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Introduction: The COVID-19 pandemic impacted the care and experiences of people with cancer, but it presented an opportunity to improve the delivery of outpatient care post-pandemic., Materials and Methods: We performed an observational cross-sectional study with people with lung cancer throughout the COVID-19 pandemic. A survey investigated patients' experiences and preferences regarding the delivery of cancer care to plan for post-pandemic care, as well as the pandemic's impact on their functional status (physical and psycho-social), exploring the role of age and frailty., Results: Amongst 282 eligible participants, 88%, 86%, and 59% of patients reported feeling appropriately supported during the pandemic by their cancer centre, friends/family, and primary care services, respectively. Remote oncology consultations were delivered to 90% of patients during the pandemic, of which 3% did not meet patients' expectations. Regarding post-pandemic outpatient care preferences, face-to-face appointments were preferred by 93% for the first appointment, by 64% when discussing imaging results, and by 60% for reviews during anti-cancer treatments. Older patients aged 70 years and above were more likely to favour face-to-face appointments (p = 0.007), regardless of their frailty status. Patient preferences changed over time, with the more recent participants preferring remote appointments during anti-cancer treatments (p = 0.0278). Regarding the pandemic's impact, abnormal levels of anxiety and depression were found in 16% and 17% of patients, respectively. Younger patients experienced higher abnormal levels of anxiety and depression (p = 0.036, p = 0.021). Amongst the older sub-group, those with frailty had higher levels of anxiety and depression (p < 0.001). Amongst all participants, 54% reported a considerable negative impact from the pandemic on different aspects of their daily life, particularly emotional and psychological health and sleep patterns, which were more marked in younger patients and the older sub-group with frailty. Older patients without frailty reported the least impact on their functional status., Discussion: There is a need for more personalised outpatient consultation options during cancer care. Whilst there is a preference for face-to-face consultations for older patients, following the pandemic there is a growing acceptance of remote consultations particularly during anti-cancer treatment. Older patients with lung cancer without frailty were less affected by the pandemic than those with frailty and younger patients, requiring less support from healthcare services., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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.

Circulating tumour DNA (ctDNA) can be used to detect and profile residual tumour cells persisting after curative intent therapy 1 . The study of large patient cohorts incorporating longitudinal plasma sampling and extended follow-up is required to determine the role of ctDNA as a phylogenetic biomarker of relapse in early-stage non-small-cell lung cancer (NSCLC). Here we developed ctDNA methods tracking a median of 200 mutations identified in resected NSCLC tissue across 1,069 plasma samples collected from 197 patients enrolled in the TRACERx study 2 . A lack of preoperative ctDNA detection distinguished biologically indolent lung adenocarcinoma with good clinical outcome. Postoperative plasma analyses were interpreted within the context of standard-of-care radiological surveillance and administration of cytotoxic adjuvant therapy. Landmark analyses of plasma samples collected within 120 days after surgery revealed ctDNA detection in 25% of patients, including 49% of all patients who experienced clinical relapse; 3 to 6 monthly ctDNA surveillance identified impending disease relapse in an additional 20% of landmark-negative patients. We developed a bioinformatic tool (ECLIPSE) for non-invasive tracking of subclonal architecture at low ctDNA levels. ECLIPSE identified patients with polyclonal metastatic dissemination, which was associated with a poor clinical outcome. By measuring subclone cancer cell fractions in preoperative plasma, we found that subclones seeding future metastases were significantly more expanded compared with non-metastatic subclones. Our findings will support (neo)adjuvant trial advances and provide insights into the process of metastatic dissemination using low-ctDNA-level liquid biopsy., (© 2023. The Author(s).)

