Non-lung Cancer Death Research Articles

What Goes into Patient Selection for Lung Cancer Screening? Factors Associated with Clinician Judgments of Suitability for Screening.

Rationale: Achieving the net benefit of lung cancer screening (LCS) depends on optimizing patient selection. Objective: To identify factors associated with clinician assessments that a patient was unlikely to benefit from LCS ("LCS-inappropriate") because of comorbidities or limited life expectancy. Methods: Retrospective analysis of patients assessed for LCS at 30 Veterans Health Administration facilities from January 1, 2015 to February 1, 2021. We conducted hierarchical mixed-effects logistic regression analyses to determine factors associated with clinicians' designations of LCS inappropriateness (primary outcome), accounting for 3-year predicted probability (i.e., competing risk) of non-lung cancer death. Measurements and Main Results: Among 38,487 LCS-eligible patients, 1,671 (4.3%) were deemed LCS-inappropriate by clinicians, whereas 4,383 (11.4%) had an estimated 3-year competing risk of non-lung cancer death greater than 20%. Patients with higher competing risks of non-lung cancer death were more likely to be deemed LCS-inappropriate (odds ratio [OR], 2.66; 95% confidence interval [CI], 2.32-3.05). Older patients (ages 75-80; OR, 1.45; 95% CI, 1.18-1.78) and those with interstitial lung disease (OR, 1.98; 95% CI, 1.51-2.59) were more likely to be deemed LCS-inappropriate than would be explained by competing risk of non-lung cancer death, whereas patients currently smoking (OR, 0.65; 95% CI, 0.58-0.73) were less likely to be deemed LCS-inappropriate, suggesting that clinicians over- or underweighted these factors. The probability of being deemed LCS-inappropriate varied from 0.4% to 74%, depending on the clinician making the assessment (median OR, 3.07; 95% CI, 2.89-3.25). Conclusion: Concerningly, the likelihood that a patient is deemed LCS-inappropriate is more strongly associated with the clinician making the assessment than with patient characteristics. Patient selection may be optimized by providing decision support to help clinicians assess net LCS benefit.

Sublobar resection is not always superior for early-stage lung cancer in high-risk patients.

The phase III trial, Japan Clinical Oncology Group 0802, illustrated the superiority of sublobar resection for early-stage lung cancer in terms of overall survival, with more non-lung cancer-related deaths after a lobectomy. The advantages of sublobar resection may be more pronounced in high-risk patients. The goal of this study was to elucidate the prognoses of high-risk patients. Patients with a risk of being ineligible for Japan Clinical Oncology Group 0802 for general conditions were classified as the high-risk group, and those who were not at risk of being ineligible were classified as the normal-risk group. Overall survival and prognostic factors were analysed in the high-risk group. There were 254 (19.4%) and 1054 patients in the high- and normal-risk groups, respectively. Five-year survival rates were 94.5% and 79.1% in the normal-risk and high-risk groups, respectively (P < 0.001). More patients in the high-risk group died of lung cancer (P < 0.001) and non-lung cancer deaths (P < 0.001) than patients in the normal-risk group.In the high-risk group, 151 lobectomies and 103 sublobar resections were performed. There was no significant difference in the numbers of lung cancer deaths and of non-lung cancer deaths between the procedures. Stratified survival analyses showed that the diffusing capacity of the lungs for carbon monoxide < 40% tended to favour sublobar resection; being female and having a high carcinoembryonic antigen level tended to favour a lobectomy. Sublobar resection is not always superior for early-stage lung cancer. Even in such cases, the surgical method should be determined by taking into consideration the patient's background and lung cancer surveillance.

Clinical impact of histologic type on survival and recurrence in patients with surgically resected stage II and III non-small cell lung cancer

