The relationship between clinicopathological variables, systemic inflammation, and CT-derived body composition with survival in patients with advanced non-small cell lung cancer receiving nivolumab as a second-line treatment.

BACKGROUND: Second-line immunotherapy is currently recognized to help only a subset of patients with advanced forms of non-small cell lung cancer (NSCLC). The current study analyzes the connection between prior treatment host/tumor characteristics and survival in advanced NSCLC patients receiving nivolumab as a second-line therapy. METHODS: A retrospective cohort analysis was carried out on individuals with advanced NSCLC receiving second-line Nivolumab with palliative intent between February 2016 and May 2019 across three health boards in NHS Greater Glasgow and Clyde, Lanarkshire, Ayrshire, and Arran in Scotland to examine the association between systemic inflammation, body composition, and survival were determined using computed tomography (CT). RESULTS: The current study investigates the connection between prior treatment host/tumor characteristics and survival in advanced NSCLC patients receiving nivolumab as a second-line therapy. The majority were 65 years of age or older (51%), female (53%), had adenocarcinoma (53%), and had good performance status (ECOG 0/1) (86%). Most patients had high SFI (70%) or VFA (54%). The median overall survival after starting Nivolumab was 15 months. ECOG-PS and hypoalbuminemia were significant predictors of 12-month survival in patients with advanced NSCLC following Nivolumab treatment, according to Cox regression (p-value = 0.047 and 0.014, respectively). CONCLUSION: In patients with advanced NSCLC receiving Nivolumab as a second-line therapy, ECOG-PS and hypoalbuminemia were strongly associated with survival. Systemic inflammation and hypoalbuminemia measurements may enhance the ECOG-PS stratification of expected outcomes.

Real-world uptake, safety profile and outcomes of docetaxel in newly diagnosed metastatic prostate cancer.

OBJECTIVES: To investigate the uptake, safety and efficacy of docetaxel chemotherapy in hormone-naïve metastatic prostate cancer (mPC) in the first year of use outside of a clinical trial. PATIENTS AND METHODS: Patients in the West of Scotland Cancer Network with newly diagnosed mPC were identified from the regional multidisciplinary team meetings and their treatment details were collected from electronic patient records. The rate of febrile neutropenia, hospitalisations, time to progression, and overall survival were compared between those patients who received docetaxel and androgen-deprivation therapy (ADT), or ADT alone using survival analysis. RESULTS: Of the 270 eligible patients, 103 received docetaxel (38.1%). 35 patients (34%) were hospitalised and there were 17 episodes of febrile neutropenia (16.5%). Two patients (1.9%) died within 30 days of chemotherapy. Patients who received ADT alone had an increased risk of progression (hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.27-3.25; log-rank test, P = 0.002) and had an increased risk of death (HR 5.88, 95% CI: 2.52-13.72; log-rank test, P = 0.001) compared to the docetaxel group. The risk of febrile neutropenia was nine-times greater if chemotherapy was started within 3 weeks of ADT initiation (95% CI: 1.22-77.72; P = 0.032). CONCLUSION: Docetaxel chemotherapy in hormone-naïve mPC has significant toxicities, but has a similar effect on time to progression and overall survival as seen in randomised trials. Chemotherapy should be started at ≥3 weeks after ADT.

Challenges in the treatment of early non-small cell lung cancer: what is the standard, what are the challenges and what is the future for radiotherapy?

In the last 15 years, the use of Stereotactic Ablative Radiation Therapy (SABRT) in the management of small peripheral lung tumours has developed considerably, so that it currently represents a standard of care for inoperable stage I non-small cell lung cancer (NSCLC), offering a survival advantage over traditional radiotherapy, local control rates at 3 years around 90%, with a low risk of toxicity. Indications have extended to larger tumours up to 5 cm and centrally located tumours. In this review we will explore the role of SABRT in early stage NSCLC, the state of the art, the challenges and the future for this technique. There are ongoing studies to optimize such approaches within a multicentric setting. Trials comparing surgery to SABRT in operable or marginally operable have failed because of poor accrual. Several questions remain that need to be addressed in prospective studies.

Association of anthracycline-related cardiac histological lesions with NADPH oxidase functional polymorphisms.

OBJECTIVE: Treatment with anthracyclines may cause cardiac dysfunction, but the sequence of anthracycline-induced heart lesions has been incompletely characterized. NADPH oxidase, a key mediator of oxidative cardiac damage and remodeling, modulates anthracycline clinical cardiotoxicity. Our aim was to determine which cardiac histological lesions are specifically induced by anthracycline treatment and to investigate the role of NADPH functional genetic polymorphisms in their development. PATIENTS AND METHODS: Using a retrospective case-control design, we evaluated cardiac histological lesions and NADPH genotype (polymorphisms rs1883112, rs4673, and rs13058338) in 97 consecutive decedents with a cancer diagnosis (48 treated with anthracyclines). RESULTS: Myocytolysis (60%), patched myocardial necrosis (19%), and myocardial fibrosis (diffuse and patched; 62% and 23%, respectively) were associated with anthracycline treatment. In patients receiving anthracyclines, NADPH oxidase polymorphism rs4673 protected against focal myocardial necrosis (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.20-0.63) whereas rs1883112 was strongly associated with cardiac fibrosis (OR, 5.11; 95% CI, 1.59-16.43), which was present in all homozygotes. CONCLUSION: Anthracyclines induce a cardiac remodeling pattern characterized by interstitial or patched fibrosis. The contribution of the functionally relevant NADPH polymorphisms rs1883112 and rs4673 to anthracycline-related heart lesions provides a plausible explanation for their modulation of cardiotoxicity. If confirmed, these findings may lead to better individualized strategies for early detection and prevention of anthracycline cardiotoxicity.

Clinical and genetic determinants of anthracycline-induced cardiac iron accumulation.

BACKGROUND: The involvement of iron in anthracycline cardiotoxicity is supported by extensive experimental data, and by the preventive efficacy of dexrazoxane, an iron chelator. However, no clinical evidence of anthracycline-induced cardiac iron accumulation is available and the influence of previous iron overload or of genetic factors in human-induced heart disease is largely unknown. Our aim was to test the hypothesis that anthracyclines increase iron heart concentration and that HFE genotype modulates this iron deposit. METHODS: We retrospectively evaluated cardiac events, cardiac iron and HFE genotype in 97 consecutive necropsies from patients with solid and hematological neoplasms. Heart and liver iron concentration was determined by atomic absorption spectroscopy. HFE gene mutations (C282Y and H63D) linked to hereditary hemochromatosis were analyzed by Fluorescence Resonance Energy Transfer (FRET) genotyping. RESULTS: Heart iron concentration was increased in cases treated with a cumulative doxorubicin dose greater than 200mg/m(2) (490 vs 240 µg/g; p=0.01), independently of liver iron load or transfusion history. HFE mutated haplotypes 282C/63D (p=0.049) and 282Y/63H (p=0.027) were associated to higher cardiac iron deposits. The haplotype C282Y-Y/H63D-H interacted with anthracyclines for increasing cardiac iron load. In a multivariate linear regression analysis both HFE genotypes and anthracyclines contributed to heart iron concentration (R(2)=0.284). CONCLUSIONS: Our data support the occurrence of an HFE-modulated heart iron accumulation in individuals treated with anthracyclines, independently of systemic iron load. If prospectively confirmed, iron-related parameters might be useful as predictive factors for anthracycline cardiotoxicity.