Purpose: The study explores experiences of lung cancer patients during COVID-19 and considers how changes to care delivery and personal lives affected patient needs., Methods: Semi-structured telephone interviews were conducted to explore experiences of lung cancer patients during COVID-19. Interviews were audio-recorded, transcribed verbatim and analysed thematically. Interview participants were purposively selected based on age, gender, treatment status, timing of diagnosis (pre/post first COVID-19 lockdown) from a sample of lung cancer patients (any histological subtype/any cancer stage/any point in treatment) who had completed a questionnaire exploring how participants' lives were impacted by the pandemic and their thoughts on clinical care and remote communication., Results: Thirty lung cancer patients who participated in the questionnaire study were approached and participated in an interview. Three themes were identified: (1) Adapting to new modes of communication (focusing on experiences of remote communication); (2) Experience of care delivery during the pandemic (describing how all aspects of care delivery had been affected); (3) Impact of the COVID-19 pandemic on quality of life (QOL) (focus on the psychological impact and feeling of reduced support). Themes 1 and 2 are heavily interlinked and both had bearing on patients' QOL experience., Conclusion: Lung cancer patients were impacted psychologically by changes to care delivery and changes in their personal life. The findings highlight some benefits to remote consultations but the stage of the treatment pathway and illness trajectory should be considered when determining if this is appropriate. Participants felt support from peers, family and friends was limited during the pandemic., (© 2022. The Author(s).)

GCSF prophylaxis is recommended in patients on chemotherapy with a >20% risk of febrile neutropenia and is to be considered if there is an intermediate risk of 10−20%. GCSF has been suggested as a possible adjunct to immunotherapy due to increased peripheral neutrophil recruitment and PD-L1 expression on neutrophils with GCSF use and greater tumour volume decrease with higher tumour GCSF expression. However, its potential to increase neutrophil counts and, thus, NLR values, could subsequently confer poorer prognoses on patients with advanced NSCLC. This analysis follows on from the retrospective multicentre observational cohort Spinnaker study on advanced NSCLC patients. The primary endpoints were OS and PFS. The secondary endpoints were the frequency and severity of AEs and irAEs. Patient information, including GCSF use and NLR values, was collected. A secondary comparison with matched follow-up duration was also undertaken. Three hundred and eight patients were included. Median OS was 13.4 months in patients given GCSF and 12.6 months in those not (p = 0.948). Median PFS was 7.3 months in patients given GCSF and 8.4 months in those not (p = 0.369). A total of 56% of patients receiving GCSF had Grade 1−2 AEs compared to 35% who did not receive GCSF (p = 0.004). Following an assessment with matched follow-up, 41% of patients given GCSF experienced Grade 1−2 irAEs compared to 23% of those not given GCSF (p = 0.023). GCSF prophylaxis use did not significantly affect overall or progression-free survival. Patients given GCSF prophylaxis were more likely to experience Grade 1−2 adverse effects and Grade 1−2 immunotherapy-related adverse effects.

Background: There is growing interest in the collection and use of patient-reported outcome measures (PROMs) to support clinical decision making in patients with non-small cell lung cancer (NSCLC). However, an overview of research into the prognostic value of PROMs is currently lacking., Aim: To explore to what extent, how, and how robustly the value of PROMs for prognostic prediction has been investigated in adults diagnosed with NSCLC., Methods: We systematically searched Medline, Embase, CINAHL Plus and Scopus for English-language articles published from 2011 to 2021 that report prognostic factor study, prognostic model development or validation study. Example data charting forms from the Cochrane Prognosis Methods Group guided our data charting on study characteristics, PROMs as predictors, predicted outcomes, and statistical methods. Two reviewers independently charted the data and critically appraised studies using the QUality In Prognosis Studies (QUIPS) tool for prognostic factor studies, and the risk of bias assessment section of the Prediction model Risk Of Bias ASsessment Tool (PROBAST) for prognostic model studies., Results: Our search yielded 2,769 unique titles of which we included 31 studies, reporting the results of 33 unique analyses and models. Out of the 17 PROMs used for prediction, the EORTC QLQ-C30 was most frequently used (16/33); 12/33 analyses used PROM subdomain scores instead of the overall scores. PROMs data was mostly collected at baseline (24/33) and predominantly used to predict survival (32/33) but seldom other clinical outcomes (1/33). Almost all prognostic factor studies (26/27) had moderate to high risk of bias and all four prognostic model development studies had high risk of bias., Conclusion: There is an emerging body of research into the value of PROMs as a prognostic factor for survival in people with NSCLC but the methodological quality of this research is poor with significant bias. This warrants more robust studies into the prognostic value of PROMs, in particular for predicting outcomes other than survival. This will enable further development of PROM-based prediction models to support clinical decision making in NSCLC., (© 2022. The Author(s).)

