Not So Nifty Fifty

I cannot recall a time when I was this upset with myself. I’m not a doctor, but I feel my background should have allowed me to piece together the clues and help come up with a differential diagnosis much earlier. The perfect opportunity to participate in my healthcare by joining in the discussion and raising the right questions.

Lorie and I made a trip to Memorial Sloan-Kettering Cancer Center’s (MSKCCs) urgent care center last Tuesday (11/6/18). This was due to a fever and breathing difficulty both after going up/down stairs and following coughing episodes. Consider what was known at the time:

  1. X-ray at urgent care suggesting pneumonia
  2. Shortness of breath
  3. Non-productive cough
  4. Low-grade fever
  5. History of radiation therapy to lungs in late July/early August

Pneumonia is a bacterial infection that inflames the air sacs in one or both lungs, but a subsequent CT scan and blood work didn’t confirm. Nonetheless, to be safe and in the absence of any other condition, I was prescribed one week’s worth of the broad spectrum antibiotic levofloxacin (Levaquin®) and instructed to follow-up with my oncologist.

Figure 1: Still untouched birthday ice cream cake

During the following week, all of the symptoms persisted. Between the breathing issues and fever, I didn’t feel like doing much other than resting on the couch all day and writing. Thankfully, I did manage to rally for an early birthday barbeque celebration this past Sunday. Then again, perhaps I jinxed myself by celebrating and posting early! Right, @23aloha? 😉

Aside from the aforementioned, recall that I’ve been suffering from back pain due to the progression of cancer to the spine. In early October, I met with a neurosurgeon at MSKCC in advance of receiving targeted radiation to two areas of my spine. To help prevent or minimize the pain flare that is common following radiation treatment to the skeleton, the neurosurgeon prescribed a steroid (dexamethasone).

Among other side effects, patients who are on steroids for three-weeks or longer are more susceptible to infections than are healthy individuals per the product prescribing information. After finishing radiation treatment to my spine on October 18th, I inquired with my health care team at MSKCC and began gradually reducing my dexamethasone dose to zero beginning on November 1st and finishing on November 6th (hint: day of my trip to urgent care, didn’t seem relevant at the time).

As referenced in my prior post, I’m not a big “birthday” person, but I was looking forward to celebrating my 50th milestone this past Monday. I hoped that the antibiotic would work and I’d be feeling somewhat better by then. No such luck. In general, I felt worse that day, and by the evening my temperature jumped to 101.9 Fahrenheit. No restaurant celebration or interest in my favorite ice cream cake (Figure 1). I took two acetaminophen, which brought the temperature down, and made an appointment the next afternoon to see my oncologist, Dr. David Pfister, and Nicole Leonhart, ANP, RN.

Of course, it wouldn’t be a commute between home and NYC without experiencing some significant delay. This time, a tugboat struck the Portal Bridge and we were held for close to an hour as the bridge was inspected for safety. We arrived at our appointment an hour late, but MSKCC was very accommodating.

After reviewing a new chest x-ray, my medical team offered a differential diagnosis of radiation pneumonitis based on empirical evidence. As soon as I heard the words, it made perfect sense. How could I have missed that! I knew radiation pneumonitis was a potential risk.

Radiation pneumonitis and pneumonia share many clinical features, including inflammation of the lung(s). Radiation pneumonitis is one of the most common toxicities of stereotactic body radiation therapy (SBRT). Most cases are either asymptomatic or manageable, with the reported rates of symptomatic radiation pneumonitis after SBRT range from 9% to 28%. However, most patients develop late pulmonary toxicity characterized by localized pulmonary fibrosis (scarring) in the region receiving the high-dose.

Sure enough, the suspicious areas on my chest x-ray correlated almost exactly with the areas targeted with SBRT over the summer. The sudden appearance of symptoms corresponding with tapering of the prior steroid dexamethasone also provided an important clue. It is likely the steroid meant to address potential bone pain flare issues was also treating the radiation pneumonitis. When I stopped the dexamethasone, the radiation pneumonitis was left untreated and suddenly became symptomatic. Ta-da!

