enabling the reconstruction of individual patient-level data on progression-free survival (PFS) following the discontinuation of immunotherapy. The primary endpoint was PFS from the date of treatment discontinuation overall and according to tumor histotype, type of treatment and reason of discontinuation. The Combersure\'s method was used to estimate meta-analytical non-parametric summary survival curves assuming random effects at study level.
UNASSIGNED: Thirty-six studies (2180 patients) were included. The pooled median PFS (mPFS) was 24.7 months (95% CI, 18.8-30.6) and the PFS-rate at 12, 24, and 36 months was respectively 69.8% (95% CI, 63.1-77.3), 51.0% (95% CI, 43.4-59.8) and 34.0% (95% CI, 27.0-42.9). Univariable analysis showed that the mPFS was significantly longer for patients with melanoma (43.0 months), as compared with non-small cell lung cancer (NSCLC, 13.5 months) and renal cell carcinoma (RCC, 10.0 months; between-strata comparison test p-value < 0.001); for patients treated with anti-PD-(L)1 + anti-CTLA-4 as compared with anti-PD-(L)1 monotherapy (44.6 versus 19.9 months; p-value < 0.001), and in NSCLC when the reason of treatment discontinuation was elective as compared with toxicity onset (19.6 versus 4.8 months; p-value = 0.003). The multivariable analysis confirmed these differences.
UNASSIGNED: The long-term outcome of patients who stopped ICIs for reasons other than PD was substantially affected by clinicopathological features: PFS after treatment discontinuation was longer in patients with melanoma, and/or treated with anti-PD-(L)1 + anti-CTLA-4, and shorter in patients with RCC or in those patients with NSCLC who stopped treatment for toxicity onset.
UNASSIGNED: The Italian Ministry of University and Research (PRIN 2022Y7HHNW).

Guillain-Barré syndrome (GBS) resulting from the use of immune checkpoint inhibitors (ICIs) is relatively uncommon but has been reported. Herein, we discuss a case of a 67-year-old patient who received neoadjuvant ICI for treatment of non-small cell lung cancer and then presented with lower extremity weakness and areflexia, progressing to respiratory muscle and upper extremity weakness. Given the increasing use of ICI in cancer management, awareness of neurological autoimmune side effects is essential. ICI-mediated GBS can be severe and fatal if not diagnosed promptly. We discuss a case of ICI-induced GBS and review literature on current management approaches.

OBJECTIVE: The objective of this article is to review the efficacy, safety, and evidence for current use and potential future uses of immune-checkpoint inhibitors (ICIs) in the management of resectable non-small cell lung cancer (NSCLC).
METHODS: A literature review was carried out through PubMed to identify completed and ongoing clinical trials evaluating the use, efficacy, and safety of ICIs in the management of resectable NSCLC.
METHODS: To date, four phase 3 trials have emerged that have changed our treatment practice concerning the utilization of ICIs during the adjuvant and neoadjuvant settings. The IMpower010 and KEYNOTE-091 trials examined the application of adjuvant atezolizumab and pembrolizumab, respectively, following surgical resection and adjuvant chemotherapy. In the CheckMate 816 trial, the combination of nivolumab and chemotherapy as a neoadjuvant therapy received approval for patients with resectable NSCLC. Also, for patients with resectable NSCLC, the use of a pembrolizumab and chemotherapy combination as a perioperative therapy received approval based on the results of the KEYNOTE-671 trial. Apart from these trials, there are numerous phase 2 and phase 3 trials, some of which have been published while others are still in progress.
CONCLUSIONS: Despite the promising outcomes from these trials there remain several unanswered questions. In this review, we will assess clinical trials involving adjuvant, neoadjuvant, and perioperative ICIs, aiming to address the unresolved questions related to these therapeutic approaches.

Non-melanomatous cutaneous spindle cell neoplasms are a rare group of malignancies that present a diagnostic challenge, and for which there is a lack of consensus on how to best manage patients with advanced disease and only limited reports of immune-checkpoint inhibitor (ICI) responses. In this study, we performed a single-center retrospective review of treatment outcomes for all advanced non-melanomatous cutaneous spindle cell neoplasms treated with ICIs. Blinded histopathology reviews occurred to confirm each diagnosis. Comprehensive tumour profiling included whole exome sequencing for tumour mutational burden (TMB) and ultraviolet(UV) signatures, and immunohistochemistry for immune-cell infiltration (CD4/CD3/CD8/CD103/CD20) and immune-checkpoint expression (PD-L1/LAG3/TIGIT). Seven patients were identified. The objective response rate was 86% (6/7) with five complete responses (CR). Responses were durable with two patients in CR > 30 months after ICI commencement. All patients had high TMB and UV signatures. One patient had PD-L1 100% (combined positive score) with abundant immune-cell infiltration and LAG3 expression. In advanced non-melanomatous cutaneous spindle cell neoplasms, excellent responses to ICIs with durable disease control were observed. ICIs are worthy of further exploration in these patients. UV signatures and high TMB could be used to help select patients for treatment.