Background: Efficacy outcomes and prognostic factors of real-world patients with advanced non-small cell lung cancer (aNSCLC) treated with first-line chemoimmunotherapy are still limited., Patients and Methods: In the retrospective Spinnaker study, data was collected from patients in six United Kingdom and one Swiss oncology centres with first-line pembrolizumab plus platinum-based chemotherapy. Efficacy outcomes and potential prognostic factors were estimated aiming at developing a prognostic model., Results: Three-hundred-eight patients were included, 32% ≥ 70 years, with ≥ 3 metastatic sites in 33%, brain or liver metastases in 10% and 12%, respectively. With a median follow-up of 18.0 months (mo.) (range, 15.9-20.1), median overall survival (OS) and progression-free survival (PFS) were 12.7 mo. (range, 10.2-15.2), and 8.0 mo. (range, 7.1-8.8), respectively. The neutrophils-to-lymphocytes ratio (NLR) and systemic immune-inflammatory index (SII) (i.e., NLR × platelet count) were both significantly higher in ECOG PS 1 (p = 0.0147 and p = 0.0018, respectively), underweight or normal body mass index (p = 0.0456 and p = 0.0062, respectively), ≥3 metastatic sites (p = 0.0069 and p = 0.112), pretreatment steroids (p = 0.0019 and p = 0.0017). By MVA, the number of metastatic sites ≥ 3 (p < 0.001 and p = 0.002), squamous histology (p = 0.033 and p = 0.013) and SII ≥ 1444 (p = 0.031 and p = 0.009, respectively) were associated with both worse OS and PFS and led to a highly discriminating three-class risk prognostic model., Conclusion: Real-world PFS with chemoimmunotherapy in aNSCLC patients is similar to that reported in clinical trials. A high number of metastatic sites, squamous histology and high SII are adverse prognostic factors that might contribute to a clinically useful prognostic model., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Patients with thoracic malignancies are at increased risk for mortality from coronavirus disease 2019 (COVID-19), and a large number of intertwined prognostic variables have been identified so far., Methods: Capitalizing data from the Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry, a global study created with the aim of describing the impact of COVID-19 in patients with thoracic malignancies, we used a clustering approach, a fast-backward step-down selection procedure, and a tree-based model to screen and optimize a broad panel of demographics and clinical COVID-19 and cancer characteristics., Results: As of April 15, 2021, a total of 1491 consecutive eligible patients from 18 countries were included in the analysis. With a mean observation period of 42 days, 361 events were reported with an all-cause case fatality rate of 24.2%. The clustering procedure screened 73 covariates in 13 clusters. A further multivariable logistic regression for the association between clusters and death was performed, resulting in five clusters significantly associated with the outcome. The fast-backward step-down selection procedure then identified the following seven major determinants of death: Eastern Cooperative Oncology Group-performance status (ECOG-PS) (OR = 2.47, 1.87-3.26), neutrophil count (OR = 2.46, 1.76-3.44), serum procalcitonin (OR = 2.37, 1.64-3.43), development of pneumonia (OR = 1.95, 1.48-2.58), C-reactive protein (OR = 1.90, 1.43-2.51), tumor stage at COVID-19 diagnosis (OR = 1.97, 1.46-2.66), and age (OR = 1.71, 1.29-2.26). The receiver operating characteristic analysis for death of the selected model confirmed its diagnostic ability (area under the receiver operating curve = 0.78, 95% confidence interval: 0.75-0.81). The nomogram was able to classify the COVID-19 mortality in an interval ranging from 8% to 90%, and the tree-based model recognized ECOG-PS, neutrophil count, and c-reactive protein as the major determinants of prognosis., Conclusions: From 73 variables analyzed, seven major determinants of death have been identified. Poor ECOG-PS was found to have the strongest association with poor outcome from COVID-19. With our analysis, we provide clinicians with a definitive prognostication system to help determine the risk of mortality for patients with thoracic malignancies and COVID-19., (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: Optimal treatment for 'potentially resectable' stage