Impact Of Prophylactic Cranial Irradiation Research Articles

The Impact of Prophylactic Cranial Irradiation and Consolidative Thoracic Radiation Therapy for Extensive Stage Small-Cell Lung Cancer in the Transition to the Chemo-Immunotherapy Era: A Single Institution Series

IntroductionExtensive-stage small-cell lung cancer (ES-SCLC) continues to have poor survival due to its aggressive behavior, despite improvements with incorporation of immunotherapy with standard chemotherapy. Controversy exists regarding the role of consolidative thoracic radiation therapy (TRT) and prophylactic cranial irradiation (PCI) in ES-SCLC due to high recurrence rates. We report our institutional result of the benefit of PCI and TRT in ES-SCLC. MethodsPatients with ES-SCLC without intracranial metastasis at diagnosis (N = 163) were included. All patients completed systemic therapy with or without immunotherapy based on time of standard of care. Cohorts were divided by systemic therapy use and further subdivided by treatment with PCI and TRT. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method with log-rank test for comparison. The effects of TRT and PCI were estimated by multivariable (MVA) Cox regression. ResultsSeventy-four patients (45.4%) received TRT, and 33.1% (n = 54) received PCI. The median follow-up was 11 months (3-85 months). PCI improved median OS to 15 months from 10 months, P = .02) and median PFS to 8.5 months from 5 months (P = .02) which remained significant on MVA, P = .02 and P = .02, respectively. TRT improved OS on UVA (P = 0.002) but was not significant on MVA. TRT did not improve PFS. ConclusionThis study including chemotherapy and chemo-immunotherapy suggests improved outcomes with addition of PCI in patients with ES-SCLC while TRT did not show benefit to either OS or PFS. A future trial is needed to evaluate the role of TRT and PCI in the era of chemo-immunotherapy.

Survival impact of prophylactic cranial irradiation in small-cell lung cancer in the modern era of magnetic resonance imaging staging

BackgroundIn the modern era of magnetic resonance imaging (MRI) staging, the benefit of prophylactic cranial irradiation (PCI) in patients with small-cell lung cancer (SCLC) has been controversial. This study evaluated the prognostic impact of PCI in patients with limited- or extensive-stage SCLC who had no brain metastases at diagnosis according to MRI.MethodsData from newly diagnosed patients in 2014 from the Korean Association for Lung Cancer Registry database were used. Patients with limited- or extensive-stage SCLC who had no brain metastases according to MRI were identified. Univariate and multivariate survival analyses were conducted to assess the prognostic association of PCI.ResultsOf 107 and 122 patients with limited- and extensive-stage SCLC, 24% and 14% received PCI, respectively. In the limited-stage SCLC group, the 2-year overall survival (OS) rates of patients who received PCI and those who did not were 50% and 29% (P = 0.018), respectively. However, there was no significant difference in OS for patients with extensive-stage SCLC (P = 0.336). After adjusting for other covariates, PCI was found to be associated with improved OS in the limited-stage SCLC group (P = 0.005). Based on the time-course hazard rate function plots in the limited-stage SCLC group, the OS benefit of PCI was maximized within the first year of follow-up.ConclusionsIn the modern era of MRI staging, PCI might be beneficial for patients with limited-stage SCLC but not for those with extensive-stage SCLC. Further studies with a large sample size are needed to verify the prognostic association of PCI.

Utility of Prophylactic Cranial Irradiation for Limited Stage Small Cell Lung Cancer in the Modern Era with Magnetic Resonance Imaging Surveillance