ObjectivesThis study aimed to investigate the clinical impact of histologic type on the survival and recurrence outcomes of patients with stage II and III non-small cell lung cancer (NSCLC). Materials and MethodsA total of 2155 consecutive adult patients who underwent complete resection of stage II and III NSCLC between 2008 and 2018 were enrolled. The primary endpoints were freedom from recurrence (FFR) and overall survival (OS). The secondary endpoint was the time to lung cancer or non-lung cancer death. ResultsOf the 2155 patients, 1436 (66.6 %) had adenocarcinoma (ADC) and 719 (33.4 %) had squamous cell carcinoma (SqCC). Patients with SqCC had better FFR than those with ADC (stage II, p < 0.001; stage III, p < 0.001). Although patients with ADC showed a slightly better OS until 5 years than those with SqCC, the difference was insignificant (stage II, p = 0.292; stage III, p = 0.196). Patients with SqCC had higher rates of non-lung cancer death than patients with ADC (stage II, p < 0.001; stage III, p = 0.039). The time from lung cancer recurrence to death was shorter in patients with SqCC than in those with ADC (stage II, median 13 vs 37 months, p < 0.001; stage III, median 11 vs 26 months, p < 0.001). ConclusionsIn stage II and III NSCLC, ADC had a higher risk of recurrence than SqCC, with no difference in OS. These results were related to significant differences in non-lung cancer mortality and recurrence-to-death time between the two histologic types.

Impact of segmentectomy and lobectomy on non-lung cancer death in early-stage lung cancer patients.

This study aimed to analyse the risk of death from non-lung cancer after segmentectomy or lobectomy for early-stage lung cancer. A total of 1385 patients underwent lobectomy or segmentectomy for clinical stage 0-I primary lung cancer, with no evidence of recurrence after surgery, between January 2008 and December 2018. Risk factors for non-lung cancer deaths (NLCD) were analysed using multivariable logistic regression analysis. The overall survival (OS) of patients with low and high comorbidities who underwent lobectomy and segmentectomy was compared using a log-rank test. Patients with NLCD (n = 126) were more likely to have undergone lobectomy than patients with non-recurrence survival (n = 1259). Multivariable analysis revealed that age (≥65 years), smoking index (≥600), body mass index (≤18.5 kg/m2), interstitial pneumonia, values for percentage of predicted vital capacity (≤9.4%) and lobectomy were risk factors for NLCD. Patients who underwent segmentectomy had significantly better 5-year OS than those who underwent lobectomy, after propensity score matching (94.6% vs 90.4%, P = 0.027). Patients with high comorbidities (patients with ≥2 of the following risks: age ≥65 years, smoking index ≥600, body mass index ≤18.5 kg/m2, Charlson Comorbidity Index ≥1, values for percentage of predicted vital capacity ≤96.4%) who underwent segmentectomy had a better 5-year OS than those who underwent lobectomy (92.8% vs 87.8%, P = 0.016). However, there was no difference in 5-year OS between segmentectomy and lobectomy in patients with low comorbidities (98.5% vs 97.4%, P = 0.867). The impact of lobectomy and segmentectomy on NLCD depends on the extent of the patients' comorbidities.

Propensity score-based analysis of stereotactic body radiotherapy, lobectomy and sublobar resection for stage I non-small cell lung cancer.

We applied two propensity score-based analyses to simultaneously compare three treatment modalities—stereotactic body radiotherapy (SBRT), lobectomy, or sublobar resection (SLR)—for stage I non-small cell lung cancer (NSCLC), with the aim of clarifying the average treatment effect (ATE) and formulating a risk-adapted approach to treatment selection. A retrospective review of 823 patients aged ≥65 years who underwent SBRT, lobectomy, or SLR for stage I NSCLC was conducted. The following two analyses using machine learning-based propensity scores were performed: (i) propensity score weighting (PSW) to assess the ATE in the entire cohort, and (ii) propensity score subclassification (PSS) to evaluate treatment effects of subgroups. PSW showed no significant difference in the 5-year overall survival (OS) between SBRT and SLR (60.0% vs 61.2%; P = 0.70) and significant difference between SBRT and lobectomy (60.0% vs 77.6%; P = 0.026). Local (LR) and distant recurrence (DR) rates were significantly lower in lobectomy than in SBRT, whereas there was no significant difference between SBRT and SLR. PSS identified four subgroups with different patient characteristics: lobectomy-oriented (5-year cumulative incidences of non-lung cancer death, 7.5%), SLR-oriented (14.2%), SBRT-oriented (23.8%) and treatment-neutral subgroups (16.1%). Each subgroup showed different survival trends regarding the three treatments. The ATE of SBRT was not significantly different from that of SLR, but it was inferior to lobectomy. Four subgroups with different risks of non-lung cancer death and different survival trends for each treatment were identified. These would help decision-making for patients with stage I NSCLC.

