Prophylactic Cranial Irradiation Group Research Articles

Prophylactic cranial irradiation for limited-stage small-cell lung cancer in the modern magnetic resonance imaging era may be omitted: a propensity score-matched analysis.

We aimed to clarify whether prophylactic cranial irradiation (PCI) is associated with improved outcomes in limited-stage small-cell lung cancer (LS-SCLC) in the current era of magnetic resonance imaging (MRI). Data from patients with LS-SCLC who achieved a complete response to definitive chemoradiotherapy (CRT) at two medical centers were retrospectively reviewed. Propensity score-matching was performed in a 2:1 ratio to balance the baseline characteristics of the no-PCI and PCI groups. The endpoints were the incidence of brain metastasis (BM), neurological causes of death and overall survival (OS). Overall, 80% patients underwent head MRI during the initial staging and 75 patients (no-PCI, n = 50; PCI, n = 25) were matched. Their baseline characteristics were generally well-balanced except for age; patients in the no-PCI group tended to be older. The median follow-up period was 29months. Although the incidence of BMs tended to be higher in the no-PCI group (1-year BM occurrence: 26% vs 17%, P = 0.22), the incidence of multiple BMs (defined as >4 metastases) was similar between groups (1-year multiple BMs occurrence: 8% vs 9%, P = 0.65). The 2-year neurological causes of death and OS rate did not significantly differ between the groups (6% and 9%; P = 0.85; and 70% and 79%; P = 0.36, respectively). The 1-year occurrence of multiple BMs did not increase, even without PCI, when modern imaging modalities were integrated into the initial diagnosis, suggesting that PCI could be omitted after CRT, if MRI was incorporated into the initial diagnosis and follow-up.

Prophylactic cranial irradiation in patients with resected small-cell lung cancer: A systematic review and meta-analysis.

Prophylactic cranial irradiation (PCI) was recommended for limited-stage small-cell lung cancer (SCLC) patients with complete or partial response to primary chemoradiotherapy. But it is still controversial regarding its role in SCLC patients who have had radical resection. This meta-analysis aims to evaluate the efficacy of PCI in resected SCLC patients. We searched PubMed, EMBASE, Web of Science, CENTRAl, and ClinicalTrials for controlled trials and cohort studies regarding PCI in postoperative SCLC patients. The correlation between PCI and post-operative outcomes in SCLC patients, including survival and brain metastasis rate (BMR), was examined using hazard ratios (HRs) and risk ratios with corresponding 95% confidence intervals. Quality of studies was assessed by the Newcastle-Ottawa Scale (NOS), and publication bias was assessed by Begg's test. Meta-analysis of eight studies with 2688 patients in total showed PCI was associated with improved overall survival (OS) for resected SCLC (HR: 0.65, 95% CI: 0.57-0.75, p < 0.01). In addition, subgroup analysis on three studies including 923 patients confirmed the protective role of postoperative PCI in N0 SCLC patients (HR: 0.79, 95% CI: 0.61-0.97, p < 0.05). There was also a significant reduction in BMR in the PCI group pooled from six studies (HR: 0.58, 95% CI: 0.40-0.85, p < 0.01). The use of PCI delayed brain recurrence and improved OS in patients with resected, stage I-III SCLC. Importantly, patients with N0 SCLC can also benefit from postoperative PCI. In future studies, PCI's role in patients with resected N0 SCLC at different T stage may need to be explored.

Effects of brain radiotherapy strategies on survival in the era of MRI for patients with limited stage small cell lung cancer