UNASSIGNED: Immune agents targeting Programmed cell death-1 (PD-1) are a new type of cancer treatment drugs. By inhibiting the interaction between PD-1 and PD-L1, the ability of the immune system to attack tumor cells is enhanced. These immune preparations have shown significant efficacy in the treatment of various malignant tumors. However, like other drugs, immune preparations targeting PD-1 may also cause side effects, including arthralgia. Therefore, we conduct a meta-analysis to assess whether immune-checkpoint inhibitors targeting programmed cell death-1 in lung cancer patients will lead to arthralgia adverse events.
UNASSIGNED: We conducted a comprehensive search across multiple databases, including PubMed, Medline (Ovid), Web of Science, Cochrane, Embase, Scopus, CKNI, Wang fang, VIP database, Sino Med, and Clinical Trails, to identify relevant studies. The search encompassed articles published up until June 20th, 2023. The primary outcome is adverse events about arthralgia and secondary outcomes are any other related with arthralgia. Data extraction was carried out by two independent individuals, and the Cochrane Risk of Bias tool version 2.0 was employed to assess the included studies. The systematic review and meta-analysis were conducted using RevMan 5.3 software.
UNASSIGNED: 12 studies are included in the meta-analysis. All included studies were determined to have a low risk of random sequence generation bias. The meta-analysis result showed that arthralgia RR = 1.11, 95% CI [0.88, 1.40], I2 = 56%, back pain RR = 1.86, 95% CI [1.07, 3.26], I2 = 84%, myalgia RR = 0.49, 95% CI [0.27, 0.88], I2 = 86% and muscular pain RR = 1.97, 95% CI [1.40, 2.77], I2 = 23%.
UNASSIGNED: The use of targeted inhibitors may lead to an increased incidence of back pain, while potentially reducing the occurrence of myalgia. On the other hand, immune-checkpoint inhibitors targeting programmed cell death-1 in lung cancer patients may not cause arthralgia and muscular pain.

OBJECTIVE: Immune-checkpoint inhibitors have recently shown great promise in treating various cancers, but often cause immune-related adverse events (irAEs). Simultaneous drug-induced hypothyroidism and isolated adrenocorticotropic hormone (ACTH) deficiency are rare irAEs. This combination of irAEs is associated with paradoxical endocrine dysfunction characterized by large amounts of thyroid-stimulating hormone (TSH) and small amounts of ACTH in the anterior lobe of the pituitary. We herein report a case of hypothyroidism with isolated ACTH deficiency during pembrolizumab therapy for recurrent lung cancer.
METHODS: Our patient was a 66-year-old man with recurrence of squamous cell lung carcinoma. Four months after chemotherapy that included pembrolizumab, the patient presented with general fatigue and laboratory tests showed high concentrations of TSH with low concentrations of free-T4. He was diagnosed with hypothyroidism and levothyroxine was prescribed. His ACTH concentration was found to be low 1 week later when he developed an acute adrenal crisis with associated hyponatraemia. We then changed his diagnosis to concurrent hypothyroidism with isolated ACTH deficiency. His condition improved after 3 weeks of administration of cortisol.
CONCLUSIONS: It is difficult to diagnose a concurrent paradoxical endocrine disorder, such as hypothyroidism with isolated ACTH deficiency, as in the present case. Physicians should pay attention to symptoms and laboratory data to identify various types of endocrine disorders as irAEs.

Immune-checkpoint inhibitors (ICIs) are immunomodulatory monoclonal antibodies, which increase antitumor immunity of the host and facilitate T-cell-mediated actions against tumors. These medications have been used in recent years as a weapon against advanced stage malignancies, such as melanoma, renal cell carcinoma, lymphoma, small or non-small cell lung cancer, and colorectal cancer. Unfortunately, they are not free from possible adverse effects (immune-related adverse events-irAEs) that mainly affect skin, gastrointestinal, hepatic, and endocrine systems. Early diagnosis of irAEs is essential to correctly and rapidly manage patients, with ICIs suspension and therapies administration. Deep knowledge of the imaging and clinical patterns of irAEs is the key to promptly rule out other diagnoses. Here, we performed a review of the radiological signs and differential diagnosis, based on the organ involved. The aim of this review is to provide guidance to recognize the most significant radiological findings of the main irAEs, based on incidence, severity, and the role of imaging.

