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Pembrolizumab is licensed for the treatment of pre-treated and PD-L1 positive non-small cell lung cancer (NSCLC), but response is heterogeneous. In this context, the Lung Immune Prognostic Index (LIPI) has been proposed as tool to prognosticate outcome.To investigate the real-world efficacy and safety of pembrolizumab in pre-treated NSCLC patients and the clinical utility of LIPI for patients' selection.Patients with pre-treated NSCLC and PD-L1 ≥ 1% treated with pembrolizumab were included in this retrospective series. The LIPI was used to classify patients in 3 prognostics subgroups according to the pre-treatment dNLR (derived neutrophil to lymphocyte ratio) and LDH in blood. The prognostic impact of the LIPI on progression free survival (PFS) and overall survival (OS) was evaluated with Cox regression. The combined effect of LIPI and other relevant prognostic factors was explored with multivariate regression.In total, 113 consecutive patients were included. Median (mPFS) and mOS was 4.3 (2.6-6.7) and 13.5 (10.3-17.7) months, respectively. Good-, intermediate-, and poor-LIPI was found in 54 (47.8%), 45 (39.8%), and 8 (7.1%) patients, respectively. Median PFS was 5.1 (2.8-9.1), 3.0 (2.5-6.8), and 1.4 (0.5-18.7) months, and mOS was 17.2 (12.0-26.4), 11.8 (8.4-17.1), and 3.7 (0.5-not calculable) months for good-, intermediate-, and poor-LIPI group, respectively. Patients with intermediate-LIPI and poor-LIPI had worse PFS versus good-LIPI, and statistically significant worse OS (p = 0.030 and p = 0.013, respectively). In the multivariate analysis, intermediate- versus good-LIPI (p = 0.190) was not independently associated to PFS or OS. Patients with both good-LIPI and high (≥ 50%) PD-L1 had better OS than all other subgroups defined by LIPI and PD-L1. Immune-related adverse events (irAEs) occurred in 47 (41.6%) patients (12.4% grade ≥ 3). In a time-varying analysis, irAEs were statistically associated with longer OS (HR 0.51, 0.31-0.84; p = 0.008).In our series, the outcome of pembrolizumab in pre-treated NSCLC is consistent with the registration trial. Lung Immune Prognostic Index is a readily available tool able to prognosticate outcome, also in PD-L1-high patients. The positive association between irAEs and OS might aid decision making.

PURPOSE The Christie NHS Foundation Trust launched their electronic patient-reported outcome measures (ePROMs) service in January 2019 in the routine clinical setting. The lung cancer questionnaires consist of 14 symptom items, adapted from the Common Terminology Criteria for Adverse Events (version 5.0) and the EuroQol EQ-5D-5L quality-of-life (QoL) tool. Patients with lung cancer are invited to complete questionnaires assessing their symptoms and QoL using an online platform. METHODS The ePROM responses and clinical, pathologic, and treatment data for patients who completed the questionnaires between January 2019 and December 2020 were extracted from electronic medical records. The symptom and QoL scores of patients who completed baseline pretreatment ePROMs and also those who completed ePROMs pre- and postpalliative lung systemic anticancer therapy (SACT) or radical thoracic radiotherapy were evaluated. Pretreatment questionnaires were analyzed according to age, Eastern Cooperative Oncology Group performance status (ECOG PS), and Adult Comorbidity Evaluation-27 (ACE-27) comorbidity score. RESULTS One thousand four hundred eighty patients with lung cancer were included. There were no statistically significant differences in symptoms and QoL scores between age groups. Cough ( P = .006) and EQ-5D-5L mobility scores ( P = .006) were significantly worse for patients with an ECOG PS of 0-1. Dyspnea ( P = .035), hemoptysis ( P = .023), nausea ( P = .041), mobility ( P = .004), and self-care ( P = .0420) were significantly worse for those with higher ACE-27 scores (2-3 v 0-1). Palliative SACT was associated with a significant improvement in cough ( P < .001) and hemoptysis ( P = .025), but significantly negatively affected mobility ( P = .013). Patients receiving radical thoracic radiotherapy reported a significant improvement in hemoptysis ( P = .042) but worse pain ( P = .002) and fatigue ( P = .01). Other changes in symptom and QoL scores were not significant. CONCLUSION The symptoms and QoL reported at baseline and before and after both palliative SACT and radical thoracic radiotherapy are clinically relevant and meaningful. We have demonstrated that routine implementation of ePROMs into clinical practice is feasible and can inform clinical practice and future research.

