David McIntosh

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.

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.

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.

PO-0713: Conformity analysis of target-volume definition for margin-directed boost in pancreatic cancer SBRT

Results: To date, 23 patients from 21 centres entered in the trial have been analysed. Mean Grey Level <399.745, Skewness >2.215, Kurtosis >0.6 were associated with improved PFS (p=0.0227, p=0.0218, p=0.0460 respectively) for medium filter 3.0. For filter 4.0, improved PFS was associated with Mean Grey Level <454.055 (p=0.0227) and Skewness >0.840 (p=0.0371). Mean Grey Levels of <565.535 (p=0.0251) and <542.5(p=0.0251) were associated with improved PFS for filters 5.0 and 6.0 respectively. For OS, mean grey levels of <34.845 (p=0.0182), <399.745 (p=0.0381) and <454.055 (p=0.0381) were associated with improved survival for filters 0.0, 3.0 and 4.0 respectively. An entropy level <5.6 was also found to be significant (p=0.0428) for improved overall survival using filter 2.0.

Conformity analysis to demonstrate reproducibility of target volumes for Margin-Intense Stereotactic Radiotherapy for borderline-resectable pancreatic cancer

Background and purpose Margin-directed neoadjuvant radiotherapy for borderline-resectable pancreatic cancer (BRPC) aims to facilitate clear surgical margins. A systematic method was developed for definition of a boost target volume prior to a formal phase-I study. Material and methods Reference structures were defined by two oncologists and one radiologist, target structures were submitted by eight oncologist investigators and compared using conformity indices. Resultant risk of duodenal bleed (NTCP) was modelled. Results For GTV, reference volume was 2.1 cm3 and investigator mean was 6.03 cm3 (95% CI 3.92–8.13 cm3), for boost volume 1.1 cm3 and 1.25 cm3 (1.02–1.48 cm3). Mean Dice conformity coefficient for GTV was 0.47 (0.38–0.56), and for boost volume was significantly higher at 0.61 (0.52–0.70, p = 0.01). Discordance index (DI) for GTV was 0.65 (0.56–0.75) and for boost volume was significantly lower at 0.39 (0.28–0.49, p = 0.001). NTCP using reference contours was 2.95%, with mean for investigator contour plans 3.93% (3.63–4.22%). Correlations were seen between NTCP and GTV volume (p = 0.02) and NTCP and DI (correlation coefficient 0.83 (0.29–0.97), p = 0.01). Conclusions Better conformity with reference was shown for boost volume compared with GTV. Investigator GTV volumes were larger than reference, had higher DI scores and modelled toxicity risk. A consistent method of target structure definition for margin-directed pancreatic radiotherapy is demonstrated.

Role of neoadjuvant treatment regimens for locally advanced pancreatic cancer.

444 Background: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality worldwide. Lymph node involvement and resection margin status play important roles in predicting relapse. Resectable disease occurs in only 15–20% of total patients who present with PDAC. Unfortunately, margin involvement (R1) occurs in 70–80% of these patients. Emerging evidence has shown that the use of neoadjuvant chemotherapy and localised radiotherapy to downsize the tumours and increase the margin clearance (R0) rate may improve the overall survival of PDAC patients.We report a neoadjuvant therapy approach in the non-clinical trial setting of our large, tertiary cancer centre. Methods: We prospectively collected the outcome data and toxicity of 53 patients diagnosed with borderline resectable or initially non-resectable PDAC between 2012 and 2014. These patients received either FOLFIRINOX (FFX) or Gemcitabine/Capecitabine (GemCap) combination chemotherapies. Following restaging by computed tomograp...

A retrospective review of treatment outcomes following definitive chemoradiotherapy or single modality radical radiotherapy among patients with locally advanced esophageal cancer.

196 Background: Definitive chemoradiotherapy (CRT) has been advocated as an alternative to surgical resection for the treatment of locally advanced oesophageal cancer (OC). We have retrospectively reviewed 4 years experience of patients (pts) who underwent contemporary staging and were treated with concurrent chemoradiotherapy (CRT) or single modality radical radiotherapy (RT) with curative intent. Methods: Retrospective analysis permitted identification of consecutive pts who underwent contemporary staging prior to non-surgical treatment for oesophageal carcinoma. The primary outcomes were overall (OS) and disease-free survival (DFS), adjusted for baseline differences in age, tumour staging and histological cell type. All patients were treated with either definitive CRT or single modality RT within a single centre treated between 2009 and 2012. Results: We identified 135 pts in total (median age 69.8 yrs, male=130pts, female=105pts, Adenocarcinoma=85pts, Squamous=150pts). 190 pts received CRT and 45pts w...