Synchronous presentation of recurrent intracranial solitary fibrous tumour and chronic myeloid leukaemia: a diagnostic challenge.

Solitary fibrous tumours (SFTs) and chronic myeloid leukaemia (CML) are both uncommon neoplasms with distinct chromosomal aberrations and clinical presentations. Here, we present a case of a male in his late 50s with a history of intracranial SFT who presented 8 years after subtotal resection and adjuvant radiotherapy with splenic infarcts, a white blood cell of 83 000 cells/mL, and liver masses. He was treated with dasatinib for CML and temozolomide/bevacizumab for SFT. This case emphasises the benefits of broad differential diagnoses that include multiple concurrent disease processes when confronted with unusual presentations. It highlights the need for interdisciplinary efforts and personalised approaches when managing patients with multiple primary malignancies.

Cancer-related cognitive impairment: updates to treatment, the need for more evidence, and impact on quality of life-a narrative review.

BACKGROUND AND OBJECTIVE: Due to advances in early detection and treatment options, non-central nervous system (non-CNS) cancer survivors are living longer, even those with metastatic disease. Many of these survivors will experience enduring symptoms of breast cancer, such as cancer-related cognitive impairment (CRCI). Although CRCI is bothersome and, in some cases, potentially debilitating, little research has been done to address this symptom. Thus, the overarching goal of this narrative review is to provide both an overview of the problem of CRCI and its impact and focus on the latest research aimed at addressing CRCI in non-CNS cancer survivors. METHODS: A MEDLINE database (PubMed) search was conducted for terms related to non-CNS cancer, cognition, impacts of CRCI, and interventions. The English-language articles published until April 8th, 2024, were included in the search. KEY CONTENT AND FINDINGS: CRCI includes self-reported cognitive complaints and/or impaired performance in multiple cognitive domains, including memory, processing speed, attention, and executive function. CRCI, in turn, can have a significant impact on everyday functioning, work ability, work engagement and productivity, and overall quality of life (QoL) of cancer survivors. While some researchers have examined pharmacological approaches, the vast majority of the interventional studies to date to address CRCI has focused on non-pharmacological approaches. Three of the most common non-pharmacological approaches are physical activity or exercise, mind-body approaches [e.g., mindfulness-based stress reduction (MBSR)], and cognitive rehabilitative approaches [e.g., cognitive training (CT) and cognitive behavioral therapy (CBT)]. CONCLUSIONS: Addressing the cognitive health of cancer survivors is imperative but has only recently been the focus of interventional research. More research in larger and more diverse samples of non-CNS cancer survivors is needed to identify effective ways to manage CRCI for all cancer survivors. Overall, maintaining cognitive health, especially in cancer survivors who are at increased risk for deficits, is a national health care priority that should not be ignored.

Fragment-based design and synthesis of coumarin-based thiazoles as dual c-MET/STAT-3 inhibitors for potential antitumor agents.

c-MET and STAT-3 are significant targets for cancer treatments. Here, we describe a class of very effective dual STAT-3 and c-MET inhibitors with coumarin-based thiazoles (3a-o) as its scaffold. Spectroscopic evidence (NMR, HRMS, and HPLC) validated the structural discoveries of the new compounds. The cytotoxic activity of these compounds was also tested against a panel of cancer cells in accordance with US-NCI guidelines. Compound 3g proved to be active at 10 µM, thus it was automatically scheduled to be tested at five doses. Towards SNB-75 (CNS cancer cell line), compound 3g showed notable in vitro anti-cancer activity with GI50 = 1.43 µM. For the molecular targets, compound 3g displayed potent activity towards STAT-3 and c-MET having IC50 of 4.7 µM and 12.67, respectively, compared to Cabozantinib (IC50 = 15 nM of c-MET) and STAT-3-IN-3 (IC50 = 2.1 µM of STAT-3). Moreover, compound 3g significantly induced apoptosis in SNB-75 cells, causing a 3.04-fold increase in apoptotic cell death (treated cells exhibited 11.53 % overall apoptosis, against 3.04 % in reference cells) and a 3.58-fold increase in necrosis. Moreover, it arrests cells at the G2 phase. Dual inhibition of c-MET and STAT-3 protein kinase was further validated using RT-PCR. The target compound's binding mechanism was determined by the application of molecular docking.