UNASSIGNED: Although upper tract urothelial carcinoma (UTUC) shares the histological appearance of urinary bladder cancer (UBC), molecular studies suggest that UTUC and UBC represent two distinct disease entities. However, treatment approaches for UTUC are virtually extrapolated from the evidence on UBC. As targeted drugs-immune-checkpoint inhibitors, fibroblast growth factor receptor inhibitors, and antibody-drug conjugates-target specific molecules, gaining more knowledge about the target-molecular profiles of each drug can help formulate optimal treatment strategies for UTUC.
UNASSIGNED: This narrative review summarized the subgroup analyses of clinical trials of FDA-approved targeted drugs to explore the differential effects of each targeted drug when administered for UTUC compared to UBC. We focused on the differences in mutation frequency, RNA expression subtype, and therapeutic target protein expressions (specifically PD-L1, Nectin-4, and Trop-2) between UTUC and UBC and discussed their relationship with the efficacy of each targeted drug.
UNASSIGNED: A clinical trial of nivolumab in an adjuvant setting (CheckMate 274) implied that immune-checkpoint inhibitors might be less efficacious in UTUC than in UBC. Genomic and transcriptomic studies suggest that UTUC has a high frequency of FGFR3 mutations and predominantly shows the luminal papillary subtype, which is immunologically cold with low T-cell infiltration. These findings are consistent with a possible lower response rate to immunotherapy in UTUC than that in UBC. Clinical trials of enfortumab vedotin in a third-line setting (EV201 and EV301) implied that enfortumab vedotin might be less efficacious in UTUC than in UBC. Previous immunohistochemical analyses suggest that UTUC might have a slightly lower rate of Nectin-4 positivity than UBC, indicating that enfortumab vedotin was less efficacious in UTUC than in UBC.
UNASSIGNED: Clinical differences in the effects of targeted drugs for UTUC and UBC may highlight the molecular differences between these diseases. The treatment strategy should be optimized based on further investigation of the molecular characteristics of UTUC.

Immune-checkpoint inhibitors (ICIs) are the most effective treatments nowadays. Nivolumab was the second ICI used for treating solid tumors with amazing results. Patients treated with Nivolumab may react differently to this treatment. Some people tolerate this treatment very well without experiencing any adverse reactions, whilst some may have mild symptoms and a part of them can present severe reactions. In our research, we sought to identify the answers to four questions: 1. what type of cancer has more severe hypersensitivity reactions to Nivolumab, 2. what is the time frame for developing these severe reactions to Nivolumab, 3. whether it is best to continue or stop the treatment after a severe hypersensitivity reaction to Nivolumab and 4. what severe hypersensitivity reactions are the most frequent reported along Nivolumab treatment. This review also highlights another problem with regard to the usage of concomitant and prior medications or other methods of treatment (e.g., radiation therapy), which can also lead to severe reactions. Treatment with Nivolumab is very well tolerated, but patients should also be warned of the possibility of severe hypersensitivity reactions for which they should urgently see a doctor for a personalized evaluation. There are some options for individuals with severe hypersensitivity reactions, for eg. switching the medication or applying a desensitization protocol.

UNASSIGNED: Immune checkpoint inhibitors and immunotherapy have been shown to improve survival rates, especially in non-small cell lung cancer (NSCLC) patients. More recently, several trials have evaluated the clinical roles of immunotherapy as neoadjuvant settings for NSCLC. There trials suggested that neoadjuvant immunotherapy may effectively reduce the risk of the local recurrence and metastasis of cancer, and significantly improved overall survival and cure rates. Here we conducted a review to summarize the possible mechanism, clinical development, and research progress of neoadjuvant immunotherapy in NSCLC.
UNASSIGNED: Relevant articles for this review were retrieved from Google Scholar, Clinicaltrials.gov., and PubMed using the terms \"non-small-cell lung cancer\", \"NSCLC\", \"neoadjuvant\", \"immunotherapy\", \"immune checkpoint inhibitors\", \"mechanisms\", and \"toxicity\". The primary focus was placed on clinical studies and conference abstracts measuring the safety and efficacy of neoadjuvant immunotherapy in NSCLC until May 2022.
UNASSIGNED: After reviewing the preclinical and clinical trial, the preclinical study showed that neoadjuvant immune checkpoint inhibitor promotes antitumor immunity through the enhancement of T cell effector function and the induction of long-term memory. The initial results of preliminary early-phase trials suggested that neoadjuvant immunotherapy is a promising therapeutic strategy for resectable NSCLC patients, with long-term response and modest toxicity, many of these regimens are currently being evaluated by randomized phase III trials. In addition, the major pathologic response of neoadjuvant immunotherapy ranged up to 45% in these studies when used alone, and up to around 83-86% when used in combination with chemotherapy, therefore it has been seen as a rather potent tumor debulking agent.
UNASSIGNED: Neoadjuvant immunotherapy has been shown to be a novel integral component of NSCLC care. However, there are also several research questions that requires further investigation, such as the side effects, the optimally treated patients, and the time of preoperative immunotherapy.