Background and purposeIn the context of the widespread availability of magnetic resonance imaging (MRI) and aggressive salvage irradiation techniques, there has been controversy surrounding the use of prophylactic cranial irradiation (PCI) for small-cell lung cancer (SCLC) patients. This study aimed to explore whether regular brain MRI plus salvage brain irradiation (SBI) is not inferior to PCI in patients with limited-stage SCLC (LS-SCLC).MethodsThis real-world multicenter study, which was conducted between January 2014 and September 2020 at three general hospitals, involved patients with LS-SCLC who had a good response to initial chemoradiotherapy and no brain metastasis confirmed by MRI. Overall survival (OS) was compared between patients who did not receive PCI for various reasons but chose regular MRI surveillance and followed salvage brain irradiation (SBI) when brain metastasis was detected and patients who received PCI.Results120 patients met the inclusion criteria. 55 patients received regular brain MRI plus SBI (SBI group) and 65 patients received PCI (PCI group). There was no statistically significant difference in median OS between the two groups (27.14 versus 33.00 months; P = 0.18). In the SBI group, 32 patients underwent whole brain radiotherapy and 23 patients underwent whole brain radiotherapy + simultaneous integrated boost. On multivariate analysis, only extracranial metastasis was independently associated with poor OS in the SBI group.ConclusionThe results of this real-world study showed that MRI surveillance plus SBI is not inferior to PCI in OS for LS-SCLC patients who had a good response to initial chemoradiotherapy.

Incidence of hippocampal and perihippocampal brain metastases and impact on hippocampal-avoiding radiotherapy: A systematic review and meta-analysis

Background and PurposeIn patients requiring prophylactic cranial irradiation (PCI) or whole-brain radiotherapy (WBRT) for brain metastases (BMs), hippocampal avoidance (HA) has been shown to preserve neurocognitive function and quality of life. Here, we aim to estimate the incidence of hippocampal and perihippocampal BMs and the subsequent risk of local undertreatment in patients undergoing hippocampal sparing radiotherapy. Materials and MethodsMEDLINE, Embase, and Scopus were searched with the terms “Hippocampus”, “Brain Neoplasms”, and related terms. Trials reporting on the incidence of hippocampal and/or perihippocampal BMs or hippocampal failure rate after PCI or WBRT were included. ResultsForty records were included, encompassing a total of 5,374 patients with over 32,570 BMs. Most trials employed a 5 mm margin to define the HA zone. In trials reporting on BM incidence, 4.4 % (range 0 − 27 %) and 9.2 % (3 − 41 %) of patients had hippocampal and perihippocampal BMs, respectively. The most common risk factor for hippocampal BMs was the total number of BMs. The reported failure rate within the HA zone after HA-PCI or HA-WBRT was 4.5 % (0 − 13 %), salvageable with radiosurgery in most cases. SCLC histology was not associated with a higher risk of hippocampal failure (OR = 2.49; p = 0.23). In trials comparing with a conventional (non-HA) PCI or WBRT group, HA did not increase the hippocampal failure rate (OR = 1.90; p = 0.17). ConclusionThe overall incidence of hippocampal and perihippocampal BMs is considerably low, with a subsequent low risk of local undertreatment following HA-PCI or HA-WBRT. In patients without involvement, the hippocampus should be spared to preserve neurocognitive function and quality of life.

Extensive‐stage small cell lung cancer: Is prophylactic cranial irradiation necessary in the era of immunotherapy with MRI surveillance?

AbstractObjectiveThe role of prophylactic cranial irradiation (PCI) in treating extensive‐stage small‐cell lung cancer (ES‐SCLC) has been controversial. This study aimed to comprehensively analyze the efficacy of PCI for the treatment of ES‐SCLC under active brain magnetic resonance imaging (MRI) surveillance.MethodsPatients with ES‐SCLC with no brain metastases (BM) confirmed by MRI at the time of diagnosis who responded well to first‐line chemoimmunotherapy at three general hospitals were retrospectively included. Overall survival (OS), progression‐free survival (PFS), and cumulative incidence of BM were compared between patients who underwent PCI and those who did not.ResultsIn total, 66 consecutive patients treated between March 2019 and December 2021 were included in our dataset. Seventeen patients underwent PCI (PCI group) and 49 patients did not (non‐PCI group). In comparison with the non‐PCI group, PCI did not provide OS (median OS: 18.53 vs. 17.35 months, p = 0.28) or PFS (median PFS: 8.61 vs. 7.56 months, p = 0.41) benefits. When death was counted as a competing risk, the difference in the cumulative incidence rate of BM was not statistically significant (1‐year: 12.79% vs. 38.09%; p = 0.14).ConclusionCompared to active MRI surveillance, first‐line chemoimmunotherapy followed by PCI did not improve the prognosis of patients with ES‐SCLC. Further studies are warranted to evaluate the therapeutic effects of PCI following chemoimmunotherapy.