On the basis of the findings of the phase 3 PACIFIC trial (NCT02125461), durvalumab is standard of care for patients with stage III, unresectable NSCLC and no disease progression after concurrent chemoradiotherapy (cCRT). Many patients are considered unsuitable for cCRT owing to concerns with tolerability. The phase 2 PACIFIC-6 trial (NCT03693300) evaluates the safety and tolerability of durvalumab after sequential CRT (sCRT). Patients with stage III, unresectable NSCLC and no progression after platinum-based sCRT were enrolled to receive durvalumab (1500 mg intravenously) every 4 weeks for up to 24 months. The primary end point was the incidence of grade 3 or 4 adverse events possibly related to treatment occurring within 6 months. Secondary end points included investigator-assessed progression-free survival (PFS; Response Evaluation Criteria in Solid Tumors version 1.1) and overall survival. Overall, 117 patients were enrolled (59.8% with performance status >0, 65.8% aged ≥65 y, and 37.6% with stage IIIA disease). Median treatment duration was 32.0 weeks; 37.6% of patients remained on treatment at data cutoff (July 15, 2021). Grade 3 or 4 AEs occurred in 18.8% of patients. Five patients had grade 3 or 4 possibly related adverse events within 6 months (incidence: 4.3%; 95% confidence interval: 1.4-9.7), including two pneumonitis cases. Two patients (1.7%) had grade 5 AEs of any cause. Survival data maturity was limited. Median PFS was 10.9 months (95% confidence interval: 7.3-15.6), and 12-month PFS and overall survival rates were 49.6% and 84.1%, respectively. Durvalumab after sCRT had a comparable safety profile with that observed with durvalumab after cCRT in PACIFIC and had encouraging preliminary efficacy in a frailer population.

INTRODUCTION: A proportion of patients with lung cancer will not be suitable for anti-cancer treatment and are managed with best supportive care (BSC). The aim of this retrospective case series analysis was to critically review the use of diagnostic and staging investigations in patients who were ultimately managed with BSC. METHODS: A retrospective review of all lung cancer patients with a multidisciplinary team outcome of BSC from 01 June 2018 to 01 June 2019 was performed. Patients were categorised into those with an early BSC decision and those that underwent further investigations prior to a BSC decision (investigations beyond initial computed tomography (CT)). Patient demographics, clinical characteristics and outcomes were collated and analysed. RESULTS: Seventy-seven lung cancer patients managed with BSC were identified. Patients were elderly (average age 79 years), functionally limited (80% World Health Organization performance status ≥3), frail (70% clinical frailty score ≥6) and had advanced stage disease (90% stage III/IV). Thirty-one (40%) underwent further investigations beyond the initial CT prior to the BSC decision. The most common types of further investigations were endobronchial ultrasound-guided transbronchial needle aspiration (27/31; 74%), positron emission tomography – CT (18/31; 45%) and CT-guided lung biopsy (7/31; 23%). This is despite high levels of consultant chest physician review at first assessment (71%), cancer nurse specialist involvement (97%), specialist palliative care involvement (65%), a high pathological confirmation rate of sampling procedures (89%) and adequacy of molecular testing. The most common reason for a BSC recommendation was a lack of fitness for systemic therapy (17/31; 55%). Six out of thirty-one (19%) patients deteriorated rapidly and died on the cancer pathway and 5/31 (16%) patients had inadequate renal function for systemic anti-cancer treatment. There was low utilisation of serum epidermal growth factor receptor mutation testing across the study cohort (2/77; 3%). DISCUSSION: In an older, functionally limited and frail patient with lung cancer, there is a risk of over-investigation. Impaired renal function is an important clinical factor to identify early to support discussions in this cohort. There will always be an unavoidable proportion of patients that undergo further investigations (often in search of rare targetable mutations) and are then ultimately recommended for best supportive care; such cases could form the basis of specific review and learning for lung cancer services.

