Watching the Calendar

Earlier this week, Lorie and I made our biweekly visit to the National Institutes of Health (NIH) for my infusion of the experimental agent M7824. The two day trip was uneventful and included a variety of imaging and other diagnostic tests, including an ultrasound of my spleen and a chest x-ray to monitor the pleural effusion in my left lung.

Fortunately, all of the tests came back fine and I was cleared to receive my regular infusion of M7824. As with all the previous treatments, there were no adverse reactions and we returned home later that evening.

However, with the month of July rapidly approaching, I can’t help but start to feel quite anxious. This is due to the published results from Bristol-Myers Squibb’s “CheckMate 141” phase 3 trial with Opdivo® (nivolumab), an anti-programmed death 1 (PD-1) monoclonal antibody also known as a checkpoint inhibitor. In that study, 361 patients with recurrent squamous-cell carcinoma of the head and neck (SCCHN) whose disease had progressed within 6 months after platinum-based chemotherapy were assigned, in a 2:1 ratio, to receive Opdivo every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end point was overall survival.

Treatment with Opdivo resulted in longer overall survival than treatment with standard, single-agent therapy. The median overall survival was 7.5 months (95% confidence interval [CI], range 5.5 months to 9.1 months) in the Opdivo group versus 5.1 months (95% CI, 4.0 months to 6.0 months) in the group that received standard therapy.

Recall from prior posts that M7824 is a completely novel, first-in-class, bispecific fusion protein of an avelumab-like, anti-PD-L1 antibody linked to two molecules of TGF-beta trap. Therefore, I always viewed M7824 as a “potentially” superior alternative to Opdivo given its added mechanism of action, hence my strong interest in participating in the M7824 clinical trial.

Assuming for a moment that M7824’s treatment effect is at least comparable to Opdivo, and considering that my disease recurred around December 2016, an expected survival of 7.5 months would translate to the July/August 2017 timeframe.

To be fair, an apples-to-apples comparison of Opdivo and M7824 isn’t possible. However, the results of Bristol-Myers Squibb’s “CheckMate 141” trial serve as a contemporary data set for checkpoint inhibitors in the treatment of recurrent SCCHN and are definitely something that I keep my eye on.

Lorie and Michael Becker enjoying ice cream in Bethesda, MD

Barring any surprises, I’ll continue biweekly treatment with M7824 and then repeat imaging in July to see whether or not my disease has progressed. In the meantime, I’ll continue to savor simple moments like enjoying ice cream on a warm summer evening with my wife (see photo).

Roller Coaster

It’s been a couple of weeks since my last clinical post, so I wanted to provide an update following this week’s NIH appointments.

Michael Becker pleural effusion
Xray images of Michael Becker’s chest showing pleural effusion both before and after drainage

First, surgical insertion of my Aspira® drainage system has dramatically improved the pleural effusion in my left lung. It’s essentially a chest tube/catheter that allows me to drain the fluid buildup on an as-needed basis into drainage bags at home. The image to the right shows before and after chest x-ray images that demonstrate just how blocked my left lung was before being drained (nearly 2/3 blocked). It also shows how my left lung is now “close” to normal following drainage.

Second, I’ve been on prednisone (steroid) to help “sculpt” the inflammatory response, which is also helping keep the fluid from building up so quickly in my left lung. Whereas I was emptying 100 mL or more on a daily basis previously, I am now only draining 15-20 mL every other day or so.

Now that the pleural effusion can be managed, attention returned to whether or not to resume treatment with M7824, a completely novel, first-in-class, bispecific fusion protein (see prior posts for more details). My last infusion of M7824 was several weeks ago.

Following another CT scan and constructive discussion with the NIH team, we came to the conclusion that there is essentially a tug-of-war occurring between the cancer in my lungs and my body’s immune system, the latter of which appears to be benefiting from M7824. The hope is that eventually M7824 will tip the scale in favor of my body’s immune system and control the cancer.

Michael D. Becker receiving IV infusion with M7824 – a novel, first-in-class, bispecific fusion protein on May 16, 2017

Accordingly, the decision was made to keep moving forward with M7824 and I received an infusion on Tuesday, May 16, 2017. As with past administrations, there were no issues and I returned home to Pennsylvania with Lorie later that evening.

