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Does Tumor Grade Matter in NSCLC?
Historically, the main task of pathologists in lung cancer has been to divide them into small cell lung cancer and non-small cell lung cancer. Beyond that, there is now more of an emphasis than there used to be on trying to clarify whether a NSCLC tumor is a squamous cell carcinoma, adenocarcinoma, large cell, or another subtype, partly because we now have drugs approved just for certain subtypes (avastin for non-squamous tumors only) and others that are commonly observed to have a higher response rate in some histologies (lung cancer categories based on microscopic appearance) than others (sucha s EGFR inhibitors consistently showing a high response rate in adenocarcinomas/bronchioloalveolar carcinomas compared with other subtypes). Several members have asked questions similar to the one reported in a recent paper from the Mayo Clinic (abstract here): is the grade of the tumor, ranging from well differentiated to moderately differentiated to poorly differentiated and even undifferentiated, associated with a better or worse prognosis for a person?
What do we mean by differentiation? The degree of differentiation of a tumor is how much it looks like normal, non-mutant lung cells. Well differentiated lung cancers are pretty close to normal appearing, while poorly and undifferentiated lung cancers look completely wild, not like the cell they originated from. It’s important to note that pathologists can readily and reproducibly say a well differentiated cancer is an adenocarcinoma, for instance, but a poorly differentiated tumor may be said to resemble an adenocarcinoma by one pathologist, while another pathologist may think that the same tumor is a poorly differentiated squamous cell carcinoma (and even give different results when the same pathologist reads a tumor at two different times). So there is a good concordance (agreement) of pathology findings only for the better differentiated tumors. In addition, there are not clear standards of what constitutes moderate differentiation and what consistutes poor differentiation, so this will differ somewhat from one pathologist to another. Continue reading
Individualizing Treatment Recommendations in Lung Cancer: Who to Treat?
I’m just coming from a meeting on Targeted Therapies in the Treatment of Lung Cancer, which had the interesting format of dozens of 5-minute presentations just introducing or giving a very brief update of many new therapies. Some of these, such as the EGFR monoclonal antibody Erbitux (cetixumab), which I spoke on, have been approved by the US FDA for several years in other cancer settings and are well tested in humans. Others are so new that all that could be said about them is their chemical structure, presumed mechanism of action, description of how they killed some cancer cells in test tube models, and plans for moving ahead in very early trials in humans. I’ll describe some of the agents and classes in the next several weeks, with the caveat that some and perhaps many of these won’t be available for broad trials in lung cancer if they don’t get through several more hurdles.
But today I’m going to talk about the very interesting Keynote Lecture by Dr. Joseph Nevins of Duke Univeristy’s Institute for Genome Sciences and Policy, on the topic of “Predictive Markers for Early Stage NSCLC”. As some of you may be aware from my prior post, other online information, or the general news, Duke has been a leading cancer center in studying genetic differences in lung cancer tumors, and it was investigators from there who recently published an important article in the New England Journal of Medicine on their ability to use genetic profiles to help predict outcomes for early, resected lung cancers. Dr. Nevins has been at the center of the efforts to individualize lung cancer care, and his lecture gave a broad overview of that work, essentially boiling down the questions he and his group are trying to answer as the following:
1) “who to treat”: which patients after surgery can be identified as having higher risk and requiring post-operative chemotherapy? which early stage patients can be identified as having a good enough prognosis to forego chemo?
2) “how to treat”: can gene arrays, the molecular signatures of a tumor, be employed to predict which particular chemotherapy drugs and/or targeted therapies would be most and least helpful for a particular lung cancer? Continue reading
The Future of the Field: “Molecular Epidemiology” and SWOG Trial 0424
It’s only been in the past few years that we have begun to appreciate that there may be many different subgroups of patients who fit within the broader lung cancer population. We now have begun to see differences in the safety and/or activity of certain drugs in never-smokers vs. smokers, patients with adenocarcinomas (and especially bronchioloalveolar carcinoma, or BAC)vs. squamous cell carcinomas or other subtypes, and even in women compared with men. This work has been primarily involved looking back retrospectively at how patients with different clinical characteristics did on various treatments. But we are also starting to move into a new era of collecting tumor tissue and blood on patients with different characteristics in order to learn about the molecular epidemiology (study of various factors in disease) to learn about the different genes and proteins that may define new subgroups of lung cancer, and how they may relate to gender, smoking status, and other factors we already recognize. SWOG trial 0424 is an important new type of research that we hope will move the field forward. Continue reading
Small Cell Lung Cancer 101: An Introduction
After several weeks of posts on other aspects of lung cancer, I am long overdue to write on small cell lung cancer (SCLC). Although it is good to see the number of SCLC cases decreasing over time, and becoming a smaller and smaller percentage of lung cancer cases overall (only about 13% in the US and steadily falling), this has translated into fewer clinical trials and less of a focus on SCLC in the lung cancer community. However, there are some promising developments that may lead to some long overdue progress in the field.
First, this post will start with some general concepts and an introduction to SCLC, and this will be followed in the next few weeks by posts describing current and emerging ideas for the basic stages of small cell lung cancer, and also a discussion of prophylactic cranial irradiation for small cell, where it has been most extensively studied. Continue reading
The Tissue is the Issue
We define whether someone has cancer, and what type of cancer it is, by a piece of tumor tissue. This evidence of cancer under a microscope is considered critical, so much so that there is a general oncology dictum of “no meat, no treat”, requiring a tissue diagnosis before starting a treatment with potentially significant side effects.
Up until very recently, the only important decision-making point once you established that someone has lung cancer was whether it is small cell lung cancer or non-small cell lung cancer (NSCLC). While there are several subtypes of NSCLC, there was not much reason to clarify whether the type of non-small cell was adenocarcinoma (the majority in the US), squamous cell (the majority in Europe, only about 30% in US), large cell carcinoma (about 5-10% in most series), a rare type like large cell neuroendocrine tumors (in the range of 5%, generally felt to have a worse prognosis than other types), or NSCLC not otherwise specified (NOS). Cancers can also have a mix of different components, such as adenosquamous, just in case it seemed too easy to understand otherwise.
Defining Bronchioloalveolar Carcinoma (BAC): One End of a Spectrum
The clinical syndrome of BAC is characterized by spread primarily through the lungs, a higher proportion of never-smokers or light former smokers, a greater proportion of women, and often progresses more slowly than most other lung cancers. This clinical and radiographic (scans) scenario isn’t necessarily seen only with “pure BAC” under the microscrope from a biopsy, but rather can be a spectrum from pure BAC to part non-invasive BAC pattern and part invasive adenocarcinoma, and on the other end of the continuum is invasive adenocarcinoma, as shown in the illustration of how these appear under a microscope.
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| Pure BAC | Adeno w/BAC Features | Invasive Adeno |
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