Prophylactic Cranial Irradiation in Patients with Limited-Stage Small-Cell Lung Cancer without Brain Metastases: A Retrospective Cohort Study

<h3>Purpose/Objective(s)</h3> Previous studies showed that prophylactic cranial irradiation (PCI) reduced brain metastases and improved overall survival of patients with limited-stage small-cell lung cancer (LS-SCLC). However, brain magnetic resonance imaging (MRI), currently recognized as the preferred modality for brain metastases detection, was not routinely used for staging and reassessment in previous trials. This retrospective study aimed to reevaluate the role of PCI for LS-SCLC patients in the modern MRI era. <h3>Materials/Methods</h3> We retrospectively reviewed LS-SCLC patients treated with definitive chemoradiotherapy (≥4 cycles of chemotherapy and thoracic intensity-modulated radiotherapy [IMRT]) between 2006 and 2014 in our center. Patients who responded to initial therapy were included and subsequently reassessed for brain metastases by MRI. The cumulative incidence of brain metastases was estimated using the Fine-Grey competing risks regression model. The overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. <h3>Results</h3> We enrolled 177 patients in this study, of which 79 were treated by PCI and 98 were not (non-PCI). The median follow-up was 76.0 months (95% confidence interval, 71.2-80.8 months). All patients achieved complete response (<i>n</i> = 50, 28.2%) or partial response (<i>n</i> = 127, 71.8%) to initial chemoradiotherapy. The cumulative incidence of brain metastases in the PCI group was lower than in the non-PCI group (6.6% vs. 30.0% at 2 years, 12.2% vs. 31.0% at 5 years, <i>P</i> = 0.004). 5-year PFS in the PCI group was significantly higher than in the non-PCI group (45.3% vs. 26.5%, <i>P</i> = 0.002). However, 5-year OS of 48.8% and 39.2% in the PCI and non-PCI groups, respectively, were similar (<i>P</i> = 0.255). In the multivariate analysis, treatment response (<i>P</i><0.001) and PCI (<i>P</i> = 0.038) were independent prognostic factors for PFS. Stratification analysis revealed that PCI did not improve 5-year PFS for patients with partial response to initial therapy (26.6% vs. 19.7%, <i>P</i> = 0.234). <h3>Conclusion</h3> In the Modern Era with MRI Surveillance, PCI is associated with a lower incidence of brain metastases and improved PFS while OS benefit wasn't observed. Patients achieving partial response to initial therapy did not gain PFS benefit from PCI. Prospective trials are still needed to further evaluate the utility of PCI for patients with LS-SCLC.

Prophylactic Cranial Irradiation (PCI) vs. Active Surveillance in Patients with Limited-Stage Small Cell Lung Cancer: A Retrospective, Multicenter study

<h3>Purpose/Objective(s)</h3> The recommendation of PCI for limited-stage small cell lung cancer (LS-SCLC) with good response to chemoradiotherapy is primarily based on the evidence from the pre-magnetic resonance imaging (MRI) era. However, as the MRI fidelity improves and stereotactic radiosurgery advances, the role of PCI for LS-SCLC becomes uncertain. This study aims to compare the contemporary survival outcomes of PCI versus active surveillance in patients with LS-SCLC. <h3>Materials/Methods</h3> We conducted a retrospective cohort study in which 1068 patients with LS-SCLC who achieved good response to first-line chemoradiotherapy were consecutively enrolled from 5 tertiary hospitals between June 2009 and June 2019. Of these, 440 patients received PCI while 628 received active surveillance with PCI omission. Propensity score matching in a 1:1 ratio with a caliper of 0.2 was performed to balance baseline characteristics of the two groups. The endpoints of this study were overall survival (OS) and the incidence of brain metastases (BM). <h3>Results</h3> In total, 324 LS-SCLC patients with PCI were matched to 324 with active surveillance. Baseline characteristics were generally well balanced between the two matched groups. At a median follow up of 64.5 months (range 2-190), patients with PCI had a significantly lower risk for BM than those with active surveillance. The 3-year cumulative incidence rate of BM was 28.2% (95% CI 22.5%-33.8%) in the PCI group and 38.5% (95% CI 32.6%-44.5%) in the surveillance group (Gray's <i>p</i>=0.002). However, the lower incidence of BM in the PCI group did not translate into a significant extension of OS. The median OS was 35.8 months (95% CI 27.6-44.0 months) in the PCI group versus 32 months (95% CI 26.4-37.6 months) in the surveillance group (HR 0.90, 95% CI 0.74-1.10, <i>p</i>=0.29). <h3>Conclusion</h3> Collectively, PCI reduces the risk for BM but did not substantially prolong OS compared with active surveillance. A Phase 3, prospective clinical trial (NCT04829708) we initiated is currently underway, which is expected to corroborate our results.

