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Objectives: Neutropenia is associated with the risk of life-threatening infections, chemotherapy dose reductions and delays that may compromise outcomes. This analysis was conducted to develop a prediction model for chemotherapy-induced severe neutropenia in lung cancer., Materials and Methods: Individual patient data from existing cooperative group phase II/III trials of stages III/IV non-small cell lung cancer or extensive small-cell lung cancer were included. The data were split into training and testing sets. In order to enhance the prediction accuracy and the reliability of the prediction model, lasso method was used for both variable selection and regularization on the training set. The selected variables was fit to a logistic model to obtain regression coefficients. The performance of the final prediction model was evaluated by the area under the ROC curve in both training and testing sets., Results: The dataset was randomly separated into training [7606 (67 %) patients] and testing [3746 (33 %) patients] sets. The final model included: age (>65 years), gender (male), weight (kg), BMI, insurance status (yes/unknown), stage (IIIB/IV/ESSCLC), number of metastatic sites (1, 2 or ≥3), individual drugs (gemcitabine, taxanes), number of chemotherapy agents (2 or ≥3), planned use of growth factors, associated radiation therapy, previous therapy (chemotherapy, radiation, surgery), duration of planned treatment, pleural effusion (yes/unknown), performance status (1, ≥2) and presence of symptoms (yes/unknown)., Conclusions: We have developed a relatively simple model with routinely available pre-treatment variables, to predict for neutropenia. This model should be independently validated prospectively., Competing Interests: Declaration of Competing Interest Dr. Wong has reported a conflict of interest outside of the submitted work (immediate family member is an employee of Genentech with stock ownership). The remaining authors have no conflicts to report., (Published by Elsevier B.V.)

Treatment options for locally advanced squamous cell carcinoma of the head and neck (SCCHN) include either surgical resection followed by radiation or chemoradiation, or definitive chemoradiation for which single-agent cisplatin is the best studied and established. The increasing understanding of the molecular biology of SCCHN has led to an interest in the development of targeted therapies. The epidermal growth factor receptor (EGFR) is over-expressed in nearly 80-90% of cases of SCCHN and correlates with poor prognosis and resistance to radiation. Preclinical evidence showed that blocking EGFR restores radiation sensitivity and enhances cytotoxicity. This finding led to clinical trials evaluating this class of agents and the approval of cetuximab in combination with radiation for the treatment of locally advanced SCCHN. This review is focused on the anti-EGFR monoclonal antibodies and their role either with radiotherapy or chemoradiation in unresectable LA SCCHN., (Published by Elsevier Ireland Ltd.)

Purpose: Prognostic models have been proposed to predict survival for non-small-cell lung cancer (NSCLC). It is important to evaluate whether these models perform better than performance status (PS) alone in stage- and age-specific subgroups., Patients and Methods: The validation cohort included 2060 stage I and 1611 stage IV NSCLC patients from 23CALGB studies. For stage I, Blanchon (B), Chansky (C) and Gail (G) models were evaluated along with the PS only model. For stage IV, Blanchon (B) and Mandrekar (M) models were compared with the PS only model. The c-index was used to assess the concordance between survival and risk scores. The c-index difference (c-difference) and the integrated discrimination improvement (IDI) were used to determine the improvement of these models over the PS only model., Results: For stage I, B and PS have better survival separation. The c-index for B, PS, C and G are 0.61, 0.58, 0.57 and 0.52, respectively, and B performs significantly better than PS with c-difference=0.034. For stage IV, B, M and PS have c-index 0.61, 0.64 and 0.60, respectively; B and M perform significantly better than PS with c-difference=0.015 and 0.033, respectively., Conclusion: Although some prognostic models have better concordance with survival than the PS only model, the absolute improvement is small. More accurate prognostic models should be developed; the inclusion of tumor genetic variants may improve prognostic models., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Outcomes following surgery are better than following radiation therapy (RT), for stage I NSCLC. Whether this is due to selection of healthier patients for surgery is unclear. This study was undertaken to compare outcomes between surgical patients and patients who were surgical candidates but did not receive surgery., Methods: Data of patients with stage I NSCLC between 1988 and 2007, included in the SEER database were analyzed. Overall survival (OS) was examined by treatment type (surgery only, radiation only, surgery and radiation, and no treatment). OS was compared between RT patients who refused surgery and those not fit for surgery. Cox proportional hazards model was used to compare outcomes by treatment type., Results: Data from 8579 patients with stage I NSCLC during 1988-2007 were analyzed. Use of RT alone increased during the study period. An increasing proportion of patients with stage I lung cancer chose to have no treatment. On multivariate analysis, OS was better among patients who had surgery. There was a 56% improvement in survival among patients who had surgery compared to fit patients who refused surgery (HR 0.437, 95% CI 0.301-0.632). Patients who refused surgery had a better OS than those who were not fit for surgery (log-rank p = 0.01). Patients who received RT alone or no treatment had a significant improvement in five-year OS during the latter part of the study period (1998-2002 vs. 1988-1992)., Conclusions: In medically fit patients, outcomes following surgery are better than those following conventional radiation. Hence surgery should be chosen over conventional radiation, whenever possible. Outcomes following RT show an improvement over time reflecting improvement in radiation techniques., (Published by Elsevier Ireland Ltd.)

Cancer is a disease of the elderly with the majority of new diagnoses and deaths from cancer occurring in persons greater than 65 years of age. A major goal of cancer therapy, in the elderly is the preservation of functional independence and quality of life. The advent of targeted therapies has raised the hope that older patients with cancer could be treated as effectively as younger patients and without added toxicities. However, caution must be exercised while addressing the use of these therapies in the elderly population and only after taking into consideration the risks, benefits and prognosis of patients on an individual basis. This article reviews the current literature on the efficacy, cost-effectiveness and toxicity of the currently approved targeted agents in the elderly population., (Published by Elsevier Ireland Ltd.)

