Prophylactic Cranial Irradiation In Patients Research Articles

Prophylactic cranial irradiation for patients with small-cell lung cancer: a systematic review of the literature with meta-analysis.

BackgroundSmall cell lung cancer (SCLC) accounts for about 13% of all lung cancer cases. Small cell lung cancer (SCLC) accounts for about 13% of all lung cancer cases. The purpose of the present article is to assess the role of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) by performing a systematic review of the randomized trials published in the literature.MethodsRandomized controlled trials were identified that compared brain metastases incidence and overall survival between PCI and No PCI in patients with SCLC. Search strategies were limited to the English language and to articles published since 1997, and included: databases searched from 1997 to March 2013 –CINAHL, Embase, Medline, Web of Science, and CENTRAL. Methodological quality was assessed with the Jadad scale. The main end points were brain metastasis and survival.ResultsThe review identified 5 trials, although few were of high quality. Two trials reported the one-year incidence of brain metastasis. PCI reduced the incidence of brain metastasis in one year, with a pooled relative risk of 0.45 (95% CI, 0.35 to 0.58; P < 0.00001). Four trials described the one year survival rate. The combined result revealed a significant (P = 0.01) survival benefit in the group assigned to PCI as compared with the control group, with a pooled relative risk of 0.87 (95% CI, 0.79 to 0.97). Three trials reported the three-year survival rate. The combined result revealed a great significant (P < 0.00001) survival benefit in the PCI group as compared with the No PCI group, with a pooled relative risk of 0.87 (95% CI, 0.83 to 0.91). the Five-year survival rate was compared in four trials Compared with the No PCI group, the PCI group had a significant (P < 0.00001) survival benefit with a pooled relative risk of 0.92 (95% CI, 0.88 to 0.95).ConclusionsThe present systematic review indicates that PCI decreases brain metastases incidence and that PCI improves survival in SCLC patients. Prophylactic cranial irradiation should be part of standard care for all patients with small-cell lung cancer who have a response to initial chemotherapy, and it should be part of the standard treatment in future studies involving these patients.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-793) contains supplementary material, which is available to authorized users.

Tolerability and toxicity of prophylactic cranial irradiation in patients with non-small cell lung cancer – Results of a phase II study (with estimation of hematological toxicity, pituitary function and magnetic resonance spectra changes)

AimTo evaluate the tolerability and toxicity of PCI in patients with NSCLC. BackgroundProphylactic cranial irradiation (PCI) is a standard treatment for patients with small cell lung cancer. There are data showing a decreasing ratio of brain metastases after PCI for non-small cell lung cancer (NSCLC-non small cell lung cancer) patients but, so far, there is no evidence for increasing overall survival. The main concern in this setting is the tolerance and toxicity of the treatment. Materials and methodsFrom 1999 to 2007, 50 patients with NSCLC treated with radical intent underwent PCI (30Gy in 15 fractions). Mean follow-up was 2.8 years. The tolerability and hematological toxicity were evaluated in all patients, a part of participants had done neuropsychological tests, magnetic resonance imaging with 1H nuclear magnetic resonance spectra, and estimation of pituitary function. ResultsDuring follow-up, 20 patients developed distant metastases, 4-brain metastases. Fourteen (30%) patients had acute side effects: (headache, nausea, erythema of the skin). The symptoms did not require treatment breaks. Six patients complained of late side effects (vertigo, nausea, anxiety, lower extremity weakness, deterioration of hearing and olfactory hyperesthesia). Hematological complications were not observed. Testosterone levels tended to decrease (p=0.062). Visual-motor function deteriorated after treatment (p<0.059). Performance IQ decreased (p<0.025) and the difference between performance IQ and verbal IQ increased (p<0.011). Degenerative periventricular vascular changes were observed in two patients. Analysis of the spectroscopic data showed metabolic but reversible alterations after PCI. ConclusionPCI in the current series was well tolerated and associated with a relatively low toxicity.

Retrospective evaluation of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer with stereotactic radiotherapy: A multi-institutional study.

7591 Background: The benefits of prophylactic cranial irradiation (PCI) on survival time have been repeatedly reported especially in patients with limited stage small cell lung cancer (LS-SCLC). Ho...

Analysis of Structural Changes in Hippocampal and Amygdala Volume After Systemic Therapy and Prophylactic Cranial Irradiation in Patients With Limited Stage-Small Cell Lung Cancer

Analysis of Structural Changes in Hippocampal and Amygdala Volume After Systemic Therapy and Prophylactic Cranial Irradiation in Patients With Limited Stage-Small Cell Lung Cancer

Prophylactic cranial irradiation in patients ≥ 70 years old with limited stage small cell lung cancer: A Surveillance, Epidemiology, and End Results analysis.

7589 Background: Prophylactic cranial irradiation (PCI) improves survival in patients with limited stage small cell lung cancer (SCLC) who have a complete response to chemotherapy and radiation (RT). Yet in clinical practice, concerns exist regarding PCI-related toxicity and the extent of benefit in elderly patients. This exploratory analysis evaluates the effect of PCI on survival among patients ≥ 70 years old. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 4,003 patients ≥70 years old with localized or regional SCLC diagnosed between 1988 and 1997. Patients with no brain RT information (n=974) were excluded. Patients with overall survival (OS) &lt;6 months (n=1103) were also excluded to eliminate patients with an aggressive disease course and minimize selection bias. Survival rates for patients who received brain RT versus no brain RT were estimated by the Kaplan Meier method and compared with the Log-rank test. A Cox proportional hazards model was further fitted to estimate the effect of brain RT on OS after adjusting for age, race, gender, and stage. Results: Of the 1926 patients included, the median age was 75 years (range, 70-94). The majority of patients were white (68%) and male (52%). According to SEER Historic Stage A, 68% of patients had regional stage and 32% had localized stage. One-hundred and thirty-eight patients (7.2%) received brain RT. Patients treated with brain RT were younger at diagnosis (p&lt;0.01) and more likely to have regional stage disease (p=0.02). Five-year OS was 11.6% (95% CI: 6.9-17.6) among patients who received brain RT versus 8.6% (95% CI: 7.32-9.91) among patients who did not (p=0.03). Younger age, female gender, white race, and localized stage were also significant factors associated with improved OS. On multi-variable analysis, receipt of brain RT remained an independent predictor of OS (HR 0.825, 95% CI: 0.69-0.98, p=0.03). Conclusions: The receipt of brain radiotherapy is associated with improved overall survival in patients ≥70 years old with localized or regional stage SCLC, suggesting the benefit of PCI is maintained in the elderly population.

Prophylactic Cranial Irradiation in Patients With Limited Stage Small Cell Lung Cancer: A Pilot Study Investigating the Effects of Radiation Therapy on Neurocognitive Function

Conclusion: Atypical and anaplastic meningiomas remain difficult tumors to treat. Previous studies have identified dose > 14 Gy, smaller tumor volume, and younger age as predictive of better tumor control. Our study also found tumor volume to predict survival and also suggests that a history of benign meningioma, nuclear atypia, or spontaneous necrosis predicts poorer outcomes. Bone and brain invasion were not significant predictors or recurrence or survival in our cohort, possibly because we identified only 1 instance of bone invasion and 7 instances of brain invasion. Clinical and pathologic predictors may help identify patients that are at a higher risk for local recurrence and need to be treated more aggressively. Author Disclosure: R. Funk: None. D.J. Ferraro: None. T.A. DeWees: None. I. Zoberi: None. K.M. Rich: None. M.R. Chicoine: None. R.E. Drzymala: None. C.G. Robinson: None. J.R. Simpson: None. J.J. Jaboin: None.

P2-001 - The Treatment Options of Recurred Brain Metastasis after Prophylactic Cranial Irradiation in Patients with Small-Cell Lung Cancer

ABSTRACT Background Even after prophylactic cranial irradiation (PCI), many small-cell lung cancer (SCLC) patients succumb to brain metastasis. Brain metastasis after PCI is an unsolved issue in SCLC in terms of its dismal prognosis and the limitation of further treatment options. Regarding the treatment option, it is not determined whether re-whole brain radiotherapy (re-WBRT) is safe or gamma-knife surgery (GKS) has its role in SCLC. We investigated which treatment option could be recommended as the up-front therapy to improve survival for SCLC patients with brain metastasis who were previously treated with PCI. Methods The medical records were reviewed for SCLC patients who experienced brain metastases after receiving PCI from 2000 to 2010. We compared overall survival according to the modality of up-front therapy. Overall survival was determined as time from brain metastasis to death due to any cause. Results In total, 245 patients had received PCI in a state of limited disease (n = 204) or extensive disease status (n = 41). Among them, 47 (19.2%) experienced brain metastases: 16.7% (34/204) in LD and 31.7% (13/41) in ED. At the time when brain metastasis developed, extracrainal disease was also on progressing state in 19 patients (40.4%). The modality of up-front therapy for brain metastasis was as follows: 17 (36.1%) got GKS, 14(29.8%) re-WBRT, 7 (14.9%) up-front chemotherapy without local therapy, and 9 (19.1%) did not receive any further treatment. The median overall survival after brain metastasis was 4.9 months. Among 31 patients who received GKS or re-WBRT, 10 patients received at least one subsequent chemotherapy in their lifetime after GKS (6/17, 35.3%) or re-WBRT (4/14, 28.6%). The median survival of GKS, re-WBRT and chemotherapy was 14.3, 3.9 and 6.0 months (P = 0.24), which showed the tendency favoring for up-front GKS. Although it failed to meet statistical significance. Conclusions The up-front GKS showed longer survival in patients who experienced brain metastasis after PCI for SCLC, compared with re-WBRT or chemotherapy only. However, the number of participants was too small to get confirmatory results requiring a prospective therapy to demonstrate the role of GKS in this setting.

Prophylactic cranial irradiation in patients with small cell lung cancer. A retrospective study of recurrence, survival and morbidity

BackgroundProphylactic cerebral irradiation (PCI) is a standard treatment for all small cell lung cancer (SCLC) patients with response to chemotherapy. The aims of this study were: to evaluate patients undergoing PCI with regard to cerebral recurrence rate, site of recurrence, and overall survival (OS) and to investigate the influence of steroid dose on acute toxicity. Materials and methodsFrom 2007 to 2010 a total of 118 consecutive patients underwent PCI (25 Gray in 10 fractions). In total, 114/118 received full PCI dose, all 118 were included in the study. Data were analyzed retrospectively with regard to disease stage, treatment, date of PCI, steroid dose during PCI, toxicity, time to recurrence, site of recurrence and time of death. The median follow up time was 16.6months (range 3–54months). ResultsOf the 118 patients undergoing PCI, 74 had limited disease (LD-SCLC) and 44 had extensive disease (ED-SCLC).The median age was 65years (range 46–80years). The median overall survival of all patients from the time of diagnosis was 16.0months (CI 95% 13.0–19.0), in LD-SCLC it was 24.0months (CI 95% 19.6–28.3), and in ED-SCLC it was 12.0months (CI 95% 9.6–14.4). Twenty-one patients (17.8%) were diagnosed with cerebral recurrence. Five of these presented with metastatic disease within the limbic system. Of these five patients, four had miliary cerebral disease and one had non-oligometastatic disease.The time from PCI to cerebral recurrence ranged from 4 to 27months. Prednisolone administration varied from 0 to 100mg/day. Forty-eight patients were not treated with steroids, 64.6% of these patients reported acute toxicity. Of the 36 patients receiving 50mg prednisolone, only 22.2% had side effects. The most common symptoms during PCI were nausea and headache. ConclusionsTwenty-one patients out of 118 developed brain metastases after PCI: five of the twenty-one had metastases located in the limbic system. The study showed that prophylactic steroid use might reduce acute toxicity to PCI. Survival data and recurrence rates are comparable to other clinical studies.

Prophylactic Cranial Irradiation for Patients With Limited-Stage Small-Cell Lung Cancer With Response to Chemoradiation

BackgroundPrevious clinical studies have generally reported that prophylactic cranial irradiation (PCI) was given to patients with a complete response (CR) to chemotherapy and chest radiotherapy in limited-stage small-cell lung cancer (SCLC). It is not clear if those with incomplete response (IR) would benefit from PCI. Patients and MethodsThe Saskatchewan experience from 1981 through 2007 was reviewed. Patients were treated with chest radiotherapy and chemotherapy with or without PCI (typical doses: 2500 cGy in 10 fractions over 2 weeks, 3000 cGy in 15 fractions over 3 weeks, or 3000 cGy in 10 fractions over 2 weeks). ResultsThere were 289 patients treated for curative intent, 177/289 (61.2%) of whom received PCI. For the whole group of 289 patients, PCI resulted in significant overall survival (OS) and cause-specific survival (CSS) benefit (P = .0011 and 0.0005, respectively). The time to symptoms of first recurrence at any site with or without PCI was significantly different: 16.9 vs. 13.2 months (P = .0006). PCI significantly delayed the time to symptoms of first recurrence in the brain: 20.7 vs. 10.6 months (P < .0001). The first site of metastasis was the brain for 12.5% and 45.5% patients with CR with and without PCI, respectively (P = .02) and in 6.1% and 27.6% of patients with IR with and without PCI, respectively (P = .05). For the 93 patients with IR, PCI did not confer OS or CSS benefit (P = .32 and 0.39, respectively). ConclusionsPatients with IR benefited from PCI, with a reduced rate of and a delayed time for the development of brain metastases, although without significant OS or CSS benefit. PCI could be considered for all patients with limited-stage SCLC responding to chemoradiation.

Feasibility of reducing the irradiation dose in regions of active neurogenesis for prophylactic cranial irradiation in patients with small-cell lung cancer

Prophylactic cranial irradiation (PCI) is performed on patients with limited or extensive small-cell lung cancer to reduce incidence of brain metastases and prolong survival. PCI may induce neurocognitive impairment. Decreasing irradiation of neural stem cells (NSC) might reduce PCI-induced toxicity. We tested the feasibility of reducing irradiation doses to neural stem cell (NSC) regions while maintaining prescribed doses to the planned target volume (PTV). Irradiation plans utilizing intensity-modulated radiotherapy (IMRT), helical TomoTherapy, and RapidArc for 10 consecutive lung cancer patients were evaluated. The dose distribution, dose-volume histograms, and dose homogeneity indexes were analyzed. Planned and actual dose distributions were compared by dosimetric analysis. Both helical tomotherapy and LINAC-based IMRT reduced the radiation dose to the NSC regions by approximately 45% while maintaining the full dose to the rest of brain. Measured dose distributions matched the planned dose distributions.Protecting the regions of active neurogenesis is technically feasible. Whether reducing the dose by 35% to 45% is sufficient to reduce treatment toxicity, however, can only be addressed in a randomized study. Further reducing the dose within the NSC region might also significantly decrease the dosage to the PTV.

123 Small cell lung cancer overall survival, incidence of brain metastases and use of prophylactic cranial irradiation for patients treated in Cambridge during 2005–2009

123 Small cell lung cancer overall survival, incidence of brain metastases and use of prophylactic cranial irradiation for patients treated in Cambridge during 2005–2009

Utilization of prophylactic cranial irradiation in patients with limited stage small cell lung carcinoma

This study reports the adoption of prophylactic cranial irradiation (PCI) in patients with limited stage small cell lung carcinoma (LS-SCLC) at Princess Margaret Hospital (PMH) and the factors that impact PCI utilization. A retrospective review was performed on all patients with LS-SCLC treated at PMH from 1997 to 2007. Clinical details including the rate of PCI utilization were determined and, for patients not receiving PCI, the documented reason was recorded. Brain failure free survival (FFS) and overall survival (OS) were estimated by the Kaplan-Meier method, comparing patients treated with or without PCI. Pearson chi-square test was used to determine factors associated with PCI use. Two hundred seven patients were treated for LS-SCLC and 61.4% (n = 127) of these patients received PCI. The most common documented reason for not receiving PCI was patient refusal, typically because of concerns about PCI toxicity. Patients older than 65 were significantly less likely to receive PCI. Brain FFS and OS rates were significantly higher in patients who received PCI. Not all eligible patients are receiving PCI, despite its significant effect on reducing brain metastases and improving OS. Emphasizing the benefits of PCI to patients, when discussing potential toxicities, may improve utilization.

Mediastinal radiotherapy after multidrug chemotherapy and prophylactic cranial irradiation in patients with SCLC – treatment results after long-term follow-up and literature overview

Introduction Curative therapy for patients with small-cell lung cancer (SCLC) is based on multidrug chemotherapy combinations and radiotherapy. After a long time follow-up, the aim of the study was to evaluate the efficacy and toxicity of sequential chemo-radiotherapy and the effect of prophylactic cranial irradiation (PCI). Methods From 1995–2005, 96 patients with SCLC (64 limited-disease [LD], 32 extensive-disease [ED]; median age 61 years [range 39–79]) were treated at our department with varying chemotherapy regimens and sequential mediastinal radiotherapy (50 Gy + 10 Gy boost in case of residual disease after chemotherapy). Afterwards, 15 patients with LD, good general condition and at least partial response after local treatment received PCI (30 Gy). Results After a median follow-up of 78.6 months, 20 patients remained alive (20.8%, median survival time 18.2 months). The 2-/5-year overall survival rates were 33.8% and 12.6%, the 2-/5-year loco-regional control rates were 30.3% and 24.5%, respectively. Distant metastases occurred in 43 patients (24 cerebral). Cerebral metastasis occurred in 6.7% and 27.2% of the patients with PCI and without PCI respectively. Only tumor stage showed a statistically significant impact on overall survival and loco-regional control in multivariate analysis. Radiotherapy was well tolerated. Grade 3/4 toxicity occurred in seven patients. Prognosis of patients with SCLC remains poor. Administration of PCI in selected patients bears a decrease in the incidence of cerebral metastases. Alternative chemotherapy schemes as well as irradiation schemes and techniques should be the substance of future randomized trials.

Comparison of the Effectiveness of “Late” and “Early” Prophylactic Cranial Irradiation in Patients with Limited-Stage Small Cell Lung Cancer

To evaluate the effectiveness of timing of application of prophylactic cranial irradiation (PCI) in patients with small cell lung cancer in limited stage of disease (LS SCLC). Between 1995 and 2004, 129 patients with LS SCLC were treated within two consecutive phase II studies assessing different schedules of combined treatment. All patients received chemotherapy and concurrent thoracic radiotherapy. In 86 patients (66.7%) who developed complete response in the thorax, PCI was performed either after chemoradiotherapy ("late" PCI , n = 45 [52.4%]) or during chemoradiotherapy ("early" PCI, n = 41 [47.7%]). In the latter case, PCI was given immediately after the end of thoracic radiotherapy and prior to the last cycles of chemotherapy to a total dose of 30 Gy in 2-Gy fractions to the whole brain. The results were evaluated with regard to 4-year rates of overall survival, disease-free survival, and brain metastases-free survival. Additionally, the prognostic role of PCI application and its time delay in relation to survival rates and incidence of brain metastases was estimated. The 4-year survival rates were 25.5% for overall survival, 26.8% for disease-free survival, and 67.8% for brain metastases-free survival. During the observation period, 32 patients (24.8%) developed brain metastases, which occurred in 20 of 43 patients (46.5%) without and only in twelve out of 86 patients (14%) with PCI. The 4-year brain metastases-free survival rates were 81.8%, if PCI was applied, versus 32.2%, if no such procedure was used (for p = 0.0000). The timing of PCI appeared to be an important factor in terms of decreasing the incidence of brain metastases. PCI significantly decreases the incidence of brain metastases and delays their development in patients with LS SCLC. "Early" PCI is more effective than PCI applied after combined therapy.

Prophylactic cranial irradiation in patients with small-cell lung cancer: the experience at the Institute of Oncology Ljubljana

BackgroundProphylactic cranial irradiation (PCI) has been used in patients with small-cell lung cancer (SCLC) to reduce the incidence of brain metastases (BM) and thus increase overall survival. The aim of this retrospective study was to analyze the characteristics of patients with SCLC referred to the Institute of Oncology Ljubljana, their eligibility for PCI, patterns of dissemination, and survival.Patients and methodsMedical charts of 357 patients with SCLC, referred to the Institute of Oncology Ljubljana between January 2004 and December 2006, were reviewed to determine characteristics of patients chosen for PCI. The following data were collected: age, gender, performance status (PS), extent of the disease, smoking status, type of primary treatment with outcome, haematological and biochemical parameters, PCI use, and finally brain metastases (BM) status at diagnoses and after treatment.ResultsPCI was performed in 24 (6.7%) of all patients. Six (25%) patients developed brain metastases after they were treated with PCI. Brain was the only site of metastases in 4 patients, two progressed to multiple organs. Median overall survival of patients with PCI was 21.9 months, without PCI 12.13 months (p = 0.004). From the collected data there were good prognostic factors: age under 65 years, limited disease (LD), performance status, normal levels of lactate dehydrogenase (LDH) and normal levels of C-reactive protein levels (CRP). Other prognostic factors did not show statistical significant values.ConclusionsSurvival of patients with LD, who have had PCI, was significantly better than those who had not. We decided to perform PCI in patients with LD, in those with complete or near complete response, and those with good performance status (≥ 80). We did not use PCI in extended disease (ED). The reason for that shall be addressed in the future. Doses for PCI were not uniform, therefore more standard approach should be considered.

