Derek Grose

Comorbidity in Lung Cancer: Important but Neglected. A Review of the Current Literature

INTRODUCTION Treatment and survival rates for patients with lung cancer in Scotland appear lower than in many other European countries. Five-year survival is quoted at 6% to 7% compared with 8% to 15% in other European countries and America. There also appear to be variations in treatment rates within Scotland. Although this variation in treatment and survival is popularly 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 demonstration that comorbidity influences treatment and survival rates will have important implications for the targeting of health services resources, screening, interpretation of cancer statistics, and the assessment and management of patients with lung cancer. METHODS In this article we have reviewed the tools currently available for assessing comorbidity and in addition have identified published works which study the effect of comorbidity in lung cancer. CONCLUSION There is no currently validated measurement tool applicable specifically to lung cancer and thus there remains a significant need for further work in this important area. STATEMENT OF SEARCH STRATEGIES USED AND SOURCES OF INFORMATION: Literature searches were undertaken via PubMed and Google Scholar using various arrays of the following keywords: cancer, comorbidity, lung lancer, performance status, survival, and tools. The search was limited to articles published in peer-review journals with English as the language.

The impact of comorbidity upon determinants of outcome in patients with lung cancer

BACKGROUND Survival from lung cancer remains poor in Scotland, UK. It is believed that comorbidity may play an important role in this. The goal of this study was to determine the value of a novel comorbidity scoring system (SCSS) and to compare it with the already established Charlson Comorbidity Index and the modified Glasgow Prognostic Score (mGPS). We also wished to explore the relationship between comorbidity, mGPS and Performance Status (PS). In addition we investigated a number of standard prognostic markers and demographics. This study aimed to determine which of these factors most accurately predicted survival. METHODS 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, clinico-pathological features, mGPS, comorbidity and proposed primary treatment modality were recorded. Univariate survival analysis was carried out using Kaplan-Meier method and the log rank test. RESULTS This large unselected population based cohort study of lung cancer patients has demonstrated that a number of important factors have significant impact in terms of survival. It has gone further by showing that the factors which influence survival are different, depending upon the stage of cancer at diagnosis and the potential treatment strategy. The novel comorbidity scoring system, the SCSS, has compared very favourably with the more established CCI. CONCLUSION This study has identified that a variety of factors are independent prognostic determinants of outcome in lung cancer. There appear to be clear differences between the early and late stage groups.

Comorbidities in lung cancer: prevalence, severity and links with socioeconomic status and treatment

Background Survival from lung cancer remains poor in Scotland, UK. Although the presence of comorbidities is known to influence outcomes, detailed quantification of comorbidities is not available in routinely collected audit or cancer registry data. The aim of the present study was to assess the prevalence and severity of comorbidities in patients with newly diagnosed lung cancer across four centres throughout Scotland using validated criteria. Methods Between 2005 and 2008, all patients with newly diagnosed lung cancer coming through the multidisciplinary teams in four Scottish centres were included in the study. Patient demographics, WHO/Eastern Cooperative Oncology Group performance status, clinicopathological features and primary treatment modality were recorded. Results Details of 882 patients were collected prospectively. The majority of patients (87.3%) had at least one comorbidity, the most common being weight loss (53%), chronic obstructive pulmonary disease (43%), renal impairment (28%) and ischaemic heart disease (27%). A composite score was produced that included both number and severity of comorbidities. One in seven patients (15.3%) had severe comorbidity scores. There were statistically significant variations in comorbidity scores between treatment centres and between non-small cell lung carcinoma treatment groups. Disease stage was not associated with comorbidity score. Conclusions There is a high prevalence of multiple, severe comorbidities in Scottish patients with lung cancer, and these vary by site and treatment group. Further research is needed to determine the relationship between comorbidity scores and survival in these patients.