Background: Previous meta-analysis on three drugs combination for treatment of advanced non-small cell lung cancer (NSCLC) did not demonstrate an improvement in survival, however many of the trials included in this meta-analysis used older and less effective cytotoxic drugs. We conducted this analysis to compare the relative efficacy of third generation triplet therapy with that of standard double therapy in the treatment of advanced NSCLC., Methods: A MEDLINE search was performed using the search terms "lung cancer" and "randomized trials". Trials not utilizing a third generation cytotoxic chemotherapeutic agent (paclitaxel, docetaxel, vinorelbine, gemcitabine) were excluded. Pooled odds ratios (OR) for the objective response and toxicity rates were calculated using the Mantel-Haenszel estimate. Pooled median ratios for median survival were calculated using the weighted sum of the log-ratio of median ratios of individual study., Results: We analyzed six randomized comparative trials involving 1932 patients. Patients receiving triplet therapy had a significantly higher response rate (OR: 1.33; 95% CI, 1.50-2.23; P<0.001). Incidence of grade III/IV hematological toxicity was higher with triplet therapy. Non-hematological toxicities, with the exception of neuropathy, were similar. Median survival of triplet therapy was not significantly different from doublet (MR: 1.10; 95% CI: 0.91-1.35; P=0.059)., Conclusions: Triplet therapy with third generation cytotoxic drugs is associated with higher tumor response rate at the expense of increased toxicity. Although triplet therapy had a better overall survival compared to doublet therapy, this did not reach statistical significance.

Background: Risk factors for development of lung cancer include a family history of the disease. The effect of family history on lung cancer outcomes is unknown. A study was conducted to investigate this., Methods: The medical records of all patients with lung cancer seen in an academic medical oncology lung cancer clinic between 1999 and 2006 were reviewed for outcomes and family history of lung cancer. chi(2)-test and Wilcoxon test were used for univariate comparisons, while Cox Proportional Hazards regression analysis was used to evaluate the adjusted risk of death. Univariate probability of survival was computed using Kaplan-Meier estimate and compared using the log-rank test., Results: Of the 560 patients evaluated, 289 (51%) were male and 519 (93%) had a smoking history. Of the 148 patients (26%) with a family history of lung cancer, 115 had an affected first-degree relative. No association between family history and histology or stage at diagnosis was detected. Median survival in patients with a family history of lung cancer was 53 months compared to 58 months in patients without such a history (p=0.06). Patients with a positive family history had an adjusted relative risk of death of 1.65 (95% CI: 1.07-2.56; p=0.02) compared to those without a family history. This risk was especially increased in those with an affected first-degree relative (RR: 1.72; 95% CI: 1.08-2.75, p=0.02)., Conclusions: Lung cancer patients with a first-degree relative with lung cancer have a poorer outcome than those without such a history.

Co-morbidity has a major impact on survival in early and late-stage lung carcinoma. Patients maintained on dialysis are potentially at increased risk of cancer. However, since very few studies have examined the clinical course of lung cancer in patients with chronic kidney disease (CKD), we felt it was important to study the course of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) in this patient population. We performed a retrospective chart review of patients diagnosed with lung cancer and co-existent CKD. 107 patients (101 males and six females), with a mean age at diagnosis of 69 years (range: 39-86 years) were included in our study. Of these, 17 (15.9%) patients had SCLC while 87 (81.3%) had NSCLC. Dyspnea, weight loss, and chest pain were the most common symptoms at presentation in our patient population occurring in 25, 20, and 15% of patients, respectively. The median survival of all the patients in the study was 10 months (range: 0-116 months). Patients with SCLC had a median survival of 7 months. Patients with NSCLC had a median survival of 10 months. We found that the clinical course and survival in patients with lung cancer and CKD appear to be comparable to that of patients with lung cancer, but without kidney dysfunction. Hence though treatment of lung cancer does need to be individualized in the setting of CKD, it should not dissuade the clinician from treating the malignancy.

Patients with CLL have an excess risk of developing second primary malignancies. The etiology of this excess risk is unclear, and has been thought to be related to smoking. HER-2/neu overexpression has evolved as a prognostic/predictive factor in some solid tumors. We reviewed our experience with non-smokers who had CLL and subsequently developed lung carcinoma, in an effort to better understand the clinical course of these patients, and to evaluate the role of HER-2/neu overexpression. We reviewed the records of all patients who had a diagnosis of both CLL and lung carcinoma between 1986 and 2000. HER-2/neu overexpression was estimated by immunohistochemistry (IHC) using the Hercep test (DAKO). An IHC score of 2+ or greater was considered positive. Overall survival was calculated from the date of diagnosis of lung carcinoma by the Kaplan-Meier product limit method. Fourteen non-smokers in whom a diagnosis of CLL was made at least 6 months prior to the diagnosis of lung carcinoma were identified. The median age for diagnosis of CLL in this group was 67 years while that for lung carcinoma was 70 years. The lung carcinomas included 10 non-small cell (NSCLC) and four small cell (SCLC) carcinomas. Nine specimens (six NSCLC and three SCLC) showed HER-2/neu overexpression. Interestingly, 90% of patients with advanced stage cancer (stage IIIB/IV NSCLC or extensive SCLC) overexpressed HER-2/neu. The presence of CLL did not alter outcome in patients with early stage lung cancer. However, after adjustment for age and performance status, patients with advanced stage NSCLC and CLL had a worse than expected outcome. HER-2/neu overexpression (independent of smoking) may be involved in the development/progression of lung cancer in patients with CLL, and has an associated worse outcome. It is appropriate to consider heightened surveillance of CLL patients for lung carcinoma.