Scan 58: Still NED, but needing a new shoulder

My semi-annual CT scans on Thursday were negative for metastatic disease ("No Evidence of Disease"). I like NED. My current remission turns 4 years old this month. Let's hope it continues for many more.

My left shoulder, however, has decided that it's done with me. I've been getting cortisone injections for 5 or 6 years, but those stopped working earlier this year. I have constant low-grade pain in my left shoulder, and moving it feels like my clutch has gone out and I'm grinding gears. I'd held off on doing anything more about it because, you know, I was going to die soon from cancer and so why subject myself to a shoulder replacement. But as it now seems that I'm not going to die in the near future, I've decided to do something about my unfunny humerus. I had some x-rays, consulted with a couple of orthopedists and was told that it was bone-on-bone, and it's only going to get worse. So I had a shoulder CT scan done when I got my others done, and the radiologist found

Severe glenohumeral osteoarthritis with bone-on-bone apposition, prominent marginal osteophytes, mild subchondral cystic changes and sclerosis. Posterior decentering of the humeral head with chronic posterior glenohumeral osseous remodeling. Multiple intra-articular ossific bodies, the largest which measures up to 12 mm in the subscapularis recess.

The good news is that my rotator cuff seems ok. I had an MRI yesterday to give further clarity, and was reminded how much I hate being stuffed in an MRI tube. I'm scheduled for a shoulder replacement on July 5. It's a strange way to celebrate my turning the corner on a durable remission, but what the hell. I'm still not going to see the dentist, however. I'll need a lot longer remission before I'm prepared to do that.

NCI Patient Advocate Seminar and Durability Data

On Friday May 10 I attended a Patient Advocate seminar at the Nation Cancer Institute in Bethesda Maryland. The seminar was to train new patient advocate volunteers, who sit on committees or task forces and help review clinical trial proposals. I, along with two other experienced patient advocates, were invited to share our experiences. Throughout the day we old-timers chimed in with our thoughts, then we wrapped up the conference with a panel. I was the mop-up guy since the moderator had to leave early. It was a good experience to meet with a mentor the volunteers who had experienced cancers, either themselves or as a caregiver, and who were willing to help remind clinicians and researchers about the person on the pointy end of the needle. 

The keynote presentation was by Dr. Stephanie Goff, a senior research physician in NCI's Center for Cancer Research. Her presentation was on immunotherapy for cancer, the when and the why. With Dr. Goff's permission, I am including her slide deck in this blog post. Her first four slides set the stage for using immunotherapy to treat cancer:

Dr. Goff's presentation focused on a subject that is of particular interest to me: how immunotherapy has increased "the tail of the curve" and helped raise the number of long-term survivors:

These charts, called Kaplan-Meier curves, graphically illustrate how long patients live after being diagnosed with various types of cancers. For example, when I was diagnosed in 2011, a Kaplan-Meier curve for metastatic bladder cancer patients between 2000-10 showed that 80% had died within two years, and 95% had died within 5 years. The chart ended at 6.5 years, suggesting that no one in that study had lived longer than that. I've learned that the focus of modern cancer research and treatment is to extend life -- to "raise the curve" -- instead of an audacious goal of "curing" everyone with one treatment. 

Dr. Goff's presentation covered the development of immunotherapy therapies:

I was astonished to hear Dr. Goff explain that there was reported data for certain cancers that had been treated with immunotherapy which showed that there is a subgroup of patients who have been treated with immunotherapy and have experienced "durable life-long regression of metastatic cancer" (slide 9):

That conclusion -- "immunotherapy can mediate durable life-long regression of metastatic cancer" -- is as close as a skilled researcher will get to the loaded "c" word: cure. Researchers do not like to speak of a cure for cancer, because "cure" is a loaded word, maddeningly vague and weighted with hope to laypersons. Instead, they speak of "progression-free survival" (PFS) and "no evidence of disease" (NED). I've learned to avoid using the "c" word and to orient my thinking around the durability of my remission. And as I approach the fourth anniversary of my fourth and current remission, I continue to nurse a hope that maybe, just maybe, this one will in fact be durable. 

Dr. Goff's presentation reinforced an emerging acceptance of the fact that I might not soon die from cancer. For 12 years I've stood on the precipice of death, with scans every 12 weeks to assess whether my mets have returned. On four different occasions those scans have revealed new metastatic activity: first in April 2012, second in September 2013, third in August 2014, and fourth in February 2017. I'm now four years into my fourth remission, and gradually am accepting that I might, just maybe, live a bit longer than I've expected. But still I doubt. 