Extraconal orbital craniopharyngioma.

A female, in her 60s, presented with pain and swelling of the right eye for 3 years. The radiological work-up revealed an extraconal solid-cystic orbital tumour suggestive of an epidermoid cyst. The patient underwent supraorbital craniotomy with a gross total excision of the tumour. An intraoperative diagnosis was sought, which on both squash smear and frozen section showed features of craniopharyngioma (CP), later confirmed on paraffin sections and immunohistochemistry. The orbit is a very rare site for ectopic CP, with only two cases reported in the literature. Many theories have been proposed to explain the occurrence of CP at ectopic sites. This report aims to provide insight into the different hypotheses of the pathogenesis of ectopic CP through a review of the literature.

A multicenter, phase 1, Adult Brain Tumor Consortium trial of oral terameprocol for patients with recurrent high-grade glioma (GATOR).

Recurrent high-grade gliomas (rHGGs) have a dismal prognosis, where the maximum tolerated dose (MTD) of IV terameprocol (5 days/month), a transcriptional inhibitor of specificity protein 1 (Sp1)-regulated proteins, is 1,700 mg/day with median area under the plasma concentration-time curve (AUC) of 31.3 µg∗h/mL. Given potentially increased efficacy with sustained systemic exposure and challenging logistics of daily IV therapy, here we investigate oral terameprocol for rHGGs in a multicenter, phase 1 trial (GATOR). Using a 3 + 3 dose-escalation design, we enroll 20 patients, with median age 60 years (range 31-80), 70% male, and median one relapse (range 1-3). Fasting patients tolerate 1,200 mg/day (n = 3), 2,400 mg/day (n = 6), 3,600 mg/day (n = 3), and 6,000 mg/day (n = 2) oral doses without major toxicities. However, increased dosage does not lead to increased systemic exposure, including in fed state (6,000 mg/day, n = 4), with maximal AUC <5 µg∗h/mL. These findings warrant trials investigating approaches that provide sustained systemic levels of transcription inhibitors to exploit their therapeutic potential. This study was registered at ClinicalTrials.gov (NCT02575794).

Omission of etoposide in the treatment of haemophagocytic lymphohistiocytosis secondary to primary central nervous system lymphoma with satisfactory response.

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory condition that can be either familial or acquired and, if untreated, frequently results in multiorgan failure and death. Treatment of HLH typically requires a combination of glucocorticoids and cytotoxic chemotherapy. We describe the case of a woman who presented with signs and symptoms concerning for HLH who was later found to have a primary central nervous system (CNS) diffuse large B-cell lymphoma. Her HLH symptoms were successfully treated with high doses of dexamethasone, and her primary CNS lymphoma was treated with high-dose methotrexate and rituximab. This is a rare case of HLH secondary to primary CNS lymphoma where HLH was controlled with steroids alone and did not require the use of an etoposide-based regimen or cyclophosphamide, doxorubicin, vincristine and prednisone.

Lomustine overdose in a patient with diffuse glioma: symptoms, management and outcome.

A male patient started PCV chemotherapy (a combination of procarbazine, lomustine and vincristine) for a recurrent oligodendroglioma grade 2. Unfortunately, our patient took an unintended overdose of lomustine during the first PCV course: instead of 160 mg absolute dose of lomustine on day 1 only, he consumed 160 mg absolute dose of lomustine for seven consecutive days to a total dose of 1120 mg. Pancytopenia became evident after 24 days, and several months of severe myelosuppression, infections, reduced general condition, and nutrition difficulties followed. Fortunately, our patient with time recovered his bone marrow function. However, the patient's quality of life was reduced for a long time and several lessons were learnt: oral and written information on chemotherapy is essential, but not always sufficient to ensure the correct dosing of patient-administered chemotherapy. Oral chemotherapeutics should be delivered as a single-dose supply or be administered by experienced health personnel.

Scalp necrosis following preoperative endovascular embolisation of the superficial temporal artery for meningioma.

A woman in her late 50s with a left frontal lobe convexity meningioma underwent an elective endovascular embolisation of the left middle meningeal artery and distal branches of the left superficial temporal artery prior to surgical resection of the tumour. On postoperative day 46, she developed scalp necrosis, leading to poor wound healing requiring wound debridement and a complex plastic surgery reconstruction with a rotational flap. Endovascular embolisation of vascular tumours prior to surgical resection does not come without risks. The lack of consistency in the literature regarding indication, technique and outcomes makes it difficult to define the exact role of preoperative meningioma embolisation.

