Friday, 19 April, 2024
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The retreat of radiation, mainstay of cancer treatment

With more advanced tools being designed to fight cancers – and with better engineered cancer-killing cells, immunotherapies and targeted drugs helping clinicians cure more patients – oncologists are decreasing the use of radiation, which has long been a mainstay of treatment.

In some cases, they are even keeping certain patients, with low-risk tumours, off radiation entirely.

“We are in an era of radiation omission or de-escalation,” Corey Speers, vice-chair of radiation oncology at the University Hospitals Seidman Cancer Centre and Case Western Reserve University told STAT News.

“Radiation is perhaps one of the most precise and most effective cancer therapies we have, so it will always play an important role in cancer management, but there are situations now, on an individual patient basis, where radiation may not be needed.”

Treating cancer has always been a balancing act between the brutal therapies that kill tumours and how much of the treatment the human body can take. At worst, the side effects of chemotherapy, radiation and surgery can leave lasting damage, disrupt key bodily functions, or permanently disfigure a patient.

So doctors have always wondered just how much of a therapy they could reduce without sacrificing efficacy.

That’s been true for medicines and surgery as well, said Abram Recht, a radiation oncologist at Beth Israel Deaconess Medical Centre.

“People have been looking at reducing the intensity of surgery, radiation and systemic therapy for a long time, and there’s always been controversy about it,” Recht said. “The balance has always been the question: will reducing the intensity of treatment affect the long-term effectiveness?”

The work over decades helped clinicians feel comfortable scaling back chemotherapy or surgery, eventually adopting less dramatic interventions as standard practice.

One example is the radical mastectomy, Recht said, where surgeons once removed not only the breast but also the chest wall muscles and nearby lymph nodes in an effort to cut down on breast cancer deaths.

It took more than a century of experimentation and clinical trials to shift to the breast sparing procedures surgeons take now.

“When I was starting out in practice as a resident, it was not unusual for women to receive two years of chemotherapy after surgery. Almost nobody completed it,” Recht said. “Then a randomised trial in Milan under the auspices of Umberto Veronesi compared 12 months of chemo versus six months. And there was no difference.”

Radiation has also undergone a century of advancements, with early cancer radiotherapy beginning shortly after Wilhelm Röntgen discovered X-rays in 1895 and Marie and Pierre Curie discovered radium in 1898.

Since then, radiation has evolved into treatments that include modern brachytherapy, inserting a radioactive source into a tumour, and focused beams of ionising radiation that kill off cells while incurring as little off-target damage as possible.

The new thinking about easing back on radiation goes beyond just easing back on the treatment, though. “There’s also been this long history of trying to reduce the morbidity of radiation in different ways – the big thing people think about reducing morbidity is to not give it at all,” Recht said.

There are more and more settings where that appears to be possible for patients, with studies showing that omitting radiation from standard therapy seems to make little or no difference in outcomes in certain low risk or early-stage disease in lymphoma, breast cancer, thyroid cancer, and more.

There are two main reasons for this. Treatments for cancer today are magnitudes beyond what they were, even two or three decades ago. Also, oncologists have more advanced tools to understand patients’ tumours, like better biomarkers or imaging, often allowing them to triage different cancers as low or high risk.

“We can do better surgeries, better supportive care, better chemotherapy, more effective chemotherapy. We have better scans to stage people properly and better molecular tests,” said Michael Cecchini, an oncologist who treats gastrointestinal cancers at the Yale Cancer Centre.

One recent example is in rectal cancer, where modern, effective chemotherapy regimens exist and radiation can cause quite a bit of collateral damage to surrounding organs.

“You have to think about where you’re radiating,” Cecchini said. “With 10 doses to a shoulder, maybe you get some short-lived blood count abnormalities. When we radiate the pelvis for rectal cancer, there are several important organs there. Radiation is very focused, but you hit more than the tumour.”

In the short term, patients who receive pelvic radiation can experience diarrhoea and other acute toxicities. In the longer term, they are more likely to have urinary incontinence and can run the risk of infertility.

Researchers at Memorial Sloan Kettering Cancer Centre wanted to see if patients with certain rectal tumours that are farther away from the anus might be able to omit radiation and only get chemotherapy. These “higher” tumours tend to be lower risk and have fewer complications.

“The investigators showed by doing this, there was no statistically significant reduction in survival. So if it’s not inferior, why take the extra potential side effects?” Cecchini said. “As an oncologist, I was thrilled. Taking it back to my own practice to some of my patients, especially younger ones where fertility may be an issue – if we can be less toxic to them, that’s huge.”

The phasing out of radiation – and the stepping down of cancer treatment in general – is piecemeal by nature, Cecchini said.

Advances in oncology tend to happen in a way that’s specific to a certain cancer subtype.

“Cancer is a heterogeneous disease. Breast cancer and colon cancer are very different. Within breast cancer, you have three major subtypes. Within that you have certain mutations that have targeted drugs, and some that don’t. As these subtypes become better defined and new drugs are developed for them, it becomes more feasible to step down treatment in other modalities.”

That doesn’t mean there is no role for radiation in the future, even as oncology continues to advance, cancer type by cancer type.

But that role will be smaller, Recht said. “If we can reduce the morbidity of treatment without harming the cure rate, in the long run, people will be better off.”

Radiation is still needed for both curative plans and palliative plans when patients have higher risk tumours or more advanced cancer.

In some settings, doctors still want to throw the kitchen sink at a patient with a tough cancer, in the hope they will live longer, better, or become cancer-free.

“Radiation’s role is expanding in patients with metastatic disease, allowing us to cure patients who were previously considered incurable,” observed University Hospitals’ Speers.

The use of radiation in more advanced cancer, even as it decreases for earlier cancer, arises in part from advances in radiation therapy as well, including the development of more precise radiotherapy technologies and techniques like proton beam therapy and stereotactic body radiotherapy.

“That delivers doses of radiation to tumours in a very safe and very effective fashion without causing damage to surrounding organs,” Speers said.

Or, as Recht put it, there will be work yet for radiation oncologists.

 

STAT News article – Radiation, a mainstay of cancer treatment, begins a fade-out (Open access)

 

See more from MedicalBrief archives:

 

Rectal cancer patients could skip radiation: US trial

 

Older breast cancer patients’ survival unaffected by no radiation – UK study

 

Faster breast cancer radiation treatment as effective as long course

 

Higher radiation doses not improving survival in prostate cancer patients

 

Radiation therapy vs active surveillance

 

 

 

 

 

 

 

 

 

 

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