GRACE :: Lung Cancer

Radiation

When might local therapy be a good choice for someone with metastatic lung cancer?

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I’ve mentioned in posts in the past about the settings in which local therapy might be appropriate for someone even when we know the cancer is advanced/metastatic.  Here’s a brief video that discusses some of these issues, including a situation in which the local treatment isn’t specifically aimed at addressing a symptom, as is the usual reason for treating with local therapy for metastatic cancer, but is rather what I’d consider the “Get the Lead Runner” strategy:

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Radiation to Address Cells with Resistance to Targeted Therapies

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Introduction

Thank you to member Craig for asking some excellent questions in response to my Highlights of 2011 webinar (http://cancergrace.org/lung/2012/03/30/qa-lc-highlights-weiss/#comment-9498 ).  Thank you also to Dr. West, who emailed me to comment more on the idea of radiation for cells with acquired resistance.

We’ve spoken at length about EGFR and related mutations such as EML4/ALK and ROS1 on GRACE.  For those who are not familiar with these subjects, I will refer you to my webinar for a summary on the most recent data on EGFR, EML4/ALK and ROS1:

http://cancergrace.org/lung/2012/03/15/2011-highlights-in-lung-cancer-by-dr-jared-weiss-part-1-the-egfr-axis/

http://cancergrace.org/lung/2012/03/18/lung-cancer-highlights-2011-by-dr-weiss-part-2-alk-and-other-new-molecular-targets/

(Parenthetically, we did also cover CT screening and optimal management of elderly patients at http://cancergrace.org/lung/2012/03/22/dr-weisss-highlights-in-lung-cancer-2011-ct-screening-optimal-management-of-elderly-patients-with-advanced-nsclc/ )

In the Q&A for this webinar that covered some of the existing approaches to resistance, Dr. West pushed me and asked if there was one that was particularly promising.  Well, I’ve spent a ton of time thinking about this problem and have written a trial to attempt to address it.  I couldn’t resist the bait and mentioned my trial.  In this post, I’d like to review the rationale for the approach that I described and address Craig (and Dr. West’s) question about how appropriate this approach will be to new mutations, such as EML4/ALK and ROS1.

The Approach:

(click on image to enlarge)

The basic idea is to take patient whose cancer has grown on tarceva, do cyberknife to the spots that have grown to eliminate the resistant clones, then continue using tarceva for the rest of the cancer that has shown evidence for ongoing sensitivity to tarceva.

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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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Dr. Le, Radiation Oncologist from Stanford, on Radiation Options for Early Stage NSCLC

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Dr. Quynh Le, radiation oncologist and Professor at Stanford University, was kind enough to participate in our NSCLC Patient Education Forum. She spoke on the topic of emerging treatment options using radiation for early stage NSCLC. The new work she’s describing on stereotactic body radiation therapy (SBRT) is looking promising enough that it’s being considered increasingly as a very strong choice for people with localized lung cancer but who aren’t good candidates for surgery or are disinclined to pursue it. In fact, much of the debate in the lung cancer community is about whether SBRT appears compelling enough to be considered as a viable alternative to surgery even in patients who are fine candidates for resection.

The podcast and additional materials from her presentation are here:

Q Le Radiation for Early Stage NSCLC Audio Podcast

q-le-radiation-for-early-stage-nsclc-figures

q-le-radiation-for-early-stage-nsclc-transcript

Some passages of the program may be a little difficult to follow, so please use the transcript if you need to clarify parts. You can also ask questions here, for clarification or follow-up. I hope you find it helpful.


Trimodality Therapy (Chemotherapy, Surgery, and Radiation) for Malignant Mesothelioma: Can Some Patients actually be Cured?

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Malignant mesothelioma is a relatively rare but particularly deadly malignancy that arises from the lining of the pleural (chest) cavity or peritoneal (abdominal) cavity. About 70% of cases of mesothelioma are directly related to asbestos exposure, usually with about 30 or 40 years between exposure and diagnosis. While there are only about 2200 cases per year in the USA, this number is expected to increase over the next decade, as workers exposed to asbestos earlier in their lives eventually begin to manifest symptoms of the malignancy. After 2015 or so, this may begin to decline due to laws regulating exposure to asbestos in recent decades, but these laws don’t exist in the developing world, so mesothelioma is likely to be a worldwide problem for the foreseeable future.

The usual patient with mesothelioma presents with chest pain and/or shortness of breath, with x-rays showing thickening of the pleural lining with as associated pleural effusion. Many times the fluid around the lung contains no cancer cells, so a biopsy of the pleura is necessary to make the diagnosis. It usually occurs only on one side; distant spread is unusual. So if it is technically “localized”, why is it so hard to cure? The main problem with mesothelioma is that most patients present with advanced disease that has no chance of curative treatment with surgery. In fact, mesothelioma is a malignancy that classically is not thought to be really “curable” at all. Surgery is usually used for palliation, to drain the fluid and peel the malignant rind away from the lung so that the patient can breathe easier and with less pain. Of course there are case reports or case series of patients with limited disease who can be aggressively treated with surgery and have lived >5 years (most oncologists’ definition of cure), but the reality is that these patients are few and far between. To date, studies of patients treated with surgery have shown about the same average overall survival as patients treated palliatively with chemotherapy alone (about 9-12 months).

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