Background: Pembrolizumab monotherapy for non-small-cell lung cancer (NSCLC) expressing PD-L1 ≥ 50% doubles five-year survival rates compared to chemotherapy. However, immune-related adverse events (irAEs) can cause severe, long-term toxicity necessitating high-dose steroids and/or treatment cessation. Interestingly, patients experiencing irAEs demonstrate better survival outcomes. Biomarkers of systemic inflammation, including the Scottish Inflammatory Prognostic Score (SIPS), also predict survival in this patient group. This study examines the relationship between inflammatory status, irAEs, and survival outcomes in NSCLC. Methods: A retrospective analysis was conducted on patients with NSCLC expressing PD-L1 ≥ 50% receiving first-line pembrolizumab monotherapy at a large cancer centre in Scotland. Regression analyses were conducted to examine the relationship between SIPS, irAEs, and survival. Results: 83/262 eligible patients (32%) experienced an irAE. Dermatological, endocrine, gastrointestinal, and hepatic, but not pulmonary, irAEs were associated with prolonged PFS and OS (p <= 0.011). Mild irAEs were associated with better PFS and OS in all patients, including on time-dependent analyses (HR0.61 [95% CI 0.41–0.90], p = 0.014 and HR0.41 [95% CI 0.26–0.63], p < 0.001, respectively). SIPS predicted PFS (HR 1.60 [95% CI 1.34–1.90], p < 0.001) and OS (HR 1.69 [95% CI 1.41–2.02], p < 0.001). SIPS predicted the occurrence of any irAE in all patients (p = 0.011), but not on 24-week landmark analyses (p = 0.174). The occurrence of irAEs predicted favourable outcomes regardless of the baseline inflammatory status (p = 0.015). Conclusion: The occurrence of certain irAEs is associated with a survival benefit in patients with NSCLC expressing PD-L1 ≥ 50% receiving pembrolizumab. We find that the association between low levels of systemic inflammation and the risk of irAEs is confounded by their independent prognostic value.

Introduction: Immune checkpoint inhibitors are the mainstay of treatment in patients with unresectable or metastatic melanoma. Combination immunotherapy with ipilimumab and nivolumab has shown to improve survival outcomes as compared to single agent immunotherapy in these patients. Neurological immune-related adverse effects (irAEs) are uncommon and cranial nerve palsies are seen even more infrequently.Case presentation: A 66-year-old woman with a background of metastatic, unresectable melanoma with supraclavicular and axillary lymph nodal involvement presented with a headache, photophobia and diplopia 3 weeks after her first cycle of ipilimumab and nivolumab. She was subsequently diagnosed with a left-sided cranial nerve VI palsy and treated with high dose oral steroids and steroid eye drops, with complete resolution of symptoms. She also experienced Grade 3 dermatitis requiring topical steroids, Grade 2 hypothyroidism and vitiligo. She continues to have an excellent clinical and radiological response, despite further immunotherapy being suspended.Conclusion: This is the first reported UK case of immunotherapy-induced isolated cranial nerve VI palsy. Multiple irAEs are more common with combination immunotherapy and its occurrence is associated with more favourable outcomes in melanoma. Immunotherapy continues to revolutionise oncological care, but clinicians must be cognizant of unpredictable irAEs, which may require prompt assessment and intervention.

Mitochondrial DNA (mtDNA) mutations are prevalent across cancer genomes, and growing evidence implicates their multifaceted role in energy metabolism with tumorigenesis. Ovarian cancer, in particular, demonstrates high mtDNA copy numbers and increased incidences of truncating and missense mtDNA mutations, with heteroplasmy levels predictive of prognosis. This review provides a comprehensive description of published mtDNA sequencing data in ovarian cancer, the majority being high-grade serous samples, encompassing both coding and non-coding regions. MtDNA mutations within non-coding regions, such as the D-loop control region, can affect mtDNA replication and transcription, hence affecting overall mtDNA copy numbers, while mtDNA mutations within coding regions can directly impact respiratory complex function and downstream metabolic pathways. MtDNA mutations may serve as clinically valuable diagnostic biomarkers for ovarian cancer and predictors for chemoresistance. We also explore ongoing efforts to deepen our understanding of mitochondrial oncogenetics through the creation of novel cancer models enabled by mitochondrial gene editing techniques. Developing robust human ovarian cancer cell models will be critical to elucidate mechanistic and phenotypic consequences of mtDNA mutations, assess drug response and resistance and identify new therapeutic targets to advance precision oncology in this emerging field.

Introduction High-dose corticosteroids are often used to treat acute relapses in multiple sclerosis (MS). A common side effect experienced by patients from treatment is an unpleasant metallic taste. This study thus aims to determine if consuming liquorice prior to corticosteroid administration can reduce the severity of metallic taste experienced. Methods An interventional study of patients attending the MS acute relapse clinic at the National Hospital for Neurology and Neurosurgery was performed. Patients completed a questionnaire without pre-administration of liquorice on day 1 and with pre-administration of liquorice on day 2 of methylprednisolone treatment. The severity of the metallic taste and tolerability of liquorice were assessed. Results 37 patients were analysed. The mean pre-intervention and post-intervention scores were 6.0±2.4 and 2.9±2.2 respectively, demonstrating an absolute reduction of 3.1±2.1 points (p<0.001) and a relative reduction of 51.5%. Statistical analysis of other variables such as gender, Expanded Disability Severity Scale, duration of MS, previous steroid usage and route of steroid administration showed no significant difference. Conclusion We have shown that administration of liquorice prior to steroid therapy reduces the severity of the metallic taste by half and was beneficial in over 90% of patients.