Trends in lung cancer incidence and survival: studies based on cancer registries

In this thesis trends in the incidence and survival of patients with lung cancer since 1960 in the southeastern part of the Netherlands are described and interpreted. These trends may provide an insight into changes in mortality due to lung cancer in a region with the oldest cancer registlY in the Netherlands. Chapter 1.2 contains a review of literature on trends in the incidence and survival of lung cancer. The methods used for the studies of this thesis are described in chapter 2. Only since the beginning of this century has lung cancer become fairly common, the incidence increasing dramatically since the 1940s. '·2 It has become by far the most frequent type of cancer among Dutch men since the 1960s, causing 35% of all cancer deaths. Among Dutch women it now ranks third, causing II % of all cancer deaths.3 Smoking is the most important risk factor for lung cancer,4,S now causing about 80% of all lung tumours in men and about 60% of all lung tmllours in women. Changes in smoking habits and lung cancer incidence in the southeastern part of the Netherlands and the marked differences between men and women are described in chapter 3. An aetiological background for each sex could be obtained from birth cohort analyses and from intraregional differences, especially since this region contained many tobaccoprocessing industries. Lung cancer is commonly classified as small-cell carcinoma and non-small-cell carcinoma. The latter includes squamous cell carcinoma, adenocarcinoma, large-cell undifferentiated carcinoma, and some rare subtypes. However, the broad division into small-cell carcinoma and non-small-cell carcinoma may obscure shifts in incidence and prognosis that affect one histological subtype rather than the entire group of nonsmall- cell lung tumours.6 Small-cell carcinoma is a highly aggressive neoplasm, which is rarely amenable to surgical treatment but often responds well to chemotherapy andlor palliative radiotherapy, albeit only for a few months. According to clinical trials, the short-term survival rate for patients with small-cell carcinoma seems to have improved since the introduction of chemotherapy. However, little is known about trends in long-term survival for unselected patients. Changes in survival rates, according to the major histological subtypes of lung cancer, are described and interpreted in chapter 4. Trends in survival rates may give an indication of variations in detection, aggressiveness of the tumour and treatment over time

Trends in incidence and prognosis of the histological subtypes of lung cancer in North America, Australia, New Zealand and Europe

Background: Since the incidence of the histological subtypes of lung cancer in industrialised countries has changed dramatically over the last two decades, we reviewed trends in the incidence and prognosis in North America, Australia, New Zealand and Europe, according to period of diagnosis and birth cohort and summarized explanations for changes in mortality. Methods: Review of the literature based on a computerised search (Medline database 1966-2000). Results: Although the incidence of lung cancer has been decreasing since the 1970s/1980s among men in North America, Australia, New Zealand and north-western Europe, the age-adjusted rate continues to increase among women in these countries, and among both men and women in southern and eastern Europe. These trends followed changes in smoking behaviour. The proportion of adenocarcinoma has been increasing over time; the most likely explanation is the shift to low-tar filter cigarettes during the 1960s and 1970s. Despite improvement in both the diagnosis and treatment, the overall prognosis for patients with non-small-cell lung cancer hardly improved over time. In contrast, the introduction and improvement of chemotherapy since the 1970s gave rise to an improvement in - only short-term (<2 years) - survival for patients with small-cell lung cancer. Conclusions: The epidemic of lung cancer is not over yet, especially in southern and eastern Europe. Except for short-term survival of small cell tumours, the prognosis for patients with lung cancer has not improved significantly. Copyrigh

Temporal trends and spatial variation in stage distribution of non-small cell lung cancer in the Netherlands