The pleural effusion will be monitored closely and managed via the catheter and steroids. As long as there are no major issues in terms of fluid in my lung, I will continue to receive an infusion of M7824 every other week. A repeat CT scan will be done in a month or so to reassess the situation.

Honestly, Not Such a Good Friday

This past Wednesday, I had a thoracentesis procedure in which a needle was inserted into the pleural space between my lungs and chest wall. This procedure was done to remove excess fluid, known as a pleural effusion, from the pleural space to help me breathe easier.

Michael Becker blogging from his laptop at NIH on April 15, 2017

During the procedure, Dr. Elliot Levy, an interventional radiologists at NIH trained in radiology and minimally invasive procedures, drained 1.5 liters from the pleural space. Almost immediately, I felt better and even while I was being wheeled back to my recovery room, I asked my wife Lorie to grab me a turkey sandwich from the cafeteria as I was quite hungry. It’s possible the large amount of fluid on my left side was putting some pressure on my stomach, which could help explain why I haven’t had much of an appetite lately.

By Thursday, however, the fluid was returning, prompting yet another thoracentesis procedure on Friday to remove 1.5 liters of fluid. The rapid nature of the fluid buildup means that I will most likely have an Aspira® drainage system surgically installed to conveniently let me drain the fluid buildup at home via a small catheter and drainage bags. That procedure is planned for Monday, so I have been staying at NIH since Wednesday and will be here over the weekend.

More importantly, however, a CT scan was also done on Friday morning with disappointing results. The cancer nodules grew since the last CT scan on March 7, 2017. This reflects true disease progression as opposed to “pseudo-progression” as discussed in a prior post. I have been taken off the clinical study with M7824.

My individual results do not reflect poorly on the future of M7824, but rather underscore that we still have a lot to learn about immunotherapy and cancer. While I may not have benefited from the drug, the resulting knowledge and clinical data may help guide future development and I am proud to play a part in that process.

At this point, if I received no further treatment and went on hospice, my likely survival would be about two months – although every patient is different. I have scheduled an appointment with my oncologist at MSKCC to discuss the pros and cons of chemotherapy at this stage, but the balance between quality of life and quantity of life is not trivial and I haven’t made a firm decision to go in this direction. Chemotherapy may only add a month or two of survival with a negative impact on my quality of life.

While I have been very open about my disease since originally being diagnosed in December 2015 and enjoy blogging, I will now be focusing much more time with my wife and daughters and finishing up my memoir, which I hope to have published. This will unfortunately mean less time for updating this blog and responding to emails.

Thank you to everyone who has offered their best wishes, thoughts, and prayers during my cancer journey. Having such an amazing support network of family, friends, and social media contacts has been a great source of strength and inspiration. Special thanks to my wife, Lorie, who has been by my side the entire time.

If you’ll indulge me, I would like to end this post with three requests:

  1. If you have a son or daughter, please talk to your doctor about the HPV vaccine, which protects against cancer of the cervix, vagina, and vulva in women; penis in men; and cancers of the anus and head/neck (including the base of the tongue and tonsils) in both men and women. HPV is a very common virus; nearly 80 million people are currently infected in the United States. About 14 million people, including teens, become infected with HPV each year, resulting in 30,700 cancers in men and women. HPV vaccination can prevent most of the cancers (about 28,000) from occurring.
  2. Help preserve federal funding levels by communicating with lawmakers about the critical importance of investing in medical research. There are far too many people suffering from cancer and this is not the time to cut the budget for the National Institutes of Health (NIH) by 18.3 percent, about $5.8 billion, as has been proposed. In an Op Ed by Harold Varmus appearing in the New York Times on March 22, 2017, he states that  only about 10 percent of the NIH’s budget supports the work of government scientists and that “over 80 percent of its resources are devoted to competitively reviewed biomedical research projects, training programs and science centers, affecting nearly every district in the country.” Harold Varmus, a professor at Weill Cornell Medicine and a co-recipient of the 1989 Nobel Prize in Physiology or Medicine, was the director of the National Institutes of Health from 1993 to 1999 and of the National Cancer Institute from 2010 to 2015.
  3. If you or someone you know is battling cancer or another disease, please talk to a physician about available clinical trial options. Clinical trials are a key research tool for advancing medical knowledge and patient care. Such trials are important to learn whether or not a new approach works well in people and is safe and which treatments or strategies work best for certain illnesses or groups of people.