Factors affecting outcome in resected EGFR-mutated lung cancer

Introduction Long-term data on disease trajectory of EGFR-mutated early-stage non-small cell lung cancer (NSCLC) is still limited. This is relevant in the context of the recently approved introduction of adjuvant EGFR-targeting therapy, specifically osimertinib in resected stage II–III EGFR-mutated NSCLC. Methods Long-term data on patients with resected adenocarcinoma of the lung and known EGFR-status were analysed with focus on site of relapse and detailed cause of death. Patients resected in the period 2006 to 2018 were included. Results Of 503 patients (286 (57%) females, median age 67.3 years), 62 (12%) harboured an EGFR-mutation, 286 (57%) were in stage I. After a median follow-up of 8.0 years, 241 (48%) patients relapsed. Recurrence occurred in 30% and 53% of EGFR-positive stage IA and IB patients, respectively. Median overall survival was longer in EGFR-mutated versus non-mutated patients (128 versus 88 months). The recurrence rate, time to recurrence and rate of brain metastases was not different between EGFR-mutated and non-mutated groups. Median time from recurrence to death was longer in EGFR-mutated patients (31 months) compared with non-mutated patients (15 months). More patients without EGFR-mutation succumbed to non-cancer related death (18%) compared to patients with EGFR-mutations (8%). Conclusions The recurrence pattern in EGFR-mutated and non-mutated NSCLC-patients is similar and the rate is high in early stages. Time from recurrence to death and overall survival is longer in the EGFR-mutated group, due to lower risk of non-lung cancer deaths, and efficient treatment upon relapse.

Development and validation of a prognostic model for non-lung cancer death in elderly patients treated with stereotactic body radiotherapy for non-small cell lung cancer.

This study sought to develop and validate a prognostic model for non-lung cancer death (NLCD) in elderly patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Patients aged ≥65 diagnosed with NSCLC (Tis-4N0M0), tumor diameter ≤5cm and SBRT between 1998 and 2015 were retrospectively registered from two independent institutions. One institution was used for model development (arm D, 353 patients) and the other for validation (arm V, 401 patients). To identify risk factors for NLCD, multiple regression analysis on age, sex, performance status (PS), body mass index (BMI), Charlson comorbidity index (CCI), tumor diameter, histology and T-stage was performed on arm D. A score calculated using the regression coefficient was assigned to each factor and three risk groups were defined based on total score. Scores of 1.0 (BMI ≤18.4), 1.5 (age ≥ 5), 1.5 (PS ≥2), 2.5 (CCI 1 or 2) and 3 (CCI ≥3) were assigned, and risk groups were designated as low (total ≤ 3), intermediate (3.5 or 4) and high (≥4.5). The cumulative incidences of NLCD at 5years in the low, intermediate and high-risk groups were 6.8, 23 and 40% in arm D, and 23, 19 and 44% in arm V, respectively. The AUC index at 5years was 0.705 (arm D) and 0.632 (arm V). The proposed scoring system showed usefulness in predicting a high risk of NLCD in elderly patients treated with SBRT for NSCLC.

A Prognostic Model for Non-Lung Cancer Death in Elderly Patients Treated with Stereotactic Body Radiotherapy for Localized Non-Small Cell Lung Cancer

A Prognostic Model for Non-Lung Cancer Death in Elderly Patients Treated with Stereotactic Body Radiotherapy for Localized Non-Small Cell Lung Cancer

Impact of low skeletal muscle mass on non-lung cancer mortality after stereotactic body radiotherapy for patients with stage I non-small cell lung cancer.

The purpose of the present study was to retrospectively evaluate impact of pre-treatment skeletal muscle mass (SMM) on overall survival and non-lung cancer mortality after stereotactic body radiotherapy (SBRT) for patients with stage I non-small cell lung cancer (NSCLC). One-hundred and eighty-six patients whose abdominal CT before the treatment was available were enrolled into this study. The patients were divided into two groups of SMM according to gender-specific thresholds for unilateral psoas area. Operability was judged by the treating physician or thoracic surgeon after discussion in a multi-disciplinary tumor board. Patients with low SMM tended to be elderly and underweight in body mass index compared with the high SMM. Overall survival in patients with the low SMM tended to be worse than that in the high SMM (41.1% and 55.9% at 5 years, P = 0.115). Cumulative incidence of non-lung cancer death was significantly worse in the low SMM (31.3% at 5 years compared with 9.7% in the high SMM, P = 0.006). Multivariate analysis identified SMM and operability as significant factors for non-lung cancer mortality. Impact of SMM on lung cancer death was not significant. No difference in rate of severe treatment-related toxicity was observed between the SMM groups. Low SMM is a significant risk factor for non-lung cancer death, which might lead to worse overall survival, after SBRT for stage I NSCLC. However, the low SMM does not increase lung cancer death or severe treatment-related toxicity.

