We highlight here a case of Moyamoya disease (MMD) developed after treatment for chronic myeloid leukemia (CML). Moyamoya, a term meaning \"a hazy puff of smoke\" in Japanese, denotes a chronic occlusive cerebrovascular condition involving bilateral stenosis or closure of the terminal part of the internal carotid arteries (ICAs) and the proximal sections of the anterior cerebral arteries (ACAs) and middle cerebral arteries (MCAs) resulting in the development of abnormal vascular collaterals. A 40-year-old African-American female with a past medical history of CML presented to the oncology clinic with expressive aphasia. Of note, she was diagnosed with CML eight years ago and was previously treated with dasatinib and nilotinib with only partial remission. She tested positive for the T315I mutation and was initiated on asciminib therapy about a month before her symptoms surfaced. Asciminib, an allosteric inhibitor targeting breakpoint cluster region-abelson murine leukemia 1 (BCR-ABL1) kinase activity, has gained approval for treating patients diagnosed with chronic-phase CML who have not responded to two prior lines of therapy or for those carrying the T315I mutation. During admission, the patient underwent brain magnetic resonance imaging (MRI) and a computed tomography (CT) angiogram of the head showed moderate to severe narrowing at the origins of the bilateral MCA and ACA, concerning Moyamoya syndrome. Although not classically associated with asciminib therapy, we report here a patient with CML who developed expressive aphasia one month after starting the medication. Due to the high index of suspicion, asciminib was discontinued, and the patient was referred for bone marrow transplant evaluation and concurrently started on cytarabine + peginterferon. The patient had improvement in her symptoms of aphasia after the drug was discontinued and returned to her baseline functional status.  No cardiovascular side effects associated with the use of asciminib are currently reported in the literature. However, we have described a case of such an occurrence. Therefore, extra caution should be taken in prescribing asciminib in patients with risk factors or a prior history of stroke.

We present a case of an adult male who presented with pancytopenia accompanied by symptomatic anemia, necessitating chronic transfusions. He was diagnosed with systemic mastocytosis with an associated hematologic neoplasm. Following an inadequate response to midostaurin therapy, the patient was initiated on the newly approved avapritinib. The patient showed significant improvements in all three blood cell lines; however, he developed leg edema, blepharedema, and gum bleeding on this medication. This case underscores the intricacies of managing a patient with advanced systemic mastocytosis, the emerging role of highly selective KIT inhibition in its treatment, and the practical management of adverse medication effects.

Gastrointestinal stromal tumors (GISTs) are rare gastrointestinal neoplasms. We are presenting a 57-year-old female patient with a GIST of considerable dimensions that was deemed unresectable during the initial intervention. The patient had a previous surgical record of a peritoneal sarcomatosis tumor that covered approximately 50% of the abdominal cavity. The patient underwent surgical procedures, including exploratory laparotomy, lumpectomy, splenectomy, proximal gastrectomy, esophagogastric anastomosis, pyloroplasty, jejunostomy, and left diaphragm plasty. One of the observed results was the presence of a 50×40 cm exophytic multilobed cerebroid-like tumor in the abdomen region, specifically dependent on the gastric fundus. The primary treatment for patients without metastases is surgical removal of the tumor, with wedge resection being recommended for the preservation of organ function and quality of life postoperatively.

Tracheoesophageal puncture (TEP) is a voice restorative option adopted by many head and neck cancer patients following laryngectomy. Though generally safe, TEP may develop leakage. Lenvatinib is a tyrosine kinase inhibitor (TKI) with anti-tumoral activity against head and neck malignancies.TKIs, including lenvatinib, have been associated with organ perforation or fistula formation. There remains a paucity of literature on the association between lenvatinib and TEP leakage. In this report, we described a patient with adenoid cystic carcinoma of the larynx who had a TEP. After approximately two weeks of treatment with lenvatinib, the patient developed a leakage of TEP. Despite several interventions, the patient died three months afterward due to a retropharyngeal abscess secondary to Fusobacterium nucleatum. To our knowledge, this is the first report of fatal lenvatinib-associated TEP leakage. Clinicians should be cognizant of a potentially rapid development of this complication when prescribing TKI for patients with TEP.

Neratinib is a tyrosine kinase receptor inhibitor used in the extended adjuvant therapy of early-stage breast cancer. After adjuvant trastuzumab therapy, neratinib reduces the risk of recurrence and, if taken within 1 year from trastuzumab, significantly improves the invasive disease-free survival of patients with early-stage human epidermal growth factor receptor-2 positive (HER2+) breast cancer with no increased risk of long-term toxicity. Diarrhea, the most common adverse event associated with neratinib use, deters some clinicians from prescribing this drug. However, neratinib-related toxicity is predictable, short-lived, mostly limited to the first month of treatment and can be managed with dose-escalation and prophylactic strategies. Thus, close surveillance and prompt management, relying on supportive care and administration schedule modification, allows discontinuation of treatment to be avoided.