Collecting More Information

Following Tuesday’s news that several of the tumors in my lungs actually increased in size and a new spot appeared on my spleen, Lorie and I headed back to the NIH on Thursday for more tests to help better guide subsequent treatment decisions.

The first test was a CT image of my brain taken Thursday mid-afternoon, which would be used to rule out the spread of cancer to that particular organ. Patients with brain metastases are often excluded from clinical trials due to historically dismal survival and concerns about blood brain barrier drug penetration. Fortunately, we learned the next morning that this test came back negative for cancer progression to the brain.

The second test on Friday was an image-guided biopsy of a single lung nodule to help guide between cancer progression and inflammation as the reason for the increase in size seen on the recent CT scan on the lungs. In my case, a core needle biopsy was performed, which is less invasive than surgical biopsy and doesn’t require general anesthesia.

Early Friday morning, Dr. Elliot Levy, an interventional radiologists at NIH trained in radiology and minimally invasive procedures, met with us first to discuss the procedure. He pulled up a cross sectional image of my lungs, which showed several of the suspicious nodules.

CT scan of my lungs, showing target nodule for biopsy with two lines representing potential needle angles for biopsy. Other nodules within the lungs circled in red, which could be more dangerous to biopsy.

One in particular was located in the pleural cavity – normally a thin membrane that lines the surface of the lungs and the inside of the chest wall outside the lungs. In the bottom of my left lung, however, fluid built up in the pleural cavity where one of the nodules was located. Dr. Levy explained to us how this nodule could be biopsied without puncturing the lung lobe, which can result in a longer hospital stay.

Sometimes, a collapsed lung (pneumothorax) occurs after a lung biopsy.  As a precaution, a chest x-ray is taken after the procedure to check for this before sending the patient home.

After meeting with Dr. Levy, I was escorted back to the biopsy procedure room and placed on my right side on a table. I was consciously sedated, produced by the administration of two medications: a single dose of fentanyl given intravenously that can produce good analgesia for 20-45 minutes, and midazolam, which has a fast-acting, short-lived sedative effect when given intravenously, achieving sedation within one to five minutes and peaking within 30 minutes. The combination produces an altered level of consciousness that still allows a patient to respond to physical stimulation and verbal commands, and to maintain an unassisted airway. Midazolam is a primary choice for conscious sedation because it causes patients to have no recollection of the medical procedure.

Dr. Levy worked out of sight behind me to perform the biopsy, as he went through my back side. I was fairly nervous going into the procedure, but everything went extremely well with absolutely no pain or unexpected events due to the sedation.

After recovery, a subsequent chest x-ray confirmed that the lungs were indeed fine after the biopsy and we left NIH shortly thereafter to head back home to Pennsylvania.

Thumbs up; recovering after biopsy procedure at NIH

The preliminary results from the biopsy should be available early this week. If the biopsy shows ample evidence of immune stimulation, an argument could be made to stay on the current drug and that the “pseudoprogression,” or the initial radiologic appearance of an increase in tumor burden, might actually be inflammation and followed by tumor regression. A remote possibility in my type of cancer, but worth confirming.

Should the biopsy results instead demonstrate increased tumor burden, then we could consider switching to another investigational agent or even chemotherapy to shrink the tumors before proceeding again with one of the immunotherapy clinical trials.

Lorie and Michael Becker in front of cherry blossoms

Determined to stay positive, Lorie and I took advantage of the warm spring day on Thursday to stop outside NIH and snap a picture in front of some cherry blossoms. Unfortunately, snow and cold returned on Friday for the commute home.

We’ll know more this week, so stay tuned…

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!

 

Starting Treatment – Again

First, my apologies for the length of time from my last clinical update. I’m not generally a superstitious person, but I wanted to wait for a few formalities to be addressed before posting.

Previously, I referenced that my next therapy would likely be at Memorial Sloan-Kettering Cancer Center (MSKCC) and include Opdivo® (nivolumab), a form of immunotherapy called a “checkpoint inhibitor.” What is that, you ask? Human cells carry certain proteins on their surface that enable them to escape attack from the body’s immune system. Some cancer cells wear one of those same proteins, called programmed death ligand 1 (PD-L1), which renders the cancer cells invisible to the body’s immune system. Blocking either PD-L1 or its receptor, programmed death 1 (PD-1), appear to be Achilles’ heels for multiple tumor types. Coincidentally, I covered the exciting early developments in the checkpoint inhibitor field in July 2013, which you can read by clicking here.