AimsTo retrospectively analyse the impact of prophylactic cranial irradiation (PCI) on survival and intracranial progression in patients with limited stage small cell lung cancer (LS-SCLC) in the modern era of widespread magnetic resonance imaging brain screening. Materials and methodsPatients with LS-SCLC treated within our network between 2009 and 2020 who responded to initial therapy were stratified by receipt of PCI and stage of disease. A propensity score match analysis was carried out for stage II–III patients. Overall and neurological survival were defined as time to death and presumed death due to uncontrolled intracranial disease, respectively. Brain metastasis-free survival and symptomatic brain metastasis-free survival were defined as freedom from intracranial progression and symptomatic intracranial progression, respectively. The effect of PCI on these outcomes was assessed using Kaplan–Meier and Cox proportional hazards models. ResultsIn total, 243 (69.6%) of 349 patients received PCI. On multivariate analysis in the propensity matched stage II–III cohort, PCI was a significant predictor of improved neurological survival (hazard ratio 0.23, 95% confidence interval 0.08–0.65; P = 0.01), brain metastasis-free survival (hazard ratio 0.25, 95% confidence interval 0.12–0.51; P < 0.01) and symptomatic brain metastasis-free survival (hazard ratio 0.21, 95% confidence interval 0.08–0.55; P < 0.01), but not improved overall survival. Two-year neurological survival estimates within the propensity matched cohort were 96.8% (95% confidence interval 87.6–99.2%) with PCI and 77.2% (95% confidence interval 63.0–86.4%) without PCI and 1- and 2-year estimates of incidence of brain metastases were 3.9% (95% confidence interval 1.3–11.7%) and 11.7% (95% confidence interval 5.6–23.5%) in the PCI group and 31.6% (95% confidence interval 22.1–43.9%) and 40.4% (95% confidence interval 29.2–54.0%) in the no PCI group, respectively. ConclusionsIn the modern era of magnetic resonance imaging screening, PCI was associated with reduced incidence of intracranial progression in patients with stage II–III LS-SCLC who respond to initial therapy. This, importantly, translated to a decreased risk of neurological death within our propensity matched cohort, without significant improvement in overall survival.

Impact of prophylactic cranial irradiation and hippocampal sparing on 18F-FDG brain metabolism in small cell lung cancer patients

Background and purposeProphylactic cranial irradiation (PCI) in small-cell lung cancer (SCLC) patients improves survival. However, it is also associated with cognitive impairment, although the underlying mechanisms remain poorly understood. Our study aims to evaluate the impact of PCI and potential benefit of hippocampal sparing (HS) on brain metabolism assessed by 18F-Fluoro-Deoxy-Glucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT). Materials and methodsWe retrospectively included 22 SCLC patients. 50% had hippocampal-sparing (HS) PCI. 18F-FDG PET/CT was performed 144.5 ± 73 days before and 383 ± 451 days after PCI. Brain 18F-FDG PET scans were automatically segmented in 12 regions using Combined-AAL Atlas from MI-Neurology Software (Syngo.Via, Siemens Healthineers). For all atlas regions, we computed SUV Ratio using brainstem as a reference region (SUVR = SUVmean/Brainstem SUVmean) and compared SUVR before and after PCI, using a Wilcoxon test, with a level of significance of p < 0.05. ResultsWe found significant decreases in 18F-FDG brain metabolism after PCI in the basal ganglia (p = 0.004), central regions (p = 0.001), cingulate cortex (p < 0.001), corpus striata (p = 0.003), frontal cortex (p < 0.001), parietal cortex (p = 0.001), the occipital cortex (p = 0.002), precuneus (p = 0.001), lateral temporal cortex (p = 0.001) and cerebellum (p < 0.001). Conversely, there were no significant changes in the mesial temporal cortex (MTC) which includes the hippocampi (p = 0.089). The subgroup who received standard PCI showed a significant decrease in metabolism of the hippocampi (p = 0.033). Contrastingly, the subgroup of patients who underwent HS-PCI showed no significant variation in metabolism of the hippocampi (p = 0.783). ConclusionPCI induced a diffuse decrease in 18F-FDG brain metabolism. HS-PCI preserves metabolic activity of the hippocampi.

