Melanoma Management: Exploring Staging, Prognosis, and Treatment Innovations.

Melanoma, a malignant neoplasm originating from melanocytes, stands as one of the most prevalent cancers globally, ranking fifth in terms of estimated new cases in recent years. Its aggressive nature and propensity for metastasis pose significant challenges in oncology. Recent advancements have led to a notable shift towards targeted therapies, driven by a deeper understanding of cutaneous tumor pathogenesis. Immunotherapy and tyrosine kinase inhibitors have emerged as promising strategies, demonstrating the potential to improve clinical outcomes across all disease stages, including neoadjuvant, adjuvant, and metastatic settings. Notably, there has been a groundbreaking development in the treatment of brain metastasis, historically associated with poor prognosis in oncology but showcasing impressive results in melanoma patients. This review article provides a comprehensive synthesis of the most recent knowledge on staging and prognostic factors while highlighting emerging therapeutic modalities, with a particular focus on neoadjuvant and adjuvant strategies, notably immunotherapy and targeted therapies, including the ongoing trials.

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.

Long-Lasting Therapeutic Response following Treatment with Pembrolizumab in Patients with Non-Small Cell Lung Cancer: A Real-World Experience.

Immune checkpoint inhibitors (ICIs), pembrolizumab in particular, have been shown to be vastly more efficacious than traditional cytotoxic or platinum-based chemotherapies in the treatment of non-small cell lung cancer (NSCLC). While there are plenty of data showing their efficacy and safety profiles, very little exists about the long-term effects of pembrolizumab. We compiled all patients with NSCLC who were treated with pembrolizumab at our institution and had progression-free survival (PFS) of at least 2 years during or after the treatment period. Within this group, we examined the long-term rates of PFS and overall survival (OS), side effect profiles, treatment, and overall disease course up to 60 months after starting treatment. This study included 36 patients with median (range) follow up times from treatment initiation in months as follows: 36 (28-65) overall; 39.5 (28-65) for adenocarcinoma; and 36 (30-58) for squamous cell carcinoma. The median (range) of OS and PFS (months) was comparable for adenocarcinoma, 36 (23-55); and squamous cell carcinoma, 35.5 (28-65). Overall, pembrolizumab shows remarkable long-term safety and efficacy in NSCLC patients. In patients who show an initially strong response and can make it to 24 months of PFS, disease progression after this period seems increasingly unlikely.

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.

Crizotinib in MET Exon 14-Mutated or MET-Amplified in Advanced Disease Non-Small Cell Lung Cancer: A Retrospective, Single Institution Experience.

Introduction: Non-small cell lung cancer (NSCLC) accounts for most lung cancers and is a leading cause of cancer-related deaths in the USA. Alterations in c-MET, a tyrosine kinase receptor, have been involved in many cases of NSCLC progression and metastasis. Crizotinib and other tyrosine kinase inhibitors (TKIs) have been used in NSCLC treatment with limited success. Methods: In this retrospective observational study, we analyzed data from patients diagnosed with lung cancer at Soroka University Medical Center between January 2015 and January 2020. We investigated patient characteristics, including disease-associated mutation type and median survival in response to different TKI treatments. Results: A total of 780 patients with lung cancer were included in the study, 134 of whom had small cell lung cancer and 646 had NSCLC. Of the NSCLC patients, 403 were diagnosed with advanced or metastatic disease, and 374 underwent molecular testing. We identified 16 patients with either c-MET mutations or amplifications who were treated with crizotinib. Of these patients, 7 expressed a c-MET exon 14 skipping mutation while the remaining 9 patients expressed c-MET amplification. Among the patients with a c-MET exon 14 skip mutation, the overall survival was 22.8 months and the median progression-free survival (PFS) on crizotinib treatment was 12.4 months. Of the patients with c-MET amplification, the median overall survival was 5.4 months and the median PFS with crizotinib treatment was 2.6 months. Discussion and Conclusions: We analyzed the data of a series of cases describing patients diagnosed with different stages of NSCLC, having either a c-MET exon 14 skipping mutation or an amplification mutation, and treated with various TKIs, including crizotinib. We investigated the characteristics of these patient groups in accordance with mutation types and compared median survival between patient groups. Crizotinib was found to be an optimal treatment for NSCLC harboring c-MET exon 14 skipping mutations.

Intravenous immunoglobulin efficacy on pembrolizumab induced severe toxic epidermal necrolysis.