Introduction To explore regional and temporal variation in clinical stage distribution of non-small cell lung cancer (NSCLC) and link the observations to the introduction of positron emission tomography (PET). Method All NSCLC patients diagnosed between 1989 and 2007 were selected from the Netherlands Cancer Registry (n=126,962). Maps of smoothed percentage distribution of clinical stage NSCLC were conducted by period of diagnosis. Join point regression analyses were performed to detect trends over time. Geographic variation in stage distribution was evaluated using spatial scan statistic. To evaluate the impact of PET in regions proportions of stage IV and Estimated Annual Percentage of Change (EAPC) were calculated for two regions in which PET was introduced between 1995 and 2000 and for two regions without a PET scanner during this period. Results The percentage of stage I and unknown decreased with 7.4% and 13.3% between 1989 and 2007, while the percentage of stage IV increased with 23.4%. The most rapid increase in stage I and IV were observed between 1997 and 2003. In two regions with a PET scan the proportion of stage IV increased annually with 10.3 and 8.5% compared to 5.4 and 6.4% in two regions without a PET scan. Conclusion The most rapid changes towards more stage IV NSCLC diagnoses correspond with the implementation of PET. However, trends were already visible before PET was introduced and regions without PET also showed considerable increases in stage IV diagnose, suggesting other factors or improvements in diagnostics also contributed substantially

Prevalence of co-morbidity and its relationship to treatment among unselected patients with Hodgkin's disease and non Hodgkin's lymphoma, 1993-l996

A population-based series of patients with cancer is likely to comprise more patients with serious co-morbidity than clinical trials because of restrictive eligibility criteria for the latter. Since co-morbidity may influence decision-making, we studied the age-specific prevalence of co-morbidity and its relationship to applied treatment. Data on all 194 patients with Hodgkin's disease (HD) and on 904 patients with non-Hodgkin's lymphoma (NHL) diagnosed between 1993 and 1996 were derived from the Eindhoven Cancer Registry. In the age-group below 60 years, 87% of patients with HD and 80% with NHL did not have a co-morbid condition. The prevalence of serious co-morbidity was 56% for patients with Hodgkin's disease who were 60 years and over and 43% and 61% for non Hodgkin patients who were 60-69 years and 70 years and over, respectively. The most common co-morbid conditions were cardiovascular disease (18%), hypertension (13%), chronic obstructive pulmonary disease (COPD; 13%), and diabetes mellitus (10%) for elderly Hodg kin's patients. For non-Hodgkin's patients of 60-69 years and 70 years and over, cardiovascular disease (15 and 22%, respectively), hypertension (14 and 14%, respectively), COPD (6 and 10% respectively), and diabetes mellitus (8 and 10% respectively) were the most prevalent co-morbid conditions. The presence of co-morbidity was not related to stage or grade of disease at diagnosis. In the presence of co-morbidity, 50% less chemotherapy was administered to elderly patients with Hodgkin's disease and 10-15% less to elderly patients with non-Hodgkin's lymphoma. The presence of co-morbidity was associated with a decreased overall survival within the first 4 months after diagnosis in both Hodgkin's disease and non-Hodgkin's lymphoma for all age-groups. In conclusion, serious co-morbidity was found for more than half of all lymphoma patients who were 60 years and older. Elderly patients with serious co-morbidity received chemotherapy less often, which is likely to affect survival adversely, as was indicated by a decreased survival within the first 4 months after diagnosis

Associations between pretreatment physical performance tests and treatment complications in patients with non-small cell lung cancer: A systematic review

This systematic review evaluated which outcome variables and cut-off values of pretreatment exercise tests are associated with treatment complications in patients with stage I-III non-small cell lung cancer (NSCLC). PRISMA and Cochrane guidelines were followed. A total of 38 studies with adult patients undergoing treatment for stage I-III NSCLC who completed pretreatment exercise tests, and of whom treatment-related complications were recorded were included. A lower oxygen uptake at peak exercise amongst several other variables on the cardiopulmonary exercise test and a lower performance on field tests, such as the incremental shuttle walk test, stair-climb test, and 6-minute walk test, were associated with a higher risk for postoperative complications and/ or postoperative mortality. Cut-off values were reported in a limited number of studies and were inconsistent. Due to the variety in outcomes, further research is needed to evaluate which outcomes and cut-off values of physical exercise tests are most clinically relevant

Small but significant excess mortality compared with the general population for long-term survivors of breast cancer in the Netherlands