Michael D. Becker being infused with M7824 for the first time
Michael D. Becker being infused with M7824 for the first time on 1/25/17 at NIH

My concern is that across clinical studies in numerous cancer types, only about 20% of patients receiving checkpoint inhibitors have a durable response. For these patients, the benefits tend to last for years – perhaps even indefinitely. Exciting, yes. But for the other 80% of patients, the results are less dramatic. For example, in the recurrent head and neck cancer study for Opdivo, the median overall survival was 7.5 months for patients that received Opdivo versus 5.1 months for patients that received standard therapy options (cetuximab, methotrexate, or docetaxel). Clearly, Opdivo was superior to standard therapies and definitely worth considering. But the median overall survival is the time period lying at the midpoint of a frequency distribution of observed values, such that there is an equal probability of falling above or below it. The prospect of being in the 80% group with less than a year to live forced me to consider alternatives.

Fortunately, I became aware of a clinical trial for an investigational agent called M7824, a bifunctional fusion protein targeting PD-L1 and TGF-β, that was developed by EMD Serono, the biopharmaceutical division of Merck KGaA, Darmstadt, Germany. M7824 is currently being studied in a Phase 1 trial for patients with advanced solid tumors (ClinicalTrials.gov Identifier: NCT02517398). The principal investigator for the study is James L. Gulley, M.D., Ph.D., F.A.C.P. of the National Institutes of Health, Center for Cancer Research. In addition to his role as Chief of the Genitourinary Malignancies Branch, Dr. Gulley is also Director of the Medical Oncology Service, Office of the Clinical Director. He is an internationally recognized expert in cancer immunotherapy and I’ve had the honor of knowing him professionally for more than a decade – starting back when I was at Cytogen Corp (just an amazing individual and I cannot say enough good things about him!). Other key members of my fabulous team so far include Dr. Julius Strauss, Lead Associate Investigator for the study and Fellow Physician in Oncology at the National Institutes of Health, Andrea D. Burmeister, Physician Assistant, and Elizabeth Lamping RN, BSN, Research Nurse Specialist.

M7824 consists of a fully human monoclonal antibody against PD-L1 plus a transforming growth factor beta (TGF-β)-neutralizing trap component. This means that M7824 should confer all of the benefits of a checkpoint inhibitor against PD-L1, but with the added punch of neutralizing TGF-β. Dual targeting of the PD-L1 and TGF-β pathways makes sense because both are key immune evasion pathways with independent yet complementary functions.

The TGF-β signaling pathway is complex – resulting in either tumor suppressor or tumor-promoting activity depending on the cellular context in which the pathway is active. In advanced disease, the tumor suppressor arm of TGF-β signaling is lost and, instead, tumor cells proliferate. Further, TGF-β overexpression in advanced disease enhances tumor growth, suppresses the immune system, and exacerbates invasive and metastatic tumor cell behavior.

The more I researched TGF-β, the more encouraged I became about enrolling in the M7824 clinical trial – especially given the specific profile of my disease. Recall that I was diagnosed with human papillomavirus “HPV” positive, squamous cell carcinoma (SCC), which is cancer that begins from squamous cells, a type of skin cell. In addition to being one of the main types of skin cancer, cancers that involve the anus, cervix, head and neck, and vagina are also most often SCC.

Only a minority of people exposed to human papillomavirus develop HPV-related cancer, such as oropharyngeal cancer (lucky me!) or cervical cancer. In a paper published December 2014 in Cancer Research, Levovitz et al. demonstrated that genetic variation in immune-related genes is a determinant of susceptibility to oropharyngeal cancer and other HPV-associated cancers, particularly those related to TGF-β signaling. In other words, it is possible that people carrying genotypes with such variants are more likely to have an HPV-positive tumor compared to patients with the wild-type genotype. The likely functional significance of altered TGF-β signaling in HPV-related cancers is further supported by the finding by Levovitz et al. that TGF-β receptor type 1 is significantly overexpressed in both oropharyngeal cancer and cervical cancer.

