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Do chemotherapy and radiation for cancer increase risk for a second cancer?

The study is not just relevant for people who had testicular cancer. Anyone who has had cancer faces this possibility of a secondary malignancy, which is different from a recurrence of the original cancer, and can occur years or even decades after the original malignancy. Fortunately, over the past several decades, there has been a decrease in secondary cancers due to radiation and chemotherapy as new studies have shown that sometimes lower doses are enough.

For survivors like me, secondary cancers are the ironic cancers — ones often born of the extra years our cures provided. There are a lot of us these days: the record 16.9 million cancer survivors in the United States, according to the American Cancer Society, is a testament to medical advances that have given us our longevity.

The questions many survivors face are complex: How do we live our lives with gratitude for our cures, knowing they may increase the risk of developing a new cancer? And what can we do to improve our odds of remaining cancer-free?

Sameer Keole, a radiation oncologist at the Mayo Clinic, says the likelihood of cancer survivors developing a new, unrelated malignancy is “about 10 to 20 percent higher” than someone in the general population. Among female pediatric cancer survivors, the statistics are even more sobering, with one study showing the risk of a new cancer among those treated as children to be six times that of the general population. Keole says the risk is elevated because, at that young age, “their bodies and cells are still developing,” and because they have many more years to develop a new cancer.

One beacon of hope is a study that found newer treatments using lower-dose radiation in children have led to a significant decrease in secondary cancer rates.

Susan Gambucci, a 55-year-old educator who lives in Minneapolis, knows firsthand what it’s like to live with the trade-offs. In 1982, at just 17, Gambucci was diagnosed with non-Hodgkin lymphoma and treated with mantle field radiation — which delivered high doses of radiation to the entire chest and neck to reach upper-body lymph nodes — which cured her. (That treatment is rarely used today because of its links to secondary cancers and significant cardiovascular issues.)

Sure enough, in 2018 — 36 years after her lifesaving treatment — Gambucci was diagnosed with breast cancer. Her radiation oncologist at the Mayo Clinic confirmed her suspicion when he told her that her new cancer was “almost certainly radiation-induced.”

Since the 1980s, when Gambucci and I were treated, oncologists have been trying to effect cures using newer technologies and lower doses of chemotherapy and radiation, especially among younger patients.

For instance, Keole says he now uses a precisely targeted form of radiation called proton beam therapy for prostate cancers instead of traditional X-rays, which can reduce radiation exposure to healthy tissue by 50 to 99 percent. Similarly, patients with testicular cancer today are treated with significantly lower doses and fewer courses of chemotherapy than I underwent 36 years ago.

Gambucci had been aware of her heightened risk for developing a secondary cancer and had been monitored closely for decades — so closely, as she put it, that “it was almost like they were waiting for it.” Like her, I’d long known about my own risk. Still, my oncologist’s email rattled me. Am I a time bomb waiting to be detonated? If so, what can I do to lessen the odds or buy more time?

Keole surprised me when he explained that about 40 percent of cancers (including secondary ones) could be avoided with certain “lifestyle modifications”:

“Tobacco-related products are the most common environmental and lifestyle risk for secondary malignancies,” just as they are for primary cancers, says Alma Rodriguez, professor of medicine in the Department of Lymphoma and Myeloma at MD Anderson Cancer Center.

Oncologists recommend we curb or avoid red meat and processed foods — which increase cancer risk — and boost the percentage of fiber, fruits and vegetables. Multiple studies indicate that survivors who don’t eat well are more at risk of secondary cancers than they’d otherwise be, Rodriguez says. Although, she adds, the evidence is clearest between diet and colorectal cancer, with less clear ties to date between what we eat and other cancers.

But here’s something I didn’t know: There’s growing evidence that obesity, defined as a Body Mass Index (BMI) of 30 or higher, is also associated with increased risk of certain types of malignancies (colorectal, postmenopausal breast, endometrial, renal cell, esophageal adenocarcinoma, pancreatic and liver). “Some epidemiologists state that obesity is approaching the same level of risk as tobacco use as a risk factor for cancer,” Rodriguez says.

Alcohol: Curb it or cut it out.

Drinking is another risk factor for several cancers, including ones of the mouth, throat, colon and liver.

Keole points to ultraviolet radiation exposure, either from direct sunlight or tanning beds, as being associated with new cancers. “I think they should be regulated like alcohol and tobacco, at minimum,” he says.

There’s more to worry about: Cancer survivors with chronic untreated infections such as the hepatitis B virus, human papilloma virus (HPV), human immunodeficiency virus (HIV), or Helicobacter pylori bacteria, which can cause peptic ulcers, are also more likely to develop secondary cancers, such as cervical and head and neck (throat) cancer, and to a lesser extent malignancies of the penis, anus, vagina and vulva, Keole says.

He especially urges young female cancer survivors to get the HPV vaccination, which can reduce the risk of developing secondary cancers by between 50 and 90 percent. (Health authorities now recommend that both boys and girls between ages 9 and 12 be vaccinated against HPV and also recommend vaccination for everyone through age 26 if they have not been adequately vaccinated previously.)

It seems that for every new answer there are more questions. How much of a role do environmental toxins and stress play in a survivor’s (or anyone’s) vulnerability to cancer? What is the cumulative effect of low-dose radiation sources like dental X-rays, airport security scans and routine screening X-rays? Will revolutionary new cancer treatments, including immunotherapy and CAR T-cell therapy, turn out to increase the risk of secondary cancers? Even more challenging, today’s answers may not be the same tomorrow.

Those questions are not just theoretical. During an interview with J. Leonard Lichtenfeld, the former deputy chief medical officer for the ACS, I mentioned that I remain in touch with my oncologist, periodically asking him questions, which is why he had emailed me that study about testicular cancer.

“You got information because you asked questions and were in a care system that responded to you,” Lichtenfeld noted. Many people who were treated for cancer do their follow-up care for a number of years, he added, then “never hear another word” from their doctors. People get lost in the shuffle, he continued, especially as they get older or if they change primary care doctors. (I must have had at least a half-dozen primary care doctors since my treatment ended.)

To help with those challenges, an increasing number of hospitals, such as the University of Minnesota’s Masonic Cancer Center, provide long-term follow-up care for cancer survivors. Anne Blaes, an associate professor of hematology/oncology and director of Cancer Survivorship Research, says its program keeps patients informed about the long-term effects of cancer treatment and recommended follow-up care, including screenings and individualized guidance that is also shared with a patient’s primary care provider.

“You are probably aware that cancer survivors do not have the same life expectancy as individuals not diagnosed with cancer, even when they are cured from their cancer. They often suffer from second cancers, cardiovascular issues, impairments in quality of life and fatigue,” she told me. That’s why it’s important to keep tethered to a knowledgeable source.

“You have to be your own advocate,” survivor Susan Gambucci says. Medical records get lost. Doctors retire. Parents who knew their child’s medical and treatment history pass away. And, of course, our own memories fade. This means my oncologist can expect to keep hearing from me over the coming years — and I hope to keep hearing from him. I remain grateful to him and to the other doctors and researchers who turned a death sentence into a cure, albeit it one with an asterisk: Warning! A secondary cancer may be ahead.

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