Construction of Brain Metastasis Prediction Model and Optimization of Prophylactic Cranial Irradiation Selection for Limited-Stage Small-Cell Lung Cancer.

Simple SummaryThe brain is a common metastasis site of small-cell lung cancer (SCLC), and up to 50% of SCLC patients are at risk of brain metastasis (BM) within 2 years. Prophylactic cranial irradiation (PCI), as an essential treatment for reducing the risk of BM, inevitably leads to neurotoxicity. Differentiating the risk of BM in patients and individualized PCI treatment decisions may play an essential role in reducing the occurrence of BM, prolonging the overall survival, and improving the quality of life. Our study constructed and validated a clinical model to predict the incidence of BM and risk stratification for individualized PCI decisions. PCI could reduce the incidence of BM and improve overall survival (OS) in patients with a high risk of BM, but there was no significant difference between PCI and non-PCI groups in patients within a low-risk cohort.Prophylactic cranial irradiation (PCI), as an essential part of the treatment of limited-stage small-cell lung cancer (LS-SCLC), inevitably leads to neurotoxicity. This study aimed to construct a brain metastasis prediction model and identify low-risk patients to avoid PCI; 236 patients with LS-SCLC were retrospectively analyzed and divided into PCI (63 cases) and non-PCI groups (173 cases). The nomogram was developed based on variables determined by univariate and multivariate analyses in the non-PCI group. According to the cutoff nomogram score, all patients were divided into high- and low-risk cohorts. A log-rank test was used to compare the incidence of brain metastasis between patients with and without PCI in the low-risk and high-risk groups, respectively. The nomogram included five variables: chemotherapy cycles (ChT cycles), time to radiotherapy (RT), lactate dehydrogenase (LDH), pro-gastrin-releasing peptide precursor (ProGRP), and lymphocytes–monocytes ratio (LMR). The area under the receiver operating characteristics (AUC) of the nomogram was 0.763 and 0.782 at 1 year, and 0.759 and 0.732 at 2 years in the training and validation cohorts, respectively. Based on the nomogram, patients were divided into high- and low-risk groups with a cutoff value of 165. In the high-risk cohort, the incidence of brain metastasis in the non-PCI group was significantly higher than in the PCI group (p < 0.001), but there was no difference in the low-risk cohort (p = 0.160). Propensity score-matching (PSM) analysis showed similar results; the proposed nomogram showed reliable performance in assessing the individualized brain metastasis risk and has the potential to become a clinical tool to individualize PCI treatment for LS-SCLC.

