The Case for Proton Therapy

From a talk at the American Society of Clinical Oncology meeting: Anita Mahajan, MD, from the University of Texas M.D. Anderson Cancer Center in Houston

Dr. Mahajan highlighted the fact that there are fewer toxic effects with proton therapy than with conventional radiotherapy, especially in pediatric cancer patients.

Conventional radiation therapy can lead to long-term toxic effects, especially in growing children, she explained. "There can be effects on all of our developing organs and on sensitive structures, including the heart, the lungs, the gonads, the eyes, the eyes, and the kidneys," she said. "And, of course, there can be the risk of secondary neoplasms."

The risk for thyroid malignancies escalates in children younger than 10 years of age, even at doses of 10 Gy. "Some people suggest that any dose to the thyroid gland increases that risk," Dr. Mahajan said.

One of the ways to reduce the toxicity of treatment is to decrease the irradiated volume. Proton therapy, she argued, is one of the most effective ways of doing that because it delivers the dose to the tumor but limits exposure to surrounding tissue. "There is less dose on the way in and less dose on the way out," she noted.

Dr. Mahajan illustrated her point by describing the "very vulnerable children" treated for retinoblastoma at her institution. Even with the most advanced conventional radiotherapy — intensity-modulated radiation therapy (IMRT) — there is a "splash of radiation everywhere," she explained. With proton therapy, "the radiation is really restricted to the orbit itself."

"If I was to treat a child who has an excess risk of a secondary tumor, I might consider electrons or protons," she explained.
She also described the treatment of genitourinary tumors. "With IMRT, you get the same dose to the tumor but you get more radiation to the rest of the pelvis," she explained. "With protons, the main thing here is that you can reduce the dose to surrounding tissue that could be developing and is at risk for side effects."

Certain areas of the body are more at risk than others, even at low doses of radiation, especially in children. Cataracts can form after exposure to just 1 to 2 Gy, and bone growth can be affected by exposure to 10 to 25 Gy, she noted. The gonads and kidneys are also sensitive to the effects of radiation. Exposure of the testes to 2 to 3 Gy leads to azoospermia and possibly permanent infertility. "So even a very low dose can have significant consequences down the road," Dr. Mahajan explained.

Proton therapy can be beneficial for tumors in the thorax region. She pointed out that IMRT delivers a longer dose to the contralateral lung in adults with lung cancer. "With the proton approach, you can restrict it to the ipsilateral site and you might be able to save some lung function."

Dr. Mahajan described a girl with Hodgkin's lymphoma who had a distribution in the upper mediastinum and the low neck and was treated with proton therapy. "With nice distribution, we were able to spare a lot of her lung. Her thyroid gland did get some radiation but, importantly, her breast tissue got very little," said Dr. Mahajan. "Knowing that these girls are at risk, we can reduce the risk with this therapy," she said.

Candidates for Proton Therapy

Who are the good candidates for proton therapy?

Patients who need a relatively high dose of radiation therapy are, said Dr. Mahajan. "There's no point in this for someone who needs 10 Gy because the benefits will be hard to measure," she said.

Those with tumors that are engulfed in a sensitive organ or tumors that are centric in the body cavity, like iliac tumors in Ewing's sarcoma, are also candidates. In general, children are good candidates, given their vulnerability to late affects and their risk for a secondary malignancy later in life, she noted.

Dr. Mahajan acknowledged that there are practical issues that need to be addressed. Many countries do not have the resources to support a center, which limits the availability of proton therapy. To equip and construct a suitable proton center can cost $25 to $150 million.

In comparison, acquisition costs for IMRT systems are much cheaper (from $1.8 to $5.4 million), according to a 2009 report by the Institute for Clinical and Economic Review on management options for low-risk prostate cancer.

In addition, proton therapy is far more expensive than any of the other radiation therapies. Some data show that the median Medicare reimbursement for prostate cancer treatment was $32,428 for proton therapy and $18,575 for IMRT.

In the United States, medical insurance does not always cover it, and treatment can take a lot longer and can involve more complex planning. "IMRT is a very good solution in certain situations," she said.

Dr. Mahajan pointed out that the cost of technology tends to decline over time. For instance, in 1983, cell phones cost $4000; now a smartphone can be purchased for under $500. "As technology develops, it will get become less expensive," she predicted. "Industry is interested in what we are doing, and they will make it more practical and more affordable as time goes by."

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