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Small cell lung cancer: where do we go from here?

ABSTRACT: Small cell lung cancer (SCLC) is an aggressive disease that accounts for approximately 14% of all lung cancers. In the United States, approximately 31,000 patients are diagnosed annually with SCLC. Despite numerous clinical trials, including at least 40 phase 3 trials since the 1970s, systemic treatment for patients with SCLC has not changed significantly in the past several decades. Consequently, the 5-year survival rate remains low at <7% overall, and most patients survive for only 1 year or less after diagnosis. Unlike nonsmall cell lung cancer (NSCLC), in which major advances have been made using targeted therapies, there are still no approved targeted drugs for SCLC. Significant barriers to progress in SCLC include 1) a lack of early detection modalities, 2) limited tumor tissue for translational research (eg, molecular profiling of DNA, RNA, and/or protein alterations) because of small diagnostic biopsies and the rare use of surgical resection in standard treatment, and 3) rapid disease progression with poor understanding of the mechanisms contributing to therapeutic resistance. In this report, the authors review the current state of SCLC treatment, recent advances in current understanding of the underlying disease biology, and opportunities to advance translational research and therapeutic approaches for patients with SCLC.

SUBMITTER: Byers LA

PROVIDER: S-EPMC5497465 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Small cell lung cancer: where do we go from here?

Byers Lauren Averett LA Rudin Charles M CM

Cancer 20141021 5

Small cell lung cancer (SCLC) is an aggressive disease that accounts for approximately 14% of all lung cancers. In the United States, approximately 31,000 patients are diagnosed annually with SCLC. Despite numerous clinical trials, including at least 40 phase 3 trials since the 1970s, systemic treatment for patients with SCLC has not changed significantly in the past several decades. Consequently, the 5-year survival rate remains low at <7% overall, and most patients survive for only 1 year or l ...[more]

PMID: 25336398

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Project description:In the US, there are ~250,000 new lung cancer diagnoses and ~130,000 deaths per year, and worldwide there are an estimated 1.6 million deaths per year from this deadly disease. Lung cancer is the most common cause of cancer death worldwide, and it accounts for roughly a quarter of all cancer deaths in the US. Non-small cell lung cancer (NSCLC) represents 80-85% of these cases. Due to an enormous tobacco cessation effort, NSCLC rates in the US are decreasing, and the implementation of lung cancer screening guidelines and other programs have resulted in a higher percentage of patients presenting with potentially curable locoregional disease, instead of distant disease. Exciting developments in molecular targeted therapy and immunotherapy have resulted in dramatic improvement in patients' survival, in combination with new surgical, pathological, radiographical, and radiation techniques. Concurrent platinum-based doublet chemoradiation therapy followed by immunotherapy has set the benchmark for survival in these patients. However, despite these advances, ~50% of patients diagnosed with locally advanced NSCLC (LA-NSCLC) survive long-term. In patients with local and/or locoregional disease, chemoradiation is a critical component of curative therapy. However, there remains a significant clinical gap in improving the efficacy of this combined therapy, and the development of non-overlapping treatment approaches to improve treatment outcomes is needed. One potential promising avenue of research is targeting cancer metabolism. In this review, we will initially provide a brief general overview of tumor metabolism as it relates to therapeutic targeting. We will then focus on the intersection of metabolism on both oxidative stress and anti-tumor immunity. This will be followed by discussion of both tumor- and patient-specific opportunities for metabolic targeting in NSCLC. We will then conclude with a discussion of additional agents currently in development that may be advantageous to combine with chemo-immuno-radiation in NSCLC.

Project description:The National Lung Screening Trial (NLST) demonstrated that low dose computed tomography (LDCT) screening could reduce lung cancer mortality by 20% in high-risk individuals. The United States Preventive Services Task Force (USPSTF) and Centers for Medicare and Medicaid Services (CMS) approved lung cancer screening. The NLST, USPSTF and CMS define high risk as smoking ?30 pack-years, smoking within the past 15 years, and being ages 55-74, 55-80 or 55-77. Retrospective studies demonstrated selection using model-estimated risk is superior to NLST-like criteria: higher sensitivity and positive predictive value (PPV), more deaths averted and higher cost-effectiveness. Projects are underway that may additionally support use of risk to determine eligibility. Firstly, the International Lung Screen Trial (ILST) is prospectively enrolling 4,000 individuals for screening if individuals have PLCOm2012 model risk ?1.5% or are USPSTF+ve. Six-year follow-up will allow comparisons. Interim results support the risk approach. Secondly, Cancer Care Ontario started the Lung Cancer Screening Pilot for People at High Risk in order to find optimal design for province-wide programmatic screening. They are enrolling 3,000 individuals to screening based on PLCOm2012 risk ?2%. Some hesitation to recommend screening selection based on model risk comes from the observation that selected individuals are older, have more comorbidities, are expected to have fewer life years and quality-adjusted life years (QALY) and are more likely to die from competing causes. We show that 25.6% of NLST eligible smokers are at low risk (6-year lung cancer incidence proportion =0.008). This group will not benefit from screening but has lower age, fewer comorbidities and fewer competing causes of death. When they are excluded from the NLST+ve group, age, comorbidity count and competing causes of death are similar to those in the PLCOm2012+ve group. In some jurisdictions, model-based lung cancer screening selection needs to take into consideration the elevated risk in blacks and indigenous peoples.

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Small cell lung cancer: where do we go from here?

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Small cell lung cancer: where do we go from here?

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