Tag Archive for: Proton Therapy

How Is Lung Cancer Treated?

How Is Lung Cancer Treated? from Patient Empowerment Network on Vimeo.

Lung cancer expert Dr. Jyoti Patel provides an overview of lung cancer treatment approaches, including radiation therapies, targeted therapies, immunotherapy, chemotherapy, and surgery.

Jyoti Patel, MD, is Medical Director of Thoracic Oncology and Assistant Director for Clinical Research at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. She is also Associate Vice-Chair for Clinical Research and a Professor in the Division of Hematology and Oncology at Northwestern University Feinberg School of Medicine. Dr. Patel is a leader in thoracic oncology, focusing her efforts on the development and evaluation of novel molecular markers and therapeutics in patients battling non-small cell lung cancer. Learn more about Dr. Patel.

See More from Thrive Lung Cancer

Related Resources:

Understanding Lung Cancer Treatment Goals

Collaborating on Lung Cancer Treatment Decisions With Your Team

Personalized Medicine: Making Lung Cancer Treatment Decisions


Transcript:

Katherine:

I’d like to walk through the types of treatments that are used today to treat lung cancer. Let’s start with surgery.  

Dr. Patel:

We think about local therapies as things like surgery. So, surgery has evolved, again, significantly.  

Now with videoscopic approaches and robotic approaches we’re able to remove a tumor either with a larger incision – more traditional incision – or some of the smaller incisions. And the goal of doing the surgery is often to want to diagnosis the cancer. So, to do a biopsy. But when it’s used in terms of cancer treatment, the goal of surgery is to get a complete resection.  

So, we only do surgery if we can remove a tumor and mass with clear margins and not compromise other vital functions. Sometimes we’ll, again, do a more palliative surgery if we need to, if there’s a problem that’s causing significant symptoms. But in that case, the surgery is generally not improving the survival of the patient. It’s trying to palliate symptoms.  

Katherine:

Mm-hmm. What about other types of therapy? 

Dr. Patel:

Other localized therapies predominately include radiation therapy. And, again, radiation has significantly changed over the past years. We’ve been able to incorporate new technologies, truly target tumors, and to minimize toxicity, with two kinds of radiation. Photon therapy, which is more traditional therapy, and proton therapy, which we see administered in a very small subset of patients.  

Primarily, photon therapy, we treat tumors, sometimes over many weeks, to decrease toxicity versus sometimes we give one or two doses of radiation in a high-dose fashion that’s very targeted.  So, often for the chest in stage III cancer, for example, a patient may end up getting six weeks of radiation Monday to Friday with chemotherapy.  

And that, again, is curative intent. It’s to ablate the cancer and to provide the best local treatment. 

Often, we’ll do something called stereotactic radiation therapy. And that is if there is a discreet mass, often that could be if the cancer is metastasized to the brain, we can give very targeted radiation there, again, to ablate the tumor.  

In patients who may not be candidates for surgery because lung surgery is a big deal, right? Removing part of your lung can lead to morbidity in someone with other medical issues. Sometimes we can use pinpoint radiation in the lung and see really good outcomes for patients with good disease control.  

Katherine:

You’re also using chemotherapy still, I would imagine? 

Dr. Patel:

The other part of treatment for lung cancer are systemic therapies. And there a number of systemic therapies. So, I sort of break it down into three major parts. One is chemotherapy. Chemotherapy remains a backbone of treatment for lung cancer.  

It’s a lot more tolerable and much more personalized than ever before. Often chemotherapy can be given to patients without significant toxicities. Not everyone loses their hair. Not everyone has neuropathy. Often, I have patients who are working and taking care of their families on chemotherapy. So, it is a good and very reasonable option. But two things that we’re really most excited about – and I think have changed the field most dramatically – are targeted therapies and immunotherapies.  

Katherine:

Mm-hmm.  

Dr. Patel:

These targeted therapies are rationally designed molecules or antibodies that block proteins that may be overexpressed in lung cancer.  

So, some of them are the byproducts of mutated genes that are upregulated and causing a cancer to grow. Others may just be that we’re seeing a high level of protein expression on the cancer cell. But these targeted therapies preferentially bind to their targets that are present on cancer cells and not so much normal cells. Because of this, often there is less toxicity to normal cells. But because we can find specific targets – and the best targets are ones that are only expressed on cancer cells.  

But because we can find a direct target, sometimes we’re able to design drugs that may have significant efficacy. So, 80 percent or 90 percent of people who have a particular target and are able to get a targeted therapy may have a response to treatment. Targeted therapy can be great for some patients. And patients may be on oral medications, sometimes for years, to control their cancer.  

The other real game-changer in the past decade for lung cancer has been the integration of immunotherapy. Approved immunotherapies currently are primarily antibodies that we give to patients. And these antibodies block proteins that are expressed by cancer cells which downregulate the immune system. By shutting down these proteins, your own immune system is able to kind of re-see the cancer cell and kill it.  

And so, now we know in patients with more advanced disease that immunotherapy or immunotherapy with chemotherapy leads to better outcomes than we’ve ever seen. We also use immunotherapy for patients with stage III lung cancer after chemotherapy and radiation. And this improves their survival significantly.  

And most recently, we’ve now integrated immunotherapy after surgery for patients with early-staged disease to decrease their chance of relapse from cancer.   

Katherine:

So, are there options for relapsed patients? 

Dr. Patel:

So, absolutely. Most of our therapies in the metastatic setting work for some time. And then cancer is a difficult adversary. It figures out how to overcome whatever strategy we’re using and becomes resistant. When that happens, often we need to change course. We need to try a new therapy. We have a number of therapies that we’re looking at in the first- and second-line settings. And we’re trying to understand best therapies for subsequent lines of treatment.  

Generally, I say treatment is appropriate if you’re feeling pretty well, right? If you’re able to tolerate treatment, then the likelihood that you would be able to benefit from therapy is significant. How that changes over time weighs heavily on our decision. So, if someone’s having more fatigue or more symptoms from their cancer, it may be that even a little bit of toxicity proves too much.  

Whereas if someone is feeling still really good, we may be willing to say, okay, I’m going to take a little bit more of a risk for the benefit of improved cancer control.  

Focusing on Proton Therapy

This blog was originally published by Cancer Today by Sue Rochman here.

Proton therapy, an alternative to standard radiation therapy, is safe and effective. But evidence is lacking that it’s always a better option than standard radiation, and some insurers balk at the higher price tag.

Photo by ​​​​gorodenkoff​ / iStock / Getty Images Plus

 

IN AUGUST 2017, Ha​uli Sioux Warrior Gray noticed a lump in her left breast. Two months later, after having seen three different health care providers, the then 33-year-old mother of two from Yukon, Oklahoma, learned she had stage IIB breast cancer. In November, she started chemotherapy to shrink the 7-centimeter tumo​r in her left breast and kill the cancer cells that had spread to her lymph nodes. In March 2018, she had a mastectomy. When it was time to start radiation, Gray says, her radiation oncologist at the Integris Cancer Institute in Oklahoma City explained that proton therapy would be a better option than standard radiation therapy because “it would save my heart and lungs.”​

Gray’s doctor sent a treatment proposal for proton therapy to her health insurer. The request was denied. “I didn’t know insurance companies did that,” says Gray. Aided by a media consultant brought in by her doctor, Gray used social media and local news outlets to tell her story. Time was ticking—the first of 34 proton therapy radiation treatments that would target her lymph nodes and any breast tissue remaining in her chest wall was scheduled for May 10, just three weeks away. When her insurer wouldn’t budge, the proton therapy center, ProCure, agreed to front the cost. The same day, says Gray, the Indian Health Service, which also provided her with health benefits, called to say they would cover the cost of the treatment. “I was surprised, shocked and happy,” says Gray. “I had been praying and asking God if this is what needed to be done.”

For about a century, radiation therapy has been a mainstay of cancer treatment. Standard radiation systems use photons, or X-rays, to kill cancer cells. Proton therapy uses particles that can be targeted at the tumor more precisely. Studies have shown that proton therapy is safe and effective. Less clear is which patients with which types of cancer should receive it instead of standard radiation. Clinical trials that compare proton and photon therapies are now underway, but enrolling patients hasn’t been easy. And in the years that it takes fo​r the answers to come in, thousands more cancer patients will find themselves in a position similar to Gray’s.

Photons and Protons

Radiation kills a cell by damaging its DNA. The photon beam used in standard radiation therapy travels through normal cells in the body, gets into the cancer cells, and then travels again through normal cells as it comes out the other side of the body. Protons are particles with a different set of physical characteristics. They accelerate and penetrate the skin quickly, explains Steven Lin, a radiation oncologist at the University of Texas MD Anderson Cancer Center in Houston. Then the particles stop at the tumor, where they deposit all their energy at once.

The U.S. Food and Drug Administration (FDA) approved proton radiation as a cancer treatment in 1988. Before the FDA can approve a new cancer drug, clinical trials must show that the treatment is safe and effective for a specific type of cancer. New devices and technologies like proton therapy are held to a different benchmark. They only have to be proved safe and effective overall, not for a specific use. This means “there is no clear indication where proton [therapy] should be the standard treatment,” says Lin. Instead, “every cancer patient who needs radiation is potentially eligible for proton treatment, but not all patients will benefit.”

When there are no specific indications for a treatment’s use, insurance coverage can vary widely. Medicare typically covers the cost of proton therapy, regardless of the type of cancer. But many private insurers do not want to pay for proton therapy when it has not been shown to be more effective than standard radiation therapy and can cost four to 10 times more. A recent study found that two-thirds of patients with private health insurance initially had their requests for proton therapy denied. (On appeal, about 68% of patients initially denied coverage had their treatment approved.)

​Determining the BenefitFor children with cancer, proton therapy is now a routine treatment. “For many pediatric patients, proton therapy offers clear benefits,” says Shannon MacDonald, a radiation oncologist at Massachusetts General Hospital in Boston. When treating children, she explains, “you are treating brain tumors and tumors close to areas that are responsible for future growth.” Before proton therapy was available, some of these children would not have been able to have radiation at all. With proton therapy, she says, they can be treated, and the tissue spared from radiation will continue to grow and develop normally. Proton therapy has also made radiation a possibility for some adults with rare or difficult-to-treat cancers, such as tumors in the central nervous system, brain, head and neck, eye, skull and spine.

In other instances, proton therapy has allowed many patients to avoid some or all of the potential side effects associated with standard radiation therapy, which can include skin problems, pain and swelling, and heart and lung problems. That was the case for Arianne Missimer of Coatesville, Pennsylvania, who was diagnosed in 2015 with a stage III liposarcoma—​a rare cancer that can start in muscle tissue—in her right thigh. The 34-year-old physical therapist, registered dietitian and athlete needed radiation therapy to treat her cancer and was concerned about her potential risk for pain, swelling, weakness and long-term bone damage. Her radiation oncologist explained the difference between photon and proton therapies and then suggested proton therapy at Penn Medicine’s Roberts Proton Therapy Center in Philadelphia. Her insurer was willing to cover it.

A Growing Business

Proton therapy centers are now ​located across the U.S.

​Waiting for Answers

It’s unclear whether proton therapy improves outcomes and reduces side effects in other cancer types, including breast and prostate cancer. The National Cancer Institute (NCI) and the Patient-Centered Outcomes Research Institute (PCORI) have funded seven phase III randomized trials comparing proton therapy and photon therapy in patients with breast, esophageal, liver, lung and prostate cancer and two types of brain tumors, glioblastoma and low-grade glioma. Some of the trials are comparing overall survival; others are looking at reductions in symptoms and side effects.

New Research Sheds Light on Side Effects

When combined with chemotherapy, proton therapy is associated with fewer severe s​ide effects than standard radiation therapy, according to a​ study.

The results of these trials have the potential to inform future treatment guidelines, but finding patients for the studies has been laborious. In 2018, almost two years after it opened, the breast cancer trial had enrolled only 317 of 1,716 patients needed; after five years, the prostate cancer trial, which needs 400 patients, had enrolled only 254. Radiation oncologists point to multiple factors contributing to the slow patient accrual. In some cases, says Lin, doctors may believe proton therapy is better, and they don’t want their patients to participate in a clinical trial where there is a chance they won’t receive the newer approach. In other instances, patients don’t want to take the chance they will be assigned to the treatment arm that doesn’t receive proton therapy.

There is also an insurance barrier. In the major proton therapy trials, insurers are asked to pay for patients’ radiation treatment, whether it’s proton or photon therapy. Justin Bekelman, a radiation oncologist at the Penn Medicine Abramson Cancer Center, says it’s all too common for insurers to say they won’t pay for an unproven treatment when a patient is selected for the proton therapy arm. Bekelman was the lead investigator for the breast cancer trial and a co-lead investigator for the prostate cancer trial.

“Naturally, insurance companies are going to question the value,” says Bekelman. “That’s precisely why we need to run these trials. We want to determine if there are benefits and if there are harms to proton therapy, and in which cancer patients which treatment will be most successful for cancer control and reducing side effects.” But researchers can’t do that if insurers won’t cover that care.

In 2012, the University of Texas MD Anderson Cancer Center launched the NCI-funded clinical trial comparing protons and photons in esophageal cancer, which aimed to enroll 180 patients. Enrollment closed this year with 104. (Another 21 patients enrolled but couldn’t be evaluated because their insurer wouldn’t pay for the proton therapy.) Lin, who is overseeing the study, says some patients declined to enroll when they learned their health insurance covered proton therapy. “We explain to [patients] that the proton therapy is experimental, which is why we are trying to do the study,” he says. “But they say they’ve heard good things about it. Others say, ‘I have money and I don’t want standard treatment. I want the best.’”

It’s easy to understand why a patient who has pored over a proton therapy center’s website might feel that way. In a study published online March 15, 2018, in Radiation Oncology​, researchers analyzed 46 websites of proton therapy centers—half of which w​ere in the U.S. The analysis found that many centers used language that could lead patients to think that choosing proton therapy would give them a better outcome, says the study’s senior author Alexander Louie, a radiation oncologist and epidemiologist at Sunnybrook Health Sciences Centre in Toronto. “Many of the websites made blanket or generic statements that may not be completely supported by evidence but have some credence potentially or theoretically, blurring the line between evidence and advertising,” he says.

“It’s not as easy as saying if proton therapy is good or bad,” adds radiation oncologist Jeffrey Buchsbaum of the NCI’s Radiation Research Program. “Proton therapy is like a vehicle for getting the patient to a better place. And it has to be used properly.” There are certain situations, he notes, in which patients wouldn’t be alive without proton therapy. “But that doesn’t mean it’s necessary for all cancers.”

Proton Therapy Tips

Follow​ these suggestions​ as you consider radiation therapy options.

​Moving Forward

The American Society for Radiation Oncology has developed model policies for insurers that delineate where there is sufficient evidence to support coverage of proton therapy. Insurers also use National Comprehensive Cancer Network treatment guidelines to support or deny a patient’s treatment with proton therapy. To move research forward, investigators are trying to work with hospitals to find ways to make insurers more amenable to covering the cost of treating patients in randomized clinical trials comparing photon therapy and proton therapy. In some cases, this may include reducing the cost of proton therapy to make it more comparable to that of standard radiation therapy. “The issues happening here are partially the result of the complexity of the health care delivery system,” says Buchsbaum.

But for patients, treatment choices must be made now. Missimer believes that proton therapy helped treat her cancer without sacrificing her athleticism. She is an active member of Penn Medicine’s proton center alumni group, which provides support to patients who are currently receiving or are considering proton therapy. She also appears in an advertisement for Penn Medicine’s proton therapy center, and an article about her experience is included on the cancer center’s website.

Missimer’s treatment began with chemotherapy, which she admits slowed her down. But during her proton therapy, which started in July 2015, she joined a ninja gym. And as she recovered from the surgery and additional chemotherapy that followed the radiation, she kept going. In May 2016, Missimer competed in the Philadelphia regional American Ninja Warrior competition. “I lost my brother to cancer,” she says. “He had radiation and had significant complications. The only thing I get is a little stiffness. But as long as I keep moving, my leg is good.”

Gray completed her proton beam treatment in June 2018, about a year after she’d first felt the lump in her breast. Skin damage is a common side effect of both types of radiation therapy. Gray says her doctor told her that her skin did well during the proton therapy. “But if that was well,” she says, “I can’t imagine what worse would be like. My chest looked like burnt hot-dog skin. And I still have a dark scar from the burn that might not ever go away.” After being out of work for a full year, Gray returned to her job as an educational specialist for Native American youth in October 2018, and she slowly started back at the gym. She wears a compression sleeve and a glove to manage lymphedema that developed in her arm—caused by either the surgery or radiation—and deals with nerve pain in her arm and chest. None of it has been easy, but, she says, “my faith has gotten me through.”​ 

Sue Rochman is a contributing editor for Cancer Today.​