Unusual case of intraosseous primary intracranial malignant melanoma.

Primary intracranial malignant melanoma (PIMM) represents 0.07% of central nervous system tumours; clinical behaviour and prognosis are not well documented. Preoperative diagnosis of PIMM is complex and it could be easily misdiagnosed, especially with malignant meningioma.We are reporting a case of a man with a history of rapidly arising motor slowing associated with urinary incontinence, presenting with mild convergent strabismus caused by paralysis in abduction in the right eye. A brain CT showed a lesion compatible with malignant spheno-orbital meningioma, and the patient underwent gross total resection. Intraoperatively, the blackish lesion infiltrated and eroded the bone; it was placed externally on the dura mater with a mild reaction and without attachment. Histological examination confirmed PIMM.Intraosseous localisation of PIMM has been observed in the basic bone structure of the oral cavity. We report the first intraosseous spheno-orbital PIMM case and present an embryological theory about how this unusual tumour can develop.

Increased microglia activation in late non-central nervous system cancer survivors links to chronic systemic symptomatology.

Prolonged inflammatory expression within the central nervous system (CNS) is recognized by the brain as a molecular signal of "sickness", that has knock-on effects to the blood-brain barrier, brain-spinal barrier, blood-cerebrospinal fluid barrier, neuro-axonal structures, neurotransmitter activity, synaptic plasticity, neuroendocrine function, and resultant systemic symptomatology. It is concurred that the inflammatory process associated with cancer and cancer treatments underline systemic symptoms present in a large portion of survivors, although this concept is largely theoretical from disparate and indirect evidence and/or clinical anecdotal reports. We conducted a proof-of-concept study to link for the first time late non-CNS cancer survivors presenting chronic systemic symptoms and the presence of centralized inflammation, or neuroinflammation, using TSPO-binding PET tracer [11 C]-PBR28 to visualize microglial activation. We compared PBR28 SUVR in 10 non-CNS cancer survivors and 10 matched healthy controls. Our data revealed (1) microglial activation was significantly higher in caudate, temporal, and occipital regions in late non-central nervous system/CNS cancer survivors compared to healthy controls; (2) increased neuroinflammation in cancer survivors was not accompanied by significant differences in plasma cytokine markers of peripheral inflammation; (3) increased neuroinflammation was not accompanied by reduced fractional anisotropy, suggesting intact white matter microstructural integrity, a marker of neurovascular fiber tract organization; and (4) the presentation of chronic systemic symptoms in cancer survivors was significantly connected with microglial activation. We present the first data empirically supporting the concept of a peripheral-to-centralized inflammatory response in non-CNS cancer survivors, specifically those previously afflicted with head and neck cancer. Following resolution of the initial peripheral inflammation from the cancer/its treatments, in some cases damage/toxification to the central nervous system occurs, ensuing chronic systemic symptoms.

Intracranial ependymoma in an adult patient with multiple primary malignancies.

The incidence of multiple primary malignancies (MPM) is increasing, and therefore, it has become highly important for clinicians to consider the concept of MPM when treating oncology patients. In this case report, we follow the clinical course of a patient diagnosed with a new intracranial lesion, an ependymoma, on a background of MPM. We explore the barriers implicating the delay in her diagnosis, dissect the challenges in managing her disease and emphasise the importance of social determinants in optimising her care.

Euvolaemic hyponatraemia as a rare first presentation of chronic hypopituitarism.

A man in his late 40s with no significant medical history presented with 2 weeks of lethargy, nausea and dizziness, alongside worsening headaches. Initial assessment revealed severe hyponatraemia and secondary hypothyroidism; urgent MRI pituitary was requested with a clinical suspicion of pituitary apoplexy. This demonstrated a likely cystic pituitary adenoma, with further testing revealing pituitary gland suppression, leading to a diagnosis of chronic secondary hypopituitarism. Initiating hormone replacement allowed substantial reported improvements in this patient's quality of life.A review of the patient's work-up revealed areas in which best practice was not followed. Cortisol measurements and paired urinary and serum osmolalities were initially not sent, nor results appropriately chased. A subsequent literature review identified that conformation with national and local guidelines on hyponatraemia management is poor. This patient's case, when combined with the literature review, provides evidence to support methods to increase educational awareness of an appropriate work-up of hyponatraemia among clinicians.

