Prophylactic Cranial Irradiation (PCI) and Lung Cancer
by Dr. C.H. Weaver M.D. 3/2019
Radiation to the brain prior to detectable spread of cancer to the brain appears to improve survival in patients with both early- and late-stage small cell lung cancer but not so much with NSCLC.
Small-cell lung cancer (SCLC) is a fast-growing type of lung cancer and accounts for approximately 25%-30% of all lung cancers. A common site spread, or metastasis, of SCLC is the brain. Once brain metastases have been detected, radiation directed to the sites of cancer is a common treatment.
Researchers have been evaluating the approach of whole-brain radiation prior to detection of brain metastases in patients with SCLC (prophylactic cranial irradiation) (PCI) in an attempt to kill any undetectable cancer cells that may have spread to the brain.
Researchers from the North Central Cancer Treatment Group (NCCTG) recently performed an analysis to further evaluate the use of PCI among patients with SCLC. The analysis included 739 patients with SCLC; 318 patients had advanced SCLC and 421 patients had early SCLC. Patients had received initial treatment with chemotherapy with or without radiation to the chest and achieved a stabilization or shrinkage of their cancer. Following initial therapy, one group of patients received PCI and the other group did not receive PCI.
- Survival was significantly improved among patients with both advanced and early-stage SCLC who were treated with PCI.
- At one year, survival was 73% for those treated with PCI and 52% for those not treated with PCI.
- At 3 years, survival was 20% for those treated with PCI and 6% for those not treated with PCI.
- Severe side effects occurred more frequently in patients treated with PCI (64%) compared with those not treated with PCI (50%).
- The most common side effects associated with PCI were loss of hair, low levels of red blood cells, inflammation of the esophagus, and fatigue.
The authors stated that “PCI was associated with a significant survival benefit” which appeared in both early and late-stage SCLC among patients who derived benefit from initial chemotherapy. However, due to the increase in side effects associated with PCI, it is important for patients to discuss their individual risks and benefits of this treatment approach with their healthcare provider.
Dutch researchers also conducted a trial to evaluate prophylactic cranial radiation among patients with extensive disease SCLC. This trial included 286 patients who demonstrated a response to 4 to 6 cycles of chemotherapy; 70% of patients had disease that had spread outside the lung. Following chemotherapy, one group of patients received prophylactic cranial radiation, while the other group of patients did not receive cranial radiation (observation group).
• At one year, brain metastases that caused symptoms occurred in 14.6% of patients treated with cranial radiation compared with 40.4% of patients in the observation group.
• Survival was doubled at one year for patients treated with cranial radiation compared to those in the observation group (27.1% versus 13.3%, respectively).
• Radiation was generally well tolerated; the most common side effects were headache, nausea and vomiting and fatigue.
These results indicate that prophylactic cranial radiation appears to significantly improve survival at one year and reduce the risk of developing brain metastasis among patients with extensive-disease SCLC who respond to chemotherapy. Furthermore, cranial radiation did not significantly reduce quality of life among these patients. Dr. Slotman, the lead investigator of this trial stated that “Prophylactic cranial irradiation should now routinely be offered to all responding SCLC patients with extensive disease.”
Patients with extensive-disease SCLC may wish to speak with their physician about the individual risks and benefits of prophylactic cranial radiation.
Non Small Cell Lung Cancer
Prophylactic Cranial Irradiation Improves Disease-Free Survival and Brain Metastasis Rates for Locally Advanced Non-Small Cell Lung Cancer
Cumulative brain metastases (BM) rates are high for patients with NSCLC. The NRG-RTOG 0214 clinical trial was designed to address this high incidence of brain metastases and determine if the addition of PCI following primary treatment improved overall survival in patients with locally advanced (LA-NSCLC).
At 5 and 10 years, PCI did not improve survival in patients with stage III LA-NSCLC without progression of disease after therapy, however, DFS increased and BM rates decreased considerably, thus providing important information that could benefit future trials. T
Overall 340 patients with LA-NSCLC were treated with PCI in 2Gy per fractions over five days a week or observed and directly compared from 291 institutions globally. Patients treated with PCI were evaluated with brain imaging with MRI or CT at 6 and 12 months, then yearly
Overall survival was 17.6% for PCI treated patients compared to 13.3% at 10-years and treated patients were less likely to experience cancer progression and reduce the number of brain metastases. Patients treated with PCI were 57% less likely to develop brain metastases.
