Role of Comorbidity on Survival after Radiotherapy and Chemotherapy for Nonsurgically Treated Lung Cancer

BACKGROUND: Comorbidity, such as diseases of the cardiovascular, pulmonary, and other systems, may influence prognosis in lung cancer and complicate its treatment. The performance status of patients, which is a known prognostic marker, may also be influenced by comorbidity. Due to the close link between tobacco smoking and lung cancer, and because lung cancer is often diagnosed in advanced ages (median age at diagnosis in Denmark is 70 years), comorbidity is present in a large proportion of lung cancer patients. METHODS: Patients with any stage lung cancer who did not have surgical treatment were identified in the Danish Lung Cancer Registry. Danish Lung Cancer Registry collects data from clinical departments, the Danish Cancer Registry, Danish National Patient Registry, and the Central Population Register. A total of 20,552 patients diagnosed with lung cancer in 2005 to 2011 were identified. Comorbidity data were extracted from the Danish National Patient Registry, which is a register of all in- and outpatient visits to hospitals in Denmark. By record linkage, lung cancer patients who had previously been diagnosed with comorbid conditions were assigned a Charlson comorbidity index. Initial cancer treatment was categorized as chemotherapy, chemoradiation, radiotherapy, or no therapy. Data on Charlson comorbidity index, performance status, age, sex, stage, pulmonary function (forced expiratory volume in 1 second), histology, and type of initial treatment (if any) were included in univariable and multivariable Cox proportional hazard analyses. RESULTS: Treatment rates for chemotherapy and chemoradiation declined with increasing comorbidity and in particular increasing age. Women received treatment more often than men. In a univariable analysis of all patients combined, stage, performance status, age, sex, lung function, and comorbidity were all associated with survival. Apart from excess mortality among patients with unspecified histological subtypes (hazard ratio), there was no clear difference between the specified subtypes. When adjusting for the other factors, particularly age, sex, performance status, and stage proved to be robust while risk estimates for comorbidity were attenuated somewhat. When grouped by the three types of cancer treatment or no treatment, there was no influence of comorbidity on radiation therapy and modest influence on survival after chemotherapy and chemoradiation. In contrast, age remained a strong negative prognosticator after multivariate adjustment as did stage and performance status. CONCLUSION: Comorbidity has a limited effect on survival and only for patients treated with chemotherapy. It is rather the performance of the patient at diagnosis than the medical history that prognosticates survival in this patient group

<i>AHRR </i>(cg05575921) methylation extent of leukocyte DNA and lung cancer survival

<div><p>Background</p><p>Prior studies have shown that <i>AHRR</i> (cg05575921) hypomethylation may be a marker of smoking, lung cancer risk and potentially lung cancer survival (in some lung cancer subtypes). It is unknown if <i>AHRR</i> (cg05575921) hypomethylation is associated with reduced survival among lung cancer patients.</p><p>Methods</p><p>In bisulfite treated leukocyte DNA from 465 lung cancer patients from the Copenhagen prospective lung cancer study, we measured <i>AHRR</i> (cg05575921) methylation. 380 died during max follow-up of 4.4 years. Cox proportional hazard models were used to analyze survival as a function of <i>AHRR</i> (cg05575921) methylation.</p><p>Results</p><p>We observed the expected inverse correlation between cumulative smoking and <i>AHRR</i> methylation, as methylation (%) decreased (Coefficient -0.03; 95% confidence interval, -0.04- -0.02, p = 8.6x10^-15) for every pack-year. Cumulative smoking > 60 pack-years was associated with reduced survival (hazard ratio and 95% confidence interval 1.48; 1.05–2.09), however, <i>AHRR</i> (cg05575921) methylation was not associated with survival when adjusted for sex, body mass index, smoking status, ethnicity, performance status, TNM Classification, and histology type of lung cancer.</p><p>Conclusion</p><p><i>AHRR</i> (cg05575921) methylation is linked to smoking but does not provide independent prognostic information in lung cancer patients.</p></div