Background: Coinciding with the relatively good and improving prognosis for patients with stage I-III breast cancer, late recurrences, new primary tumours and late side-effects of treatment may occur. We gained insight into prognosis for long-term breast cancer survivors. Patients and methods: Data on all 205 827 females aged 15-89 diagnosed with stage I-III breast cancer during 1989-2008 were derived from the Netherlands Cancer Registry. Conditional 5-year relative survival was calculated for every subsequent year from diagnosis up to 15 years. Results: For stage I, conditional 5-year relative survival remained ~95% up to 15 years after diagnosis (a stable 5-year excess mortality rate of 5%). For stage II, excess mortality remained 10% for those aged 15-44 or 45-59 and 15% for those aged 60-74. For stage III, excess mortality decreased from 35% at diagnosis to 10% at 15 years for those aged 15-44 or 45-59, and from ~40% to 30% for those aged ≥60. Conclusions: Patients with stage I or II breast cancer had a (very) good long-term prognosis, albeit exhibiting a small but significant excess mortality at least up to 15 years after diagnosis

Associations of Pretreatment Physical Status Parameters with Tolerance of Concurrent Chemoradiation and Survival in Patients with Non-small Cell Lung Cancer

Objective The aim of this study was to evaluate associations between pretreatment physical status parameters and tolerance of concurrent chemoradiation (cCHRT) and survival among patients with stage III non-small cell lung cancer (NSCLC). Methods A retrospective cohort study was conducted among patients with stage III NSCLC who had received cCHRT between 2006 and 2015. Multivariate independent associations were analysed between the pretreatment parameters age, Charlson comorbidity index, World Health Organization performance status (WHO performance status), body mass index (BMI), fat-free mass index (FFMI), maximal handgrip strength, forced expiratory volume in one second and carbon monoxide lung diffusion capacity on the one hand with tolerance of cCHRT (defined as a received radiation dose at least equal to the prescribed radiation dose) and survival on the other hand. Results 527 of 577 patients (91.3%) tolerated cCHRT. A WHO performance status >= 2 (odds ratio (OR) 0.43) and BMI = 2 (hazard ratio (HR) 1.73), low FFMI (HR 1.23) and intolerance of cCHRT (HR 1.55) were associated with poorer survival. Conclusion In patients with stage III NSCLC receiving cCHRT, poor WHO performance status and BMI< 18.5 kg/m(2) were independently associated with tolerance of cCHRT. Physical status parameters and intolerance of cCHRT were independently associated with poorer survival. Besides using this information for treatment decisions, optimizing physical status in patients at risk for intolerance of cCHRT might be a next step for improving treatment outcomes. [GRAPHICS]

A high tumour-stroma ratio (TSR) in colon tumours and its metastatic lymph nodes predicts poor cancer-free survival and chemo resistance

Purpose Despite known high-risk features, accurate identification of patients at high risk of cancer recurrence in colon cancer remains a challenge. As tumour stroma plays an important role in tumour invasion and metastasis, the easy, low-cost and highly reproducible tumour-stroma ratio (TSR) could be a valuable prognostic marker, which is also believed to predict chemo resistance. Methods Two independent series of patients with colon cancer were selected. TSR was estimated by microscopic analysis of 4 mu m haematoxylin and eosin (H&E) stained tissue sections of the primary tumour and the corresponding metastatic lymph nodes. Patients were categorized as TSR-low ( 50%). Differences in overall survival and cancer-free survival were analysed by Kaplan-Meier curves and cox-regression analyses. Analyses were conducted for TNM-stage I-II, TNM-stage III and patients with an indication for chemotherapy separately. Results We found that high TSR was associated with poor cancer-free survival in TNM-stage I-II colon cancer in two independent series, independent of other known high-risk features. This association was also found in TNM-stage III tumours, with an additional prognostic value of TSR in lymph node metastasis to TSR in the primary tumour alone. In addition, high TSR was found to predict chemo resistance in patients receiving adjuvant chemotherapy after surgical resection of a TNM-stage II-III colon tumour. Conclusion In colon cancer, the TSR of both primary tumour and lymph node metastasis adds significant prognostic value to current pathologic and clinical features used for the identification of patients at high risk of cancer recurrence, and also predicts chemo resistance