Archives for August 2017

How do checkpoint inhibitors work, anyway?

How do checkpoint inhibitors work, anyway?

Picture a common movie scenario: the police have the bad guys surrounded, locked down inside a building – but there are hostages in there too, and if the cops go in shooting they won’t be able to tell the victims from the villains.

“Die Hard”, “Inside Man”, and “The Dark Knight Rises” have all done variations on this idea. I bet you can even think of a few more. 

But this familiar movie scenario can help us better understand the difficulty the immune system has trying to fight cancer, and how the new class of cancer drugs called checkpoint inhibitors can overcome it.  

So, let’s apply our “bad-guys-with-hostages standoff” analogy to an immune system trying to eradicate cancer, and see what we can learn:  

  1. Your immune system, like a good police officer, must sometimes restrain itself. A SWAT team storming in at every opportunity can cause terrible collateral damage, just as an unrestrained immune system can cause terrible diseases like rheumatoid arthritis and lupus. That’s why your immune system’s T-cells have special receivers sticking out of them like antennae dishes, listening for the signal to “stop” – and when the T-cell gets that signal, it backs off. We call these “stop signal” receivers checkpoint inhibitors – one of which is PD1. 
  2. Some cancer cells fool the immune system the same way the villain fooled Bruce Willis in “Die Hard”. When Bruce Willis’ character got the drop on the main villain Hans Gruber (who he’d spoken to but never seen), Hans faked an American accent and passed as a hostage (“Oh no please don’t shoot, you’re one of them aren’t you…”). In a similar way, some cancer cells have learned how transmit the “stop” signal by making a special molecule that sticks from its surface and binds to PD1 on attacking T-cells – which turns them off. We call this “stop signal” molecule PDL1. 
  3. Preventing the PDL1 “STOP” signal from reaching T-cells invigorates the immune system enough to attack some cancers Drugs like nivolumab and pembrolizumab (which interrupt the PD1/PDL1 interaction) put the fight back into the T-cells, allowing them to attack the cancer – but with much less of the “collateral damage” that we’ve seen in other types of immune enhancers.  

Here’s a video that explains the process visually. 

We should celebrate the success of these drugs, but have to remember that no cancer drug in history has ever been a “cure-all”. We have to remember that there a great many more checkpoint inhibitors than PD1, so there’s many other ways for cancer cells to escape the immune system.  

We have to remember we still need good clinical trials, and patients willing to participate in them.

(Up Next: Pembrolizumab approved for a slew of cancers all at once)

Cancer Pain

Cancer Pain

Whenever I meet a new cancer patient, especially one with incurable cancer, pain always comes up in the conversation – whether they have it or not.

It’s the most commonly reported symptom of cancer, and it’s also one of the most widely feared.  

Most patients with advanced stage cancer do, in fact, experience pain; 75-90% according to a 2007 cohort study conducted in the Netherlands and published in the Journal of Pain and Symptom ManagementAnd for much of the history of cancer medicine, most of these patients suffered terribly during their illness – and many died in agony – before the importance of relieving terminal cancer pain was widely accepted. It’s little wonder that the hospice movement began first among cancer caregivers who’d borne witness to one painful death too many and rose en masse to say “enough, no more.” 

Despite the strides made in the last half-century, there’s still a lingering belief out there that having cancer means unrelenting pain– but I’m happy to tell you that hasn’t been true for a long time. 

In honor of Cancer Pain Awareness Month, here are a few important facts about cancer pain (some of which might surprise you): 

  • Cancer pain can almost always be controlled. Data from the World Health Organization shows that following simple treatment guidelines and using widely-available medications controls cancer pain over 90% of the time. 
  • Though narcotics are usually required to control cancer pain, addiction rates are extremely low in cancer patients – probably no higher than 4% according to several studies. That’s 5-10 times lower than the addiction rates among patients with other types of chronic pain. 
  • Pain relief doesn’t require that patients be “drugged out”.  Pain medications can certainly cause sleepiness, for the majority of patients this is short-lived and can be counteracted by dose adjustment. 
  • Dying in pain is a thing of the past. With good hospice care, no one need suffer when dying. 
  • Using narcotics DON’T hasten death. The best evidence indicates that dying patients – even comatose ones – live longer when given narcotics to control pain.

Grief is for Sharing

Grief is for Sharing

Why do we have an urge to avoid people who’ve lost a loved one?

Well, mainly because we don’t know how to make them (or us) feel better so we wind up saying stupid, empty things – like Let me know if I can do anything. 

We blurt that out desperately, knowing we’re just talking to talk, as do the people we’re saying it to – why else do they never taken us up on the offer?  

Please don’t feel bad if you’ve done it, because we all have. I certainly have.  

We don’t say these things because we’re bad, insensitive, or dumb. We say them because at some level we understand that simple human contact and empathy is the most important thing we can give, but giving it requires us to sit peacefully in the presence of pain, and resisting that overpowering urge to fix it. Healthcare professionals especially struggle with the “don’t try to fix the unfixable” urge, and that’s why so many of us are bad at talking about end-of-life or dealing with grief. But it’s those behaviors that put distance between us and the ones we’re trying to comfort, just when closeness is exactly what’s needed most. 

There are few things I try to keep in mind in these situations, and maybe they’ll help you too: 

  • Ask sincere questions, and make space for the answers. “How are you doing?” is fine, but “What are you feeling?” and “What are your days like right now?” are good too. If your loved one wants to talk, listen. But sometimes your loved one won’t have much to say, and it’s important not to take this personally either. Sometimes the most comforting thing you can do is sit quietly with your grieving friend and share the silence.  
  • Let there be room for tears.  Tears can be cleansing, but we’re taught to be ashamed of and embarrassed by crying. Not only is it unnatural to suppress tears, it also dishonors the importance of pain and loss generally. Be that person who can make a safe place for tears, rather than hurriedly reaching for the tissues to hide them.  
  • Help with the daily chores without being asked. One of my favorite quotes is “human to human we help each other through good and bad.” For some people, these simple “acts of devotion” mean much more than words, touch, or gifts. So bring over a meal, cut the grass, or fold laundry. If there are children involved, offer to watch them or transport them to or from school. Grief and loss drain energy for chores, and pitching in can free up the time for the grieving person to rest. We are in this world together, why not help each other carry the load when it’s too heavy. 
  • Don’t forget.  Contrary to popular belief, grief isn’t finished after a certain period of time or “moving through the stages”. Grief comes and goes likes the tides, even years after the loss – especially around anniversaries, birthdays, or major holidays. Remember to still offer support even long after the acute loss. 
  • Embrace the pain like you’re embracing your loved one.  Getting out of this unaffected isn’t possible for anyone with a heart, and you’ve got one. Be prepared to feel sad, scared, confused, helpless – and maybe lots of other things too. 
  • Remember this isn’t about you. Don’t be that person who’s so overwhelmed that the bereaved person winds up having to comfort you.  You’re suffering along with your loved one, but remember whatever you’re feeling is only a fraction of what they’re feeling.