The next dozen of of Dr. Goff's slides illustrate when immunotherapy is indicated, and provides examples from several types of cancers of immunotherapy successes. (slides 10-21)

This data from CRI is fascinating. On their CRI, you can click on each datapoint and bring up the underlying studies and drug approvals for each of the listed cancers or drugs. It's incredible to see how rapidly the landscape has changed for approving new immunotherapy drugs for so many different cancers. 

Interestingly, the data suggests that cancers with high mutations (like my bladder cancer) are more likely to respond to immunotherapy:

Dr. Goff's conclusion was that checkpoint blockage immunotherapy, like the Nivolumab therapy that I've had, is "more likely to lead to a long duration response than chemotherapy":

Dr. Goff closed with a caution of how much we still don't know: while immunotherapy can have a durable benefit (still avoiding the "cure" word), we don't have sufficient predictive tools of whether immunotherapy will work on any specific patient. The biomarkers from genetic sequencing of tumors are not consistently predictive or whether immunotherapy will work. Likewise, biomarkers do not predict which which patients will suffer which adverse side effects.  In addition, new immunotherapy drugs are being approve not based upon overall survival (OS), which is the best data for drug approval, but instead upon progression-free survival (PFS) or relapse-free survival (RFS). True, these drugs show a promising capacity to extend life, but more time is needed to give definitive proof. But this class of drugs shows great promise, and without a doubt has saved my life. 

Jennifer's Obituary

Jennifer Marberger Brothers 

Jennifer Marberger Brothers eased into immortality on January 6, 2024, after 60 years of love, compassion, and grace. Born in Chicago, IL on the first of April 1963, she was nobody’s fool. Raised in Ogden, she was a beacon of mindfulness and creativity, known for her caring and thoughtful approach to life. She was a woman of many talents and accomplishments, including a Sterling Scholar at Ogden High School (class of 1981), a Spencer W Kimball Scholar at BYU (class of 1984), an empathetic therapist and social worker, and skilled artist and musician. Most importantly, she partnered with her husband, Ken, whom she married in 1983, as they raised four children as they lived in the Washington, DC area between 1985 and 2018. After she was diagnosed with frontotemporal dementia at the age of 54, her family moved back to Utah and Jennifer resided at memory care facilities in Layton, Utah.

In her professional life, Jennifer was a talented designer who worked in the creative side of advertising and commercial design in the 1980s. She helped establish supplemental art programs at five different schools in the Washington, DC area. In the 2000s, Jennifer began working with adolescents in crisis, which led to her earning a Master of Social Work from George Mason University in Fairfax, Virginia. Jennifer was an award-winning watercolor artist and a skilled musician on the silver and spirit flute; she led groups in art and music therapy, organized djembe drum circles, and taught clinics at schools and non-profit organizations in Maryland, Virginia, and West Virginia. She was a dedicated social worker who ceaselessly provided mindful service to others. Jennifer loved to share her creative spirit with others, making her an inspiration to hundreds of students, clients, friends and family.

Jennifer’s life was a testament to her compassion and thoughtfulness. She was a woman of faith and provided lifelong service to her neighbors and community as a member of The Church of Jesus Christ of Latter-day Saints. She loved to serve and worship in the temple. She believed in prayer and in her years of illness often asked those around her to pray with her. She had a deep and abiding respect for the Lakota culture and participated in sweat lodges, drum circles, and sun dances. What mattered most to her was raising her four children with her husband, Ken Brothers. She is survived by her husband Ken, who moved back to Huntsville when she entered memory care, her daughters Chelsea Slade (Josh; Huntsville, Utah) and Kirsten Brightman (Jason; Parker, Colorado), her sons Spencer Brothers (Layton, Utah) and Garrett Brothers (Salt Lake City, Utah), her father and stepmother, Douglas and Liz Marberger (Uintah, Utah), her sister, Jamie Campbell (Brad; Enoch, Utah), half-siblings Adam Marberger (Heidi; Salt Lake City, Utah), Jack Marberger (Kristen; South Ogden, Utah), Abby Cragun (Chet; Layton, Utah), and her 7 grandchildren. Jennifer was preceded in death by her mother, Narlene Baird.

Jennifer loved travel and adventure. After she and Ken graduated from college, they spent a summer backpacking through 14 European countries. She frequently returned to Europe with family and friends. She loved exploring the Mayan ruins in Yucatán and Peru, witnessing the wonders of God’s creations on safaris to South Africa and Botswana, and delighting in the diversity of the Galapagos. She and Ken were certified scuba divers and they enjoyed exploring reefs and wrecks in the Caribbean. She looked forward to basking on ocean beaches and collecting seashells from different states and countries. Years later, she could pick up one of her shells and identify the beach and date of its discovery.