Risk stratification of symptomatic brain metastases by clinical and FDG PET parameters for selective use of prophylactic cranial irradiation in patients with extensive disease of small cell lung cancer

PurposeTo identify risk factors for developing symptomatic brain metastases and evaluate the impact of prophylactic cranial irradiation (PCI) on brain metastasis-free survival (BMFS) and overall survival (OS) in extensive disease small cell lung cancer (ED-SCLC). Materials and methodsAmong 190 patients diagnosed with ED-SCLC who underwent FDG PET/CT and brain Magnetic Resonance Imaging (MRI) prior to treatment, 53 (27.9%) received PCI while 137 (72.1%) did not. Prognostic index predicting a high risk of symptomatic brain metastases was calculated for the group without receiving PCI (observation group, n = 137) with Cox regression model. ResultsMedian follow-up time was 10.6 months. Multivariate Cox regression showed that the following three factors were associated with a high risk of symptomatic brain metastases: the presence of extrathoracic metastases (p = 0.004), hypermetabolism of bone marrow or spleen on FDG PET (p < 0.001), and high neutrophil-to-lymphocyte ratio (p = 0.018). PCI significantly improved BMFS in high-risk patients (1-year rate: 94.7% vs. 62.1%, p = 0.001), but not in low-risk patients (1-year rate: 100.0% vs. 87.7%, p = 0.943). However, PCI did not improve OS in patients at high risk for symptomatic brain metastases (1-year rate: 65.2% vs. 50.0%, p = 0.123). ConclusionThree prognostic factors (the presence of extrathoracic metastases, hypermetabolism of bone marrow or spleen on FDG PET, and high neutrophil-to-lymphocyte ratio) were associated with a high risk of symptomatic brain metastases in ED-SCLC. PCI was beneficial for patients at a high risk of symptomatic brain metastases in terms of BMFS, but not OS. Thus, selective use of PCI in ED-SCLC according to the risk stratification is recommended.

The impact of prophylactic cranial irradiation for post-operative patients with limited stage small cell lung cancer.

To evaluate the impact of prophylactic cranial irradiation (PCI) on the prognosis of patients who received definitive surgery for surgically resected small cell lung cancer (SCLC).A retrospective analysis was performed on post-operative SCLC patients treated in Zhejiang Cancer Hospital from January 2003 to December 2015. According to the treatment modality, patients were allocated to PCI group and non-PCI group. Univariate survival analysis was performed by the Kaplan–Meier method. Multivariate survival analysis was performed by a Cox proportional hazards model.A total of 52 patients were included for analysis, among which, 19 patients were in PCI group and 33 were in non-PCI group. Multivariate analysis revealed that PCI (HR = .330; P = .041) was an independently favorable prognostic factor for the overall survival. The median overall survival (OS) time was 32.9 months in PCI group, and 20.4 months in non-PCI group. The 2-year OS rates were 78.0% and 38.0% in PCI and non-PCI group respectively (P = .023). The brain metastasis-free survival (BMFS) rate at 2-year in PCI group was significantly higher than those of non-PCI group (89.0% vs 53.0%, respectively, P = .026).In conclusion, PCI might be suggested for limited SCLC patients who received definitive surgery.

The effects of prophylactic cranial irradiation versus control on survival of patients with extensive-stage small-cell lung cancer: a meta-analysis of 14 trials

BackgroundA recent Japanese study suggested prophylactic cranial irradiation (PCI) failed to improve survival of extensive-stage small-cell lung cancer (SCLC). However, previous studies showed that PCI was beneficial in reducing the rate of mortality for extensive-stage SCLC. In this study, we aimed to evaluate the impact of PCI on the survival of patients diagnosed with extensive-stage SCLC by meta-analysis.MethodsPubMed, Embase, the Cochrane library and Chinese Biomedical Literature database (CBM) were systematically searched to identify eligible clinical studies assessing the efficacy of PCI in extensive-stage SCLC patients. After extracting survival data, brain metastasis, and response rates, the pooled estimates were calculated.ResultsA total of 14 clinical studies were included, involving 1221 cases in the PCI group and 5074 in the control group. The results showed that PCI significantly improved overall survival (Hazard ratio (HR) = 0.57; 95% confidence interval (CI): 0.47, 0.69; p < 0.001) and brain metastasis (risk ratio (RR) =0.47, 95%CI: 0.33, 0.69; p < 0.01). Subgroup analysis along with sensitivity analysis suggested that PCI effects on overall survival were independent of region, pre-PCI brain metastasis status and PCI administration timing.ConclusionPCI improves overall survival in extensive-stage SCLC. More randomized controlled trials are needed to verify our findings.