Variation in Comorbidity and Clinical Management in Patients Newly Diagnosed with Lung Cancer in Four Scottish Centers

Background: Treatment and survival rates within Scotland for patients with lung cancer seem lower than in many other European countries. No study of lung cancer has attempted to specifically investigate the association between variation in investigation, comorbidity, and treatment and outcome between different centers. Methods: Patient demographics, World Health Organization/Eastern Cooperative Oncology Group performance status, and primary treatment modality were recorded. In addition to recording the comorbidities present in each patient, the severity of each comorbidity was graded on a 4-point scale (0–3) using validated severity scales. Data were collected as the patient was investigated and entered in an anonymized format into a database designed for the study. Results: Prospectively collected data from 882 patients diagnosed with lung cancer in four Scottish centers. A number of statistically significant differences were identified between centers. These included investigation, treatment between centers (i.e., surgical rates), age, tumor histology, smoking history, socioeconomic profile, ventilatory function, and performance status. Predictors of declining performance status included increasing severity of a number of comorbidities, age, lower socioeconomic status, and specific centers. Conclusions: This study has identified many significant intercenter differences within Scotland. We believe this to be the first study to identify nontumor factors independent of performance status that together limit the ability to deliver radical, possibly curative, therapy to our lung cancer population. It is only by identifying such factors that we can hope to improve on the relatively poor outlook for the majority of Scottish patients with lung cancer.

Sequential TPF chemotherapy followed by concurrent chemoradiotherapy in locally advanced head and neck cancer--a retrospective analysis of toxicity and outcomes.

Background and aims Phase III trials have shown that the addition of a taxane to cisplatin/5FU-based induction chemotherapy (TPF) improves response rates and overall survival in unresectable stage III/IV head and neck cancer. We sought to assess the tolerability, compliance and clinical outcomes of this treatment regime. Methods A retrospective study of patients treated within a single centre between September 2007 and November 2010. Toxicities were graded according to CTCAE version 3.0. Survival, distant metastasis and local control rates are expressed as percentages at two years using the Kaplan–Meier method. Results A total of 100 patients were identified (11% stage III, 86% stage IV) and 32% of patients were admitted as an emergency after TPF. The rate of neutropenic fever was 31%, this number fell to 9% when prophylactic G-CSF was used. In addition, 89% of patients underwent radical chemoradiation. Of these, 96% completed the full radiotherapy course. However, only 64% of patients received a minimum of two cycles of concurrent platinum chemotherapy. The two-year overall survival, metastasis free survival and local control rates were 62.6%, 88.5% and 73.3%, respectively. Conclusions TPF chemotherapy can be delivered safely in a non-trial cohort of patients. There is, however, a significant reduction in concurrent chemotherapy dose intensity. The long-term impact of this remains unclear.

Chronic obstructive pulmonary disease: a complex comorbidity of lung cancer

Chronic obstructive pulmonary disease (COPD) is a major burden throughout the world. It is associated with a significantly increased incidence of lung cancer and may influence treatment options and outcome. Impaired lung function confirming COPD is an independent risk factor for lung cancer. Oxidative stress and inflammation may be a key link between COPD and lung cancer, with numerous molecular markers being analysed to attempt to understand the pathway of lung cancer development. COPD negatively influences the ability to deliver radical treatment options, so attempts must be made to look for alternative methods of treating lung cancer, while aiming to manage the underlying COPD. Detailed assessment and management plans utilising the multidisciplinary team must be made for all lung cancer patients with COPD to provide the best care possible.

Simple and Objective Prediction of Survival in Patients with Lung Cancer: Staging the Host Systemic Inflammatory Response