Durvalumab with chemoradiotherapy for limited-stage small-cell lung cancer

BackgroundThe current standard treatment for limited-stage small-cell lung cancer (LS-SCLC) is chemotherapy with concurrent chemoradiotherapy (CCRT). MethodsIn this single-arm phase II study, patients with LS-SCLC received four cycles of etoposide, cisplatin, and durvalumab every 3 weeks. Thoracic radiotherapy of 52.5 Gy in 25 once-daily fractions was started with the third cycle of chemoimmunotherapy. After CCRT plus durvalumab, patients received durvalumab consolidation therapy every 4 weeks for a maximum of 2 years after study enrolment. Prophylactic cranial irradiation (PCI) was recommended. ResultsFifty-one patients were enrolled, and 50 were included in the full analysis set. With the median follow-up duration of 26.6 months, the median PFS was 14.4 months (95% confidence interval: 10.3–NA), and the 24-month PFS rate was 42.0%. The median overall survival was not reached with a 24-month overall survival rate of 67.8%. The positive PD-L1 group (n = 22) was not associated with longer PFS (hazard ratio, 0.70; 0.31–1.58) and overall survival (0.64; 0.22–1.84) compared with the negative PD-L1 group (n = 20). Among the 43 patients who were candidates for PCI treatment, the PCI group (n = 22) had significantly fewer events of brain metastasis as the first failure sites compared to the no PCI group (n = 21) (13.6% vs. 42.9%, P = 0.033). There were several grade 3 or 4 adverse events which were well managed with appropriate supportive care. ConclusionsDurvalumab with CCRT for LS-SCLC exhibited promising clinical efficacy with a tolerable safety profile, prompting its validation in a randomized study. Trial registrationNCT03585998.

Benefits of Prophylactic Cranial Irradiation in the MRI Era for Patients With Limited Stage Small Cell Lung Cancer.

PurposePrevious studies have shown that prophylactic cranial irradiation (PCI) can improve the survival of patients with limited-stage small cell lung cancer (LS-SCLC). PCI is recommended for patients who respond well to chemoradiotherapy. However, whether PCI could be extrapolated to the LS-SCLC patients in the modern era of MRI is unknown. This study aimed to explore the value of PCI in patients with LS-SCLC in the era of brain MRI.MethodsThis study included 306 patients with LS-SCLC at the Cancer Hospital of China Medical University. All patients received brain MRI at diagnosis and after radiochemotherapy to exclude brain metastases. A propensity score matching was performed to reduce the influence of potential confounders. Overall survival (OS), progression-free survival (PFS), and recurrence failure types were compared between PCI and non-PCI groups.ResultsAmong the 306 eligible patients, 81 underwent PCI, and 225 did not. After propensity score matching, there was no statistical difference in baseline data between the two groups, with 75 patients in each group. PCI did not achieve OS (median OS: 35 vs. 28 months, p = 0.128) or PFS (median PFS: 15 vs. 10 months, p = 0.186) benefits. During follow-up, 30 patients (20.0%) developed brain metastases, including 13 patients (17.3%) in the PCI group and 17 patients (22.7%) in the non-PCI group. Regarding death as a competitive risk, patients who received PCI had a lower cumulative incidence of brain metastasis than those who did not (3 years: 14.7% vs. 22.7%; Gray’s test, p = 0.007).ConclusionsWhen brain MRI was performed at diagnosis and pre-PCI, PCI could reduce the cumulative rate of brain metastases, but it did not achieve survival benefits for LS-SCLC patients.

Re-evaluation of prophylactic cranial irradiation in limited-stage small cell lung cancer: a propensity score matched analysis.

We attempted to re-evaluate the efficacy of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC) with more recent data. A total of 179 patients with LS-SCLC received radical thoracic radiotherapy and chemotherapy at our institution between 1998 and 2018. One hundred twenty-eight patients who achieved complete response (CR), good partial response (PR), and PR without progression for at least for one year after initial therapy were enrolled in this study. These patients were divided into a PCI group (group A, n = 43), and a non-PCI group (group B, n = 85). Survival outcomes were retrospectively evaluated. Because several background factors differed significantly between groups A and B, propensity score (PS) matching was performed as 1:1 match of the two groups. Finally, we analyzed 64 patients (group A/B = 32/32). Median follow-up periods were 53 and 31 months in groups A and B, respectively. There were no significant differences between the groups’ backgrounds. Two-year overall survival (OS) rates were 77% in group A and 62% in group B (p = 0.224). Two-year brain metastasis free survival (BMFS) rates were 85% in group A and 57% in group B (p = 0.008). The number of patients who underwent a brain imaging test for confirmation of no brain metastasis (BM) after radical thoracic radiotherapy and chemotherapy (before PCI) was 84 (group A/B = 32/52). A PS matched analysis for cases of pre-PCI brain imaging group, two-year OS rates for group A/B were 73/59% (p = 0.446). Two-year BMFS rates for group A/B were 91/52% (p = 0.021). Retrospectively, PS matched analysis revealed that adding PCI to LS-SCLC patients who achieved good thoracic control significantly improved BMFS, but OS did not improve.