Background: PJP causes atypical pneumonia in immunocompromised patients with significant morbidity and mortality. There are no PJP management guidelines for non HIV populations and mortality is significantly higher in patients without HIV (34-39%) compared to HIV patients (6-7%). Aims and Objectives: To describe risk factors for PJP in lymphoma patients, management and clinical outcomes. Methods: We performed a retrospective case note review of PJP positive lymphoma patients at the Christie Hospital NHS Foundation Trust from January 2010-January 2016. Standards identified were that all patients receiving > 2 weeks of ≥ 20mg prednisolone daily should receive prophylaxis. All hypoxic patients with confirmed PJP should receive appropriate steroids. Results: 41 patients were identified: 27% Hodgkin lymphoma, 73% non Hodgkin lymphoma. Potential identifiable risks were lymphopenia (all grades ‍= 95%; grade 3-4 = 38%), steroid use (61% of patients, majority for Conclusions: PJP occurs in lymphoma patients despite prophylaxis and risks are unclear, especially as most patients are lymphopenic and/ or treated with short course steroids. We developed extended guidelines for patients recommending PJP prophylaxis for those receiving purine analogue chemotherapy, ≥20mg prednisolone or equivalent daily for > 2 weeks and patients with lymphopenia ≤0.5 and CD4 ≤200. Results will be prospectively evaluated with scope for a national audit.

The incidence of drug-induced structural cardiotoxicity, which may lead to heart failure, has been recognized in association with the use of anthracycline anti-cancer drugs for many years, but has also been shown to occur following treatment with the new generation of targeted anti-cancer agents that inhibit one or more receptor or non-receptor tyrosine kinases, serine/threonine kinases as well as several classes of non-oncology agents. A workshop organized by the Medical Research Council Centre for Drug Safety Science (University of Liverpool) on 5 September 2013 and attended by industry, academia and regulatory representatives, was designed to gain a better understanding of the gaps in the field of structural cardiotoxicity that can be addressed through collaborative efforts. Specific recommendations from the workshop for future collaborative activities included: greater efforts to identify predictive (i) preclinical; and (ii) clinical biomarkers of early cardiovascular injury; (iii) improved understanding of comparative physiology/pathophysiology and the clinical predictivity of current preclinical in vivo models; (iv) the identification and use of a set of cardiotoxic reference compounds for comparative profiling in improved animal and human cellular models; (v) more sharing of data (through publication/consortia arrangements) on target-related toxicities; (vi) strategies to develop cardio-protective agents; and (vii) closer interactions between preclinical scientists and clinicians to help ensure best translational efforts.

More and more people are living with the consequences of cancer and its treatment (living with and beyond cancer), yet the level of relevant research is low compared to other types of cancer research in the UK. NCRI aims to increase the level of research in this area and to ultimately improve the lives of those affected by cancer. Undefined research priorities in this broad area has been a barrier to research. The 2015 NHS Independent Cancer Taskforce report also recommends defining research priorities and to enable this research to happen. To address this barrier the NCRI has undertaken a James Lind Alliance Priority Setting Partnership (PSP) to identify priorities that matter most to people affected by cancer and the health and social care professionals.A PSP consists of patients and carers, health and social care professionals. PSPs have several stages and begin with a UK-wide survey to gather questions about uncertainties in living with and beyond cancer. Once the results were analysed, an interim exercise takes place to further prioritise the uncertainties. The last stage is a final workshop where partners debate and finally arrive at a top 10 list of shared uncertainties.The living with and beyond cancer PSP received 3500 questions submitted by people affected by cancer and healthcare professionals. Through a 18-month established rigorous process, the questions are prioritised down to the Top 10 living with and beyond cancer priorities for research in June 2018. This is the first time that clear research priorities have been identified in this area. They are the most impactful research questions that will help improve the lives of people affected by cancer. The Top 10 uncertainties will be publicised widely to ensure that researchers and those who fund research really understand what matters to people affected by cancer. The top uncertainties will be promoted to many research organizations and relevant funders in the UK. We anticipate they will directly influence future research. Citation Format: Feng Li, Adrienne Morgan, Angela McCullagh, Anne Johnson, Ceinwen Giles, Diana Greenfield, Graeme Crawford, Jacqui Gath, Jane Lyons, Jervoise Andreyev, Jonathan Tobutt, Julia Tugwell, Karen Robb, Laura Cove-Smith, Lindsey Bennister, Natalie Doyle, Nicolas Lee, Rebecca Nash, Richard Simcock, Richard Stephens, Sabine Best, Susan Moug, Kristina Staley, Sandra Regan, Patricia Ellis, Stuart Griffiths, Ian Lewis. Top 10 living with and beyond cancer research priorities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3348.

