Comorbidity in lung cancer: influence on treatment and survival

Lung cancer is the commonest cancer in Scotland and survival rates for patients in Scotland appear lower than in many other European countries. Although this variation in survival is usually interpreted as evidence of variation in facilities, access to care and clinical practice it is possible that the increased comorbidity and poor performance status of the Scottish population may contribute to the observed disparities in treatment and outcomes, although this has never been proven. The overall aim of the Thesis was to examine the impact of comorbidity in lung cancer, to attempt to quantify the extent and severity of comorbidity and to explore its relationship with treatment and survival. Between 2005 and 2008 all newly diagnosed lung cancer patients coming through the Multi-Disciplinary Teams (MDTs) in four Scottish Centres were included in the study. Patient demographics, World Health Organization/Eastern Cooperative Oncology Group performance status (PS), clinic-pathological features, stage, comorbidity, markers of systemic inflammation and proposed primary treatment modality were all recorded. Information on date of death was obtained via survival analysis undertaken by the Information Service Division (ISD) of NHS Scotland. Death records were complete until 1 June 2011, which served as the censor date for those alive. Chapter 4 examines the variations in demographics and baseline characteristics seen between the centres and reveals significant differences between the centres such as deprivation, stage at presentation, PS and treatments offered. Chapter 5 explores the relationship between comorbidity and the patient cohort. It shows that comorbidity can be quantified using a scoring index (the Scottish Comorbidity Scoring System (SCSS)) and that increasing comorbidity is associated with treatment centre and socio-economic status, with the most deprived patients having increased levels of co-morbidity. It also demonstrates that comorbidity appears to have an impact on treatment offered. Chapter 6 examines the relationship between systemic inflammation (utilizing the well established modified Glasgow Prognostic Score (mGPS)) and outcome in the patient cohort. It confirms previous work supporting the use of the mGPS in predicting lung cancer survival and also shows how it might be used to provide more objective risk stratification in patients diagnosed with lung cancer. Chapter 7 explores the relationship between a novel comorbidity scoring system (SCSS) and the already established Charlson Comorbidity Index (CCI) and the modified Glasgow Prognostic Score (mGPS). This study aimed to determine which of these factors provided the most accurate information on survival. The novel comorbidity scoring system, the SCSS compares very favourably with the more established CCI. In addition this study demonstrates clear differences between patients having potentially radically treatable disease (NSCLC stage I – IIIa) and disease which would generally be considered incurable (NSCLC IIIb/IV and SCLC). Chapter 8 examines the reasons for the clinician decision-making process and if these reasons do indeed mirror the individual patient’s demographics, fitness and stage. In the majority of patients, both in the early and advanced stage at presentation, the treatment decision appears to be appropriate given the recorded fitness, PS and comorbidity. However in a small but significant number of patients there did appear to be discrepancies between the clinician’s reasons for sub-optimal therapy and the recorded objective assessment of the patient in question. The work presented in this thesis has demonstrated the significant extent of comorbidity in lung cancer and the important role it appears to play (along with systemic inflammation) in determining treatment choice and survival

Reply to Comment on "The UK consensus position on the treatment of pancreatic cancer during the COVID-19 pandemic".

Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/50110000028

Neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer: a systematic review and patient-level meta-analysis

BACKGROUND: FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated. METHODS: We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. Primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), resection rate, R0-resection rate, and grade 3-4 adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method. RESULTS: We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n=20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% CI: 60.1 - 74.6), the R0-resection rate was 83.9% (95% CI: 76.8 - 89.1). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data was obtained for 20 studies representing 283 BRPC patients. Patient-level median OS was 22.2 months (95% CI: 18.8 - 25.6), patient-level median PFS was 18.0 months (95% CI: 14.5 - 21.5). Pooled event rates for grade 3-4 adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI: 10.3 - 28.3), diarrhea (11.1 per 100 patients, 95% CI: 8.6 - 14.3), and fatigue (10.8 per 100 patients, 95% CI 8.1 - 14.2). No deaths were attributed to FOLFIRINOX. CONCLUSION: This patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial

Costly Signaling Theory in Archaeology

Why do people engage in seemingly wasteful behaviors and invest in extravagant material displays? Since its introduction into anthropological archaeology two decades ago, costly signaling theory (CST) has been used to provide an answer to this question. With broad origins in biology and social theory, costly signaling theory seeks to provide an evolutionary explanation for why humans engage in seemingly wasteful behaviors. In this chapter, I take stock of costly signaling theory in archaeology by (1) tracing its theoretical origins and history of adoption into anthropological archaeology, (2) highlighting key issues that archaeologists have been wrestling with in order to make CST applicable to the past, (3) discussing the breadth of uses of CST in the recent archaeological literature, and (4) presenting an analytical framework that can make CST more rigorous and in the future. Despite persistent doubts about the explanatory utility of CST, the study of signaling from an evolutionary perspective remains a key aspect of evolutionary archaeology