The Long Shots: When Patients with Cancer Defy All Odds with New Treatments

It was around New Year's when Dr. Heloisa Soares made her way through the family gathered around her 68-year-old patient's hospital bed.

The outlook was not promising.

Dr. Soares, a gastrointestinal (digestive system) cancer specialist at Huntsman Cancer Institute in Salt Lake City, delivered the bad news: the patient had small cell carcinoma of unknown origin, probably arising from gynecological organs (the female reproductive organs).

Soares explained that half of patients with this disease die within a year, and almost all—90-95%—within two years. One more test was needed. The patient was unlikely to have molecular markers that would make her eligible for immunotherapy , but “we need to check”, she said.

That was December 2021.

Today, the patient has lived for almost three years without evidence of cancer.

Genetic testing after diagnosis showed that the patient was a candidate for immunotherapy. Soares prescribed an immunotherapy drug, and the patient responded quickly.

"Every time I see her, I remember that hospital visit around New Year's, with her family gathered around,” Soares said. This patient is a reminder not to give up, because “you never know whether a patient is in that 5% without doing the detailed testing."

Grief and loss are inevitable in cancer care. But sometimes that long-shot or last-resort treatment works, often without an explanation of how.

It is difficult to predict who these exceptional responders will be. Yet these extraordinary few allow oncologists to bring hope into every examination room.

Restless to Do More

For Dr. Sonikpreet Aulakh, a neuro-oncologist at West Virginia University, patients' odds are often grim.

Every brain cancer treatment Aulakh recommends involves risk. A treatment is generally more likely to fail than to work. And when a medicine fails, the disease continues to grow.

So when a patient beats the odds, “it humbles me,” she said. “And it makes me restless to do more."

In early 2020, a patient with severe headaches was referred to Aulakh. One look at the golf-ball-sized mass on the patient's MRI was enough to tell her that the cancer was aggressive.

Follow-up tests after surgery to remove the tumor confirmed a diagnosis of glioblastoma.

When Aulakh entered the clinic to explain the situation to the patient and their spouse, she could sense their fear.

She did not mince words. The cancer was aggressive and fast-growing, she said. In most cases, patients had less than 2 years to live.

"Doctor, we will do whatever you recommend,” she remembers the patient saying.

Aulakh started the patient on radiation and chemotherapy, then added a head-worn device that emits mild electromagnetic fields that can slow the progression of a brain tumor, known as tumor treating fields .

A year later, the tumor showed signs of growth, so Aulakh prescribed an oral targeted therapy off-label (outside its approved indication) alongside the device.

It was still a long shot. “I did not know which way it would go,” Aulakh said. “Once the disease starts progressing, it is unlikely to respond to treatment."

And she knew that if this treatment did not work, they would quickly need to try a new approach.

The targeted therapy worked for about a year, but when scans showed growth in early 2023, Aulakh switched to PD-L1-based immunotherapy .

It has been 5 years since the first surgery and 8 months since the patient began using immunotherapy together with the electric-field therapy device. The patient has not only survived but has also remained active and spent meaningful time with loved ones.

"This is the greatest achievement in my day-to-day career – keeping patients alive with quality of life,” Aulakh said.

Balancing Hope and Reality

When Dr. Danielle Kirkey, a pediatric oncologist at Fred Hutch Cancer Center and Seattle Children's Hospital, thinks of extraordinary survivors, an 8-year-old patient comes to mind.

He was just 4 when he received his first diagnosis: Philadelphia chromosome-positive acute lymphoblastic leukemia—a disease that, only a decade earlier, had been almost universally fatal.

Targeted therapies have improved patient outcomes, but the road to recovery remains difficult, particularly for children.

During an especially intensive phase of chemotherapy, the young patient developed acute heart failure and a fungal infection, the most feared adverse effect.

"The complications we faced seemed insurmountable,” Dr. Kirkey said.

Kirkey told the boy's mother she could not leave the hospital—her son probably would not survive the night.

It was “heartbreaking,” Kirkey recalls. You never want to give up, especially in pediatrics, but at that moment the patient and his family needed to understand the full gravity of the situation, she said.

The single mother of three took Kirkey's warning to heart. She stayed beside her son that evening.

The boy survived the night and the fungal infection, but a long road still lay ahead. After two relapses (recurrences of leukemia) over the following years, he finally received a stem cell transplant .

"At many points, I felt defeated, especially during the relapses,” she noted. “Balancing hope and realism is a very difficult, fine line,” she said.

Today, a year after the transplant, the patient is doing well, Kirkey said.

But his long struggle shows that treatment goals can change throughout a patient's journey. A long and healthy life may be the ideal, but on difficult days the goals may become smaller and more focused—helping a patient reach the next birthday or reducing distressing adverse effects.

"Anything we can do to provide the best quality of life for as long as possible is always our priority,” Kirkey said. And on the best days, you may achieve even more than you hoped.

A New Era in Melanoma

Dr. Wade Swenson, an oncologist working in rural Minnesota, said his melanoma patients were recovering more often than ever before, although this was still far from the norm.

"It has been a really exciting time to be in this field,” Swenson said.

Swenson remembers a patient early in his career who had metastatic melanoma and was among the first candidates for immunotherapy. The man, in his early 60s, had come to Swenson's clinic from a major academic center in Chicago, where he had been told to consider hospice (end-of-life care) .

Before referring him to hospice, Swenson suggested one final treatment option: the first-generation immunotherapy ipilimumab.

The patient responded within just a few weeks and has remained in remission for more than 12 years.

Today, doctors expect such outcomes from immunotherapy for melanoma, but at the time they were astonishing and reflect the field's rapid evolution, Swenson said.

"If you look at the materials I used for my first board exam and for recertification a decade ago, it is crazy. It just looks like the dark ages,” Swenson said.

Exceptions That Nourish the Spirit

When Dr. Don Dizon thinks of a patient who defied all odds, he remembers a young woman he treated more than a decade ago while working at Massachusetts General Hospital in Boston.

Her endometrial cancer with DNA mismatch repair deficiency did not respond to chemotherapy. Her pain became so severe that Dizon had to refer her to hospice. He also prescribed pembrolizumab.

"Immunotherapy was a final effort,” said Dr. Dizon, now director of the Pelvic Malignancies Program at Lifespan Cancer Institute and director of Medical Oncology at Rhode Island Hospital.

Within 4 weeks, the patient stopped taking pain medication. And today she remains in remission.

When a patient beats the odds, there is an intense sense of relief, Dizon said.

But a lasting mystery remains as well.

"The scientist in us always tries to understand,” to discover why something worked and for whom it might work, Dizon said. These cases are so rare that you cannot expect this outcome for everyone, but when it happens, “you start holding on to much more hope."

Commentary

In oncology, hope must be carried carefully.

Although rare, stories of patients who defy the odds may misdirect the expectations of other patients and oncologists. It is important to strike a delicate balance between a positive outlook and a realistic prognosis.

It is critical that patients know the possible “good, bad, and worst-case” outcomes of their disease.

Yet these extraordinary recoveries cannot be dismissed as mere coincidence. They are a powerful reminder that prognoses can change and medicine is continually advancing.

As oncologists, we know the value of these exceptional recoveries very well; these patients are important sources of inspiration that nourish the spirit of our profession and instill hope.