Some of our best memories with Jennifer were days boating on Lake Anna in central Virginia with the family poodle, Nephi. She made a dynamite chicken broccoli casserole. She kept a paper planner her entire life and reveled in her analog methods. She earned a black belt in taekwondo in her 40s. She tolerated Ken’s awful puns to beyond a reasonable degree. She would laugh until she cried while watching “Whose Line is it Anyway?” We will forever miss our sweet wife and mother.

Jennifer’s life was a symphony of love, creativity, and service. Her legacy will live on in the hearts of those she touched with her art, her music, her service, and her kindness. Those who knew Jennifer are encouraged to share their memories and upload photos to her memorial page as a tribute to her vibrant life. Let’s keep the memory of Jennifer alive and celebrate the remarkable life she led.

Funeral services will be held at 11 am on Saturday, January 13, 2024, at Myers Mortuary, 845 Washington Blvd., Ogden, UT, a viewing will be held prior from 9:30 to 10:30 am. Interment, Ben Lomond Cemetery.

In lieu of flowers, the family encourages donations to the Chris Atwood Foundation (www.thecaf.org).

Condolences may be sent to the family at https://www.myers-mortuary.com/obituary/Jennifer-Brothers-1#obituary.

Published on January 8, 2024 in the Ogden Standard Examiner

 

No hard feelings

No Hard Feelings

When my body won't hold me anymore
And it finally lets me free
Will I be ready?
When my feet won't walk another mile
And my lips give their last kiss goodbye
Will my hands be steady when I lay down my fears, my hopes, and my doubts?
The rings on my fingers, and the keys to my house
With no hard feelings

When the sun hangs low in the west
And the light in my chest won't be kept held at bay any longer
When the jealousy fades away
And it's ash and dust for cash and lust
And it's just hallelujah
And love in thought, love in the words
Love in the songs they sing in the church
And no hard feelings

Lord knows, they haven't done much good for anyone
Kept me afraid and cold
With so much to have and hold
Mmm, hmm

When my body won't hold me anymore
And it finally lets me free
Where will I go?
Will the trade winds take me south through Georgia grain?
Or tropical rain?
Or snow from the heavens?

Will I join with the ocean blue?
Or run into a savior true?
And shake hands laughing
And walk through the night, straight to the light
Holding the love I've known in my life
And no hard feelings

Lord knows, they haven't done much good for anyone
Kept me afraid and cold
With so much to have and hold

Under the curving sky
I'm finally learning why
It matters for me and you
To say it and mean it too
For life and its loveliness
And all of its ugliness
Good as it's been to me
I have no enemies

 

by the Avett Brothers  (link)

Jennifer died yesterday

Tomorrow, and tomorrow, and tomorrow,


Creeps in this petty pace from day to day,


To the last syllable of recorded time;


And all our yesterdays have lighted fools


The way to dusty death. Out, out, brief candle!


Life's but a walking shadow, a poor player


That struts and frets his hour upon the stage


And then is heard no more. It is a tale


Told by an idiot, full of sound and fury


Signifying nothing.

 

(Macbeth Act 5, Scene 5, lines 17–28)

Howling at the moon

I've held off on any new posts because my focus has been on holding my shit together while my wife is dying. Jennifer has been in memory care for more than six years due to her disastrous diagnosis of early onset dementia (frontotemporal dementia). She has been slowly declining and a couple of months ago was placed on hospice. She's transitioning. No one knows how long she will live. We've had active dying, vigils, rallies, stable status, and all of the misery in between. People look to me to be the source of information and coordinator of everything and it's exhausting. I don't know how many times I've been told that it's hard, they're sorry, blah blah blah. Tell me something I don't know. Worse is when people ask me what can they do. There is no socially acceptable answer that is honest. How about you find a cure for FTD? I'm bone-weary of putting on a happy face and placating others who just want a pat on their head and go on with their lives. 

Earlier this year one of Jennifer's doctor's told me that the woman I married 40 years ago no longer existed: FTD took Jennifer from me in 2017, but her body kept going. When I visit her each day, I feel that I am performing a duty while honoring the memory of a relationship. The crush of the passage of years has weighed down on my soul. I've looked for alternative sources of joy with some success: travels, spending time with family, long motorcycle rides, reconnecting with old friends, skiing. But the trip or the visit ends, and I'm right back where I was before, wading through my cesspool of loneliness and pain, witnessing the savage silence of my wife whither into nothingness.

