Article and Video CATEGORIES

Cancer Journey

Search By

Alice T. Shaw is the Director of the Center for Thoracic Cancers and the Paula O’Keeffe Endowed Chair of Thoracic Oncology at Massachusetts General Hospital. She is also an Associate Professor of Medicine at Harvard Medical School. She received her A.B. in Biochemistry from Harvard and her M.D. and Ph.D. degrees from Harvard Medical School. She did her residency in Internal Medicine at Massachusetts General Hospital and completed a fellowship in Hematology/Oncology at Dana-Farber/Massachusetts General Hospital. She completed her postdoctoral work in the laboratory of Dr.

Lung Cancer Video Library - Controlling Brain Metastases in Patients with Molecular Driven Advanced NSCLC
Author
Alice Shaw, MD, Ph.D, GRACE Faculty

 

 

 

 

Controlling Brain Metastases in Patients with Molecular Driven Advanced Non-Small Cell Lung Cancer (NSCLC) Presented by Alice Shaw, MD, PhD Associate Professor, Medicine, Harvard Medical School Attending Physician, Thoracic Cancer Program, Massachusetts General Hospital TRANSCRIPT

 

My name is Alice Shaw, I am director of the Center for Thoracic Cancers at Massachusetts General Hospital in Boston. CNS metastases are a very common problem in patients with metastatic non-small cell lung cancer and in particular for patients who have driver oncogenes like EGFR mutation, ALK or ROS1 rearrangements, and other drivers. ALK positive patients in particular have a very high propensity for having spread to the central nervous system or CNS. We’ve seen in a number of studies over the years that at the time of diagnoses patients with metastatic ALK positive lung cancer about 40% of them may have brain metastases even at the time of diagnosis so very common issue. And what we’ve also seen in clinical trials of first and next generation ALK inhibitors is that as patients continue on these ALK inhibitors that the chance of developing CNS metastases rises even further. So, in many of our studies now of next generation ALK inhibitors that allow multiple prior ALK inhibitors as treatments we see that over 60-70% of patients may have brain metastases so it’s a very common problem and it is a critical issue that we’ve been trying very hard to address. For ROS1 we also have patients who can develop brain metastases. However, the incidence of brain metastases for this particular molecular subset seems a little bit lower than that of ALK. We recently published a study comparing this exact question: the frequency of CNS metastases in ALK versus ROS1 patients. What we found is ROS1 patients at diagnosis are less likely to have brain metastases than ALK patients; a little less than 20% of our ROS1 patients were found to have brain metastases when they were first diagnosed. What we also showed is that over time, accumulated incidence of brain metastases was higher for ALK compared to ROS. Nevertheless, for a significant proportion of patients with ROS1, brain metastases can be a very important issue that must be addressed. Now, fortunately over the last five years or so we have developed a number of next generation ALK and ROS1 inhibitors that actually are very CNS penetrable. So Crizotinib, the first generation ALK/ROS1 inhibitor that has been the standard of care since 2011 at least for ALK positive patients, is a very good drug but it has relatively weak CNS activity because it is limited by the blood-brain barrier. We do see relapses in the CNS quite commonly for the ALK and ROS1 patients while they’re on Crizotinib. However, what we’ve now seen with the more potent ALK and ROS1 inhibitors is that these drugs can get into the CNS at much higher levels and we’ve seen remarkable activity in the CNS. So as an example, with Alectinib, used after failure of Crizotinib, the intercranial response rate is pretty much the same if not higher than what we call the systemic or the body response rate. In the brain we often see a response rate of 60% or more meaning really significant shrinkage or response in the CNS metastases. Often times we can see a complete response where all the CNS lesions are no longer identifiable on scans. We have had very good success in treating patients with CNS metastases with these new targeted agents and this has really allowed us now to actually postpone or entirely forgo the use of radiation therapy and I would say particularly whole brain radiation therapy. Whole brain radiation therapy has been the standard of care for patients who develop multiple brain metastases. That was done very frequently in the past however fortunately with the CNS penetrable drugs that we now have many of my patients will actually forgo whole brain radiation. Their CNS disease will be entirely controlled by these new next generation drugs. Occasionally, we will need to use radiation and often times we can use more focused radiation like Gamma Knife or stereotactic radio surgery and those more focused approaches tend to be much better tolerated than whole brain radiation therapy.


 We would like to thank the following companies for their support of this program

 

                

 

 

                        

 

 
 

 

 


  

Video Language

Next Previous link

Previous PostNext Post

Related Content

Image
Blood Cancers OncTalk 2024
Video
  This event was moderated by Dr. Sridevi Rajeeve, Memorial Sloan Kettering, joined by speakers: Dr. Hamza Hashmi, Memorial Sloan Kettering, Dr. Michele Stanchina, University of Miami, Dr. Muhammad Salman Faisal, Oklahoma University, and Dr. Andrew Srisuwananukorn, Ohio State University Topics include: - Myeloma 101: Facts and Fiction of the 'Myeloma Marathon' - Updates in DLBCL - Treatment Basics of Bone Marrow Transplant - Frontline Therapies in Myelofibrosis - Panel Discussions and a Question-and-Answer session
Image
Trial data ASCO 2024
Video
In this video series from ASCO 2024, Drs. Aakash Desai and Fauwzi Abu Rous discuss trial dates and clinical data as presented at the 2024 ASCO. To watch the complete playlist, click here.         
Image
Bladder Cancer Video Library 2024
Video
Dr. Petros Grivas discusses intravesical treatment for patients with nonmuscle invasive, or early-stage, bladder cancer, the importance of participating in clinical trials for bladder cancer, combination therapy options for patients with metastatic or incurable bladder cancer, and the importance of family history of cancer and discussing that history with your doctor.

Forum Discussions

Hi Stan,

It's so good to hear you and yours are doing well and that you were able to spend time with both families for Thanksgiving.  I know it meant a...

Hi Stan!  It is good to hear from you -- I am so very happy you are doing well.  I agree with Janine that family and friends - our chosen family...

Recent Comments

JOIN THE CONVERSATION
Hey Bluebird,

I understand…
By JanineT GRACE … on
So good to hear from you Stan
By dbrock on
Hi Stan,

It's so good to…
By JanineT GRACE … on