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.

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!