BCG vaccination policy, natural boosting and pediatric brain and CNS tumor incidences.

Bacille Calmette-Guérin (BCG) vaccination supposedly imparts and augments "trained immunity" that cross-protects against multiple unrelated pathogens and enhances general immune surveillance. Gradual reductions in tuberculosis burden over the last 3-5 decades have resulted in the withdrawal of BCG vaccination mandates from developed industrialized countries while reducing to a single neonatal shot in the rest. Concurrently, a steady increase in early childhood Brain and CNS (BCNS) tumors has occurred. Though immunological causes of pediatric BCNS cancer are suspected, the identification of a causal protective variable with intervention potential has remained elusive. An examination of the countries with contrasting vaccination policies indicates significantly lower BCNS cancer incidence in 0-4-year-olds (per hundredthousand) of countries following neonatal BCG inoculations (n=146) vs. non-BCG countries (n=33) [Mean: 1.26 vs. 2.64; Median: 0.985 vs. 2.8; IQR: 0.31-2.0 vs. 2.4-3.2; P=<0.0001 (two-tailed)]. Remarkably, natural Mycobacterium spp. reexposure likelihood is negatively correlated with BCNS cancer incidence in 0-4-year-olds of all affected countries [r(154): -0.6085, P=<0.0001]. Seemingly, neonatal BCG vaccination and natural "boosting" are associated with a 15-20-fold lower BCNS cancer incidence. In this opinion article, we attempt to synthesize existing evidence implying the immunological basis of early childhood BCNS cancer incidence and briefly indicate possible causes that could have precluded objective analysis of the existing data in the past. We draw the attention of the stakeholders to consider the comprehensive evaluation of immune training as a potential protective variable through well-designed controlled clinical trials or registry-based studies as feasible for its potential applications in reducing childhood BCNS cancer incidence.

Fertility Preservation Techniques in Neuro-Oncology Patients: Protocol for a Systematic Review.

BACKGROUND: Advancements in cancer treatments have successfully improved central nervous system (CNS) cancer survivorship and overall quality of life. As a result, the awareness of the importance of fertility preservation techniques is increasing. Currently, a range of established techniques, such as oocyte cryopreservation and sperm cryopreservation, are available. However, oncologists may be hesitant to refer patients to a reproductive specialist. OBJECTIVE: The primary aim of the proposed systematic review is to assess the best evidence for fertility preservation techniques used in patients with CNS cancers. It also aims to evaluate outcomes related to their success and complications. METHODS: This protocol was produced in adherence with the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols). Electronic databases will be systematically searched to identify studies that meet our eligibility criteria. Studies will be included if they report at least one type of fertility preserving or sparing technique in male patients of any age and female patients aged <35 years. Animal studies, non-English studies, editorials, and guidelines will be excluded from the review. From the included studies, data will be extracted and synthesized by using a narrative approach and summarized in tables. The primary outcome will be the number of patients successfully undergoing a fertility preservation technique. The secondary outcomes will include the number of retrieved oocytes, the number of oocytes or embryos vitrified for cryopreservation, clinical pregnancy, and live birth. The quality of the included studies will be assessed by using the National Heart, Lung, and Blood Institute risk-of-bias tool for any type of study. RESULTS: The systematic review is expected to be completed by the end of 2023, and results will be published in a peer-reviewed journal and on PROSPERO. CONCLUSIONS: The proposed systematic review will summarize the fertility preservation techniques available for patients with CNS cancers. Given the improvement in cancer survivorship, it is becoming increasingly important to educate patients about fertility preservation techniques. There are likely to be several limitations to this systematic review. Current literature is likely to be of low quality due to insufficient numbers, and there may be difficulty in accessing data sets. However, it is our hope that the results from the systematic review provide an evidence base to help inform the referral of patients with CNS cancers for fertility preservation treatments. TRIAL REGISTRATION: PROSPERO CRD42022352810; https://tinyurl.com/69xd9add. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/44825.