Background. Prediction of survival in patients diagnosed with lung cancer remains problematical. The aim of the present study was to examine the clinical utility of an established objective marker of the systemic inflammatory response, the Glasgow Prognostic Score, as the basis of risk stratification in patients with lung cancer. Methods. Between 2005 and 2008 all newly diagnosed lung cancer patients coming through the multidisciplinary meetings (MDTs) of four Scottish centres were included in the study. The details of 882 patients with a confirmed new diagnosis of any subtype or stage of lung cancer were collected prospectively. Results. The median survival was 5.6 months (IQR 4.8–6.5). Survival analysis was undertaken in three separate groups based on mGPS score. In the mGPS 0 group the most highly predictive factors were performance status, weight loss, stage of NSCLC, and palliative treatment offered. In the mGPS 1 group performance status, stage of NSCLC, and radical treatment offered were significant. In the mGPS 2 group only performance status and weight loss were statistically significant. Discussion. This present study confirms previous work supporting the use of mGPS in predicting cancer survival; however, it goes further by showing how it might be used to provide more objective risk stratification in patients diagnosed with lung cancer.

Semi-automatic segmentation of tongue tumors from magnetic resonance imaging

Radiation therapy is one of the most effective modalities for treatment of tongue cancer. In order to optimize radiation dose to the tumor region, it is necessary to segment the tumor from normal region. This paper presents a new semiautomatic algorithm that is demonstrated to be able to segment tongue tumor from gadolinium-enhanced T1-weighted magnetic resonance imaging (MRI) to support radiation planning. This algorithm takes sequential MRI slices with visible tongue tumor. The Tumors region from each slice is segmented using three steps (i) preprocessing, (ii) initialization and (iii) localized region-based level set segmentation. The segmentation results obtained from proposed algorithm are compared with manual segmentation from clinical expert. Results from 9 MRI slices show that there is a good overlap between semi-automatic and manual segmentation results with dice similarity coefficient (DSC) of 0.87±0.05.

The role of induction chemotherapy + chemoradiotherapy in localised pancreatic cancer: initial experience in Scotland

BACKGROUND Despite being relatively rare pancreatic cancer is one of the highest causes of death. Even within the potentially resectable group outcomes are poor. We present our initial experiences utilising a neoadjuvant approach to localised pancreatic cancer, evaluating survival, response rates and tolerability. METHODS This was a retrospective analysis of a prospectively maintained database. Patients from 2012 to 2015 referred to a busy regional Hepato-Pancreatic Biliary (HPB) MDT were included. Patients were classified according to respectability criteria (utilising NCCN guidelines) and a treatment plan agreed. Systemic therapy with either FOLFIRINOX or Gem/Cap was delivered followed by chemoradiotherapy if disease remained localised. Toxicity, response, pathological outcomes and survival were all recorded. RESULTS A total of 85 patients were included in the study: 45 had initially resectable disease; 19 required a response for resection and 21 had locally advanced inoperable disease; 34 patients underwent resection. The median survival for the potentially resectable group was 22.2 months while for those undergoing resection it was 37 months. CONCLUSIONS We have demonstrated that a neoadjuvant approach is deliverable and tolerable. In addition we have demonstrated impressive survival results in patients undergoing resection with no detriment in outcome for those not proceeding to surgery.

Automatic pharynx and larynx cancer segmentation framework (PLCSF) on contrast enhanced MR images

A novel and effective pharynx and larynx cancer segmentation framework (PLCSF) is presented for automatic base of tongue and larynx cancer segmentation from gadolinium-enhanced T1-weighted magnetic resonance images (MRI). The aim of the proposed PLCSF is to assist clinicians in radiotherapy treatment planning. The initial processing of MRI data in PLCSF includes cropping of region of interest; reduction of artefacts and detection of the throat region for the location prior. Further, modified fuzzy c-means clustering is developed to robustly separate candidate cancer pixels from other tissue types. In addition, region-based level set method is evolved to ensure spatial smoothness for the final segmentation boundary after noise removal using non-linear and morphological filtering. Validation study of PLCSF on 102 axial MRI slices demonstrate mean dice similarity coefficient of 0.79 and mean modified Hausdorff distance of 2.2 mm when compared with manual segmentations. Comparison of PLCSF with other algorithms validates the robustness of the PLCSF. Inter- and intra-variability calculations from manual segmentations suggest that PLCSF can help to reduce the human subjectivity.