III-N2 non-small cell lung cancer (NSCLC) requires multimodality treatment: local treatment (surgery or radiotherapy) and systemic anticancer therapy. There is no clear evidence of superiority for survival between the two approaches and little research has explored quality of life (QOL). This study will inform the design of a phase III randomised trial of surgery versus no surgery as part of multimodality treatment for stage III-N2 NSCLC with QOL as a primary outcome., Methods and Analysis: Patient participants will be randomised to receive multimodality treatment (1) with surgery OR (2) without surgery. The Quintet Recruitment Intervention will be used to maximise recruitment. Eligible patients will have 'potentially resectable' N2 NSCLC and have received a multidisciplinary team recommendation for multimodality treatment. Sixty-six patients and their carers will be recruited from 8 UK centres. Patient/carer QOL questionnaires will be administered at baseline, weeks 6, 9, 12 and month 6. Semistructured interviews will be conducted. Quantitative data will be analysed descriptively and qualitative data will be analysed using framework analysis., Ethics and Dissemination: Ethical approval has been obtained. Results will be disseminated via publications, national bodies and networks, and patient and public involvement groups., Trial Registration: NCT04540757., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The use of granulocyte colony-stimulating factors (G-CSF) during concurrent chemo-radiotherapy (cCTRT) for small cell lung cancer is not recommended by the American Society of Clinical Oncology due to safety concerns. This secondary analysis explored the safety and the role of prophylactic G-CSF (proG-CSF) in the delivery of cCTRT., Material and Methods: Secondary analysis of 487 patients treated as per protocol on the phase 3 CONVERT trial which randomized patients between once-daily RT or twice-daily., Results: 180 of 487 eligible patients (37 %) received proG-CSF, 60 (33 %) as primary prophylaxis and 120 (67 %) as secondary prophylaxis following myelotoxic events. The regimen incidence of febrile neutropenia (FN) was 22 %. Its incidence in the proG-CSF group reduced significantly when proG-CSF was administered (22 % vs 10 %; OR 0.4; 95 %CI 0.2-0.7; p = 0.002). The rate of blood transfusion was higher in the proG-CSF group (51 % vs 31 %; OR 2.4; 95 %CI 1.6-3.5; p < 0.001). The incidence of severe thrombocytopenia was also higher is this group (28 % vs 15 %; OR 2.2; 95 %CI 1.4-3.5; p = 0.001). But this was significantly higher in those on secondary vs primary prophylaxis (34 % vs 15 %; OR 2.9; 95 %CI 1.3-7.4 p = 0.009) No differences observed in RT-related toxicity, treatment-related mortality or any survival outcomes. The optimal dose intensity (85 % or higher) of cisplatin was achieved in more patients within the proG-CSF group (75 % vs 67 %; OR 1.5; 95 %CI 0.9-2.3; p = 0.056)., Conclusion: There was no evidence that G-CSF directly caused myelotoxicity, instead most patients started G-CSF due to higher myelotoxicity risk. G-CSF maintained the planned dose intensity and there was no detrimental effect on survival. G-CSF may be considered as a supportive measure in this setting., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Immunotherapy with checkpoint inhibitors against programmed cell death receptor (PD-1) and programmed cell death ligand (PD-L1) has been implemented in the treatment pathway of patients with non-small cell lung cancer (NSCLC) from locally advanced disease to the metastatic setting. This approach has resulted in improved survival and a more favourable toxicity profile when compared with chemotherapy. Following the successful introduction of single-agent immunotherapy, current clinical trials are focusing on combination treatments with chemotherapy or radiotherapy or even other immunotherapeutic agents. However, most of the data available from these trials are derived from, and therefore might be more applicable to younger and fitter patients rather than older and often frail lung cancer real-world patients. This article provides a detailed review of these immunotherapy agents with a focus on the data available regarding older NSCLC patients and makes recommendations to fill evidence gaps in this patient population.

