Thursday, August 3, 2017

The One Thing No One Ever Says About Grieving

(And a 4 step plan to move through your grief.)

Another way to say that you are grieving is that a part of you is stuck in a moment in time. 
 Sometimes the cause of the stuckness isn’t the grief itself, but the fact that you don’t even recognize that you’ve lost something and that you need to grieve. 
Grief is a word that is used interchangeably with bereavement, but grief is not exclusively about the physical death of a person.
Grief doesn't fit in a box, either. Some forms of grief take years to work through, other types take a few solid months, some take a single moment of deep acknowledgement.
Everyone grieves differently and for different reasons, but one thing remains constant in the process. It's the one thing no one has ever said about grieving:
“I did it right on time.”
Grieving is marked by a lag, a delay, a freezing, “Wait. What just happened?”
Grieving is also not a linear process
One moment you feel you’ve fully moved past something, the next moment it’s right back in front of your face.
That’s because grief is insidious, imposing and demands to be felt. Even if you’re able to somehow avoid it all day long, grief comes back to you in your sleep. It’s laying right on your heart as you wake up.
Grief doesn’t say, “I’ve been here long enough, I think it’s time for me to leave.” 
No. Grief crowds the heart, eats up all your energy and chronically imposes upon your peace.  But grief isn't some evil force that's only there to cause pain, grief is escorting up an even deeper feeling, a truth about your life, what you value and what you need.  Perhaps how much you wanted something, how deeply you care about someone, how far you've come from where you were. 
As Mark Nepo so beautifully puts it, "The pain was necessary to know the truth, but we don't have to keep the pain alive to keep the truth alive."  
Still, grief isn’t necessarily a depression. People can be grieving and heartbroken about something and not even know it.
Here are some examples of events that cause grieving:
A break up
The selling of your childhood home
What you always wanted but never got
A person who died
A person who is still alive but is electively absent in your life
The loss of a dream
Loving someone who is self-destructive
The loss of a pet
The end of a friendship
Job loss or the end of a career
The typical route for grieving begins with denial, and that’s actually a good thing
Ultimately, your defense mechanisms are there to protect you. Denial kicks in when it would otherwise be too overwhelming to feel it all at once. Ideally, denial slowly fades away and the grief is felt. (Ideally.)
More typically, you swallow your grief. 
 It comes up in small spurts when you’re not paying attention, then you numb yourself to it somehow, then it jumps up more forcefully, then you numb yourself more heavily.
That is the path of staying stuck in grief. The path loops. People lose themselves on that path.
Is there a better path?
The answer is yes. But you don’t have to walk it unless you choose to. 
Some losses are so exquisitely painful, in a way that no one else could ever fully understand, that no one would fault you for staying in the loop.
If you do choose to get out of the disorienting, dizzying loop of grief, here are 4 ways to begin:
1. UNDERSTAND - That your heart is broken, even if it’s not visible to others. 
 Keep in mind that there's no ‘right way’ to grieve and that grieving is not a linear process. 
Just because its been 6 months, 4 years, 15 years, whatever – none of that means anything to your grief. The clock starts when you begin to recognize your grief. In other words, when you genuinely begin to address what happened (or perhaps what never happened).
2. RECOGNIZE - Before you can grieve, you have to recognize that you need to grieve.
Something happened, or didn’t happen, that burdened you. 
Ironically, when you’re burdened, something is given to you and taken away from you at the same time. What do you feel was taken from you? What do you feel you are burdened with? The answers to those questions help you recognize what you need to grieve.
3. TOUCH - You have to touch the loss (as well as all the anger, sadness, bitterness, resilience, compassion and any other feelings you encountered during your loss). 
You're in touch with your grief when you make space for the feelings your loss brought into your life. It may feel counter-intuitive to go back to the feelings that you want so desperately to let go of, but there's simply no way to move through grief without making contact with it, without fully touching it, without fully feeling it. 
You have to pick it up, hold it, feel the weight of it in your hands, on your heart and within your life. You have to feel the whole loss. Grief demands to be felt with an insistence that needs no sleep.  You either allow yourself to encounter the feelings or you remain encased in a shell of yourself under a misguided sense of self-protection.  
4. MOVE - The feeling of grief can linger for so long that you almost befriend the grief.
The grief becomes oddly soothing in its familiarity and its predictability. Dealing with the grief means letting go of this familiarity and moving towards something less predictable and less familiar, which is scary. 
Still, if you want to genuinely address the grief, you have to continue to move through the peripheral, familiar parts of your grief and go right into the epicenter of your grief. As the classic hero's journey goes, you have to get inside the belly of the whale. There (and only there) you will find the door to the unpredictable pieces of life that are patiently waiting for you on the other side of your pain.
Understand your heart is broken.
Recognize why it’s broken.
Touch the grief.
Move towards the epicenter of your grief, as it's the only path to other side of your pain.
Please remember, the grief you're experiencing is yours, and you can carry it with you for as long as you like. Let go of it only when you feel ready-enough, and if you never feel ready, that’s okay. If you do feel ready to move through it, recruit professional support here, or here, or here. Navigating through grief is unpredictable, dangerous terrain. You don’t have to do it alone.
Katherine Schafler is an NYC-based psychotherapist, speaker and writer.  For more of her work, join her newsletter community, read her blog, or follow her on Instagram