Lung cancer screening and the effects of competing causes of death in the ACRIN-NLST sub-study

Background: CT screening for lung cancer is limited to older heavy smokers, in whom the risk of death from all the complications of smoking is high relative to the unscreened population. We have shown that airflow limitation is a marker of premature death from all causes and affects about 35% of National Lung Screening Trial (NLST) participants. The role of competing causes of death, relative to lung function, has not been examined in the NLST. Using 10,054 subjects from the ACRIN-NLST sub-study, this study aimed to compare disease-specific mortality according to the presence of airflow limitation to better understand its relationship with dying from lung cancer and dying from other smoking-related diseases. Methods: We stratified 10,054 NLST participants according to their FEV1%predicted values and compared rates of lung cancer, lung cancer death, and death from other causes, after a mean of 6.4 years of follow-up. Findings: There were 699 deaths; 189 (27%) attributed to lung cancer, 166 (24%) to cardiovascular disease, 61 (9%) to respiratory disease, and 150 (21%) to other cancers. After stratification according to baseline FEV1%predicted, we found a strong inverse relationship between FEV1%predicted and developing lung cancer as previously shown. We also found a strong inverse relationship between FEV1%predicted and dying of lung cancer and dying of disease other than lung cancer. As the FEV1%predicted decreased, the effect on increasing death from lung cancer and non-lung cancer causes diverged, favouring greater non-lung cancer deaths. Interpretation: In a CT screening study, where smokers were followed for a mean of 6.4 years, worsening lung function was associated with a greater tendency to die of non-lung cancer causes. We suggest smokers at the greatest risk of lung cancer (worse lung function) are at greatest risk of dying of diseases other than lung cancer, creating an important competing cause of death effect in screening. Funding: This study was supported by funding from Johnson and Johnson and grants from the National Cancer Institute, NIH, USA. Conflicts of interest: RPY is a shareholder of Synergenz Bioscience, which holds patents for gene-based risk prediction in COPD and lung cancer. All other authors declare that they have no conflicts of interest.

Causes of death and competing risk analysis of the associated factors for non-small cell lung cancer using the Surveillance, Epidemiology, and End Results database.

To investigate the probability of death (POD) from any causes by time after diagnosis of non-small cell lung cancer (NSCLC) and the factors associated with survival for NSCLC patients. A total of 202,914 patients with NSCLC from 2004 to 2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The overall survival (OS) and lung cancer-specific survival (LCSS) were calculated and POD from any causes at different time periods after diagnosis was explored. The predictive factors for OS, LCSS and survival from non-lung cancer deaths were investigated using multivariate analysis with Cox proportional hazards regression and competing risk regression analysis. The 5- and 10-year OS were 20.4% and 11.5%, accordingly that for LCSS were 25.5% and 18.4%, respectively. Lung cancer contributed 88.3% (n=128,402) of the deaths. The POD from lung cancer decreased with time after diagnosis. In multivariate analysis, advanced age and advanced stage of NSCLC were associated with decreased OS and LCSS. Comparing to no surgery, any kind of resection conferred lower risk of death from lung cancer and higher risk of dying from non-lung cancer conditions except lobectomy or bilobectomy, which was associated with lower risk of death from both lung cancer and non-lung cancer conditions. Most of the patients with NSCLC died from lung cancer. Rational surveillance and treatment policies should be made for them. Early stage and lobectomy or bilobectomy were associated with improved OS and LCSS. It is reasonable to focus on early detection and optimal surgical treatment for NSCLC.

Ambient Air Pollution and Cancer Mortality in the Cancer Prevention Study II.

