GRACE :: Lung Cancer

Poorly differentiated carcinoma

The Predicament of Poorly Differentiated NSCLC/NSCLC NOS

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A topic that came up in a recent expert round table case discussion was the issue of how to manage a patient with a lung cancer for which the pathology report says “NSCLC not otherwise specified (NOS)”, or “poorly differentiated NSCLC, NOS”. What does this actually mean, and what does it mean in terms of treatment options?

Tumors of pretty much all types are categorized by their tumor grade, how “differentiated” they are, which basically means, “how much do the cancer cells look like the cells they started out as?”. Different cells of the body start out as stem cells, which means that they’re not specialized to be any special kind of cell, like one that detects light in the back of the retina, lines the esophagus, or is optimized for lung function. Most cells of the body are differentiated, so that the appearance under a microscope shows that it’s a liver cell, part of the kidney filtering mechanism, heart muscle, etc.

Cancer cells, however, have mutations in them that make them grow and divide faster than other cells (that’s why they make a tumor that pushes other tissues aside), and they usually have several. As they grow and divide, they often make sloppy copies of their DNA that leads to more mutations. Cancers therefore are made of cells that may look a lot like the normal cells they originated from (well-differentiated), or they have lots of mutations that make the cells look so chaotic that they don’t look at all like the cells they started out as (poorly differentiated).

Today, oncologists want to know whether a non-small cell lung cancer (NSCLC) is an adenocarcinoma, squamous cell carcinoma, large cell neuroendocrine carcinoma, etc. But about 20% of the time on various studies, we get an answer back of “NSCLC not otherwise specified”. As explained by Dr. Matt Horton, expert lung cancer pathologist, a lung tumor may be classified as NSCLC NOS because of either of two reasons:

1) there isn’t enough tissue, because the biopsy material was very scant, or

2) the tumor is so poorly differentiated that even with all of the material in the world, a good pathologist couldn’t identify the underlying NSCLC histology

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Case Discussion with Experts, Drs. Julie Brahmer & Greg Riely, Part 1

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Here’s a webinar case discussion I did with Drs. Julie Brahmer from Johns Hopkins in Baltimore, and Greg Riely from Memorial Sloan Kettering Cancer Center in New York. They’re great thoracic oncologists as wellas friends, and they were kind enough to join me for discussion of several complex cases that don’t have clear answers and illustrate the reality that even when we know the evidence, there’s plenty of room for judgment.

Our first case is about a 63 year-old woman who has a poorly differentiated NSCLC that is just outside of the range we’d feel feasible for radiating, and it brings up issues related to trying to integrate chemo and possible radiation, the debatable role of agents like Avastin (bevacizumab) and Alimta (pemetrexed) for cancers that are hard to classify, and then how we approach managing patients who have responded well — observation or maintenance?

Here is the audio and video versions of the podcast, along with the associated transcript and figures.

rt-brahmer-riely-webinar-case-1-audio-podcast

rt-brahmer-riely-webinar-case-1-transcript

rt-brahmer-riely-webinar-case-1-figures

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