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by Lee Hong, MD/PHD Year 6

[Names have been altered to protect the patient’s identity.]“Do you still play piano at church?” Dr. M asked, as I stood unobtrusively to the side, my back uncomfortably pressing against the magazine-stuffed mounted plastic folder. My short white coat looked too pristine against Dr. M’s long coat, his embroidered name slightly faded from excessive bleaching, pen stains dotting the pocket. He finished washing his hands, the patter of the faucet and mechanical whir of the paper towel dispenser filling the room. I looked expectantly at Mrs. Loome.

“Yeah, I do,” Mrs. Loome replied noncommittally, her gaze unfocused. She had gotten her hair styled the week before and short brilliant black strands framed her heavily made up face, but today she seemed unusually muted. Her husband, a mustached gentleman with mottled sunspotted arms, briefly exchanged a worried glance with me and looked on as she trudged slowly to the exam table. Dr. M and I examined her tumor, visible only by gently splaying open her buttocks. Today it was about 7 cm in length and 5 cm in width, an unnerving dark black patch embedded in her smooth pale skin, about the same size since her previous visit. Too persistently the same size.

This was one of my many visits with Mrs. Loome under Dr. M’s direction every other Thursday for the past year. As an MD/PhD student in the middle of graduate school, I along with my peers were “strongly encouraged” (nay, required) to become immersed in a clinical setting related to our field of research, both as a preview of what life will be like as a physician-scientist (walking briskly between the hospital and the laboratory, exchanging one white coat for another) and to help us understand the “translational” opportunities of our research. In my third year of my PhD training, I felt more confident in designing and performing experiments, but in the melanoma clinic I felt like I was transported back to my first year in medical school – slightly lost, feeling wholly inadequate, but wanting to help.

It was October 2014, and intravenous antibody-based immunotherapies were up and coming in the oncology clinic. As a graduate student, I was more intimately familiar with their effects in promoting an anti-tumor immune response in mice. For the first time, oncologists could finally prescribe a treatment for late-stage melanoma patients that prolonged their overall survival. Things were looking up.

I still remember vividly the first time Dr. M and I opened Mrs. Loome’s chart together. Her full name was so delightful – Daisy Loome. I usually have a hard time associating names with faces, but with Mrs. Loome there was, and in subsequent visits, never a doubt to me who she was and what her medical history entailed. I could envision her plump frame, (dyed) jet black hair and made-up face – mid 60s, with a perfect smile – and a fashionable outfit that was never repeated twice. Mrs. Loome’s cancer was unusual – a stubborn anal melanoma that she first noticed when it was increasingly uncomfortable for her to sit. Dr. M explained to me that, not only are mucosal melanomas rare, these cancers may have a different etiology compared to sun-exposed melanomas. I had seen tumors in mice, but was unprepared for how grotesque her melanoma looked that first clinic visit. Dr. M gingerly pulled away the folds of her buttocks to reveal a dull gray, stubbornly embedded, rough patch.

To further characterize Mrs. Loome’s cancer, Dr. M ordered a biopsy of her tumor to be sequenced. As we scrolled through the genetic mutations that came up in the panel of commonly mutated genes, Dr. M pointed to one in particular – c-Kit. “This is a bad mutation,” he said, and shook his head. “Unfortunately, one we still don’t know too much about.” Nevertheless, based on Mrs. Loome’s staging, Dr. M started her on immunotherapy. Does immunotherapy really make sense for Mrs. Loome if she has a cancer that may be of a different etiology?, I wondered silently. Then again, do we have a choice?

After a few weeks, we saw Mrs. Loome again. At her first infusion, Dr. M had warned her about potential side effects due to an overactive immune system – rash, fatigue from hypothyroidism, diarrhea from colitis… the list was overwhelming. But that day, Mrs. Loome simply said, “I’m not feeling anything bad.” By this point, we were starting to see more of her family at her appointments – the quiet oldest daughter, who looked gaunt relative to her large family; the son with a prickly goatee who was never seen without a camo baseball cap; the gregarious youngest daughter who played piano with her mother at church. They all nodded and looked at us expectantly.

“Well, let’s keep with it,” Dr. M said, gently touching Mrs. Loome’s knee.

It was after the third infusion and time for scans. Dr. M and I sat huddled at a computer screen, scrolling through the CT images looking for signs of cancer, dark clusters lurking. When we got to the abdomen, a small, 1cm measurement popped up – where the radiologist had labeled a tumor. Then another, then another. The cancer was spreading. Dr. M sighed and leaned back in his chair. I looked at him, then back at the screen.

Dr. M switched immunotherapies, and after a few months we repeated scans. But it was as if we were infusing saline – the melanoma kept spreading and now had taken root in her brain. He broke the difficult news while Mrs. Loome and her husband were driving back to their hometown.

Dr. M switched her treatment again – this time with a drug that directly targets the c-kit mutation of Mrs. Loome’s tumor. It’s an off-label use, he and the pharmacist explained to me before stepping inside her room, but it may be better than nothing. I nodded, but I couldn’t help but feel that we were beginning to grasp at straws, anything that could stem the cancer’s relentless spread.

The pharmacist came to explain this new drug to Mrs. Loome – it was a pill that could be taken at home, unlike the infusions she has been receiving. “One of the side effects is hair loss,” she said. Mrs. Loome nodded, and then – I saw a single tear fall down her cheek. Her youngest daughter and the pharmacist put a hand on her thigh, gently trying to comfort her. It was at that moment that I realized that Mrs. Loome, far from being aloof during her visits, was trying to stay strong and quell the storm inside. Losing her vibrant black hair was, in a way, an outward sign of her internal chaos.

While the pharmacist went over other side effects, Mr. Loome stepped outside the room with Dr. M. I followed closely, shutting the door behind me. He locked eyes with Dr. M and asked, with a hushed but firm voice, “Realistically, what are our chances that this drug is going to work?”

There was a moment of quiet – the hum of clinic died away and it was just the three of us, standing in the glaring white light. Dr. M looked down at his worn loafers. Finally, he returned Mr. Loome’s gaze. “I have hope for this. We must have hope.”

We stepped back into the room, but I knew, at that moment, that modern medicine had failed Mrs. Loome. Researchers have access to many tools to characterize cancers, but physicians have only just begun to learn what these data mean for patients. Yes, immunotherapies have revolutionized the way doctors treat metastatic melanoma, but nothing is as simple as it seems, especially in medicine. My work in the lab is one small contribution to our pool of knowledge, but my challenge as a future physician is to drink in what I need to alleviate suffering.

It’s been several months since I’ve returned back to lab full-time, but I still think about Mrs. Loome and her lovely family. Unlike Dr. M, I won’t get to see if Mrs. Loome does better; her story is left unfinished for me. Even though my labmates and I are at the cutting edge of immunotherapy research, I’m still humbled by how much we still don’t know about the disease we call cancer. I’m still working towards that day when, instead of simply looking in my patient’s eyes, I will also say, “We have something for you.”