In analysis of 225 patients who did not have surgery for their primary lung tumor PCI treated patients exhibited statistically significant improvements in cancer free survival and the development of brain metastases. This analysis suggests PCI may prolong survival in this subgroup, as the median survival time of 2.3 years on the PCI arm compared favorably to 1.9 years without PCI.
The authors of the study concluded “As the incidence of brain metastases rise in patients living longer with improved control of loco-regional and distant disease, the need to establish an accepted means of prevention of brain metastases remains important. Researchers need to identify the appropriate patient population and a safe intervention on future trials,” stated Alexander Sun, MD, of the Department of Radiation Oncology at the University Health Network’s Princess Margaret Cancer Centre and corresponding author of NRG-RTOG 0214.
Other Research Confirms Preventive Radiation to Brain Doesnt Improve Survival with Non-Small Cell Lung Cancer
For patients with Stage III non-small cell lung cancer, prophylactic (preventive) radiation therapy to the brain reduces the risk of brain metastases but carries a risk of memory problems and doesn’t appear to improve overall survival. These results were published in the Journal of Clinical Oncology.
To further explore the role of PCI in the management of locally advanced NSCLC, researchers conducted a Phase III clinical trial among patients with Stage IIIA or IIIB NSCLC. The researchers initially planned to enroll more than 1000 patients, but because of slow accrual they were only able to enroll 356 patients. Study participants were assigned to receive either PCI or observation. The primary objective of the study was to determine whether PCI improved overall survival.
- Brain metastases developed in 7.7% of patients in the PCI group and 18% of patients in the observation group.
- One-year overall survival was 75.6% among patients in the PCI group and 76.9% among patients in the observation group.
- Patients in the PCI group were more likely to experience a decline in memory.
Although there was no significant survival difference between the groups, the researchers note “It is possible that a survival advantage may become evident with longer follow-up.”
In summary, although preventive radiation therapy reduces the risk of brain metastases among patients with NSCLC, it may cause memory problems and may not improve overall survival. The researchers note that at this time, “PCI is not recommended as standard therapy on the basis of this study or the available data, because there is no evidence of a survival benefit in patients with [locally advanced] NSCLC.”
- Slotman B, Faivre-Finn C, Kramer G, et al. A Randomized Trial of Prophylactic Cranial Irradiation (PCI) Versus no PCI in Extensive Disease Small Cell Lung Cancer After a Response to Chemotherapy (EORTC 08993-22993). Proceedings from the 2007 annual meeting of the American Society of Clinical Oncology. Abstract #4.
- Reference: Schild S, Foster N, Meyers J, et al. Prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC): Findings from the North Central Cancer Treatment Group (NCCTG) pooled analysis. Paper presented at the 2011 American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract 7074.
- Gore EM, Bae K, Wong SJ et al. Phase III comparison of prophylactic cranial irradiation versus observation in patients with locally advanced non-small-cell lung cancer: primary analysis of Radiation Therapy Oncology Group Study RTOG 0214. Journal of Clinical Oncology. 2011;29:272-278.
- Sun A, Bae K, Gore EM et al. Phase III trial of prophylactic cranial irradiation compared with observation in patients with locally advanced non-small-cell lung cancer: neurocognitive and quality-of-life analysis. Journal of Clinical Oncology. 2011;29:279-286.
- Sun A, Hu C, Wong SJ, Gore E, Videtic G, Dutta S, Suntharalingam M, Chen Y, Gaspar LE, Choy H. Prophylactic Cranial Irradiation vs Observation in Patients With Locally Advanced Non-Small Cell Lung Cancer: A Long-term Update of the NRG Oncology/RTOG 0214 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2019 Mar 14. doi: 10.1001/jamaoncol.2018.7220. [Epub ahead of print] PubMed PMID: 30869743.