Background Cancer survivorship is an international priority and mortality from cardiac damage is one of the greatest concerns. Anthracycline chemotherapy is cardiotoxic but remains highly effective against cancer. Methods This translational project involved the development of a pre-clinical rat model of progressive anthracycline-induced cardiotoxicity (1.25mg/m 2 doxorubicin weekly for 8 doses) and a concurrent clinical study of 30 cancer patients receiving 6 cycles of curative anthracycline therapy (doxorubicin 50mg/m 2 ). A bespoke cardiac magnetic resonance imaging (CMR) protocol was developed which included longitudinal T1 mapping (modified look-locker) to estimate extracellular volume (ECV), T2 mapping (to quantify oedema) and strain analysis. A panel of circulating biomarkers (including inflammatory, ischaemic and fibrosis markers) was evaluated by multiplex ELISA. Longitudinal histological analysis was performed in the rats and correlated with imaging and biomarker findings. Results Left ventricular function (LVEF) declined steadily during treatment in rats and humans. Persistent LV dysfunction was seen in 23% of patients 12 months after therapy. Peak Troponin I levels correlated with fall in (LVEF) and circulating levels translated well between rat and humans. However, levels did not peak until the final cycle of chemotherapy when significant LV decline had already occurred. There was no significant change in the other circulating biomarkers. ECV did not change significantly during treatment but lower baseline ECV correlated with a greater fall in LVEF. Microscopic changes were seen in the rat myocardium after 6 doses of doxorubicin but electron-microscopy revealed mitochondrial damage after just one dose. Conclusions This translational approach enabled forward and back translation leading to the development of a clinically relevant pre-clinical cardiotoxicity model. Troponin I was the most informative circulating biomarker but peaked at the end of therapy too late to modify treatment and prevent LV decline. The model has the potential to be used to identify earlier biomarkers and evaluate cardioprotective strategies. The imaging findings showed that fibrosis cannot be detected on CMR within one year of chemotherapy but generated a new hypothesis that patients with ‘healthier hearts’ may be a greatest risk of drug-induced cardiotoxicity.

High-dose interleukin 2 (HD-IL2) is one of the therapeutic options for patients with metastatic renal cell carcinoma. In well-selected patients with favorable clinical and pathologic features, it offers impressive response and potential long-term remission. It also has a place for treatment for metastatic malignant melanoma and in adoptive cell therapy. However, it is known for its intensive course and toxicities. Myocarditis is one of the known complications of this treatment and can pose a diagnostic challenge to treating oncologists because of its nonspecific and similar presentation to acute coronary syndrome (ACS). We report 3 short cases of HD-IL2-related myocarditis, which were either missed or misdiagnosed as ACS using conventional assessment but subsequently accurately diagnosed by cardiac magnetic resonant imaging (CMR). We discussed the clinical presentation of these cases and demonstrated the diagnostic advantage of CMR compared with standard investigations including its superior capability to assess myocardial reversibility, which has important short-term and long-term implications. The use of CMR also avoided unnecessary invasive intervention such as coronary angiogram in all 3 patients. These example cases call for effort to conduct prospective research to assess and confirm the utility of CMR, thus informing a more effective management pathway for immune-related myocarditis in HD-IL2 and other cancer immunotherapy.

Many efficacious cancer treatments cause significant cardiac morbidity, yet biomarkers or functional indices of early damage, which would allow monitoring and intervention, are lacking. In this study, we have utilized a rat model of progressive doxorubicin (DOX)-induced cardiomyopathy, applying multiple approaches, including cardiac magnetic resonance imaging (MRI), to provide the most comprehensive characterization to date of the timecourse of serological, pathological, and functional events underlying this toxicity. Hannover Wistar rats were dosed with 1.25 mg/kg DOX weekly for 8 weeks followed by a 4 week off-dosing "recovery" period. Electron microscopy of the myocardium revealed subcellular degeneration and marked mitochondrial changes after a single dose. Histopathological analysis revealed progressive cardiomyocyte degeneration, hypertrophy/cytomegaly, and extensive vacuolation after two doses. Extensive replacement fibrosis (quantified by Sirius red staining) developed during the off-dosing period. Functional indices assessed by cardiac MRI (including left ventricular ejection fraction (LVEF), cardiac output, and E/A ratio) declined progressively, reaching statistical significance after two doses and culminating in "clinical" LV dysfunction by 12 weeks. Significant increases in peak myocardial contrast enhancement and serological cardiac troponin I (cTnI) emerged after eight doses, importantly preceding the LVEF decline to