Patterns of Care for Lung Cancer in Radiation Oncology Departments of Turkey

To determine the patterns of care for lung cancer in Turkish radiation oncology centers. Questionnaire forms from 21 of 24 (87.5%) centers that responded were evaluated. The most frequent histology was non-small cell lung cancer (NSCLC) (81%). The most common postoperative radiotherapy (RT) indications were close/(+) surgical margins (95%) and presence of pN2 disease (91%). The most common indications for postoperative chemotherapy (CHT) were ">/= IB" disease (19%) and the presence of pN2 disease (19%). In Stage IIIA potentially resectable NSCLC, the most frequent treatment approach was neoadjuvant concomitant chemoradiotherapy (CHRT) (57%). In Stage IIIA unresectable and Stage IIIB disease, the most frequent approach was definitive concomitant CHRT (91%). In limited SCLC, the most common treatment approach was concomitant CHRT with cisplatin+etoposide for cycles 1-3, completion of CHT to cycles 4-6, and finally prophylactic cranial irradiation in patients with complete response (71%). Six cycles of cisplatin + etoposide CHT and palliative thoracic RT, when required, was the most commonly used treatment (81%) in extensive SCLC. Sixty-two percent of centers did not have endobronchial brachytherapy (EBB) facilities. There is great variation in diagnostic testing, treatment strategies, indications for postoperative RT and CHT, RT features, and EBB availability for LC cases. To establish standards, national guidelines should be prepared using a multidisciplinary approach.

An Update on the Treatment of CNS Metastases in Small Cell Lung Cancer

Brain metastases occur frequently and are a significant threat to the quality of life in patients with small cell lung carcinoma. The primary treatment modality has historically been whole brain radiation, which can provide a moderate extension of life and improvement in neurologic symptoms. Despite increasing interest in the use of alternative therapeutic agents-primarily chemotherapy-these have yet to be demonstrated to be superior to radiation in management of brain metastasis. Prophylactic cranial irradiation prevents or delays the occurrence of brain metastases in patients with small cell lung carcinoma. Until recently, this benefit has been thought to be primarily restricted to a minority of patients with limited stage disease. A large European trial, however, has now shown a survival benefit to the use of prophylactic cranial irradiation in patients who have any response to systemic chemotherapy. This finding should significantly shift management practices for this aggressive disease for most patients.

Decision Analysis for Prophylactic Cranial Irradiation for Patients With Small-Cell Lung Cancer

Decision Analysis for Prophylactic Cranial Irradiation for Patients With Small-Cell Lung Cancer

The Impact of Prophylactic Cranial Irradiation in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Trimodality Therapy

The Impact of Prophylactic Cranial Irradiation in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Trimodality Therapy

Prophylactic Cranial Irradiation in Extensive Small-Cell Lung Cancer

We conducted a randomized trial of prophylactic cranial irradiation in patients with extensive small-cell lung cancer who had had a response to chemotherapy. Patients between the ages of 18 and 75 years with extensive small-cell lung cancer were randomly assigned to undergo prophylactic cranial irradiation (irradiation group) or receive no further therapy (control group). The primary end point was the time to symptomatic brain metastases. Computed tomography or magnetic resonance imaging of the brain was performed when any predefined key symptom suggestive of brain metastases was present. The two groups (each with 143 patients) were well balanced regarding baseline characteristics. Patients in the irradiation group had a lower risk of symptomatic brain metastases (hazard ratio, 0.27; 95% confidence interval [CI], 0.16 to 0.44; P<0.001). The cumulative risk of brain metastases within 1 year was 14.6% in the irradiation group (95% CI, 8.3 to 20.9) and 40.4% in the control group (95% CI, 32.1 to 48.6). Irradiation was associated with an increase in median disease-free survival from 12.0 weeks to 14.7 weeks and in median overall survival from 5.4 months to 6.7 months after randomization. The 1-year survival rate was 27.1% (95% CI, 19.4 to 35.5) in the irradiation group and 13.3% (95% CI, 8.1 to 19.9) in the control group. Irradiation had side effects but did not have a clinically significant effect on global health status. Prophylactic cranial irradiation reduces the incidence of symptomatic brain metastases and prolongs disease-free and overall survival. (ClinicalTrials.gov number, NCT00016211 [ClinicalTrials.gov].).