Survival of patients with small cell lung cancer undergoing lung resection in England, 1998–2009

Introduction: Chemotherapy or chemoradiotherapy is the recommended treatment for small cell lung cancer (SCLC), except in stage I disease where clinical guidelines state there may be a role for surgery based on favourable outcomes in case series. Evidence supporting adjuvant chemotherapy in resected SCLC is limited but this is widely offered. Methods: Data on 359 873 patients who were diagnosed with a first primary lung cancer in England between 1998 and 2009 were grouped according to histology (SCLC or non-SCLC (NSCLC)) and whether they underwent a surgical resection. We explored their survival using Kaplan-Meier analysis and Cox regression, adjusting for age, sex, comorbidity and socioeconomic status. Results: The survival of 465 patients with resected SCLC was lower than patients with resected NSCLC (5-year survival 31% and 45%, respectively), but much higher than patients of either group who were not resected (3%). The difference between resected SCLC and NSCLC diminished with time after surgery. Survival was superior for the subgroup of 198 'elective' SCLC cases where the diagnosis was most likely known before resection than for the subgroup of 267 'incidental' cases where the SCLC diagnosis was likely to have been made after resection. Conclusions: These data serve as a natural experiment testing the survival after surgical management of SCLC according to NSCLC principles. Patients with SCLC treated surgically for early stage disease may have survival outcomes that approach those of NSCLC, supporting the emerging clinical practice of offering surgical resection to selected patients with SCLC

Analysis of patient-reported outcomes from the LUME-Lung 1 trial: A randomised, double-blind, placebo-controlled, Phase III study of second-line nintedanib in patients with advanced non-small cell lung cancer

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Durable Clinical Responses and Long-Term Follow-Up of Stage III–IV Non-Small-Cell Lung Cancer (NSCLC) Patients Treated With IDO Peptide Vaccine in a Phase I Study—A Brief Research Report

Background: Long-term follow-up on a clinical trial of 15 stage III-IV NSCLC patients treated with an Indoleamine 2,3-Dioxygenase (IDO) peptide vaccine (NCT01219348).Methods: Fifteen HLA-A2-positive patients with stable stage III-IV NSCLC after standard chemotherapy were treated with subcutaneous vaccinations (100 μg IDO5 peptide, sequence ALLEIASCL, formulated in 900 μl Montanide) biweekly for 2.5 months and thereafter monthly until progression or up to 5 years. Here we report long-term clinical follow-up, toxicity and immunity.Results: Three of 15 patients are still alive corresponding to a 6-year overall survival of 20 %. Two patients continued monthly vaccinations for 5 years (56 vaccines). One of the two patients developed a partial response (PR) of target lesions in the liver 15 months after the first vaccine and has remained in PR ever since. The other patient had a solitary distant metastasis in a lymph node in retroperitoneum at baseline which normalized during treatment. All following evaluation scans during the treatment have been tumor free. The vaccine was well tolerated for all 5 years with no long-term toxicities registered. The third long-term surviving patient discontinued vaccinations after 11 months due to disease progression. Flow cytometry analyses of PBMCs from the two long-term responders demonstrated stable CD8+ and CD4+ T-cell populations during treatment. In addition, presence of IDO-specific T-cells was detected by IFN-γ Elispot in both patients at several time points during treatment.Conclusion: IDO peptide vaccination was well tolerated for administration up to 5years. Two of 15 patients are long-term responders with ongoing clinical response 6 years after 1st vaccination

Protein-altering germline mutations implicate novel genes related to lung cancer development

Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.82, P = 1.18 × 10−15) and replication (adjusted OR = 2.93, P = 2.22 × 10−3) that is more pronounced in females (adjusted OR = 6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR = 2.61, P = 7.98 × 10−22) and replication datasets (adjusted OR = 1.55, P = 0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk