Immunotherapy is a source of great hope in cancer care. It has rescued some patients from the brink, while giving others a reason to believe that they, too, could beat the long odds.

But these therapies are also creating a vexing dilemma for doctors: Their patients, citing television ads and media accounts of miraculous recoveries, are pushing hard to try them, even when there is little to no evidence the drugs will work for their particular cancer.

Doctors want to give their patients every shot at survival, but can they justify prescribing a drug when it hasn’t been tested for that patient’s type of cancer? Many of these treatments bring risks of painful — even life-threatening— side effects and carry total price tags pushing $1 million. In some cases, insurers won’t pay.

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“Whether it works or not, the burden both financially and emotionally on families and patients is massive,” said Dr. Vicki Jackson, chief of Massachusetts General Hospital’s palliative care unit, which helps patients with their decision-making process. “If you try it and it doesn’t work, then you’ve used up all your life savings.”

There are few objective guideposts to determine which patients should get which treatments, or even undergo genetic testing to determine whether they are among the minority of patients who might benefit substantially from immuno-oncology medicines. The dividing line is often drawn by variations in age, tumor stage, and underlying health status — and the weight given to those measures still relies on physician discretion.

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“Is it ethically and morally appropriate to not offer these potentially curative options on the basis of a very slight difference in kidney or liver function?” asked Dr. Ephraim Hochberg, a Mass. General oncologist who specializes in lymphoma.

Precision medicine, and the use of genetic markers to predict the success of treatments, promises to help answer these questions. Scientists at Stanford, for example, engineered a radioactive molecule, detectable by PET imaging, to track whether a patient’s T cells are activated and thus capable of fighting cancer if the patient is given immunotherapy.

The technique worked in lab mice but has not yet been tried in human patients, and other such approaches are further off. Meanwhile, patients and doctors are left to make life and death treatment decisions on uncertain terrain.

This struggle plays out on a near-daily basis at Mass. General, a Harvard-affiliated academic medical center with a deep well of resources and expertise. STAT interviews with specialists at the hospital reveal both the complexity of the variables at play, and the difficulty of establishing clear treatment protocols when data on real-world outcomes is still lacking.

“Whether it works or not, the burden both financially and emotionally on families and patients is massive.” Dr. Vicki Jackson, Massachusetts General Hospital.

The extent of these difficulties is only magnified for oncologists working with fewer resources in smaller community hospitals, where the vast majority of the nation’s cancer patients receive their care.

The uncertainty over treatment eligibility primarily pertains to a new class of treatments that harness the power of a patient’s immune system to attack cancer cells. These drugs have reached the market fairly recently, and have been tested in patients with a limited number of cancer types. And even in those types, the drugs work only some of the time.

These treatments include the checkpoint inhibitors Keytruda and Opdivo, CAR-T drugs such as Yescarta and Kymriah, and neo-antigen vaccines.

Hochberg often deals with patients who want to try CAR-T therapy, which re-engineers a patient’s T cells to recognize molecules on cancer cells and attack them. CAR-T drugs cost between $375,000 and $475,000, and the administration of treatment and follow-up care adds hundreds of thousands of thousands of dollars to the total bill.

In theory, CAR-T therapies can be tried on older patients whose bodies cannot withstand chemotherapy and radiation, but the National Comprehensive Cancer Network, which publishes treatment guidelines, has not established detailed eligibility criteria.

A similar struggle is playing out over the use of checkpoint inhibitors. It is not always clear which patients should get tested for a rare genetic condition, known as mismatch repair syndrome, that indicates receptivity to these drugs. While the testing is routinely conducted in treatment for patients with uterine and colon cancers, it is not always done for patients with other types of cancer.

“The fundamental problem is that it’s a costly test, so people are reluctant to make it automatic,” said Dr. David Ryan, clinical director of Mass. General’s Cancer Center. “Right now we’re relying on the oncologist to pick up those patients where there’s a reasonable chance of having mismatch repair deficiency, and ordering that test from pathology. Everybody’s having a hard time figuring out how to do this.”

Insurers play a key role in making sure that sky-high spending for these drugs is based on evidence of efficacy. But their involvement cuts both ways. In some cases, they deny coverage for treatments even when they are recommended by oncologists who believe there is a strong scientific basis to back up their decisions.

That scenario arose recently for Dr. Zosia Piotrowska, a medical oncologist at Mass. General who specializes in treating lung cancer. She recommended a combination of targeted therapies for a 50-year-old mother of four who has struggled with metastatic lung cancer for five years.

The patient’s cancer is exceedingly rare and marked by a gene mutation that indicates greater receptivity to targeted therapies. Piotrowska said various combinations of treatments had allowed the patient to live a normal life for several years, but her insurer recently denied coverage for the new round of treatment, which comes with a price of $16,000 a month.

Piotrowska appealed the decision, but the insurer still denied coverage, citing a lack of support for the treatment option in National Comprehensive Cancer Network guidelines. Though such guidelines set forth detailed protocols, they do not address the myriad nuances of each type of cancer and rapid changes in treatment options.

“The guidelines can’t keep up with the pace of research,” Piotrowska said. “As we learn more and more and develop better treatments, certain patients fall into these loopholes where we understand the biology of what’s going on, we have a treatment, but you can’t explain it to the insurer.”

That denial of coverage means the patient must decide whether to pay out of pocket and drain family savings for an uncertain benefit. Piotrowska said this patient has enough resources to continue with treatment, but for the vast majority of patients, the price would mean certain financial ruin.

The advent of immune-based therapies is only making the decisions harder. For a small percentage of patients, the treatments can be a savior, but without comprehensive insurance coverage, they are guaranteed to lead to financial distress. And because there is not yet much data on how the patients who initially benefit are faring in the long run, it is nearly impossible for new patients and their families to assess costs and benefits.

Doctors said the confusion over who should get immune-based treatments is bound to be exacerbated by the passage last month of the controversial “right-to-try” legislation, which aims to give patients with terminal illness a different pathway to try experimental medicines that haven’t yet been approved by the Food and Drug Administration. It will not be clear how the law will affect patients until regulations are clarified in the coming months.

In some ways, the pressures and uncertainties posed by new cancer treatments are good problems to have. Julie Guillot said she wishes she’d had the luxury of such challenges when her son was sick.

Zach was diagnosed with acute myeloid leukemia when he was 5. For a boy of that age, concerns about unclear clinical benefits of treatments and sky high costs do not apply in the same way they might for an older patient. All the calculations point to the same answer: Try everything you can.

Zach received heavy doses of chemotherapy and three bone marrow transplants during years of expensive treatment that left him suffering from uncontrollable fevers, nausea, and infections. He died in 2014.

Guillot now works as an advocate to help other patients get access to the best treatments and to ensure that experimentation in cancer care can continue to proceed on its inevitably hard and messy course toward cures.

“If we are avoidant of new therapies because of the risk, the lack of data, or the cost, breakthrough therapies like CAR-T and bone marrow transplant would never be developed,” she said. “When you are faced with this, people are willing to take risks for a chance to live.”