The good news is that with adequate steroid treatment, most patients achieve complete recovery from their symptoms. As a result, I was prescribed an initial two-week supply of another steroid (prednisone). But a diagnosis of pneumonitis does increase the risk of developing subsequent pulmonary complications, including fibrosis, a permanent scarring of the lungs.

While it wasn’t a perfect birthday in the traditional sense (whatever that even means), I prefer to focus on the fact that Lorie, Rosie, and Megan (and the zoo!) were with me on this 50th milestone, and that the recent symptoms weren’t due to further cancer progression (my initial concern) but rather a manageable radiation treatment side effect. Honestly, that is the best gift I could have received.

I would be remiss if I didn’t also acknowledge how important all of the happy birthday calls, texts, gifts, and social media posts were to me. It is one thing to hear from family and friends, but some messages from people I’ve never met in person were also truly lovely and brought a smile to my face. I do read EVERY post! So, to everyone who took time out of their day to acknowledge my birthday—thank you from the bottom of my heart!

 

Up to Eleven

Late last month, I experienced severe pain in my left hip/buttock that warranted a trip to the urgent care facility at Memorial Sloan-Kettering Cancer Center (MSKCC). With random movement, a sharp, electric-like pain radiated down my left leg. It was like nothing I’ve experienced before. Lying down on my right side made the pain better, but sitting or climbing stairs was unbearable.

During my stay at urgent care, an x-ray of my pelvis showed no evidence of fracture. There was also no indication that cancer had spread to that area, which was naturally my initial concern.

While waiting to see the doctor, I was given a non-steroidal anti-inflammatory drug (NSAID) called ketorolac via intravenous infusion to help address the pain. It worked so well that I was later released. The pain was attributed to an inflammatory condition, possibly bursitis according to the discharge papers.

Since the cancer wasn’t responsible for my pain, I was instructed to follow up with a local orthopedist for further evaluation and treatment. In the meantime, I found it unusual that oral NSAIDs and even narcotics like oxycodone failed to address my growing pain.

An x-ray of my spine was taken by the orthopedist, which also came back normal. I was prescribed physical therapy for 4-6 weeks and a steroid regimen to help address inflammation that was possibly putting pressure on my sciatic nerve. I required a walking cane, as it felt like my left leg was going to collapse every time I experienced a bolt of pain.

Completing the steroid regimen and two weeks of physical therapy, I was feeling only marginally better. During a follow-up appointment with my orthopedist, I received a steroid injection directly into the left sacroiliac (SI) joint region. I was told pain relief could take a few days, for which I anxiously awaited.

At this point, I was due for a periodic CT scan of my chest, abdomen, and pelvis at MSKCC. It would reveal how cancer responded to the recent stereotactic body radiation therapy (SBRT) directed to three areas—a lesion in each lung and also my spleen. It was hoped that the SBRT would decrease the size of targeted tumors in the lungs enough to alleviate a nagging cough that I developed.

Given the unique pain I was experiencing, thoughts of cancer progression still swirled in my mind. Bone is the third most common site for the spread of cancer, with half or more of patients diagnosed with cancer experiencing bone pain.

Coincidentally, I became quite familiar with pain arising from metastatic bone disease (MBD) during my tenure as CEO of Cytogen Corporation. The company had developed and commercialized Quadramet®—an injectable radiopharmaceutical used to treat bone pain associated with cancer.

Pain from MBD results from bone destruction and fragility. A pain scale measures a persons pain intensity based on self-report, with pain levels between 0 (pain-free) and 10 (pain that makes you pass out). Since late August, my daily pain went from a low of 5 at rest up to 11 with movement (“Up to eleven” coined in the 1984 movie This Is Spinal Tap).

Since I was scheduled to travel to MSKCC for the CT scan, I asked my treatment team if an MRI of my spine made sense to plan for that same day. I couldn’t help but think the severe pain was caused by cancer progression to bone. They agreed, and both imaging procedures were scheduled for September 19, 2018.

