Terminal disease is a thief that announces its intentions. It lets the afflicted know that it waits to steal their final breaths. It tells those who will be left behind that their shared memories will end.

Yet these deaths can also offer new beginnings. The body and its organs, robbed of life, can yield new understanding of the roots of disease – and possibly new treatments and cures for the living and those as yet unborn.

Until the last moment, “There is science going on inside of every patient,” said Ross Camidge, MD, PhD, director of the Lung Cancer Program at the University of Colorado Cancer Center.

Camidge in recent months has been part of two compelling stories of battles with end-stage lung cancer. Both involve individuals who decided that they would respond to death by agreeing to autopsies. They hope that bodies stilled by death will stir scientific inquiry and help to solve the mysteries of the malignancy.

Autopsies are vital to the ongoing search for the roots of cancer and other diseases. Tissue taken from organs, for example, may reveal alterations in DNA, RNA and proteins that drive illness, Camidge said. A patient who requests an autopsy is offering clinicians access to a precious commodity, he added.

“It feels like they are giving the ultimate gift,” Camidge said. “They are saying, ‘I trust you and respect you. This is my endowment to you. Do something great with it.’”

Search for answers

Suzi Evans has seen the tangible results of an autopsy, a note of closure in a story riddled with painful memories. Evans, 60, lost her husband Jerry to lung cancer in December of last year, a couple of days before his 62nd birthday. They had been married for 35 years. Jerry, a “never smoker,” had been diagnosed in February 2015 with lung cancer caused by an acquired change in the ROS1 gene. Although ROS1 is implicated in only 1 to 2 percent of non-small-cell lung cancers, never smokers are among the subset of patients most vulnerable to it.

That fact illustrates the cruelty of disease. Jerry Evans, a commercial pilot who had retired in 2013, wasn’t just a guy who didn’t smoke, Suzi said. She described him as an “aerobic animal” who grew up in Fort Collins and habitually hiked, ran, cross country-skied, and cycled long distances.

Shortly after he retired, however, Jerry found himself habitually short of breath and unusually fatigued when he exerted himself. He had a cough and burning in his throat that Suzi initially chalked up to “crappy air” from wood-burning stoves in Grand Junction, where they lived. But their concern grew when Suzi pulled ahead of him during hill climbs on their bikes. “That wasn’t right,” she recalled.

Difficult diagnosis

A series of tests and encounters with physicians in February of 2015 in Grand Junction proved both frustrating and frightening. Jerry was diagnosed with what providers initially called “lymphatic cancer,” then with liver cancer. He and Suzi immediately sought a second opinion at MD Anderson Cancer Center in Houston, a logical choice since they’d bought a condo in the area during Jerry’s time as a pilot.

Providers at MD Anderson diagnosed Jerry with stage 4 lung cancer and with the ROS1 change in February. He was put on crizotinib, a lung cancer treatment that targets the ROS1 protein and another, better known, molecular subtype of lung cancer called ALK.

Jerry initially had good results with crizotinib, Suzi said, but in September, he developed resistance to it, and his providers at MD Anderson enrolled him in a trial of Ceritinib, a drug which was a known ALK inhibitor, but whose activity against ROS1 was unknown. That went poorly, Suzi said. Jerry suffered through nausea, constipation and general discomfort. After finding Camidge’s name and seeing that he is routinely involved in lung cancer research and clinical trials, Suzi contacted him, “looking for another avenue.”

In November, Camidge put Jerry back on crizotinib, which initially helped to relieve the terrible pressure of fluid build-up in his lungs. A follow-up appointment was scheduled Dec. 15, but a few days before that, Jerry began to have trouble breathing. Two days before the appointment, he sat in a chair with the curtains open, looking at a beautiful morning view of western Colorado.

“I remember thinking, ‘He’s ready,’” Suzi said. Shortly thereafter on that day, he passed away.

Journey within

Intent on getting a better understanding of what had claimed her husband, Suzi called Camidge to ask if he could help her arrange an autopsy. With that, the Cancer Center, working closely with University of Colorado Hospital’s Office of Decedent Affairs, set it up; Suzi had only to pay for transportation to get Jerry’s body to University of Colorado Hospital.

Analysis of tumor samples taken from Jerry during the autopsy contributed to a Cancer Center study of resistance mechanisms to therapies that target ROS1 and ALK alterations in patients with non-small-cell lung cancer. The research team presented their findings at the American Society of Clinical Oncology annual meeting in Chicago in early June (see box). The information could help clinicians “unravel the mysteries” of why targeted therapies stop working in some patients, Camidge said.