Background:The International Agency for Research on Cancer classified both outdoor air pollution and airborne particulate matter as carcinogenic to humans (Group 1) for lung cancer. There may be associations with cancer at other sites; however, the epidemiological evidence is limited.Objective:The aim of this study was to clarify whether ambient air pollution is associated with specific types of cancer other than lung cancer by examining associations of ambient air pollution with nonlung cancer death in the Cancer Prevention Study II (CPS-II).Methods:Analysis included 623,048 CPS-II participants who were followed for 22 y (1982–2004). Modeled estimates of particulate matter with aerodynamic diameter () (1999–2004), nitrogen dioxide () (2006), and ozone () (2002–2004) concentrations were linked to the participant residence at enrollment. Cox proportional hazards models were used to estimate associations per each fifth percentile–mean increment with cancer mortality at 29 anatomic sites, adjusted for individual and ecological covariates.Results:We observed 43,320 nonlung cancer deaths. was significantly positively associated with death from cancers of the kidney {adjusted hazard ratio (HR) per [95% confidence interval (CI): 1.03, 1.27]} and bladder [ (95% CI: 1.03, 1.23)]. was positively associated with colorectal cancer mortality [HR per (95% CI: 1.02, 1.10). The results were similar in two-pollutant models including and and in three-pollutant models with . We observed no statistically significant positive associations with death from other types of cancer based on results from adjusted models.Conclusions:The results from this large prospective study suggest that ambient air pollution was not associated with death from most nonlung cancers, but associations with kidney, bladder, and colorectal cancer death warrant further investigation. https://doi.org/10.1289/EHP1249

ED08.03 Adjuvant Chemotherapy of Completely Resected

ED08.03 Adjuvant Chemotherapy of Completely Resected

Lung Cancer Prognosis in Elderly Solid Organ Transplant Recipients.

Treatment-related immunosuppression in organ transplant recipients has been linked to increased incidence and risk of progression for several malignancies. Using a population-based cancer cohort, we evaluated whether organ transplantation was associated with worse prognosis in elderly patients with non-small cell lung cancer (NSCLC). Using the Surveillance, Epidemiology, and End Results Registry linked to Medicare claims, we identified 597 patients aged 65 years or older with NSCLC who had received organ transplants (kidney, liver, heart, or lung) before cancer diagnosis. These cases were compared to 114,410 untransplanted NSCLC patients. We compared overall survival (OS) by transplant status using Kaplan-Meier methods and Cox regression. To account for an increased risk of non-lung cancer death (competing risks) in transplant recipients, we used conditional probability function (CPF) analyses. Multiple CPF regression was used to evaluate lung cancer prognosis in organ transplant recipients while adjusting for confounders. Transplant recipients presented with earlier stage lung cancer (P = 0.002) and were more likely to have squamous cell carcinoma (P = 0.02). Cox regression analyses showed that having received a non-lung organ transplant was associated with poorer OS (P < 0.05), whereas lung transplantation was associated with no difference in prognosis. After accounting for competing risks of death using CPF regression, no differences in cancer-specific survival were noted between non-lung transplant recipients and nontransplant patients. Non-lung solid organ transplant recipients who developed NSCLC had worse OS than nontransplant recipients due to competing risks of death. Lung cancer-specific survival analyses suggest that NSCLC tumor behavior may be similar in these 2 groups.

Prognosis in HIV-infected patients with non-small cell lung cancer

Background:We conducted a population-based study to evaluate whether non-small cell lung cancer (NSCLC) prognosis was worse in HIV-infected compared with HIV-uninfected patients.Methods:Using the Surveillance, Epidemiology and End Results (SEER) registry linked to Medicare claims, we identified 267 HIV-infected patients and 1428 similar controls with no evidence of HIV diagnosed with NSCLC between 1996 and 2007. We used conditional probability function (CPF) analyses to compare survival by HIV status accounting for an increased risk of non-lung cancer death (competing risks) in HIV-infected patients. We used multivariable CPF regression to evaluate lung cancer prognosis by HIV status adjusted for confounders.Results:Stage at presentation and use of stage-appropriate lung cancer treatment did not differ by HIV status. Median survival was 6 months (95% confidence interval (CI): 5–8 months) among HIV-infected NSCLC patients compared with 20 months (95% CI: 17–23 months) in patients without evidence of HIV. Multivariable CPF regression showed that HIV was associated with a greater risk of lung cancer-specific death after controlling for confounders and competing risks.Conclusion:NSCLC patients with HIV have a poorer prognosis than patients without evidence of HIV. NSCLC may exhibit more aggressive behaviour in the setting of HIV.

