Prophylactic cranial irradiation (PCI) is a technique used to combat the occurrence of

metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, the ...

to the brain in highly aggressive

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

s that commonly metastasize to brain, most notably

small-cell lung cancer Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell ca ...

. Radiation therapy is commonly used to treat known tumor occurrence in the brain, either with highly precise stereotactic radiation or therapeutic cranial irradiation. By contrast, PCI is intended as preemptive treatment in patients with no known current intracranial tumor, but with high likelihood for harboring occult microscopic disease and eventual occurrence. For small-cell lung cancer with limited and select cases of extensive disease, PCI has shown to reduce recurrence of brain metastases and improve overall survival in complete remission. __TOC__

History

During the fervor to develop treatments for pediatric leukemia in the 1960s, there was initial experimentation with PCI for children with ALL. Although advances in

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemother ...

had been able to successfully treat tumor throughout the body, there remained an alarming incidence of brain metastasis following systemic chemotherapy. A theory was developed that the brain was likely a pharmacologic sanctuary where sub-clinical metastases were protected from

cytotoxic drugs Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

by the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of the central nervous system where ne ...

. Oncologists hypothesized that treatment of this sub-clinical disease with radiation therapy may stamp out the malignant process before it could advance to cause symptoms. Indeed, subsequent studies showed that an increased rate of disease-free survival and overall survival in those children treated with PCI. Due to successes with pediatric blood cancers, the concept of PCI was enlisted for the treatment of other types of cancers. Over time, there has slowly been a shift away from PCI due to incidence of long-term side effects and secondary cancers, as well as evidence of equivalent control with alternate forms of treatment such as long-term

intrathecal chemotherapy Intrathecal administration is a route of administration for drugs via an injection into the spinal canal, or into the subarachnoid space so that it reaches the cerebrospinal fluid (CSF) and is useful in spinal anesthesia, chemotherapy, or pain m ...

. For ALL, PCI had been reserved only for high-risk cases; however, a 2009 study by Ching-Hon et al. reporting on the results of clinical trial NCT00137111 suggesting that PCI is unwarranted even in high-risk cases. Despite changing recommendations for ALL, PCI continues to play an important role in treatment of small-cell lung cancer.

Dosing

Early trials for PCI in ALL utilized high-dose treatments, up to 24 Gy cumulative dose, that resulted in significant toxicity. Further experiments showed that lower-dose treatments (12–18 Gy) administered in smaller fractions provide equivalent benefit with lower neuro-toxicity.

References

{{Radiation oncology Cancer treatments Oncology Medical treatments Radiation therapy