Not as We Had Hoped

The results of today’s CT imaging procedure were not as we had hoped. Ideally, the dozen or so tumors in my lungs would have shown signs of shrinkage – indicating that the investigational drug was having a positive effect on the cancer. Instead, several of the tumors actually increased in size and a new spot even appeared in my spleen.

One of the hallmarks of immunotherapy, such as the checkpoint inhibitors, is the potential for a “delayed” response, which is not routinely seen with chemotherapy or other cytotoxic agents. Another biologic phenomenon unique to immunotherapy is “pseudoprogression,” or the initial radiologic appearance of an increase in tumor burden subsequently followed by tumor regression¹.

The CT imaging study cannot distinguish between cancer progression or inflammation as the reason for the increase in tumor size, so there is a chance that it’s due to inflammation and subsequent imaging tests in a month could demonstrate a reversal. However, it is also possible that the cancer isn’t responding to the investigational treatment.

To get more details, I’m undergoing a biopsy this Friday so that one of the lung tumors can be sampled. The preliminary information from that biopsy, which should be available next week, will help guide between cancer progression and inflammation. Decisions regarding how to proceed will depend on that outcome.

Needless to say, everyone’s hope was to have seen some sign of cancer regression on today’s CT scan and many teardrops were shed. The chances for a favorable outcome have diminished and must be acknowledged, but for now I’m persevering and will evaluate next steps following the biopsy results.

Sincere thanks to everyone who has offered their positive thoughts, prayers, and support. It is difficult to respond to each and every communication, but please know that I read “everything” and your time and effort is greatly appreciated. Special thanks to everyone at NIH for being so wonderful — even when faced with delivering bad news.

Now, more than ever, please keep all those positive vibes coming my way.

References:
¹ Amidst the excitement: A cautionary tale of immunotherapy, pseudoprogression and head and neck squamous cell carcinoma. Baxi SS, Dunn LA, Burtness BA.
Oral Oncol. 2016 Nov;62:147-148. doi: 10.1016/j.oraloncology.2016.10.007. Epub 2016 Oct 21.

Positive Mental Attitude (PMA)

Monday evening, my wife Lorie and I traveled to Bethesda, MD in advance of my third infusion with M7824, a completely novel, first-in-class, bispecific fusion protein (see prior posts for more details). However, this was my first time being infused as an outpatient in the day hospital, as prior infusions required a short stay in the hospital for blood work, observation, etc. As with the first two infusions, everything went smoothly yesterday, with no adverse reactions during or following treatment. We caught a 9pm train home and were in bed by 12:30am ET.

image
Caught sleeping on the Amtrak train ride home by Lorie on February 21, 2017. Long day!

As I posted on social media throughout the day while at the NIH, I was truly humbled by the outpour of support – especially hearing from people I haven’t seen in years or decades. Amid the sea of political rants and opinions via these channels, it was nice to be reminded that social media can be a positive experience. Throughout the emails, Tweets, and posts, a lot of people remarked that I sound and appear “surprisingly positive” and “happy.” And truth be told – they’re RIGHT.

Sure, I have advanced cancer – and I’m not Pollyanna about what the future may have in store for me as a result. But, I was very fortunate to participate in a clinical study with a quite promising, investigational immunotherapy that has, so far, had no negative impact on my day-to-day quality of life. That is a very stark contrast from what I experienced after going through chemoradiation. While the outcome is far from certain, participating in this clinical study has given me every reason to “hope” that the therapy will work. And it is that hope that gets me up in the morning…smiling…ready to face the new day.

Michael D. Becker receiving IV infusion with M7824 - a novel, first-in-class, bispecific fusion protein
Michael D. Becker receiving his third IV infusion with M7824 – a novel, first-in-class, bispecific fusion protein on February 21, 2017

If anything has changed recently, it has been for the better. I’m now focusing my existing time and energy where I want, and it has been liberating. Death is always knocking on our doors, but it isn’t until the sound becomes louder later in life that you discover new priorities and sense of urgency. In this regard, I’ve started writing my memoir covering a +20-year biotechnology career and have been working with an amazing editor. I always enjoyed writing blogs and newsletters, but Lorie strongly encouraged me to finally write a book and it has been quite rewarding thus far. My goal is to get it done by late summer or so (30,000 words so far…), and I will definitely let everyone know more details via this blog as the project advances. I also recently started a coffee table book project to showcase my photography work over the past few years, with approximately 200 images selected and a draft layout complete. To fund the latter, I plan on launching a KickStarter campaign to finish the design and secure a larger order to reduce the per unit cost. And most importantly, through my disease openness and this patient blog, I’m exploring numerous opportunities to help raise awareness for currently available vaccines that can protect boys and girls against human papillomavirus (HPV) subtypes that most commonly cause anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancers.