My six month scans showed no evidence of disease. I am doomed to continue on alone. 

And so it goes.

Three years of remission, fewer scans in my future

Last fall I reserved a place in a University of Utah-sponsored tour of the D-Day Beaches and battle sites in Normandy. It was an amazing trip, led by a retired Colonel and our group of 17. It was humbling to stand on Omaha beach at low tide and look at the 500+ yards those Americans had to walk under murderous crossfire before they could even fire any weapons. Our guide told us that we could draw a circle with a 10 foot radius anywhere on that beach and it would intersect with a spot where a GI died on June 6, 1944. Yet they persevered and within six hours had broken through the beach defenses, starting the liberation for France and Western Europe. My 10-year old mother was living with her family in occupied Holland and eagerly followed the news of the allied invasion, eagerly awaiting the arrival of the American soldiers. It would take another eleven months for Germany to surrender. Six years later, my mother and her family emigrated to America. She carries with her a profound gratitude for the soldiers who fought to give her and the rest of Europe her freedom. As I stood on that sacred sand and later at the American Cemetery, I uttered a prayer of gratitude for those GIs.

The D-Day tour was a week long. I decided that I didn't want to just spend a week in Europe and considered my options, finally settling on Croatia. After briefly considering renting a motorcycle and exploring the country on two wheels, I realized it would be better to be joined by family. I offered to pay for the flights and lodging, and three of my four kids accepted (My oldest, Chelsea, is expecting and was unable to join us.) Each of the kids selected a different destination for the first week in Europe (Amsterdam and Prague for Spencer; Switzerland and Northern Italy for Kirsten and Jason; Paris and Milan for Garrett), then we all met in Dubrovnik. We explored the Adriatic Coast, going from Dubrovnik to Korcula to Hvar to Split. Everyone seemed to have a good time. It was also a bit poignant, as I realized that it might be the last time that all of us would be able to visit Europe as a family.

Last Thursday, I had another scan (number 56 for those keeping score). It was routine. Dr. Maughan got the quick readout and told me that there was no sign of any metastatic disease. This remission started in June 2020, with the elimination of my last persistent tumor through radiation. Dr. Maughan was pleased to mark my three-year anniversary of being disease-free. We discussed the big question: how durable was this remission. Dr. Maughan drew upon the studies of metastatic melanoma and renal carcinoma -- two cancers where nivolumab had been tested on patients prior to my first enrolling in the clinical trial in January 2015. He said that, for a small subset of each cohort (14% for melanoma, 7% for renal), patients had a complete and durable response. If those patients made it to 24 months without a relapse, then the likelihood of relapse dramatically decreased. Put another way, the Kaplan-Meier curve of the cohort flattened after 24 months. Dr. Maughan was cautiously optimistic that, because I was disease-free after 36 months, the odds of my relapsing were very low. He proposed, and I agreed, that we wait six months for the next scan, and stay on that schedule for two years. If I make it to five years without a relapse, then we'll discuss extending the period between scans to a year. 

This is a dramatic shift from the past eleven years. Wen I was first diagnosed with metastatic disease in April/May 2012, my odds of dying within 2 years was 80%, and 95% odds that I'd die within 5 years. Of course, that data was accumulated before immunotherapy revolutionized cancer therapy. Plus I have had the very good fortune to have received a complete response. I had one post-immunotherapy relapse in early 2018, and it took another two years and four months before I was once more NED (no evidence of disease). 

In the past few months, as this emerging promise of a durable remission became more clear, I have shifted my life view from waiting for death to looking forward to life. I have been given a new lease on life, and I am still adjusting my mindset on how to live it. Stay turned for future developments.

This is not to say that everything is peachy-keen. Two of my three scans had some troubling non-cancer findings: my neck scan confirmed that my left vocal cord was still paralyzed, and I had "moderate left spinal canal and neural foraminal narrowing at C3-C4. And my chest scan noted a hiatal hernia, and my lungs showed "moderate multiregional mosaic attenuation pattern in the lungs, suggesting a small airways or small vessel disease."

 

I emailed Dr. Maughan and Dr. Slade (my daughter) about those findings. Dr. Maughan said that he was focused on looking for metastatic disease and apologized for not discussing the non-mets findings. He explained that I had increasing arthritis in my neck, that I might be having some acid reflux from the tiny hiatal hernia, and the lung inflammation could either be secondary to that, or more likely the residue of a cold. I could follow up with a GI doc or pulmonologist if the problems persisted. Chelsea was more definitive: I'm getting old and had a cold. Don't sweat it.