Real-World Journey of Unresectable Stage III NSCLC Patients:Current Dilemmas for Disease Staging and Treatment

Daily-practice challenges in oncology have been intensified by the approval of immune checkpoint inhibitors (ICI). We aimed to outline current therapy policies and management of locally advanced unresectable stage III non-small-cell lung cancer (NSCLC) in different countries. One thoracic oncologist from each of the following countries—Belgium, Croatia, Greece, Israel, the Netherlands, Norway, Poland, Portugal, Romania, Slovenia, and Switzerland—participated in an electronic survey. Descriptive statistics were conducted with categorical variables reported as frequencies and continuous variables as median and interquartile range (IQR) (StataSE-v15). EBUS (endobronchial ultrasound bronchoscopy) was used either upfront or for N2 confirmation. Resectability is still a source of disagreement; thus, decisions vary within each multidisciplinary team. Overall, 66% of stage III patients [IQR 60–75] undergo chemoradiation therapy (CRT); concurrent CRT (cCRT) accounts for most cases (~70%). Performance status is universally used for cCRT eligibility. Induction chemotherapy is fairly weighted based on radiotherapy (RT) availability. Mean time to evaluation after RT completion is less than a month; ICI consolidation is started within six weeks. Durvamulab expenditures are reimbursed in all countries, yet some limiting criteria exist (PD-L1 ≥ 1%, cCRT). No clear guidance on therapies at Durvamulab progression exist; experts agree that it depends on progression timing. Given the high heterogeneity in real-world practices, standardized evidence-based decisions and healthcare provision in NSCLC are needed

Neoadjuvant and Adjuvant Immunotherapy in Early-Stage Non-Small-Cell Lung Cancer, Past, Present, and Future

Lung cancer is worldwide the most common malignancy. Standard of care treatments for early-stage non-small-cell lung cancer (NSCLC) include surgery and adjuvant chemotherapy. However, these patients continue to have poor prognosis due to systemic or local relapse. Immunotherapy has been considered as a novel approach to improve survival in patients with early-stage NSCLC. Since immune checkpoint inhibitors have transformed the treatment of advanced NSCLC, there is a growing interest in the role of immunotherapy in early-stage NSCLC. In this review, we summarize reported and ongoing clinical trials of immunotherapy in both neoadjuvant and adjuvant settings. We also highlight unaddressed issues in this field of research, such as the predictive markers, the optimal combination therapy, and the need for adjuvant immunotherapy. More studies are needed to optimize the treatment regimen of immunotherapy in patients with early-stage NSCLC

Tolerated Re-Challenge of Immunotherapy in a Patient with ICI Associated Myocarditis: A Case Report and Literature Review

Many different types of cancer can be treated with immunotherapy drugs called immune checkpoint inhibitors (ICIs). These drugs have altered the landscape of cancer treatment options since they function by triggering a stronger immune response to malignancy. As expected, ICIs’ modification of immune regulatory controls leads to a wide range of organ/gland-specific immune-related side effects. These adverse effects are uncommonly deadly and typically improve by discontinuing treatment or administering corticosteroid drugs. As a result of a number of factors—including a lack of specificity in the clinical presentation, the possibility of overlap with other cardiovascular and general medical illnesses, difficulties in diagnosis, and a general lack of awareness—the true incidence of ICI-associated myocarditis is likely underestimated. Currently, protocols for the surveillance, diagnosis, or treatment of this condition are unclear. Several questions remain unanswered, such as how to best screen for this rare toxin, what tests should be run on patients who are suspected of having it, how to treat myocarditis once it has developed, and who is at most risk. In this article, we provide a case study of ICI-associated myocarditis and explain its key characteristics and treatment options

Cemiplimab as First Line Therapy in Advanced Penile Squamous Cell Carcinoma: A Real-World Experience

In the treatment of cancer, immune checkpoint inhibitors (ICIs) have demonstrated significantly greater effectiveness compared to conventional cytotoxic or platinum-based chemotherapies. To assess the efficacy of ICI’s in penile squamous cell carcinoma (pSCC) we performed a retrospective observational study. We reviewed electronic medical records of patients with penile squamous cell carcinoma (SCC), diagnosed between January 2020 and February 2023. Nine patients were screened, of whom three were ineligible for chemotherapy and received immunotherapy, cemiplimab, in a first-line setting. Each of the three immunotherapy-treated patients achieved almost a complete response (CR) after only a few cycles of therapy. The first patient had cerebral arteritis during treatment and received a high-dose steroid treatment with resolution of the symptoms of arteritis. After tapering down the steroids dose, the patient continued cemiplimab without further toxicity. The other two patients did not have any toxic side effects of the treatment. To the best of our knowledge, this is the first real world report of near CR with cemiplimab as a first-line treatment in penile SCC

Perimyocarditis Associated with Immune Checkpoint Inhibitors: A Case Report and Review of the Literature