So, yes…I’m a cancer survivor and I’m positive because I have “hope” and will continue until life shows me otherwise. Inspired? Good…that’s my goal!

Finally, special thanks to everyone for the thoughts, gifts and support. Hearing from people I haven’t seen in years has also been amazing. A truly humbling experience and greatly appreciated.

Round Two

It’s been two weeks since my last blog update, so I thought it was about time for a status report.

Earlier today I had my periodic clinic evaluation at the NIH following last Wednesday’s second infusion of M7824. Recall M7824 is a completely novel, first-in-class, bispecific fusion protein of an avelumab-like antibody linked to two molecules of TGF-beta trap (see prior posts for more details). At 22 days into this Phase 1 study, I’m still feeling good and haven’t experienced any side effects. Blood work, vitals, etc. all okay.

Michael and Lorie Becker; Valentine's Day 2017
Michael and Lorie Becker; Valentine’s Day 2017

It was a quick roundtrip between home and the NIH today, which allows me to be back home to spend dinner with my Valentine, wife, best friend and birthday girl (ps – all the same person). Before I headed out for my appointment in the morning, we had a few minutes to exchange cards and snap a quick photo (see right).

I’m now done with the inpatient infusions for the study, so my next dose will be administered one week from today and I can go home afterwards. Here’s hoping for more, completely uneventful updates in the coming weeks!

 

Feelin’ Alright

Standing on the train platform this morning on my way to NYC, the late British rocker Joe Cocker’s version of Feelin’ Alright was playing over the sound system. Not only a good song to start the daily commute, it seemed an appropriate theme for this blog post.

It was exactly one week ago today that I received my first infusion of an experimental cancer immunotherapy agent, called M7824, as part of a Phase 1 clinical trial at the National Institutes of Health (NIH). Recall from my prior post that M7824 is a completely novel, first-in-class, bispecific fusion protein of an avelumab-like antibody linked to two molecules of TGF-beta trap. While very early in the process, I’m happy to report that so far I’m feelin’ alright.

As someone who has received three cycles of chemotherapy and a total radiation dose of 70 Gray over seven weeks, I can say with conviction that, so far, being treated with an immunotherapy agent has been a proverbial walk in the park. In fact, if it weren’t for the fact that this clinical study is not placebo controlled, I would seriously question whether or not I was in the active arm of the study.

For example, in contrast to chemotherapy and radiation, I haven’t experienced any of the hallmarks of traditional cancer therapy, such as nausea or fatigue, with the experimental immunotherapy agent. Important to note, however, every drug has side effects and checkpoint inhibitors like M7824 are associated with their own unique spectrum of immune-related adverse events. These include dermatologic, gastrointestinal, hepatic, endocrine, and other less common inflammatory events. In some cases, these side effects can be managed with corticosteroids or diphenhydramine. Less frequently, clearly defined autoimmune systemic diseases, such as lupus, have been reported.

In fact, approximately 30-40% of patients treated with approved PD-1/PD-L1 checkpoint inhibitors (nivolumab/pembrolizumab) will have dermatologic complications. For most patients, dermatologic toxicity is the earliest immune-related adverse event experienced, with onset an average of 3.6 weeks after treatment initiation¹. Accordingly, it may be too early for me to be experiencing any such side effects.

Of course, having a “safe” drug is important – but for me, the real hope is that M7824 is effective in treating my recurrent disease. In this regard, in an interview with EP Vantage earlier this month, Luciano Rossetti, Merck KGaA’s head of R&D, told EP Vantage that M7824 is “the most exciting clinical asset in our pipeline right now” adding that it has yielded “spectacular” early data. You can read the full interview by clicking here.