Meanwhile, after completing oral steroids, two weeks of physical therapy, a steroid injection, and walking with a cane, my resting pain level slightly improved. Regretfully, I second-guessed my request for an MRI of my spine due to the modest pain improvement and canceled that appointment after consulting with my treatment team.

The day of the CT scan, my pain was back to full force. I knew that I couldn’t hold still long enough to complete the CT scan. It took 10 mg of oxycodone to sedate me and alleviate my pain just enough to get through the 10-minute procedure.

Yesterday, Lorie and I reviewed the CT scan results with my oncologist at MSKCC, Dr. David Pfister, and Nicole Leonhart, ANP, RN. My cough disappeared, so I was very confident that the inferior left hilar node decreased in size following SBRT. The radiology report confirmed that it declined from 1.3 cm x 1.3 cm on the prior scan to 0.6 cm x 0.6 cm.

Unfortunately, that was the only good news contained in the CT scan results. While the tumor on my spleen also received radiation, it nearly doubled in size from 4.0 cm x 2.7 cm to 7.4 cm x 5.1 cm. Could this be inflammation following the radiation treatment, or did it genuinely represent tumor growth? No one could be sure based merely on imaging.

Figure 1. Vertebral body

Our hearts sunk as the discussion turned to the suspicious new lesions found on my spine. Specifically, the L5 and T7 vertebral bodies—spool-shaped structures that constitute the weight-bearing portion of a vertebra (see Figure 1). Most spine tumors are metastatic, representing the spreading of cancer from a different part of the body. Unfortunately, metastatic or primary tumors, trauma, and infection are prominent pathologies of L5.

Figure 2: MRI images showing the location of cancer spread to the spine (dark areas near arrows). Click to enlarge.

Correlation of the findings using an MRI was needed. Immediately, I regretted second-guessing my decision to get an MRI done while in town for the CT scan last week. Amazingly, I was able to get an MRI done the same day of my appointment at MSKCC. The results confirmed that cancer had now spread to my T7, L5, T5, and S2 vertebral bodies (see Figure 2).

When cancer spreads to the spine, it can replace your bones or compress your nerves, resulting in compression fractures, pain, and reduced blood supply to the spinal cord. Fortunately, cancer has not yet contacted my spinal cord. Otherwise, I would likely have been admitted for emergency spinal surgery. Spinal cord compression needs to be treated right away to try to prevent permanent damage to the spinal cord.

The good news, if there is any, is that radiation therapy provides excellent relief for painful bone metastases and retreatment is safe and effective. Within a week or so, I will undergo both mapping and radiation treatment for the painful spine metastases. In the majority of patients, radiation therapy can provide substantial pain relief.

Figure 3: Michael Becker’s disease and treatment milestones. Click image to enlarge.

After finishing my third cancer treatment in March 2018 (nine months of combination chemotherapy—carboplatin and paclitaxel), I decided to take my first treatment break after being diagnosed (see Figure 3). As I had hoped, the past six months were precisely what I needed and left me feeling refreshed and reenergized.

Assuming my bone pain is addressed, I’m faced with the option of pursuing novel therapies or merely continuing my treatment hiatus. For example, I have not yet been exposed to cetuximab, a biologic agent that blocks the epidermal growth factor receptor (EGFR) and is FDA approved for the treatment of metastatic colorectal cancer, metastatic non-small cell lung cancer, and head and neck cancer. Alone or in combination with an investigational agent, cetuximab could be a viable treatment option that doesn’t negatively impact my quality of life in the same manner as chemotherapy.

As soon as I get past the bone pain issue, I plan on meeting with Dr. Pfister to continue hearing his thoughts on potential next steps that could achieve my goal of maintaining a decent quality of life while still pursuing active treatment. To be continued…

Update: Stereotactic Body Radiation Therapy (SBRT)

In my prior post, I discussed a worsening cough and recommendation from my oncologist, Dr. David Pfister at Memorial Sloan-Kettering Cancer Center (MSKCC), to consider stereotactic body radiation therapy or SBRT. This treatment is designed to deliver extremely precise, very intense doses of radiation to cancer cells while minimizing damage to healthy tissue.