Pembrolizumab is an immune checkpoint inhibitor used in many different cancers. Several immune-related adverse events (irAEs) have been associated with pembrolizumab, including toxic epidermal necrolysis. Here, we are presenting a patient with non-small cell lung cancer that developed toxic epidermal necrolysis 3-days following initiation of pembrolizumab. Following high-dose steroid therapy, intravenous immunoglobulin 2 g/kg was initiated and resulted in complete resolution of all his irAEs. To our knowledge, this is the first reported case of total re-epithelialization and resolution of immune checkpoint inhibitor-induced toxic epidermal necrolysis following the use of intravenous immunoglobulin.

Novel Biomarkers and Therapeutic Targets for Melanoma.

Malignant melanoma is one of the most common cancers in the world. In the disease's early stages, treatment involves surgery, in advanced stages however, treatment options were once scarce. There has been a paradigm shift in advanced melanoma treatment with the introduction of immunotherapy and targeted therapies. Understanding the molecular pathways and their pathologic counterparts helped identifying specific biomarkers that lead to the development of specific targeted therapies. In this review we briefly present some of these markers and their relevance to melanoma treatment.

Pulmonary toxicity following administration of granulocyte colony-stimulating factor during chemotherapy for breast cancer: a case report and literature review.

In this report, we aim to present a case of pulmonary toxicity in a patient that received neoadjuvant chemotherapy treatment with doxorubicin and cyclophosphamide for triple-negative breast cancer that was followed with granulocyte colony-stimulating factor (G-CSF) for prevention neutropenia, our patient presented with chest discomfort and dyspnea, with radiologic evidence of radiologic investigations showed acute respiratory distress syndrome, after investigation and follow up we came to the conclusion that it was G-CSF adverse effect.

Metastatic small cell lung cancer - an aggressive disease: a case report and literature review.

In the present case study, we describe a 53-year-old male with an aggressive small cell lung cancer (SCLC) that was diagnosed in January 2019. Our patient was treated as first line of systemic chemotherapy consisting of cisplatin and etoposide followed by mediastinal prophylactic radiotherapy with good response later he received for his metastatic disease (M-SCLC) a rechallenge of systemic chemotherapy consisting of carboplatin, etoposide and dulvalumab with stable disease and after progression his disease he was treated with lurbinectedin and after four cycles he reached a complete radiologic response. To the best of our knowledge, this is the first case to be reported of M-SCLC patient treated with prior of two types of platinum combination with immunotherapy and reaching a complete radiologic response.

Oncology Treatments during the COVID-19 Pandemic in Israel: the ONCOR Study.

BACKGROUND: The increased susceptibility of cancer patients to coronavirus disease-2019 (COVID-19) infections and complications calls for special precautions while treating cancer patients during COVID-19 pandemics. Thus, oncology departments have had to implement a wide array of prevention measures. OBJECTIVES: To address issues associated with cancer care during the COVID-19 pandemic and to assess the implementation of measures aimed at containment of COVID-19 diffusion while allowing continuation of quality cancer care. METHODS: A national survey among oncology departments in Israel was conducted between 12 April 2020 and 14 April 2020. Eighteen heads of hospital-based oncology departments completed a self-report questionnaire regarding their institute's preparedness for treatment of cancer patients during the COVID-19 pandemic. RESULTS: In this national survey, prevention measures against COVID-19 spread were taken prior to patients' arrival and at arrival or while staying in the departments. Most participants (78-89%) reported using a quick triage of patients and caregivers prior to their entrance to the oncology units, limiting the entrance of caregivers, and reducing unnecessary visits to the clinic. Switching to oral therapies rather than intravenous ones when possible was considered by 82% and shortage in personal protective equipment was reported by five (28%) heads of oncology departments. Some differences between large and small/medium sized medical centers were observed regarding issues related to COVID-19 containment measures and changes in treatment. CONCLUSIONS: Oncology departments in Israel were able to prepare and adapt their services to guidelines and requirements related to the COVID-19 pandemic with little harm to their treatment capacity.

Recent Changes and Innovations in Melanoma Treatment: A Review.

BACKGROUND: Malignant melanoma is one of the most extensively studied diseases in the last few decades. The outcome of these studies and the treatment changes that followed have dramatically altered the landscape of not only melanoma therapy, but all solid tumors. In this review we presented the recent advances of surgical and adjuvant management of patients with cutaneous malignant melanoma. This review focuses on stage III melanoma since this stage of disease requires surgical treatment as well as adjuvant therapy.

Malignant Melanoma in Association With a Thymic Nevus in a Patient With a Giant Congenital Nevus.

Nevi and melanocytic proliferations are known to appear in multiple extracutaneous sites, including lymph nodes and meninges. We report a case of an anterior mediastinal mass in a patient with a giant congenital nevus and neurofibromatosis type I. Histologically, the tumor was found to be a malignant melanoma in the thymus arising in association with a nevus that involved most of the thymic tissue. There was no sign of cutaneous melanoma on skin examination. We suggest that the tumor originated from the benign nevus in the thymus, a rare extracutaneous location for nevi and malignant melanoma.