I remain hopeful and strongly believe that my generation could be among the last to experience toxic upfront treatments like chemotherapy and radiation thanks to the many advances being made with immunotherapy.

References:

¹ Source: http://www.uptodate.com/contents/toxicities-associated-with-checkpoint-inhibitor-immunotherapy

Complete Response

Cancer - Three Arrows Hit in Red Target Hanging on the Sack on Green Background.

In my prior post, I referenced seeing my head and neck surgeon to investigate recent changes to my voice and swelling in my neck. Although there was nothing suspicious upon visual examination, he wanted to confer with both my medical oncologist and radiation oncologist to determine whether or not an imaging study was warranted. Much to my surprise, I received a call back after the Memorial Day holiday stating that they wanted to move up the date for my first post-therapy PET scan, which was originally scheduled for July 19.

For head and neck cancer, this first PET scan following chemoradiation therapy is a big deal. A “complete response” to therapy based on PET assessment is associated with a high probability of regional control (only 2.3% regional failure rate) and a five year overall survival rate of 79.8% based on long-term follow-up in a large uniform cohort at Memorial Sloan-Kettering Cancer Center (MSKCC, see reference below). With a suspected incomplete response on the first PET scan, the 5-year overall survival rate dropped to 57.0% in the same study.

My PET scan was rescheduled for late in the day last Friday (June 3), which meant that I wouldn’t receive a phone call with the results until today (Monday). It was worth the wait, however, as the report from my PET scan couldn’t have been better. There was no accumulation of the radio tracer in my tonsil, the previously enlarged lymph node, vocal cords or any other area of concern. Sometimes there is inflammation and other artifacts from treatment that radiologists can’t rule out as residual disease and therefore cautious language can be used in the radiology report, which wasn’t the case for me. Additionally, there was a marked decrease in the size of the infected lymph node.

Personally, I’m not a fan of the terms “cure” or “cancer free” – since right now there’s no way for doctors to know with certainty that all of the cancer cells in my body are gone. In fact, some cancer cells can remain unnoticed in the body for years after treatment. So for now I prefer to embrace the phrase “complete response,” which references the disappearance of all signs of cancer in response to treatment.

If cancer cells do come back, it often happens within the 5 years following the first diagnosis and treatment. In this regard, I’m optimistic about the expected 80% 5-year survival rate  – especially when compared to some other aggressive cancers, such as pancreatic cancer, which is associated with a 5-year survival rate of only 8% (American Cancer Society. Cancer Facts & Figures 2016. Atlanta: American Cancer Society; 2016).

I meet with my radiation oncologist in a few weeks and will learn more about how frequently I will need to have follow-up PET scans and other visits. Until then, I’m trying to digest the positive news, looking forward to slowly regaining some control over my life, and appreciating the coincidence that yesterday cancer survivors and supporters in communities around the world gathered to celebrate the 29th annual National Cancer Survivors Day® (June has been designated National Cancer Survivors Month).

Thank you to everyone (far too many to name…) who supported me during this difficult period – but especially my wife Lorie who has been absolutely amazing through all the ups and downs (luvya!).

References:

Int J Cancer. 2013 Sep 1;133(5):1214-21. doi: 10.1002/ijc.28120. Epub 2013 Mar 29.
Long-term regional control in the observed neck following definitive chemoradiation for node-positive oropharyngeal squamous cell cancer.
Goenka A, Morris LG, Rao SS, Wolden SL, Wong RJ, Kraus DH, Ohri N, Setton J, Lok BH, Riaz N, Mychalczak BR, Schoder H, Ganly I, Shah JP, Pfister DG, Zelefsky MJ, Lee NY.

Three Month Mark

Hard to believe, but later this week will be the three-month anniversary since I finished chemoradiation. Unfortunately, it’s also been nearly that long since my last blog post, although I did write a brief article for Cure Magazine published in April 2016 that can be viewed here.

I haven’t been writing much lately because I wanted this blog to be somewhat uplifting and inspirational. Frankly, the past few months have been extremely frustrating and difficult. It occurred to me, however, that sharing the bad along with the good may be equally important to others facing head and neck cancer. So here it goes…

In my last post from March 2016 I noted that my weight declined by 20 pounds since the start of chemoradiation. I’m now down a total of about 30 pounds (which I still think is okay since I was overweight to start). The additional weight loss comes from a combination of taste disturbances, reduced salivary output, and general loss of appetite during the period.

