Deciding between radition w/Crizotinib versus 2nd generation ALK inhibitors - 1269911

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Summary of my wife's medical history:
2012: diagnosed with Stage IV NSLC with ALK, immediately placed on Crizotinib with positive response
2013: still going strong on Crizotinib, but based on the Crizotinib literature, I asked her oncologist if she shouldn't be receiving regular brain scans to catch the onset of brain metastasis. I was convinced that the benefit of brain scans was miminal, better to wait for "symptoms to appear" as a more reliable indicator of progression in the brain. I didn't agree, but my wife was tired of scans and elected to listen to the oncologist.
2014: My wife began experiencing numbness and weakness in her left arm. After months of discussion and testing, they finally order a brain scan and it reveals DOZENS of brain tumors. Whole Brain Radiation is recommended by oncologist and neurologist. I wanted a second opinion since Ceritinib and Alectinib was already showing very positive results against brain metastases, and at very high response rates (from 60% - 90%). We spoke with someone at Stanford and while he wasn't familiar with Ceritinib or Alectinib, he recommend WBR as well. I was outnumbered by the "experts" and I reluctantly agreed to proceed with WBR. Four weeks of WBR at five days a week. Twenty total radiation treatments. She was placed on powerful steriods to combat the swelling in her brain, but made her too weak to walk. Her hair fell out. Her memory and speech were impaired. She loses her appetite and begins losing muscle mass. These effects last over six months. I'm told this is normal for WBR. For a brief period at the end of 2014, she appears to rebound from the radiation and her appetite starts to come back though her trouble walking never goes away.
2015: She begins complaining of constant bouts of vertigo and nausea. She started vomiting randomly several times month. Her oncologist thinks it may be crizotinib side effects.

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He orders a brain scan but the brain scan reveals nothing. However, her regular PET scan reveals that the tumors in her lung have grown. It appears that Crizotinib is no longer controlling her disease. We debate if she should begin with FDA approved Ceritinib, or try to enroll in a clinical trial for Alectinib (fewer side effects). As we decide to enroll in the clinical trial and make arrangements to travel to southern California to the study site, my wife experiences a mild seizure on her left arm. She is taken to the hospital. The seizures rapidly worsen. Four weeks later, she passes away. The diagnosis: leptomeningeal metastases.

Lesson 5: In hindsight, she might be still alive and healthy today if she had switched from Crizotinib to either Ceritinib or Alectinib back in 2014, instead of sticking with Crizotinib complemented with brain radiation. It is my opinion that brain radiation is a poor choice in our particular situation. Number one, it is impossible to monitor all disease progression in the brain because leptomeningeal metastases is notoriously hard to detect until it's already too late. It is also extremely difficult to treat leptomeningeal disease with radiation, especially if it has traveled outside the skull through the CNS. Not to mention the terrible side effects of radiation treatment. On the other hand, we already knew of two ALK inhibitors which can penetrate the CNS barrier and control the disease, assuming you find one you respond to (remember the 60% - 90% response rate of these drugs). The 2nd generation inhibitors work on average a year or so, buying you more time as the pipeline matures and new drugs become available. In this scenario, allowing the disease to grow unchecked in your brain with periodic radiation treatment (Crizotinib w/radiation) doesn't make sense because you are only catching what you can see. As with my wife, leptomeningeal disease may be spreading undetected and untreated.

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Keep in mind that doctors are people too. They are far from infallible, and most of them are not specialists in the field of ALK inhibitor research. I happen to have a career in research, making me more informed than most. And most people will recommend something they are familiar with and has worked in the past. This was my experience. I ran up against an institutionalized reluctance to admit that there might be better treatments for brain cancer OTHER than radiation. Sure, it is effective when the location of the disease is identified and they can zap it. However, what they are still unwilling to factor into the equation is that leptomeningeal metastases is almost inevitable if no treatment is reaching the brain in patients diagnosed with brain metastases (Crizotinib), it's almost impossible to detect with certainty when it occurs, and treatment success is incredibly low. Conclusion: regular MRI's and radiation cannot detect, prevent or treat the fatal onset of leptomeningeal metastases.

Maybe because it sounds to good to be true, but oncologists have to consider the possibility that 2nd generation inhibitors that penetrate the CNS barrier are the answer to the problem that radiation cannot solve for patients on Crizotinib w/brain metastases. Instead of recommending that patients stay on Crizotinib (+Radiation) because it's still controlling the ALK in the neck and below, I believe they should be recommending an immediate transfer to either Ceritinib or Alectinib in order to ensure that treatment is reaching all parts of the body under attack by cancer. I know they are only temporary solutions until the disease progresses again, but they allow you or your loved one to live a normal life while research continues for a longer term solution, without the horrible and permanently crippling effects of WBR and the medicines that go with radiation, not to mention the risk of leptomeningeal metastases. I wish you all the best.