Long-Term Results of the International Adjuvant Lung Cancer Trial Evaluating Adjuvant Cisplatin-Based Chemotherapy in Resected Lung Cancer

PURPOSE Based on 5-year or shorter-term follow-up data in recent randomized trials, adjuvant cisplatin-based chemotherapy is now generally recommended after complete surgical resection for patients with non-small-cell lung cancer (NSCLC). We evaluated the results of the International Adjuvant Lung Cancer Trial study with three additional years of follow-up. PATIENTS AND METHODS Patients with completely resected NSCLC were randomly assigned to three or four cycles of cisplatin-based chemotherapy or to observation. Cox models were used to evaluate treatment effect according to follow-up duration. Results The trial included 1,867 patients with a median follow-up of 7.5 years. Results showed a beneficial effect of adjuvant chemotherapy on overall survival (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.02; P = .10) and on disease-free survival (HR, 0.88; 95% CI, 0.78 to 0.98; P = .02). However, there was a significant difference between the results of overall survival before and after 5 years of follow-up (HR, 0.86; 95% CI, 0.76 to 0.97; P = .01 v HR, 1.45; 95% CI, 1.02 to 2.07; P = .04) with P = .006 for interaction. Similar results were observed for disease-free survival. The analysis of non-lung cancer deaths for the whole period showed an HR of 1.34 (95% CI, 0.99 to 1.81; P = .06). CONCLUSION These results confirm the significant efficacy of adjuvant chemotherapy at 5 years. The difference in results beyond 5 years of follow-up underscores the need for the long-term follow-up of other adjuvant lung cancer trials and for a better identification of patients deriving long-term benefit from adjuvant chemotherapy.

Male tobacco smoke load and non-lung cancer mortality associations in Massachusetts

BackgroundDifferent methods exist to estimate smoking attributable cancer mortality rates (Peto and Ezzati methods, as examples). However, the smoking attributable estimates using these methods cannot be generalized to all population sub-groups. A simpler method has recently been developed that can be adapted and applied to different population sub-groups. This study assessed cumulative tobacco smoke damage (smoke load)/non-lung cancer mortality associations across time from 1979 to 2003 among all Massachusetts males and ages 30–74 years, using this novel methodology.MethodsAnnual lung cancer death rates were used as smoke load bio-indices, and age-adjusted lung/all other (non-lung) cancer death rates were analyzed with linear regression approach. Non-lung cancer death rates include all cancer deaths excluding lung. Smoking-attributable-fractions (SAFs) for the latest period (year 2003) were estimated as: 1-(estimated unexposed cancer death rate/observed rate).ResultsMale lung and non-lung cancer death rates have declined steadily since 1992. Lung and non-lung cancer death rates were tightly and steeply associated across years. The slopes of the associations analyzed were 1.69 (95% confidence interval (CI) 1.35–2.04, r = 0.90), and 1.36 (CI 1.14–1.58, r = 0.94) without detected autocorrelation (Durbin-Watson statistic = 1.8). The lung/non-lung cancer death rate associations suggest that all-sites cancer death rate SAFs in year 2003 were 73% (Sensitivity Range [SR] 61–82%) for all ages and 74% (SR 61–82%) for ages 30–74 years.ConclusionThe strong lung/non-lung cancer death rate associations suggest that tobacco smoke load may be responsible for most prematurely fatal cancers at both lung and non-lung sites. The present method estimates are greater than the earlier estimates. Therefore, tobacco control may reduce cancer death rates more than previously noted.

Long-term results of the International Adjuvant Lung Cancer Trial (IALT) evaluating adjuvant cisplatin-based chemotherapy in resected non-small cell lung cancer (NSCLC)

