GRACE :: Lung Cancer

lung cancer histology

Redefining Lung Cancer: Seeing the Patterns from Individual Colors

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This month’s Journal of Thoracic Oncology includes a landmark article, written by a multidisciplinary group of lung cancer experts that features several of the leading lung cancer pathologists in the world, that is attempting to do no less than present a new categorization of the pathology of lung cancer, focusing primarily on adenocarcinomas, but also touching on other lung cancer subgroups. Among the concepts included is a proposal that the term bronchioloalveolar carcinoma (BAC) be discontinued and recategorized based on whether patients have any invasive component to their lung cancer or not, and whether is is mucinous or non-mucinous. As significant as it is to redefine an entire disease of BAC, the concepts it introduces have implications that actually lead to a fundamentally different way of thinking about lung cancer, or at least NSCLC.

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Rising to the Challenge of Narrowed Patient Subgroups

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Only a few years ago, oncologists saw lung cancer as divisible into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with very little relevance to any division beyond that point. We knew that patients with NSCLC could be categorized into having adenocarcinoma (including the subset of that larger group, bronchioloalveolar carcinoma (BAC), squamous, large cell and large cell neuroendocrine carcinoma, and into those with and without a significant smoking history, and other demographic variables, but they weren’t a primary focus when we didn’t perceive that these differences had clinical significance in our treatment recommendations. And at that time, most people received remarkably similar treatments, with first line trials in advanced NSCLC incredibly commonly designed as carbo/Taxol (paclitaxel) +/- new drug, and second line trials of Taxotere (docetaxel) +/- new drug, or a direct comparison to placebo in previously treated patients.

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Lung Cancer FAQ: I’ve just been diagnosed with advanced NSCLC. What treatment should I be starting with??

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The initial or “first line” management of advanced NSCLC has evolved quite a bit over the past 10 years, in that time moving from a much more uniform approach of very similar treatment for just about everyone to a revised approach that is far more individualized. First, we assess key issues like the subtype of NSCLC, focusing largely on whether it is squamous cell or non-squamous NSCLC, because treatment tends to diverge very early based on this factor. Second, a patient’s performance status is another important issue, as patients who are frail often need a customized approach, because a more aggressive standard approach may be prohibitively difficult and even harmful. Third, a minority of patients (about 10% in North America and Europe, closer to 1/3 in Asia) will have a particular molecular marker, specifically a mutation in the epidermal growth factor receptor (EGFR), that is associated with a high probability of having a dramatic and long-lasting response to targeted therapy that inhibit the EGFR pathway. This particular activating mutation is most typically seen in never-smokers or people with a minimal, remote prior smoking history who also have an adenocarcinoma subtype of NSCLC.

Recommendations for first line therapy are most typically for a two drug chemotherapy combination, often with the drug Avastin (bevacizumab) — a targeted therapy that blocks the blood supply to the cancer — added for many patients who don’t have squamous NSCLC. However, for patients with an EGFR mutation identified before they have started treatment, several recent studies have demonstrated that the rate of significant tumor shrinkage and the time before the cancer progresses are significantly longer with an oral agent that works as an EGFR inhibitor, such as Iressa (gefitinib) or Tarceva (erlotinib). Consequently, one of these agents is increasingly recognized as a very appealing first line treatment approach.

Elderly patients are often treated the same as younger patients if they have minimal limitations in their activity level. In contrast, frail patients are sometimes recommended to receive single agent chemotherapy rather than a multi-agent combination that may be prohibitively difficult to tolerate. The available evidence suggests that elderly and frail patients who have an EGFR mutation also typically have a very significant response to EGFR inhibitor therapy.

Further information is available through the following links:

Podcast on introduction to first line chemotherapy for advanced NSCLC

Podcast on personalization of first line therapy

Reference library summary on selecting optimal first line treatment for advanced NSCLC

Using molecular markers to guide treatment: The IPASS trial

Alimta (pemetrexed) benefit is histology-specific

Treatment approaches for first line therapy in frail patients with advanced NSCLC

Podcast discussion of managing advanced NSCLC in the frail and/or elderly

Iressa (gefitinib) for frail patients with an EGFR mutation


Introduction to Small Cell Lung Cancer: Prevalence, Initial Symptoms, Work-Up, and Staging

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General Introduction to Small Cell Lung Cancer

Lung cancer consists of two major types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Approximately 85% percent of all lung cancer patients have NSCLC, and the remaining 15% have SCLC.

histology-breakdown-of-lung-cancer (click on image to enlarge)

In 2010, the American Cancer Society has estimated that approximately 222,000 new cases of lung cancer will be diagnosed, of which 35,000 will have SCLC. Even though both subtypes are lung cancers, they are considered as separate diseases in most ways, and the management of these two cancers is different. It is important to recognize that the treatments applicable for NSCLC, including many newer agents that have been approved and are the subject of increasing research and media attention, are not clearly relevant for patients with SCLC.

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Dr. Suresh Ramalingam on Personalizing First Line Therapy for Advanced NSCLC: Podcast Available

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I’m very pleased to offer the excellent podcast produced from the recent webinar by Dr. Suresh Ramalingam, a leader in the lung cancer field who heads the Thoracic Oncology Program at Emory University in Atlanta. He’s also a good friend I’ve known since our fellowship training days, and he was kind and generous enough to refuse the honorarium we offered for his participation, instead requesting that it be donated back and used for other GRACE programs. Instead, he was happy to do this entirely out of a commitment to the lung cancer community. This is part of a small series of programs supported by an educational grant from Eli Lilly, so we are now enabled to do an additional program because of his generosity.

His webinar provides a very brief historical overview of NSCLC in general and then advanced NSCLC in particular, including a historical perspective of the evolving standards of care first with chemotherapy alone, and then with the integration of targeted therapies. He describes how our approach now individualizes our treatment recommendations based on such issues as particular NSCLC histology, molecular factors, performance status, and sometimes age to offer what we hope will deliver the best combination of efficacy and safety for a patient.

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