Background: Studies of older patients with colorectal cancer(CRC) have found inconsistent results about the correlation of various comorbidities with overall survival(OS) and treatment tolerance. To refine our understanding, we evaluated this correlation using the Cumulative Illness Rating Scale-Geriatric(CIRS-G) and heat maps to identify subgroups with the highest impact., Methods: We retrospectively reviewed 153 patients aged 65 years and older with stage IV CRC undergoing chemotherapy. We calculated CIRS-G scores, and a Total Risk Score(TRS) derived from a previous heat map study. The association between CIRS-G scores/TRS and OS, unplanned hospitalizations, and chemotoxicity was examined by the Cox proportional hazards model., Results: Median age was 71 years. Median MAX2 score of chemotherapies was 0.134(0.025-0.231). The most common comorbidities were vascular(79.8%), eye/ear/nose/throat(68%), and respiratory disease(52.4%). Median OS was 25.1 months(95% confidence interval: 21.2-27.6). In univariate analysis, ECOG PS ≥ 2(HR 1.86(1.1-3.17), p = 0.019), poorly differentiated histology(HR 2.03(1.27-3.25), p = 0.003), primary site(rectum vs colon)(HR 0.58 (0.34-0.98), p = 0.04), age at diagnosis(HR per 5y 1.20 (1.04-1.39), p = 0.012), and number of CIRS-G grade 4 comorbidities(HR 1.86 (1.1-3.17), p = 0.019) were associated with OS. In multivariate analysis, the number of CIRS-G grade 4 comorbidities lost significance, although it retained it in the subgroup of patients with colon cancer. Conversely, the TRS was associated with OS in patients with rectal cancer. No association of comorbidity with unplanned hospitalization or chemotoxicity was observed., Conclusions: In older adults with metastatic CRC, the number of CIRS-G grade 4 comorbidities was associated with worse OS but no specific CIRS-G category was independently associated with OS, unplanned hospitalization, or toxicities., (Copyright © 2019. Published by Elsevier Ltd.)

Lung cancer is predominantly a disease of the elderly. This subgroup of patients poses many challenges and an appropriate geriatric assessment is crucial for treatment personalisation in order to reduce the risk of over- or under-treatment. Whilst cytotoxic chemotherapy has been the backbone of advanced non-small cell lung cancer (NSCLC) treatment for decades, the development of targeted agents for driver mutations such as EGFR, ALK, BRAF and ROS1 has changed the treatment paradigm and natural history of this disease. More recently, the development of immune checkpoint inhibitors has revolutionised treatment for a larger group of patients with locally advanced/metastatic disease. Limited data exist on safety and efficacy of these agents in the elderly population. Many questions remain regarding the available evidence for targeted therapies and immune checkpoint blockade in NSCLC and, in particular, their role in this subgroup of patients.

SCLC accounts for 15% of lung cancer worldwide. Characterised by early dissemination and rapid development of chemo-resistant disease, less than 5% of patients survive 5 years. Despite 3 decades of clinical trials there has been no change to the standard platinum and etoposide regimen for first line treatment developed in the 1970's. The exceptionally high number of genomic aberrations observed in SCLC combined with the characteristic rapid cellular proliferation results in accumulation of DNA damage and genomic instability. To flourish in this precarious genomic context, SCLC cells are reliant on functional DNA damage repair pathways and cell cycle checkpoints. Current cytotoxic drugs and radiotherapy treatments for SCLC have long been known to act by induction of DNA damage and the response of cancer cells to such damage determines treatment efficacy. Recent years have witnessed improved understanding of strategies to exploit DNA damage and repair mechanisms in order to increase treatment efficacy. This review will summarise the rationale to target DNA damage response in SCLC, the progress made in evaluating novel DDR inhibitors and highlight various ongoing challenges for their clinical development in this disease., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)