Impact of prophylactic cranial irradiation on pattern of brain metastases as a first recurrence site for limited-disease small-cell lung cancer.

This study sought to evaluate the impact of prophylactic cranial irradiation (PCI) on the pattern of brain recurrence after radical treatment in patients with limited-disease small-cell lung cancer (LD-SCLC). Patients treated with radiotherapy and chemotherapy between January 2006 and December 2014 at a single institution were retrospectively examined. Radiotherapy was performed using accelerated hyperfractionated radiotherapy (twice daily, 45 Gy in 30 fractions) or conventional fractionated radiotherapy (once daily, 50 Gy in 25 fractions). The chemotherapy regimen consisted of intravenous platinum–etoposide. A total of 162 patients were included and the median follow-up duration was 38 months. Ninety-three patients underwent PCI, and the 3-year overall survival (OS) rates were 14% among patients without PCI and 41% among those with PCI (P < 0.001). The frequency of brain metastases as a first recurrence site (BMFR) was significantly lower among patients who underwent PCI, compared with those who did not (P = 0.002). The median time to the l of BMFR was significantly shorter among patients without PCI than among those with PCI (P = 0.012). In addition, 68% of the BMFR patients who did not undergo PCI exhibited five or more lesions, while only 12% of BMFR patients who did undergo PCI exhibited five or more lesions (P < 0.001). PCI had a significant positive impact on patient prognosis after radical treatment for LD-SCLC, and the difference in the number of, and time to the appearance of, BMFR between patients treated with PCI and those treated without PCI might affect the clinical outcomes.

Impact of Prophylactic Cranial Irradiation on Overall Survival in Metastatic Small Cell Lung Cancer: A Propensity Score Matched Analysis of Patients in the National Cancer Database

Impact of Prophylactic Cranial Irradiation on Overall Survival in Metastatic Small Cell Lung Cancer: A Propensity Score Matched Analysis of Patients in the National Cancer Database

Decline in Tested and Self-Reported Cognitive Functioning After Prophylactic Cranial Irradiation for Lung Cancer: Pooled Secondary Analysis of Radiation Therapy Oncology Group Randomized Trials 0212 and 0214

To assess the impact of prophylactic cranial irradiation (PCI) on self-reported cognitive functioning (SRCF), a functional scale on the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Radiation Therapy Oncology Group (RTOG) protocol 0214 randomized patients with locally advanced non-small cell lung cancer to PCI or observation; RTOG 0212 randomized patients with limited-disease small cell lung cancer to high- or standard-dose PCI. In both trials, Hopkins Verbal Learning Test (HVLT)-Recall and -Delayed Recall and SRCF were assessed at baseline (after locoregional therapy but before PCI or observation) and at 6 and 12 months. Patients developing brain relapse before follow-up evaluation were excluded. Decline was defined using the reliable change index method and correlated with receipt of PCI versus observation using logistic regression modeling. Fisher's exact test correlated decline in SRCF with HVLT decline. Of the eligible patients pooled from RTOG 0212 and RTOG 0214, 410 (93%) receiving PCI and 173 (96%) undergoing observation completed baseline HVLT or EORTC QLQ-C30 testing and were included in this analysis. Prophylactic cranial irradiation was associated with a higher risk of decline in SRCF at 6 months (odds ratio 3.60, 95% confidence interval 2.34-6.37, P<.0001) and 12 months (odds ratio 3.44, 95% confidence interval 1.84-6.44, P<.0001). Decline on HVLT-Recall at 6 and 12 months was also associated with PCI (P=.002 and P=.002, respectively) but was not closely correlated with decline in SRCF at the same time points (P=.05 and P=.86, respectively). In lung cancer patients who do not develop brain relapse, PCI is associated with decline in HVLT-tested and self-reported cognitive functioning. Decline in HVLT and decline in SRCF are not closely correlated, suggesting that they may represent distinct elements of the cognitive spectrum.