In a paper published in February 2015 in Cell, Oshimori et al. establish a surprising non-genetic paradigm for TGF-β signaling in fueling heterogeneity in squamous cell carcinoma (SCC) stem cells, tumor characteristics, and drug resistance. Armed with this insight as well as the relevance for HPV-positive cancers, I decided to enroll in the study and passed the screening process.

In December 2016, Dr. Gulley presented preliminary data from the ongoing Phase 1 study of M7824 at the 28th symposium on Molecular Targets and Cancer Therapeutics, also known as the ENA symposium. Early results were encouraging, with M7824 associated with complete (CR) and partial responses (PR) in patients with advanced refractory cancer.

Today is my first one-hour infusion of M7824 and I look forward to reporting on my experience with immunotherapy in subsequent posts. With just a few minutes remaining for the infusion – so far, so good!

Crossroads

It’s coincidental that after spending so many years leading a few small, oncology-focused biotechnology companies developing immunotherapies, radiopharmaceutical agents, and supportive care oncology products, I am now utilizing that experience, knowledge and network to make informed treatment decisions following my cancer diagnosis. Like driving down a familiar road, I am constantly seeing landmarks and signs that I know quite well from my time in the industry.

For example, some of the common side effects from chemotherapy and radiation therapy include oral mucositis (painful ulcers in the mucosa) and xerostomia (dry mouth). I studied these two side effects extensively as part of the due diligence process when I licensed and launched an advanced electrolyte solution called Caphosol® back in 2006. Based on this experience, I know what to expect from my chemoradiation treatment and hope to incorporate Caphosol into my arsenal against these debilitating side effects.

295077-smallWhile the streets may be familiar at times, I am still faced with difficult decisions at some of the crossroads. The latest example arose during yesterday’s follow-up visit with Dr. David Pfister, my medical oncologist at Memorial Sloan-Kettering Cancer Center (MSKCC). Separate from my upcoming daily radiation treatments, the appointment largely focused on scheduling my three chemotherapy infusions and discussing what to expect in terms of side effects from the treatment. The chemotherapy I will receive is called cisplatin, which was first approved for use in testicular and ovarian cancers back in 1978.  The list of potential toxicities includes nausea, constipation, kidney issues, hearing issues, and others.  The conversation shifted to potential clinical trials and Dr. Pfister mentioned one that is exploring an alternative to chemotherapy that may have less side effects. In the study, the chemotherapy agent (cisplatin) is replaced by Erbitux® (cetuximab) – another FDA approved agent for treating head and neck cancer. Erbitux is an inhibitor of the epidermal growth factor receptor (EGFR), a receptor found on both normal and tumor cells that is important for cell growth. But the study also adds an investigational agent BYL719, which is an inhibitor of PI3K, an enzyme which fuels the growth of several types of cancer. Having worked at several companies developing inhibitors of the PI3K pathway, this was more familiar territory. However, trading the proven results with cisplatin for “potentially” similar efficacy with lower side effects from the investigational combination is a difficult crossroad.

On the one hand, the aforementioned clinical trial includes an approved agent for treating head and neck cancer (Erbitux).  This is different from some other clinical trial designs that include a placebo arm or an arm with only an investigational agent. However, Erbitux has its own side effects and there are unanswered questions in the medical community regarding whether or not Erbitux is “as good” as cisplatin. As a result some physicians only use Erbitux as a replacement for cisplatin when the patient cannot tolerate cisplatin’s toxicities. In my mind, forgoing cisplatin and its proven efficacy could jeopardize the potential for cure. Partially offsetting this risk is the inclusion of a promising new investigational agent – the PI3K inhibitor BYL719 being developed by Novartis. The PI3K pathway is widely known in the oncology community as a potential target for cancer therapy – and in particular head and neck cancer. Preclinical data suggest that simultaneous inhibition of PI3K and EGFR leads to synergistic antitumor activity in head and neck cancer, but future randomized trials are required to answer the question of whether or not the combination is equal to (or better than) cisplatin. Lastly, BYL719 is an investigational agent and although it appears well-tolerated in studies to date, side effects may arise as more and more patients are exposed to the drug.