I’m pleased to report that my taste buds are now ~90% back to normal and that “most” foods taste the same as before therapy. Unfortunately, my saliva output is still greatly diminished and eating dry foods, such as bread, is very challenging. I have managed to eat a hamburger by taking off the top bun and eating the rest with a fork and knife along with a fair amount of ketchup. The biggest issue relates to a general lack of interest in eating, which I originally thought was due to the taste disturbances. Most days I have a high protein, nutritional shake for both breakfast and lunch and then a “normal” dinner and dessert. I haven’t been out to a restaurant since the start of therapy, as I am self-conscious about my eating habits.

Fatigue is still an issue, although it has improved over the past month or so. I returned to work full-time around mid-March, which meant getting up early and commuting to New York. Until recently, I would come home and literally pass out on the couch from exhaustion at the end of the day. Now I am able to stay awake through dinner, watch some television, and go to bed at a reasonable hour. I do still sleep on the morning train ride to New York and look forward to the weekends where I normally sleep until noon or later to catchup on rest.

The one major issue I haven’t discussed at length in this blog is the psychological impact of being a cancer survivor – namely depression. Societal expectations have taught men not to display any emotions. We are trained from an early age to be confident, stoic and strong. It is extremely difficult to fulfill this role or expectation as a male cancer survivor. On more than one occasion I have burst into an emotional crying session lasting a good 15-minutes. I’m not talking about the quiet episode of crying with sniffles and a tear or two down the side of your cheek. I mean full-fledged bawling your eyes out accompanied by nasal discharge and the near inability to speak normally – “I…I…I…nuh…na…nah…need…ah…uh…t…t…tis…tissue.”

The first such breakdown occurred around the start of chemoradiation when my wife and oldest daughter first came to my temporary apartment in New York. In retrospect, I had bottled up all of the emotion from first discovering the growth on my neck, to receiving a formal cancer diagnosis, to my first infusion of chemotherapy, etc. and let it all out at once. More recently, however, I broke down after showering the morning of my oldest daughter’s prom. I started to think about how happy I was to get home from New York during therapy to see my youngest daughter for her freshman formal and recalled the photographs from that evening with my neck visibly red from the radiation therapy. Then I started to think – are these going to be the last “big” events I will be around to see for each of my daughters? That spiraled into a series of awful “what if” questions that left me in a giant puddle.

Most of the time I am able to maintain a positive outlook and not let cancer “win” by occupying my every thought (insert ZOLOFT® ad here…). This is made harder by the requirement for periodic tests and imaging studies to determine whether or not the cancer has returned. Aside from those periodic tests, it feels like I am constantly watching over my shoulder for signs or symptoms of cancer’s return.

For example, in early May my wife noticed my voice had changed. At first she dismissed it as that froggy, lower tone you sometimes get first thing in the morning or when you have a head cold. But it didn’t go away and eventually even I noticed it. Subsequently, I found that the neck area under my chin was swollen. My first thought was “#@$&!” – the original cancer had now spread to the vocal cords, larynx (voice box), or other areas of the throat, as these would all be relevant symptoms. I saw my head and neck surgeon last week and he didn’t see anything suspicious upon visual examination. His initial diagnosis was that the voice change and neck swelling were simply the after-effects of radiation therapy, which can manifest even months after treatment. Nonetheless, he wanted to confer with both my medical oncologist and radiation oncologist to determine whether or not an imaging study is warranted. In the meantime, I’m trying to adjust to my new bass-baritone “Barry White” voice…which may or may not return to normal.

So that’s about it…you are now caught up on my life over the past few months. The next major event will be my PET scan on July 19, which will be the first such imaging test following treatment. Still hoping for a positive outcome from that study and will update as appropriate.

 

Home Sweet Home

This week I was able to move out of my temporary apartment in New York and return home to Bucks County, PA. I don’t know whether it was being away from the loud traffic noises or just finally sleeping in my own bed, but the first night home was the best night’s sleep I’ve had in weeks.