Prophylactic cranial irradiation for small-cell lung cancer: how, when and for whom?

Prophylactic cranial irradiation (PCI) reduces the incidence of brain metastases and improves overall survival in both limited disease (LD) and extensive disease (ED) small-cell lung cancer (SCLC), in complete and good responders to initial chemo(radio)therapy. In LD-SCLC, a standard dose of 25 Gy given in ten fractions is recommended, whereas in ED-SCLC a shorter schedule of 20 Gy in five fractions could be used. The issues of acute neurotoxicity (NT) and the potential impact of PCI on quality of life are of particular concern in ED-SCLC patients, as their expected survival is short. In LD-SCLC late neurologic sequelae may worsen quality-adjusted life expectancy for long-term survivors, as the pronounced effect of NT becomes apparent after several years. Some novel potential approaches to reduce the PCI-related late NT have recently been investigated. Despite the growing incidence of lung cancer in elderly people, there are no established standards of treatment for this subset of the population.

Decline in Tested and Patient-reported Cognitive Functioning Following Prophylactic Cranial Irradiation for Lung Cancer: Secondary Analysis of RTOG 0212 and 0214

To assess the impact of prophylactic cranial irradiation (PCI) on cognitive functioning, tested using the Hopkins Verbal Learning Test (HVLT) and patient-reported on the EORTC QLQ-C30 questionnaire, following curative-intent treatment for limited-disease small cell lung cancer (LD-SCLC) and locally advanced Non-small cell lung cancer (LA-NSCLC). Patients with LD-SCLC and LA-NSCLC were enrolled on RTOG trials 0212 and 0214, respectively. Recall (R) and delayed recall (DR) from HVLT and patient-reported cognitive functioning (PRCF) from EORTC QLQ-C30 were assessed as secondary endpoints at baseline (following locoregional therapy but before PCI or observation) and at 6 and 12 months follow-up. After pooling data from all enrolled patients, patients who developed brain relapse prior to follow-up evaluation were excluded. Deterioration in HVLT-R, HVLT-DR, and PRCF was defined compared to baseline using the reliable change index method and correlated with receipt of PCI using multivariate logistic regression at a significance level of p < 0.05 for HVLT-R and HVLT-DR correlations and p < 0.001 for PRCF correlations due to multiple testing of EORTC QLQ-C30. Covariates included age, gender, partner status, education level, Zubrod performance score, and PCI dose. Deterioration in HVLT-R and HVLT-DR was also correlated with deterioration in PRCF using Fisher's exact test at a significance level of p < 0.001. Five hundred fifty-two (91%) and 562 (93%) of the 604 eligible patients accrued to RTOG 0212 and RTOG 0214 had baseline EORTC QLQ-C30 and HVLT assessments, respectfully, and were included in this pooled analysis. Compliance was 59% at 6 months and 48% at 12 months for HVLT and 66% at 6 months and 54% at 12 months for EORTC QLQ-C30 and did not differ between RTOG 0212 and 0214. After adjusting for covariates, deterioration in HVLT-R, HVLT-DR and PRCF at 6 and 12 months follow-up was associated with receipt of PCI (Table). At 6 or 12 months, deterioration in PRCF was not correlated with deterioration in HVLT-R (p = 0.05 and p = 0.86, respectively) or HVLT-DR (p = 0.02 and p = 0.54, respectively). In lung cancer patients who do not develop brain relapse, receipt of PCI is associated with deterioration in HVLT-tested and patient-reported cognitive functioning. Decline in HVLT and decline in patient-reported cognitive functioning are not closely correlated.TableImpact of PCI (Referent Group: No PCI)Time to deterioration from baselineHVLT-recallHVLT-delayed recallPatient-reported cognitive functioning6 Months12 Months6 Months12 Months6 Months12 MonthsAdjusted odds ratio4.905.272.072.793.603.4495% Confidence interval1.87-12.871.98-14.021.04-4.121.08-7.162.34-6.371.84-6.44p value0.0010.00090.040.03<0.0001<0.0001 Open table in a new tab