The purpose of this case report is to present the first case of neratinib maculopathy. We describe the initial presentation, baseline characteristics, imaging findings, and outcomes. The case report is accompanied by a thorough literature review including possible mechanisms of tyrosine kinase inhibitor (TKI) maculopathy. Neratinib is a novel TKI that is commonly used in the treatment of breast-associated malignancies. Neratinib toxicity presents similarly to macular telangiectasia type II but differs with the fine granular hypofluorescent areas spanning the limit of the posterior pole and vascular arcades as well as the nasal aspect of the optic nerve.  We report a case of suspected macular toxicity secondary to neratinib. Concomitant use of neratinib in conjunction with docetaxel and other chemotherapeutics with known retinal side effects should alert clinicians of an increase in the risk of macular toxicity. Albeit commonly reported ocular side effects of TKIs, maculopathy is a rare and potentially overlooked side effect. Patients that have planned chemotherapy should undergo a baseline retinal examination.

Current non-small cell lung cancer (NSCLC) treatment consists of various combinations of surgery, chemotherapy, and/or radiation, depending on the tumor stage. Individuals with stage II-IIIa NSCLC undergo surgery, followed by combination chemotherapy containing cisplatin, such as vinorelbine + cisplatin. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib, act by inhibiting any signaling pathway containing the EGFR mutation and inhibiting the growth of NSCLC. TKI is a treatment option in advanced NSCLC, resulting in more prolonged progression-free survival (PFS). This manuscript aims to evaluate the influence of utilizing gefitinib - either alone or in combination with conventional chemotherapeutic drug regimens upon NSCLC patient profile survival parameters. A systematic literature review was conducted across multiple scientific literature repositories. The review was performed using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020. There were six randomized clinical trials (RCT) and five retrospective studies. The overall consensus based on the end outcome of each published journal on the effectiveness of gefitinib as a treatment option for NSCLC indicated that there was a notable difference in overall survival (OS) and progression-free survival (PFS) and disease-free survival (DFS) datasets. Gefitinib use correlated with increased timeframes for multiple patient survival parameters within articles shortlisted in this investigation. However, more comprehensive investigations are required to validate such correlations. Gefitinib did demonstrate the potential to provide beneficial effects and counteract NSCLC within such patients.

Nail changes elicited by Ibrutinib are relatively infrequent but are reported in the literature. Herein, we report on two cases that developed Ibrutinib-induced nail toxicities. A 63-year-old female, with relapsing mantle cell lymphoma on Ibrutinib 560mg/day for seven months developed paronychia, onychomadesis, Beau\'s lines, nail fragility, and brittleness over fingernails and toenails. On the other hand, an 80-year-old male with chronic lymphoid leukemia developed a bloody papule with hemorrhagic crust and nail-plate abnormalities. Skin toxicities manifested eight months after initiating Ibrutinib therapy. From a clinical perspective, Ibrutinib-induced chronic paronychia and PG have been established. All other PG triggers have been ruled out. After the cessation of Ibrutinib, the PG improved for both cases. The exact pathogenesis of PG induced by Ibrutinib is not yet understood but it had been compared to retinoid-related changes. Thus, further research and reporting of similar cases should be done to further understand the pathophysiology of such manifestations.

Dasatinib is a second-generation BCR-ABL tyrosine kinase inhibitor (TKI) that is approved for the treatment of chronic myeloid leukemia (CML), a myeloproliferative disorder seen commonly in adults over the age of 50. Dasatinib is superior in tolerance and efficacy to first-generation TKIs such as imatinib, given its ability to target mutation products that are resistant to first-generation TKIs. One of the common side effects of dasatinib includes pleural effusion which can be seen in up to 25% of patients on treatment. These effusions are predominantly exudative; however, they tend to resolve upon discontinuation of the drug. While infrequent, chylous effusions have been reported with the use of dasatinib; they tend to resolve following discontinuation of the drug. We present a case of a patient who was treated with dasatinib and developed a chylous effusion which was refractory to the discontinuation of the medication. Our patient was switched to imatinib and since his first episode, he has had multiple reaccumulation requiring thoracentesis, all of which have revealed chylous pleural fluid as per fluid analysis. We present this case to highlight a rare adverse effect of dasatinib which, via an unknown mechanism, can potentially lead to irreversible damage to the lymphatic duct resulting in recurrent chylous effusions.

One of the biggest challenges in neuro-oncology is understanding the complexity of central nervous system tumors, such as gliomas, in order to develop suitable therapeutics. Conventional therapies in malignant gliomas reconcile surgery and radiotherapy with the use of chemotherapeutic options such as temozolomide, chloroethyl nitrosoureas and the combination therapy of procarbazine, lomustine and vincristine. With the unraveling of deregulated cancer cell signaling pathways, targeted therapies have been developed. The most affected signaling pathways in glioma cells involve tyrosine kinase receptors and their downstream pathways, such as the phosphatidylinositol 3-kinases (PI3K/AKT/mTOR) and mitogen-activated protein kinase pathways (MAPK). MAPK pathway inhibitors include farnesyl transferase inhibitors, Ras kinase inhibitors and mitogen-activated protein extracellular regulated kinase (MEK) inhibitors, while PI3K/AKT/mTOR pathway inhibitors are divided into pan-inhibitors, PI3K/mTOR dual inhibitors and AKT inhibitors. The relevance of the immune system in carcinogenesis has led to the development of immunotherapy, through vaccination, blocking of immune checkpoints, oncolytic viruses, and adoptive immunotherapy using chimeric antigen receptor T cells. In this article we provide a comprehensive review of the signaling pathways underlying malignant transformation, the therapies currently used in the treatment of malignant gliomas and further explore therapies under development, including several ongoing clinical trials.