My radiation oncologist, Dr. Nancy Lee at MSKCC, developed a treatment plan using SBRT to target single tumor sites in each of my lungs and spleen. Starting with my left lung, the first treatment took place Monday, July 23, 2018, and continued on Wednesday and Friday of that same week. The same schedule was used the following week for my right lung. A single SBRT session was used to target the lesion on my spleen, which was completed last Wednesday, August 15, 2018.

The unit for radiation measurement of absorbed dose is “gray” (Gy). I received a total of about 27 Gy to each lung site (9 Gy per session / 3 sessions) and about 9 Gy to my spleen in a single session. In contrast, I received about 70 Gy to my head/neck over the course of 7 weeks back in early 2016 as part of my conventional chemoradiation treatment.

With SBRT, only a small area of your body is exposed to radiation. This means that SBRT usually causes fewer side effects than other types of radiation therapy. According to patient education materials provided by MSKCC, about half of the people who have SBRT don’t have any side effects from treatment.

So far, the SBRT “experience” has been exactly as billed. Other than post-traumatic stress from going through the radiation procedure again, along with some mild fatigue, I haven’t experienced any significant side effects from SBRT. Encouragingly, my cough has already diminished both in frequency and severity. So, the radiation is likely doing its job of shrinking tumors that may be obstructing my airway.

Towards the end of September, I’ll have another CT scan to see how the radiated (and non-radiated) tumors responded to the SBRT. Radiation can cause inflammation in the short-term, which hampers the interpretation of scan results. Accordingly, it is prudent to wait at least a month before imaging.

Until then, I’m continuing my human papillomavirus (HPV) awareness activities and encouraging vaccination of preteen boys and girls to help prevent six cancers linked to HPV. Sadly, there is still a lot of room for improvement in vaccination rates.

In 2017, nearly 49 percent of adolescents received all the recommended doses to complete the HPV vaccination series according to a new study. This is less than a 5% increase from 2016 when 43.4% of adolescents (49.5% of females; 37.5% of males) were up to date with the HPV vaccination series. Today, 51 percent of adolescents still have not completed the HPV vaccine series!

To be meaningful, HPV vaccination rates need to be closer to the Centers for Disease Control and Prevention’s (CDC) Healthy People 2020 target of 80 percent coverage. This isn’t unrealistic, as around 80 percent of adolescents receive two other recommended vaccines—a vaccine to prevent meningococcus, which causes bloodstream infections and meningitis, and the Tdap vaccine to prevent tetanus, diphtheria, and pertussis.

Parents, I beg you again—please vaccinate your children against HPV.

Radioactive

As I compose this post, I cannot get the 1985 song “Radioactive” by English rock band The Firm out of my mind. But perhaps this will make more sense in a moment.

At the end of June 2018, I announced my intent to remain off cancer treatment. A decision so complex that it couldn’t be adequately addressed in a blog post. Simply put, after going through three very difficult therapies from 2016-2018, I decided to emphasize the quality of life over quantity of life.

My last palliative systemic treatment consisted of nine cycles/months of combination chemotherapy (carboplatin and paclitaxel). For a while, it significantly reduced the size of tumors in my lungs and spleen. Most importantly, it prolonged my life—and for that, I am very grateful.

But most cancer treatments are associated with toxicities, which can range from mild to severe. For example, my initial treatment consisted of daily radiation to my head/neck in combination with chemotherapy and was brutal with regard to side effects. In exchange for these toxicities, however, chemoradiation offered the “potential” for a cure at the time. It seemed like a fair trade.

Once my disease spread (metastasized) to distant sites, including my lungs and spleen, the intent of treatment switched from curative to palliative—providing relief from disease symptoms and helping me live longer. Accordingly, I became less willing to endure the side effects of palliative systemic treatment (chemotherapy, cetuximab, etc.) with cure no longer a likely option. This largely resulted in my decision to discontinue treatment.