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

There are scant data regarding the effects of prophylactic cranial irradiation (PCI) on neurocognitive function (NCF) and quality of life (QOL). Radiation Therapy Oncology Group trial 0214 showed no overall survival (OS) benefit for PCI in stage III non-small-cell lung cancer (NSCLC) at 1 year. However, there was a significant decrease in brain metastases (BM). This analysis focuses on the impact of PCI on NCF and QOL. Patients with stage III NSCLC who completed definitive therapy without progression were randomly assigned to PCI or observation. NCF was assessed with Mini-Mental Status Examination (MMSE), Activities of Daily Living Scale (ADLS), and Hopkins Verbal Learning Test (HVLT). QOL was assessed with the European Organisation for Research and Treatment of Cancer (EORTC) core tool (QOL Questionnaire-QLQC30) and brain module (QLQBN20). There were no statistically significant differences at 1 year between the two arms in any component of the EORTC-QLQC30 or QLQBN20 (P > .05), although a trend for greater decline in patient-reported cognitive functioning with PCI was noted. There were no significant differences in MMSE (P = .60) or ADLS (P = .88). However, for HVLT, there was greater decline in immediate recall (P = .03) and delayed recall (P = .008) in the PCI arm at 1 year. PCI in stage III NSCLC significantly decreases the risk of BM without improving 1-year OS. There were no significant differences in global cognitive function (MMSE) or QOL after PCI, but there was a significant decline in memory (HVLT) at 1 year. This study provides prospective data regarding the relative risks and benefits of PCI in this setting and the need to use sensitive cognitive assessments.

A phase III comparison of prophylactic cranial irradiation versus observation in patients with locally advanced non-small cell lung cancer: Initial analysis of Radiation Therapy Oncology Group 0214

7506 Background: The incidence of central nervous system (CNS) metastases is high in patients with locally advanced non-small cell lung cancer. Brain as an only site of relapse appears increasingly common as loco-regional and extra-cranial systemic treatment improves. There is not standard agreement as to how to address this risk. Methods: Patients with stage III NSCLC without progression of disease after loco-regional treatment with surgery and/or radiation therapy with or without chemotherapy were eligible. Participants were randomized to prophylactic cranial irradiation (PCI) or observation and stratified by stage (IIIA or B), histology (non-squamous or squamous) and therapy (surgery or no surgery). PCI was delivered once daily at 2Gy per fraction to 30Gy. The primary endpoint of the study was overall survival (OS). Secondary endpoints were disease free survival (DFS) and the impact of PCI on incidence of CNS metastases, neuropsychological function, and quality of life (QoL). Kaplan- Meier estimation with the log-rank test was used for OS and DFS and the logistic regression model was used for calculating the incidence of CNS metastasis. Results: Total accrual was 356 patients of the targeted 1058 between 9/19/02 and 8/30/07. The study was closed early due to slow accrual. 340 patients were evaluable. One year OS (p=0.86, 75.6 % and 76.9% for PCI and observation) and one year DFS (p=0.11, 56.4% and 51.2% for PCI and observation) were not statistically significantly different. However, CNS metastatic rate at 1 year was statistically significantly different with CNS relapse 7.7% vs. 18% for PCI vs. observation (p=0.004). Logistic regression showed that the patients in the observation arm are 2.52 times more likely to develop CNS metastases than those in the PCI arm (odds ratio=2.52, 95% CI=(1.32–4.80)). Conclusions: PCI in patients without progressive disease after loco-regional therapy for III NSCLC significantly decreases the rate of CNS metastases. This study did not show a statistically significant difference in OS or DFS. Forthcoming analysis of the impact of PCI on neuropsychological function and QoL will influence the recommendations regarding the standard use of PCI. No significant financial relationships to disclose.