Patient prognoses have been significantly enhanced by immune checkpoint inhibitors (ICIs), altering the standard of care in cancer treatment. These novel antibodies have become a mainstay of care for metastatic non-small-cell lung cancer (mNSCLC) patients. Several types of adverse events related to ICIs have been identified and documented as a result of the launch of these innovative medicines. We present here a 74-year-old female patient with a stage IV lung adenocarcinoma, treated with nivolumab plus ipilimumab, who developed perimyocarditis two weeks after receiving the third cycle of immune checkpoint inhibitor therapy. The patient was diagnosed using troponin levels, computed tomography (CT) angiography, and echocardiography. After hospitalization, her cardiac condition was successfully resolved with corticosteroids, colchicine, and symptomatic treatment. To the best of our knowledge, this is one of the rarest cases to be reported of perimyocarditis as a toxicity of immunotherapy in a patient treated for adenocarcinoma of the lung

The Association between Acute Myocardial Infarction-Related Outcomes and the Ramadan Period: A Retrospective Population-Based Study

Fasting throughout the Muslim month of Ramadan may impact cardiovascular health. This study examines the association between the Ramadan period and acute myocardial infarction (AMI)-related outcomes among a Muslim population. The data were retrospectively extracted from a tertiary hospital (Beer-Sheva, Israel) database from 2002–2017, evaluating Muslim patients who endured AMI. The study periods for each year were: one month preceding Ramadan (reference period (RP)), the month of Ramadan, and two months thereafter (1840 days in total). A comparison of adjusted incidence rates between the study periods was performed using generalized linear models; one-month post-AMI mortality data were compared using a generalized estimating equation. Out of 5848 AMI hospitalizations, 877 of the patients were Muslims. No difference in AMI incidence between the Ramadan and RP was found (p = 0.893). However, in the one-month post-Ramadan period, AMI incidence demonstrably increased (AdjIRR = 3.068, p = 0.018) compared to the RP. Additionally, the highest risk of mortality was observed among the patients that underwent AMI in the one-month post-Ramadan period (AdjOR = 1.977, p = 0.004) compared to the RP. The subgroup analyses found Ramadan to differentially correlate with AMI mortality with respect to smoking, age, sex, diabetes mellitus, and hypertension, suggesting the Ramadan period is a risk factor for adverse AMI-related outcomes among select Muslim patients

Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review

Immune checkpoint inhibitors are immune stimulatory drugs used to treat many types of cancer. These drugs are antibodies against inhibitory proteins, such as CTLA-4 and PD-1/PD-L1, that are expressed on immune cells. When bound, they allow for increased stimulation of T cells to fight tumor cells. However, immune checkpoint inhibitors have several immune-related adverse effects. Many cases have come to light recently of cardiotoxicity as a result of treatment with these drugs. Cardiotoxicity from immune checkpoint inhibitors is unique due to its rarity and high mortality rate. Patients with this toxicity may present with myocarditis, pericarditis, Takotsubo cardiomyopathy, conduction disorders, and others within just a few weeks of starting immune checkpoint inhibitors. We present here a review of the current research on immune checkpoint inhibitors, their associated cardiotoxicities, the timing of presentation of these conditions, lab tests and histology for each condition, and finally the treatment of patients with cardiotoxicity. We observe a positive skew in the onset of presentation, which is significant for the treating physician

Is Elevation of Alkaline Phosphatase a Predictive Factor of Response to Alectinib in NSCLC?

In the following report, we describe a case of alkaline phosphatase (ALP) elevation occurring during treatment with alectinib (Alecensa™), which was administered for anaplastic lymphoma kinase (ALK) mutated metastatic non-small cell lung cancer (mNSCLC). A 51 year-old female with widespread metastatic disease exhibited a rapid and significant response within a very short period to alectinib therapy, accompanied by a rapid increase of ALP to more than six times the upper limit of normal (grade 3) ALP, decreasing to within normal limits within 3 weeks after initiation of therapy without any dose modification

Dermatomyositis Associated with Lung Cancer: A Brief Review of the Current Literature and Retrospective Single Institution Experience

Dermatomyositis is a rare inflammatory myopathy that is often related to lung cancer. In this retrospective observational study, we analyzed data from patients diagnosed with lung cancer at Soroka University Medical Center between January 2017 and July 2021. A total of 689 patients with lung cancer were included in this study, 97 of whom had small cell lung cancer and 592 had non-small cell lung cancer. We identified a single patient (60-year-old female) who presented with signs and symptoms of dermatomyositis, which was later confirmed to be associated with lung cancer as a paraneoplastic syndrome. Both our study and a recent review of the literature illustrate the temporal link between dermatomyositis and lung cancer, as well as reinforce the need for heightened cancer screenings in DM patients

Carpal Tunnel Syndrome Associated with Immune Checkpoint Inhibitors

Immune checkpoint inhibitors (ICIs) have transformed the therapeutic approach to diverse malignancies, leading to substantial enhancements in patient prognosis. However, along with their benefits, ICIs also increase the incidence of immune-related adverse events (irAEs). In the present paper, we highlight four cases of carpal tunnel syndrome (CTS) as an uncommon manifestation of toxicity induced by ICIs. Although diagnosed with different malignancies, the patients were undergoing ICI therapy when they developed CTS-consistent side effects accompanied by severe neuropathy. Prompt treatment with corticosteroids, intravenous immunoglobulins, or methotrexate resulted in complete symptomatic relief for all patients. This article therefore emphasizes the importance of recognizing and managing rare adverse events associated with ICI use to ensure optimal patient care