Studies on the Effects of the Prophylactic Radiation
Question
I have limited-stage small cell lung cancer. I had four cycles of chemotherapy with carboplatin and etoposide, which was extremely effective. I will complete 30 treatments of radiation therapy next week to my lung area. My oncologist wants me to have 10 prophylactic cranial irradiation (PCI) treatments to my head. My mother also has lung cancer (mixed small and large cell) and had radiation to get rid of two small cerebellum brain tumors. I feel that the radiation therapy that she had significantly affected her mental functioning. My oncologist sent me links to literature on toxicity and statistical studies on the effects of the prophylactic cranial irradiation, and I was not convinced. The studies are small, old, and not conclusive about toxicity. Do you recommend PCI? By the way, my mother's side of the family has a history of early onset Alzheimer's disease.
Are there any new studies with larger samples?
Answer
Mitch Machtay, MD, Radiation Oncologist, responds:
PCI is the use of moderate doses of radiation therapy to the entire brain in an effort to prevent cancer recurrence in or metastasis to the brain. It is well known that the brain is often the first, and sometimes the only, site of small cell lung cancer recurrence after successful chemotherapy +/ – chest radiotherapy. The brain has, in fact, often been referred to as a "sanctuary" site for small cell cancer since chemotherapy is less able to treat metastasis to the brain than cancer in the rest of the body. If small cell lung cancer recurs in the brain, it is likely to cause devastating neurologic (brain) problems. Radiation therapy and/or additional chemotherapy rarely eradicate the disease at that point. PCI has been used for many years in the hopes of preventing recurrence in the brain and is relatively successful in this regard (though certainly not 100% successful). As you have noted, there have been well-controlled studies showing differences in "cure" rates with or without PCI. There is now a proven improvement in the chance for long-term survival with PCI, though the magnitude of this benefit is modest since recurrences with small cell lung cancer can occur in other parts of the body outside of the brain.
The downside of PCI is the potential risk of permanent radiation damage to the brain. Radiation therapy to any part of the body usually causes side effects, some of which are temporary and some of which can be permanent. Radiation therapy to the brain can cause the gradual loss of brain cells (neurons) over months to years that can lead to problems with memory, coordination, strength and/or other brain functions. This has been well demonstrated among survivors of childhood cancers who received brain radiation therapy. In rare cases, these neurologic problems can progress to very serious stroke-like episodes and/or "dementia" similar to Alzheimer's disease. These "anecdotal" risks have led some physicians and patients to refuse any consideration of PCI for small cell lung cancer.
The medical literature on brain problems after PCI for small cell lung cancer is admittedly poor, with few well-controlled modern studies. However, several points have emerged from these data:
- The risk of brain problems after radiation therapy is increased by the use of large daily doses of radiation to a high total dose, doses above and beyond the doses that are used for successful PCI.
- The risk of brain problems after PCI is increased by giving chemotherapy at the same time or immediately before or after PCI, which is no longer a standard practice.
- Many patients with small cell lung cancer already have detectable brain problems before starting PCI, so it is not clear how much PCI is contributing to these problems over the ensuing years. Thus, studies which report brain problems after PCI without the patients having "baseline" (pre-PCI) tests of their brain function should be viewed with skepticism.
- Most of the brain problems following moderate-dose PCI are subtle and most typically manifest as mild short-term memory loss, and not severe dementia. In contrast, cancer recurrence in the brain (which PCI can help to prevent) usually causes very serious, obvious brain problems and is usually quickly fatal.
In summary, as with any cancer treatment, one must weigh the benefits of that treatment against its risks. While some physicians call the use of PCI a "no-brainer" due to the clear survival benefit associated with this therapy that has a relatively well-tolerated side-effect profile, I can understand the continued reluctance of some patients and physicians to undergo this frightening treatment. However, I personally recommend PCI for most patients without pre-PCI neurocognitive problems who have successfully completed treatment for limited-stage small cell lung cancer and are in a complete remission or extensive-stage small cell lung cancer and are in complete remission or who have had a partial response or stable disease. In my practice, this typically consists of 10 daily fractions of 250 cGy each to the whole brain given at least 3 weeks after the last dose of any chemotherapy. A brain MRI should be performed prior to starting PCI to be sure that the cancer has not already shown up in the brain.
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