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

158: Impact of Prophylactic Cranial Irradiation on Neurocognitive Function in Patients With Small Cell Lung Carcinoma

Prophylactic cranial irradiation (PCI) has been shown to provide a survival benefit in patients with small cell lung (SCLC) in complete remission. Despite this the use of PCI has been tempered as retrospective studies have suggested deleterious effects on neurocognitive function. We undertook a prospective study conducting formal neuropsychological testing at baseline and following PCI. Between 1989 and 2002 ninety-six patients were tested (median follow-up 23 months, range 6 to 120 mo for all cases). 93 patients presented with limited stage SCLC and 3 with extensive disease. All had a complete or partial response to initial therapy and underwent formal neurocognitive testing prior to PCI. Testing was conducted in the domains of memory, verbal fluency and learning, frontal lobe function, attention, abstract reasoning, language, visual perception and fine motor coordination. Twenty-two patients did not receive further radiation while 74 received PCI (mean dose 25Gy in 10 fractions). Forty-one patients were available for evaluation following cranial irradiation (mean 301days following baseline, standard deviation 335 days). A subset of 17 patients had extended follow-up with ≥ three assessments (mean 539 days, standard deviation 435 days). Two patients were found to have CNS metastasis at the time of testing and were excluded from the analysis. Impairment was defined as less than or equal to 1.5 standard deviations below the normative mean, a level where only 6.7% of the population would be expected to score. At baseline 47% showed impairment in any area prior to PCI. Nearly one third of patients displayed deficits in verbal learning (32% of patients) and/or mental flexibility (38%). Substantial deficits were also identified in the areas of verbal memory (21%), cognitive processing speed (28%), fine motor coordination (28%), and frontal lobe function (18%). Repeat testing following PCI was conducted on forty-one patients. On univariate analysis (T-tests for paired samples, with a two tailed test of significance) significant declines in attention span (pre-PCI mean 14.02, post 12.95, p=0.009) and visual-spatial construction (pre-PCI mean 22.41, post 20.30, p=0.027) were noted. In the subset of patients with extended follow-up, improvements were seen in verbal reasoning (N=15 patients, p=0.048) and verbal fluency (N=17, p=0.009). A decline in executive function (N=8, pre-PCI mean 10.62, post 18.75, p=0.029) was noted. Using highly refined neurocognitive testing we found that a substantial portion of patients with SCLC had impaired brain functioning at baseline. Following PCI patients did decline in the areas of attention span, visual spatial construction and executive function. However this was offset by improvement in the areas of verbal reasoning and fluency. While the changes were statistically significant, mean differences were small and the clinical impact of these changes is likely minimal. While this data is based on relatively small number of patients, it does not favor the omission of PCI based on fears of neurocognitive impairment.

Prophylactic cranial irradiation in adenocarcinoma of the lung. A possible role.

Seventy-eight patients with modified Stage II or Stage IIIM0 adenocarcinoma of the lung were evaluated retrospectively with regard to the impact of prophylactic cranial irradiation (PCI) (30 Gy in 15 fractions) in preventing central nervous system (CNS) metastases. Twenty patients received PCI and 58 did not. There were no significant differences between these groups with respect to age, sex, stage, or median survival (17.4 months with PCI versus 16.9 months without PCI; P = 0.6). One (5%) of 20 patients receiving PCI developed CNS metastases, compared with 14 (24%) of 58 patients not receiving PCI (P = 0.06). The time from diagnosis to development of CNS metastases and survival after CNS involvement was 51 weeks and 14 weeks, respectively, for the patient who received PCI; and a median time of 50 weeks and 26 weeks, respectively, for the patients not receiving PCI. In nine (64%) of the 14 non-PCI patients the CNS was the first and only site of relapse. A Cox regression analysis demonstrated that nodal involvement was significantly associated with an increased risk of CNS metastases. These data suggest that PCI may decrease the incidence of CNS metastases, and that it may be beneficial in the management of patients with N1 or N2 disease.