Friday, July 28, 2017

Fighting Cancer with the Body’s Immune System

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Immunotherapy Cancer Treatment
Turning our immune system against tumor cells seems like an elegantly simple strategy to defeat cancer. After years of failure, immunotherapy is finally working wonders for some cancers, transforming death sentences into long-term remission. But it doesn’t work in most cancers—at least not yet.
Wouldn’t it be great if your immune system could snuff out cancer as easily as it conquers the common cold? Scientists have been dreaming about that possibility for more than 100 years, but today, the idea of harnessing the immune system to fight cancer is no longer a pipe dream. It’s real—and it’s big.
Wouldn't it be great if your immune system could snuff out cancer as easily as it conquers the common cold?CLICK TO TWEET
“For decades, the backbone of cancer treatment has been surgery, radiation, and chemotherapy. Then we moved to an era of targeted medicine,” explains Dr. Robert Figlin, deputy director of the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute. “Now, we are entering the era of immunotherapy.”
While today’s immunotherapy takes many forms, the most talked-about breakthrough is a class of drugs called checkpoint inhibitors. The drugs have made their biggest splash with melanoma but now are approved for such cancers as kidney, lung, bladder, and head and neck. They’re being studied in dozens more malignancies, and pharmaceutical companies have been filling their pipelines to capacity with new compounds. Clinical trials abound.
But immunotherapy has a sobering side, too. First, revving up the immune system comes with the very real risk that it will go into overdrive, attacking healthy organs. Second—and perhaps most troublesome—immunotherapy doesn’t work for everyone.
Actually, it doesn’t work for most patients.
Now, scientists are on a mission to find out why, while also expanding immunotherapy to more patients and more cancers—without making it too toxic in the process. Along the way, they’re slowly cracking the code to one of cancer’s oldest and most closely guarded secrets: how it evades the one enemy that could easily destroy it.

Checkpoint inhibitors

“Checkpoints” are proteins in our bodies that normally protect healthy cells from immune system attack by attaching to special receptors on T cells (powerful immune cells). The receptors act like “brakes” or “off switches,” and by activating them the proteins tell the T cells, “Stop! Don’t attack; this is healthy tissue.”
“There’s no doubt in my mind that immunotherapy will eventually be a standard in almost every cancer.”
It’s an effective system. But cancer plays a sneaky trick: It uses those same proteins to masquerade as healthy tissue and tell approaching T cells to hit the brakes and turn off. This keeps cancer safe from immune system attack.
Enter checkpoint inhibitors. The drugs block certain checkpoint proteins so cancer can’t use them to disarm T cells. As a result, T cells now have free rein to attack and kill tumor cells.
Since 2011, four checkpoint inhibitors have been approved by the Food and Drug Administration: ipilimumab, nivolumab, pembrolizumab, and atezolizumab.
Not everyone responds to checkpoint inhibitors. In fact, most patients don’t respond at all.
Melanoma patients have had the most success. 30-40% of patients respond when taking just one checkpoint inhibitor; that number nears 60% when taking two drugs. That’s remarkable success for a disease that previously was a near-certain death sentence in advanced cases. But still, only about 34% of melanoma patients on checkpoint inhibitors survive five years or more.
So far, other cancers haven’t been able to match melanoma’s response rates. Kidney, bladder, and non-small-cell lung cancer have the next best results, with about 20-40% of patients responding. In other cancers, like breast and ovarian, response rates are a dismal 10%—the treatment doesn’t work for 90% of patients.

The question: Why?