However, I discussed my worsening cough during a recent appointment at Memorial Sloan-Kettering Cancer Center (MSKCC) with my oncologist, Dr. David Pfister, and Nicole Leonhart, ANP, RN. Absent chemotherapy, the tumors in my lungs continue to grow and create additional problems—chronic coughing, wheezing, shortness of breath, etc. To address my cough, Dr. Pfister introduced the concept of stereotactic body radiation therapy, or SBRT, to deliver extremely precise, very intense doses of radiation to cancer cells while minimizing damage to healthy tissue.

For more than a century, radiotherapy has been an effective treatment for cancer patients. But the new millennium saw the affirmation of SBRT, especially for the treatment of metastatic tumors. In fact, select patients with limited metastases treated with SBRT are long-term survivors.

During a follow-up appointment with my radiation oncologist, Dr. Nancy Lee at MSKCC, she informed me that SBRT is associated with fewer side effects than the conventional radiation therapy I received as part of my initial treatment back in 2016. Conventionally fractionated radiation involves low-dose fractions given once a day (e.g., 10–30 fractions of 1.8–3 Gy each), while SBRT involves giving smaller numbers of higher-dose fractions (e.g., 1–5 fractions of 6–30 Gy each). Accordingly, SBRT can usually be given in five or fewer daily sessions within a week. Fast, safe, and effective—there was a lot to like about SBRT.

SBRT involves the use of sophisticated image guidance that pinpoints the exact three-dimensional location of a tumor so that the radiation can be more precisely delivered to cancer cells. Adverse events associated with SBRT can include pneumonitis, cough, pain, esophagitis, and dermatitis. However, severe toxicities (Grade 3 and 4) are fairly uncommon, occurring in 5% to 10% of patients after SBRT.

Possibly due to my background working with radiopharmaceuticals, I’ve long been interested in the role of radiation therapy beyond its cytotoxic effects. Radiation therapy interacts with cancer and immune system through a variety of mechanisms. It promotes the release of tumor neoantigens during cancer cell death in addition to stimulating immune adjuvant effects, engaging the two key arms of the immune system and functioning like an in situ vaccine, generating tumor-specific T cells.

In fact, localized radiation can infrequently trigger systemic antitumor effects, called the “abscopal effect.” Recent studies presented at ASCO 2018 have explored SBRT in combination with checkpoint inhibitors to potentially improve the abscopal effect with mixed results.

In one study, cancer patients were treated with SBRT and at least 1 cycle of pembrolizumab. Results of the study showed an abscopal response defined by 30% reduction in any single non-irradiated measurable lesion was present in 27% of patients, but only 13% of patients when defined by a 30% reduction in aggregate diameter of non-irradiated measurable lesions. It is difficult from these data to separate out whether the effects seen were because of the combination or from SBRT alone.

In another study, head/neck cancer patients with at least two measurable lesions were randomized to either nivolumab alone for 2 cycles or nivolumab with SBRT to a single lesion (9 Gy x 3) between the 1st and 2nd doses of nivolumab. While safe, the addition of SBRT to nivolumab failed to improve objective response rate (ORR), progression-free survival (PFS), or overall survival (OS).

For now, a treatment plan was developed using SBRT to target tumor sites in each of my lungs. Starting with my left lung, the treatment takes place Monday, Wednesday, and Friday of this week. The same schedule will be used next week for my right lung. For reasons still unclear, questions remain regarding the use of SBRT to also target the lesion on my spleen.

Yesterday was my first SBRT session. Lorie stopped me for a quick kiss before I disappeared into the men’s locker room at MSKCC to change clothes. It was traumatic to see the same rooms and equipment from my prior chemoradiation experience. And while my body needs to be kept in the same position for each treatment, thankfully this is accomplished through the use of a mold of my back instead of being pinned to the table by a face/shoulder mask like last time.

The SBRT session was quick and painless. I thought readers might enjoy seeing what the process is like, so embedded in this post is a brief time-lapse video of me holding still on the table in my shorts and shoes as the linear accelerator components twirl around me.

I’ll update the blog with any significant updates on my SBRT experience. For now, I’m simply hoping to get some relief from coughing.