Advanced and Metastatic Non-Melanoma Skin Cancer: Epidemiology, Risk Factors, Clinical Features, and Treatment Options.

Non-melanoma skin cancers (NMSC) form the majority of skin cancers, with basal cell carcinoma (BCC) being the most common and cutaneous squamous cell carcinoma (cSCC) being second. Prolonged ultraviolet (UV) exposure, aging, male gender, and immunosuppression represent most of the causes of this category of diseases. BCCs and cSCCs both include different types of skin cancers, such as nodular or morpheaform BCC or flat cSCC. Locally advanced and metastatic NMSCs cannot be treated surgically; thus, systemic therapy (TKI and Immunotherapy) is needed. Interestingly, NMSCs are frequently linked to abnormal Hedgehog (HH) signaling which most systemic immunotherapies for these cancers are based upon. Of note, the first line therapies of BCC, sonidegib and vismodegib, are HH inhibitors. Programmed death receptor 1 antibody (PD-1) inhibitors such as cemiplimab, pembrolizumab, and nivolumab have been approved for the treatment of cSCC. Thus, this paper reviews the epidemiology, risk factors, clinical features, and treatment options for both BCC and cSCC.

Efficacy of Pembrolizumab vs. Nivolumab Plus Ipilimumab in Metastatic NSCLC in Relation to PD-L1 and TMB Status.

The efficacy of immune checkpoint inhibitor (ICI) therapy concerning programmed death ligand 1 (PD-L1) status is well established in patients diagnosed with non-small cell lung cancer (NSCLC). However, there remains a paucity of evidence regarding the efficacy concerning tumor mutational burden (TMB) in both clinical trials and real-world data (RWD). In the current article, clinicopathological and molecular epidemiological data were meticulously collected, and treatment modalities were meticulously recorded. The final analysis included a study population of 194 patients. Median age was 67 years (range 37-86), with the majority being male (71.13%), and 85.71% of patients were either current or former smokers at diagnosis. Adenocarcinoma accounted for most diagnoses (71.65%), followed by squamous cell carcinoma (24.23%). In terms of PD-L1 status, 42.78% had an expression level below 1%, 28.35% had an expression between 1-49%, and 28.87% had an expression above 50%. The TMB ranged from 0 to 75, with a median of 10.31 (range 0-75) for PD-L1 expression below 1%, with a median of 9.73 (range 0.95-39.63) for PD-L1 expression between 1-49%, and a median of 9.72 (range 0.95-48) for PD-L1 expression above 50%. Corresponding to patients with low PDL-1 less than 1% and low TMB (0-5), the median overall survival (mOS) was 16 (p = 0.18), and 15 months (p = 0.22), patients with medium PDL-1 (1-49%) and medium TMB (5-10), the mOS was 15 (p = 0.18) and 16 months (p = 0.22), patients with high PDL-1 (>50) and high TMB (>10), the mOS was 24 (p = 0.18) and 21 (p = 0.22) months. This study represents the largest academic RWD dataset concerning PD-L1 and TMB status in patients with locally advanced and metastatic NSCLC.

PD-1 Inhibitors in Elderly and Immunocompromised Patients with Advanced or Metastatic Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) of the skin is the second most common form of skin cancer, with aging and prolonged exposure to ultraviolet rays being the main causes of the disease. Cemiplimab and pembrolizumab recently gained regulatory approval for the treatment of locally advanced and metastatic cSCC-conditions that are not treatable by surgical resection and/or radiotherapy. Although the results from the clinical trials have been promising, these studies have not included immunosuppressed, elderly patients. In this study, we included all immunocompromised and immunocompetent patients over the age of 75 years diagnosed with locally advanced or metastatic cSCC and treated with cemiplimab or pembrolizumab. The median duration of follow-up from cSCC diagnosis was 35.6 months, 82.9% of patients were male, and the median age was 83 years old. The median progression-free survival was 8.94 months. The incidence of treatment-related adverse events was 85.6%, the majority of which were grades 1 or 2. The disease control rate was 91.4%, the complete response rate was 17.1%, the partial response rate was 51.4%, the stable disease rate was 23%, and the progressive disease rate was 8.7%. Based on this study, cemiplimab and pembrolizumab for the treatment of locally advanced or metastatic cSCC in elderly, immunocompromised patients are efficacious, with acceptable safety profiles.

Unexpected Adverse Events of Immune Checkpoint Inhibitors.