As predicted by my physicians and nurses, the weeks following chemoradiation were the most difficult in terms of toxicities due to the delayed effects of therapy. For me, week #8 was the worst and I required additional hydration pretty much every other day during that week. This was due to the fact that my electrolyte levels, in particular magnesium, were low. Fatigue was probably the greatest side effect, but in general I just felt like I had a really bad case of the flu.

By week #9 the physicians indicated that my electrolyte levels had stabilized and/or improved, meaning that I didn’t require as frequent hydration. That gave me the freedom to return home since I didn’t need to be near MSKCC.

My salivary output and taste buds are still off as a lingering effect from the chemoradiation therapy, although I understand they should return over time. This makes it difficult to eat – or at least find food that is appealing. I’ve lost more than 20 pounds since the start of treatment, which doesn’t disappoint me as much as my doctors.

I’m hoping to return to my daily commute to NY for work later this week and get back to a relatively normal life. The radiation burn marks on my neck are nearly gone and you’d hardly know by looking at me that I just went through seven weeks of pure hell.

My post-treatment visit with Dr. Nancy Lee has been scheduled for mid-May 2016 which is when I’ll get my first update on the treatment efficacy. She did order a PET scan on my last day of treatment, which looked encouraging although you cannot draw any definitive conclusions at this early stage. Nonetheless, there was decreased fluorodeoxyglucose (FDG) uptake in the right tonsil and in the rim corresponding with the neck nodal mass. Interestingly, the neck nodal mass also originally measured 4.0 x 2.6 centimeters and now measures 2.3 x 1.6 centimeters, which is a dramatic decrease in size.

Week #7 – Done and Done

Friday marked the last day of my seven week chemoradiation therapy journey. Aside from some routine follow-up appointments and recovering from lingering toxicities, I will now wait several months for the repeat PET scan that will provide some insight as to whether or not the treatment was a success. Of course, I’m trying to stay optimistic that the combination of radiation and chemotherapy treatments that I endured over the past seven weeks successfully eliminated all of the cancer – but there is always that nagging thought that it did not and that leaves a pit in my stomach.

Michael Becker's Radiation Mask
Michael Becker’s Radiation Mask

Fortunately, on Friday I was able to take home with me the dreaded radiation mask (see enclosed image). No longer will I need to wear this mask for daily radiation therapy, which makes me VERY happy. The nuclear technicians offered humorous insight as to what other patients do with their masks after radiation treatment is done.  Some make decorative items, such as flower pots. Others simply burn them in a sadistic revenge ceremony, which I must admit holds a certain type of appeal. Although it somehow conjures up thoughts of Darth Vader’s helmet, last seen burning in a funeral pyre in ‘The Return of the Jedi,’ winding up in the hands of Kylo Ren in the ‘Star Wars: The Force Awakens’ movie…

Regardless of what I do with my mask, I am enjoying a certain freedom knowing that I’m no longer beholden to a daily treatment schedule and that I have received the very best treatment possible for my disease by the entire team at Memorial Sloan-Kettering Cancer Center (MSKCC). It is amazing how quickly the seven week treatment cycle passed and it all seems like a blur right now. While I did not look forward to the daily radiation treatment, the appointments were at least a reminder that I was doing something to treat the disease. Now I have that same empty feeling that plagued me when I was first diagnosed and searching for the best treatment – the feeling that I should be doing something but cannot.

Snake Eyes

It seems as though each time I make an optimistic blog post, something goes wrong. Since my last post was titled “Lucky Seven,” it seemed appropriate to keep with the gambling theme and title this one “Snake Eyes.” For those unfamiliar with the term, a throw of two ones with a pair of dice results in the lowest possible score, and by extension the term is also used to reference bad luck¹.

image
Snake Eyes

Today was supposed to be the start of my final round of chemotherapy, with the second and final day on Tuesday. Sunday night, however, I started running a temperature of 102 degrees Fahrenheit that prompted my second trip to the urgent care center at MSKCC over the weekend. The obvious concerns being influenza, bacterial infection, etc. that would delay receiving chemotherapy.