Dara Aisner, MD, PhD, a pathologist and director of the Colorado Molecular Correlates Laboratory at the CU School of Medicine, added that the lab “extensively sampled” Jerry’s tumor, with the aim of eventually genetically mapping alterations that are linked to resistance to treatment.

The autopsy report confirmed Jerry’s cancer had metastasized to his liver, lymph nodes, esophagus and bone marrow, and that the Parkinson’s disease diagnosis he’d received in the spring of 2014 was correct. For Suzi Evans, it provided a sense of peace, especially given the unanswered questions that surrounded Jerry’s disease while she was living through it with him. She thinks others might experience the same thing.

“They might get comfort out of knowing what was really going on,” with their loved ones, she said. “Knowing that everyone was doing everything they could, but they didn’t have enough information to be able to do more. Now they have more information for the next guy to do more. Something positive can come from this; it wasn’t all just a drill.”

Living for the future

Suzi’s statement echoes the sentiments of a 75-year-old patient also diagnosed with stage 4 non-small-cell lung cancer. Marilyn (not her real name) is now receiving home hospice care in Denver. A tumor that penetrated her pulmonary artery requires her to be on 10 to 12 liters of oxygen and she manages her symptoms with nebulizers and morphine.

Marilyn has been treated at a hospital separate from the Cancer Center. Camidge said two tests at the other institution failed to reveal what drives her cancer, and the facility doesn’t allow for additional tests to be conducted as part of its standard of care.

Camidge got involved when Marilyn sent him an email, thinking he might be interested in the particulars of her case. Her current condition and the location of her disease make a further biopsy unfeasible while she is alive. But she volunteered to donate her tumor tissue for research after she has died as an aid to increasing knowledge of cancer biomarkers and the discovery of new therapies targeting them.

Camidge needed a team to deal with the request, so he started with Joan Hart, a social worker in the Cancer Center. She in turn, Aisner, to see what would be needed to arrange an autopsy.

Hart also advised Marilyn to talk with her family about her decision and connected her with Decedent Affairs, which would work with the funeral home and act as a crucial go-between in arranging the logistics of transfer.

Reality pathology

These are details that must be attended to, said Carrie Marshall, MD, assistant professor of Pathology at CU. Marshall explained that an individual can’t consent to his or her own autopsy. “The patient might feel strongly about it, but the family may have other thoughts,” Marshall said.

Marilyn said her daughter has given verbal permission, understanding Marilyn’s hope that the autopsy could contribute to “increasing knowledge of a complicated and difficult disease.”

That’s one of the main purposes of hospital autopsies, Marshall said. They are distinct from forensic autopsies, the stuff of television dramas in which grim pathologists probe bodies for signs of crime. Pathologists at UCH and other medical centers work with researchers who require fresh tumor samples; residents learning to dissect and examine organs for signs of injury and disease; and medical teams seeking to understand the pathologic findings of their deceased patients.

“As pathologists, we’re looking at whole-body function,” Marshall said. She and her pathology colleagues have particular areas of expertise – hers is in head and neck cancers, bone and soft tissue tumors, and gynecologic pathology – and collaborate with one another in making their findings.

Autopsies of patients whose cancer has metastasized also may yield valuable information to researchers, Marshall said. Tissue taken from separate organs could reveal if the cancer cells from each site differ genetically or have developed resistance to therapies in separate ways, she said.

Marilyn hopes her autopsy will “help to make a difference in this world.” She sees her decision as a way to set an example and guide others in making a difficult decision. “People might take a bad experience and get something good from it,” she said.

Camidge, who drew strong praise from both Marilyn and Suzi Evans for his clinical knowledge and sensitivity, emphasized that the decision for an autopsy lies solely with the patient and his or her family.

“We’re here to try to help them maximize their quality of life and I guess sometimes that includes helping them to help others even after that life has finished,” he said.

Targeted therapy team

The findings from Jerry Evans’ autopsy contributed to a University of Colorado Cancer study, presented at the American Society of Clinical Oncology annual meeting in early June. The authors:

• Carolyn McCoach, MD, PhD, medical oncology fellow
• Anh T. Le, medical oncology, senior professional research assistant
• Dara Aisner, MD, PhD, pathology
• Katherine Gowan, biochemistry and molecular genetics, senior professional research assistant
• Kenneth L. Jones, PhD, biochemistry and molecular genetics
• Daniel Merrick, MD, pathology
• Paul Bunn, MD, medical oncology
• Tom Purcell, MD, MBA, medical oncology
• Marileila Varella Garcia, PhD, medical oncology
• Ross Camidge, MD, PhD, medical oncology
• Robert Doebele, MD, PhD, medical oncology