7507 Background: Based on 4 to 5-year follow-up data in recent randomized trials, adjuvant cisplatin-based chemotherapy is now generally recommended after complete surgical resection for patients with non-small-cell lung cancer. We evaluated the results of the IALT study, initially reported with a 4.7 year follow-up (ASCO 2003), with three additional years of follow-up. Methods: Patients with completely resected NSCLC were randomly assigned to three or four cycles of cisplatin-based chemotherapy or to observation. The dose of cisplatin (total 300–400 mg/m2), the drug to be combined with cisplatin (etoposide or vinorelbine or vindesine or vinblastin) and the use of adjuvant radiotherapy were predefined at each center. Cox models were used to evaluate treatment effect according to follow-up duration. Results: Between February 1995 and December 2000, there were 1,867 patients included. Median follow-up was 7.5 years at the cut-off date of September 1, 2005. The survival status was known for 1,807 patients. Results showed a beneficial effect of adjuvant chemotherapy on overall survival (HR: 0.91; 95% CI: 0.81–1.02, p= 0.10) and on disease-free survival (HR: 0.88; 95% CI: 0.78–0.98, p= 0.02). However, there was a significant difference between the results of overall survival before and after 5 years (HR: 0.86; CI: 0.76–0.97, p = 0.01 versus HR: 1.45; CI: 1.02–2.07, p =0.04); p-value for interaction was 0.006. Disease-free survival benefit was also different according to the follow-up duration (p-value for interaction: 0.04; global, first 5 years, HR=0.85, p=0.006; after five year, HR=1.33, p=0.16). The analysis of non-lung cancer deaths for the whole period showed a HR of 1.34 (CI: 0.99–1.81; p=0.06). Conclusions: These results confirm the efficacy of chemotherapy for the first 5 years after surgery. The difference in results between less than and more than 5 years of follow-up may suggest possible late adjuvant chemotherapy-related over-mortality. This potential effect underscores the need for the long-term follow-up of adjuvant lung cancer trials in order to evaluate results in terms of treatment benefits and long-term hazards. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline

Age-related macular degeneration and cancer mortality in the atherosclerosis risk in communities study.

To examine the prospective association of early age-related macular degeneration (AMD) with cancer mortality. A population-based cohort study of 10 029 persons aged 49 to 73 years free of cancer. The AMD signs were evaluated from retinal photographs taken in 1993 through 1995. Cancer mortality was determined from death records. There were 464 cases of early AMD. Over 10 years, there were 234 cancer deaths (71 lung cancer deaths). After controlling for age, sex, race, field center, education, smoking status, pack-years of smoking, body mass index (calculated as weight in kilograms divided by height in meters squared), and diabetes mellitus, early AMD was associated with cancer mortality (rate ratio [RR], 1.68; 95% confidence interval [CI], 1.03-2.73). This association was overall stronger in African American individuals (RR, 3.93; 95% CI, 1.67-9.22) than white individuals (RR, 1.28; 95% CI, 0.71-2.32) and for lung cancer deaths (RR, 2.14; 95% CI, 0.97-4.72) than non-lung cancer deaths (RR, 1.50; 95% CI, 0.81-2.78). In African American individuals, early AMD was associated with a 5-fold higher risk of lung cancer deaths (RR, 5.28; 95% CI, 1.52-18.40). Middle-aged African American individuals with early AMD may be at increased risk of dying of cancer, particularly lung cancer. This association was not present in white individuals and needs confirmation in other studies.

Male Tobacco Smoke Load and Non-Lung Cancer Mortality Associations in Massachusetts

We assessed cumulative tobacco smoke cumulative damage (smoke load)/cancer mortality associations across time from 1979 to 2003 among Massachusetts males overall and at ages 30–74. Annual lung cancer death rates were used as smoke load bio-indices, and lung/all other (non-lung) cancer death age-adjusted rate linear regressions were run for analysis to calculate smoking-attributable fractions (SAF). Death rate SAFs are equal to: 1- estimated unexposed rate/observed rate. Fairly steady all age and ages 30–74 years lung and non-lung cancer death rate declines occurred since 1992. Non-lung cancer death rates were tightly and steeply associated with smoke load across year. The slopes of those associations are 1.69 (95% confidence interval (CI) 1.35–2.04, r=0.90, or 1.36 (CI 1.02–1.96, r=0.95) when adjusted for possible autocorrelation) and 1.36 (CI 1.14–1.58, r=0.94) without detected autocorrelation (Durbin-Watson statistic = 1.8), respectively. The lung/non-lung cancer death rate associations suggest 2003 all-sites cancer death rate SAFs of 73% (SR 61–82%) at all ages and 74% (SR 61–82%) at ages 30–74. The observed strong lung/non-lung cancer death rate associations suggest that tobacco smoke load may cause most prematurely fatal cancers at both lung and non-lung sites in Massachusetts male populations. Therefore, tobacco control may greatly reduce the overall cancer death rates.