The introduction of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment standards and significantly enhanced patient prognoses. However, the utilization of these groundbreaking therapies has led to the observation and reporting of various types of adverse events, commonly known as immune-related adverse events (irAEs). In the following article, we present four patients who encountered uncommon toxicities induced by ICIs. The first patient was a 59-year-old female diagnosed with stage 4 lung adenocarcinoma. She received immunotherapy (pembrolizumab) together with chemotherapy and subsequently developed autonomic neuropathy (AN). The next two patients also received chemo-immunotherapy (pembrolizumab) and were both 63-year-old males with stage 4 lung adenocarcinoma. One of the two experienced palmoplantar keratoderma, while the other presented with Reiter's syndrome (urethritis, conjunctivitis and arthritis). The 4th patient, an 80-year-old male with stage 4 squamous cell carcinoma of the lung, received chemo-immunotherapy (pembrolizumab) and developed myasthenia gravis.

Bullous Pemphigoid Occurring after Stopping Imatinib Therapy of CML: Is a Continuation of Post-Treatment Follow-Up Needed?

Advancements and the use of tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of Chronic Myeloid Leukemia (CML), achieving unprecedented success rates and expanding their applications to various neoplasms. However, the use of TKIs is not without its drawbacks. Skin, gastrointestinal, and central nervous systems are particularly susceptible to adverse effects, including a higher incidence of autoimmune responses in treated individuals. In this report, we present a unique case of bullous pemphigoid, a rare autoimmune disease, which has not been previously associated with TKI therapy as an adverse effect, particularly appearing after discontinuing Imatinib® treatment.

Safety and rapid response of dabrafenib and trametinib therapy during hyperbilirubinemia in metastatic melanoma.

This case report describes the occurrence of hyperbilirubinemia as a complication of metastatic melanoma. A 72-year-old male patient was diagnosed with BRAF V600E-mutated melanoma with metastases in the liver, lymph nodes, lungs, pancreas, and stomach. Due to a lack of clinical data and specific guidelines for the treatment of mutated metastatic melanoma patients with hyperbilirubinemia, a conference of specialists debated between initiating treatment or providing supportive care. Ultimately, the patient was started on the combination therapy of dabrafenib and trametinib. This treatment resulted in a significant therapeutic response via normalization of bilirubin levels and an impressive radiological response of metastases just one month post-treatment initiation.

Radiotherapy-Induced Atrial Myxoma: A Case Report and Literature Review.

In this particular case study, we present a 66-year-old male who was diagnosed with an atrial myxoma eight years after receiving treatment for non-small cell lung cancer. The patient underwent chemo-radiotherapy (mediastinal area) in 2012 to address stage III-A adenocarcinoma of the lung. During follow-up imaging in 2020, a left atrial mass displaying characteristic features of a cardiac myxoma was detected. Upon reviewing a computed tomographic (CT) scan from 2017 within the previously irradiated mediastinal region, the cardiac mass was retrospectively identified. The surgical excision of the cardiac mass was performed, and a subsequent pathological examination confirmed the diagnosis of myxoma. To the best of our knowledge, this is the first reported case of a left atrial myxoma in a patient previously treated for adenocarcinoma of the lung and the first instance of an atrial myxoma occurring in a site that had undergone prior radiation therapy.

Avelumab for the treatment of locally advanced or metastatic Merkel cell carcinoma-A multicenter real-world experience in Israel.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive malignancy of the skin, affecting predominantly the fair-skinned older population exposed to high levels of ultraviolet light. Immune suppression is considered a significant risk factor. With the recent advances in the field of immunotherapy, the treatment paradigm for advanced MCC, traditionally based on chemotherapy, has largely shifted to anti-PD-L1 and PD-1 agents such as avelumab and pembrolizumab, respectively. However, real-world data remain sparse. The aim of this study was to assess real-world evidence of the effectiveness of avelumab in a diverse group of patients with MCC in Israel. METHODS: The electronic databases of five university hospitals in Israel were searched for all consecutive patients with MCC treated with at least one dose of avelumab in 2018-2022. Data on baseline, disease-related, treatment-related, and outcome parameters were collected and analyzed. RESULTS: The cohort included 62 patients of whom 22% were immune-suppressed. The overall response rate to avelumab was 59%. The median progression-free survival was 8.1 months, and the median overall survival, 23.5 months, with no differences between immune-competent and immune-suppressed patients. Treatment was well tolerated; any-grade toxicity developed in 34% of patients, and grade 3-4 toxicity, in 14%. CONCLUSIONS: Avelumab was found to be effective and safe for the treatment of advanced MCC in a diverse group of patients, including some with immune suppression. Further studies are warranted to evaluate the optimal sequence and duration of treatment and to assess the potential role of avelumab for earlier stages of MCC.