Ultimately, I decided to stick with the more established cisplatin for a variety of reasons. First, it is my understanding that the radiation therapy, which would be included regardless of whether I opted for cisplatin or the investigational Erbitux/BYL719 combination, is the driving force for both cure AND debilitating side effects.  Most of cisplatin’s side effects, such as nausea, constipation, and other issues, can be partially offset with medication and hydration. Second, cisplatin has been around for decades and appears to be the gold standard in combination with radiation for Stage IV head and neck cancer and it is hard to argue with the clinical data supporting its use to date. Lastly, in the unfortunate event that my chemoradiation therapy isn’t effective – I can always explore investigational treatments as a next step.

 

Pointillism

One of my wife’s favorite artists is Georges Seurat, a French post-Impressionist painter known for his role in devising the painting technique called “pointillism.” This technique uses small, distinct dots of color that are applied in patterns to form an image. Looking at such a painting from afar, our eyes and brains blend all of the dots of color into a fuller range of tones that then form an image.

Yesterday’s meeting with the radiation oncology team at Memorial Sloan-Kettering reminded me of pointillism. Prior to the visit, I saw the complete picture from afar – it would be 6-7 weeks of treatment and the associated side effects, but there was the prospect of being cured by the end.  After the meeting, however, I started seeing the hundreds or thousands of individual dots of color that represented my treatment.

IMRT mask
Example of the type of mask used during radiation therapy for head & neck cancer

For example, during the day they created the “mask” that will be used to keep my head and shoulders in the exact same place for my daily (Mon-Fri) radiation treatment. The mask is secured where you lay and prevents any movement of the head and shoulders (see example image). Unlike the older masks, there is a cutout for your eyes, nose, and mouth but coverage of the jaw largely prevents you from speaking. Frankly, it is terrifying! They did three imaging procedures in the afternoon (MRI, CT, and PET) and each one involved the mask being worn for about 30-minutes. Each time I was rolled into the imaging tube, I couldn’t help but think – what happens if I start coughing or choking? With my jaw immobilized I wouldn’t be able to do much. Trying to get past that fear, I quickly realized – wearing the mask would become a daily routine for the next 6-7 weeks.

The side effects of radiation therapy were another one of the individual dots of color that came into focus as I looked more closely at my treatment “image.” I’ve lost count of how many physicians and nurses have told me to “bulk up” now before starting therapy. Gain 10 pounds or more they say. This is due to the fact that in a few weeks it will be difficult to chew, swallow, etc. as a result of oral mucositis and dry mouth from the radiation therapy. As a result, weight loss and fatigue are to be expected.

During the day, I enrolled in two clinical trials – one for imaging and another for blood tests.  The imaging study looks at levels of oxygen deficiency (hypoxia) in the tumor tissue. Hypoxic tumor cells are resistant to radiation and to many anticancer drugs and therefore tumor hypoxia influences the outcome of treatment with radiotherapy, chemotherapy and even surgery.  The hope is that ruling out hypoxia in the area of the tumor could reduce the amount of radiation therapy needed to cure the disease – and thus reduce side effects. The blood test can be viewed as a type of “liquid biopsy” that detects circulating tumor cells and fragments of tumor DNA that are shed into the blood from the primary tumor and from metastatic sites. Changes in these markers may be able to predict the likelihood of disease recurrence after therapy.

FullSizeRender
The doctor uses a flexible, lighted tube called an endoscope to examine areas of the head and neck that are less accessible. The tube is inserted through the nose after applying a topical anesthetic (lidocaine – applied directly to the nose and throat) to make the examination more comfortable.

It was a very long day with my first appointment starting at 9am and not finishing until around 6pm, but aside from the aforementioned and putting aside more poking and prodding (including my fourth endoscope procedure – see tiny camera getting stuck up my nose in the embedded image…), by the end of the day I felt somewhat better knowing the timeframe for starting radiation treatment, which looks like it will be Monday, January 18. In addition, I felt much better after meeting my radiation oncologist Dr. Nancy Lee (you can watch a video interview with her under the “Videos” menu tab at the top of my blog). She is fantastic! I have a follow-up appointment with my medical oncologist this Thursday, where I will learn more about the timing for starting chemotherapy.

Since I couldn’t eat all day due to potential interference with the imaging tests, the best part of the day was grabbing a quick dinner in NYC with my wife before taking the train back to Pennsylvania. It is so great having her by my side during this ordeal!