“We don’t fully know,” says Dr. Omid Hamid, chief of Clinical Research and Immuno-Oncology and director of the Melanoma Program at The Angeles Clinic. “Those cancers might not be as immune-stimulated, and they may have more immune-suppressive factors. So far, we’re not seeing the long-term durable responses with the majority of cancers that we’re seeing with melanoma. We have to do better. But we’ll get there. We’re slowly unlocking it.”
Not everyone responds to checkpoint inhibitors. In fact, most patients don’t respond at all.
One major effort underway is to find more precise biomarkers—substances or molecules in the body that could predict which patients will benefit from which immunotherapy drugs. Finding better biomarkers is especially important because immunotherapy comes with risks and a high price tag—$3,000 or more per infusion.
Biomarkers also could help scientists better understand why certain patients respond so well—and help them re-create those conditions in patients who don’t.
“We have to find out what makes the patients who do respond special,” Dr. Hamid says. “It’s not man or woman. It’s not young or old. It’s likely something in their genome or their mutational status or their tumor microenvironment. That’s our focus.”
Researchers also are working to boost patient response rates. One strategy, which is already having success, is to borrow a page from chemotherapy’s playbook: Combine two or more drugs. Giving two checkpoint inhibitors releases more brakes on T cells, increasing the odds they’ll go after the cancer.
Immunotherapy - T Cells Attacking Cancer
Of course, it also increases risk. And while newer combinations are showing signs of being less toxic, tactics to get more cancers and more patients to benefit from immunotherapy make more side effects seem inevitable.
“The big question is: Is there going to be that sweet spot where you can dial up the immune response enough to get the response you want without tipping into excess toxicity?” says Dr. Jethro Hu, a neuro-oncologist at Cedars-Sinai and an investigator for a Phase II clinical trial studying checkpoint inhibitors in glioblastoma, an aggressive brain tumor.
That over-amping of the immune system is the Achilles’ heel of checkpoint inhibitors. After all, those brakes on T cells are there for good reason. Release them too much and the T cells start attacking healthy organs, including the gut, liver, lungs, and pancreas. An article published last fall in The New England Journal of Medicine highlighted a new concern: heart problems. The study cited rare, scattered cases in which patients died after their immune systems attacked their own hearts, rejecting them as if they were transplants.
The key to preventing problems from escalating out of control is to catch warning signs early and put treatment on hold while calming the immune response, usually with steroids.
“The toxicity profile for some checkpoint inhibitors is modest, but there can be infrequent, life-threatening adverse events,” Dr. Figlin says. “Usually, we can manage those risks. But it’s not like taking a blood pressure pill.”
“We have to find out what makes the patients who do respond special. It’s not man or woman. It’s not young or old. It’s likely something in their genome or their mutational status or their tumor microenvironment.”
When researchers examine tumor tissue from patients who have not responded to immunotherapy, they sometimes see astonishing scenes.
In some patients, they find T cells lined up, completely encircling the tumor but unable to get inside, blocked by some kind of chemical “moat.” Other times, T cells are inside the tumor but not attacking. They’re just sitting there, stupefied, like victims of a “stunning spell” straight out of Harry Potter.
“For a number of patients, activating T cells is not enough,” says Dr. Ronald Natale, director of the Lung Cancer Clinical Research Program at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute. “There’s something inhibiting their trafficking to the tumor and penetrating into it and actually killing the cancer cells.”
Investigators now are studying several novel molecules designed to direct T cells into a tumor and boost their ability to attack the cancer.
In fact, one of the problems with checkpoint inhibitors is that releasing the brakes on T cells only works if the T cells already are trying to mount an assault. It’s like a car: There’s no point hitting the brake and gas pedals unless the engine is running.
That’s likely why checkpoint inhibitors tend to be more successful against so-called “hot” tumors—tumors that have lots of T cells already roaming the area, snooping around, suspicious. Those T cells aren’t killing the tumor, but they’re there and, if you take their brakes off, they’ve got a fighting chance at knocking out the cancer, or at least landing a few well-placed punches.
Experts don’t envision immunotherapy as a substitute for traditional therapies like surgery, radiation, and chemotherapy—at least not in most cases.
Other tumors are “cold,” attracting few, if any, T cells. How do you make a cold tumor hot? The key is to stimulate an immune response. Scientists are now actively testing multiple ways to do this. One strategy? Turn up the heat—literally—with radiation.
“Radiation kills off tumor cells, and when those cells die, they release all of their contents, all these antigens,” Dr. Hu says. “That’s the window when we might have the most opportunity to mount an immune response.”
Indeed, most experts don’t envision immunotherapy as a substitute for traditional therapies like surgery, radiation, and chemotherapy—at least not in most cases.
“There’s no doubt in my mind that immunotherapy will eventually be a standard in almost every cancer,” Dr. Hamid says. “But I don’t see it as a replacement for things like chemotherapy. I see it as becoming another tenet of cancer therapy. It’s going to be its own discipline.”

This post is an abridged version of “The Weapon Inside” from Discoveries magazine, which covers medical research at Cedars-Sinai and its impact on patient care. To learn more about immunotherapy research and see how it’s working for one melanoma patient, read the full story.