After a variety of tests, influenza and infection were ruled out. While it is possible to run a low grade temperature from daily radiation, a high temperature such as mine is unexpected. This left all of us wondering what was causing my fever and why it was so high. Since there was no immediate cause for concern, they decided not to admit me overnight and said that I could use Tylenol for the fever. They acknowledged that it was unlikely I’d be receiving chemotherapy on Monday.

The next day (Monday) I saw Nicole – the nurse practitioner. I could tell she was on the fence proceeding with chemotherapy that day given that my temperature was again above 100 degree Fahrenheit. She conferred with Dr. David Pfister my medical oncologist and they opted to be cautious and postpone chemotherapy by one day. The only good news is that this shouldn’t change my final day of chemoradiation therapy which is this Friday.

Around the time of my daily radiation treatment, my temperature had dropped to low grade and I’m hopeful that we can continue with chemotherapy tomorrow morning. Separate from having cancer or receiving treatment, my lower back pain continues to be a problem so they switched me to some stronger opioid medications. I’m not talking minor pain or discomfort – but rather debilitating pain making it tough to get out of bed or getting up from a sitting position. I’ve experienced lower back pain issues in the past, but they usually only last a day or two and aren’t this severe.

It’s the final stretch and I “should” be done with therapy this Friday, so I’m trying not to complain. Hopefully these are just minor speed bumps on the road to Friday and then recovery. Until then, keep those thoughts, prayers, and good vibes coming!

¹ http://wordsmith.org/words/snake_eyes.html

 

Visit Home Cut Short

A repeat of my bloodwork confirmed that the elevated serum creatinine levels were a concern regarding my kidney function, so the physicians ordered more intravenous hydration with saline and potassium to flush them out. As mentioned in my prior post, this is a common issue with chemotherapy (cisplatin).

They originally wanted to do the hydration Friday late afternoon. Unfortunately, that would have interfered with my getting back to Pennsylvania in time to see Megan before her Freshman formal dance. After explaining the situation, they came up with the solution of hydrating Saturday instead. While this would allow me to see Meg, it made for a short trip to Pennsylvania before heading back to NYC.

Michael And Megan Becker photographed by Saron Mastrosimone
Michael And Megan Becker photographed by Sharon Mastrosimone

It was definitely worth the short trip. Our friend and fellow photographer Sharon Mastrosimone was kind enough to come over and take pictures before the dance. The image in this blog post is one of my favorites and alone made the night worthwhile. Many thanks Sharon!

So, here I sit at MSKCC with Lorie getting hydration on a Saturday afternoon instead of being back home in Pennsylvania. But I’m doing it with a smile on my face looking at pictures from last night. Megan looked beautiful and I’m so glad I was able to be there.

Radiation Dermatitis

During Week #5, another common side effect from chemoradiation treatment emerged – radiation dermatitis. Just like oral mucositis discussed in a prior post, radiation dermatitis is graded on a scale – with Grade 1 being mild and Grade 4 being severe. In most patients, radiation dermatitis is mild to moderate (grades 1 and 2), but ∼20%–25% of patients experience severe reactions¹.

Photo of Michael Becker's neck with mild/moderate radiation dermatitis.
Photo of Michael Becker’s neck with mild/moderate radiation dermatitis.

Right now, I have mild to moderate radiation dermatitis on my neck in the area that is being targeted. This is characterized by mild erythema (red rash), which you can see in the accompanying image. The more severe forms of radiation dermatitis are associated with itchy, peeling skin and ultimately open wounds and ulceration. I’m hoping that my condition doesn’t advance to those stages.

The treatment for radiation dermatitis is basically keeping the skin moist by applying Aquaphor ointment. No creams or ointments have shown superior efficacy over another in randomized clinical trials.  This includes topical steroids and other agents.

Other than that, there is some indication that my kidney function might be impaired due to elevated serum creatinine levels. They are still running more tests, but worse case would be more frequent intravenous hydration to flush out the kidneys. Kidney function can be negatively impacted by the chemotherapy (cisplatin).

I did have intravenous hydration today and have been feeling pretty good overall. Fatigue is still my major complaint, but also par for the course.

¹ Consensus guidelines for the management of radiation dermatitis and coexisting acne-like rash in patients receiving radiotherapy plus EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck. Ann Oncol (2008) 19 (1): 142-149. doi: 10.1093/annonc/mdm400. First published online: September 4, 2007