Prophylactic cranial irradiation confers favourable prognosis for patients with limited-stage small cell lung cancer in the era of MRI: A propensity score-matched analysis.

Prophylactic cranial irradiation (PCI) is recommended for patients with limited-stage small cell lung cancer (LS-SCLC) who achieve good response after chemoradiotherapy. But PCI is neurotoxic. Magnetic resonance imaging (MRI) is the standard tool for evaluating brain metastasis (BM). This study was to retrospectively analyse the necessity of PCI in the era of MRI in LS-SCLC. From July 2013 to June 2017, 190 patients with LS-SCLC who were treated with definitive chemoradiotherapy were included and analysed in this study. They were divided into the PCI group and non-PCI group. Propensity score matching (PSM) analysis was used to balance the variable differences. The Kaplan-Meier method was applied to estimate survival with log-rank test to ascertain significance between different groups. Seventy-seven patients (40.5%) received PCI after chemoradiotherapy. After adjustment for propensity scores, 69 pairs of patients were matched between two groups. After PSM, the 1-year and 3-year OS rates were 96.9% and 48.5% in PCI group versus 89.9% and 25.0% in non-PCI group (HR: 0.419, 95% CI: 0.251-0.701, P=0.001). The 1-year and 3-year BMFS in PCI group were 96.8% and 67.5% versus 62.3% and 37.9% in non-PCI group (HR: 0.247, 95% CI: 0.132-0.460, P<0.001). For patients showing no BM on MRI after definitive CRT, PCI confers less BM and better OS in LS-SCLC.

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.

Prophylactic cranial irradiation reduces the incidence of brain metastasis in a mouse model of metastatic, HER2-positive breast cancer

Prophylactic cranial irradiation (PCI) can reduce the incidence of brain metastasis and improve overall survival in some patients with acute lymphoblastic leukemia or small-cell lung cancer. We examined the potential effects of PCI in a mouse model of breast cancer brain metastasis. The HER2+ inflammatory breast cancer cell line MDA-IBC3 was labeled with green fluorescent protein and injected via tail-vein into female SCID/Beige mice. Mice were then given 0 Gy or 4 Gy of whole-brain irradiation 2 days before tumor-cell injection or 5 days, 3 weeks, or 6 weeks after tumor-cell injection. Mice were sacrificed 4-weeks or 8-weeks after injection and brain tissues were examined for metastasis by fluorescent stereomicroscopy. In the unirradiated control group, brain metastases were present in 77% of mice at 4 weeks and in 90% of mice at 8 weeks; by comparison, rates for the group given PCI at 5 days after tumor-cell injection were 20% at 4 weeks (p=0.01) and 30% at 8 weeks (p=0.02). The PCI group also had fewer brain metastases per mouse at 4 weeks (p=0.03) and 8 weeks (p=0.006) versus the unirradiated control as well as a lower metastatic burden (p=0.01). Irradiation given either before tumor-cell injection or 3-6 weeks afterward had no significant effect on brain metastases compared to the unirradiated control. These results underscore the importance of timing for irradiating subclinical disease. Clinical whole brain strategies to target subclinical brain disease as safely as possible may warrant further study.

Treatment and toxic effects of prophylactic cranial irradiation in stage II-III non-small cell lung cancer: A meta-analysis.

To determine the role of prophylactic cranial irradiation (PCI) in non-small cell lung cancer (NSCLC) patients using meta-analysis. PubMed, Embase, the Cochrane Database of Systematic Review and the China National Knowledge Infrastructure databases were systematically searched for studies published between 1 January 1980 and 31 March 2019. Search terms included "non-small cell lung cancer," "prophylactic cranial irradiation" and "clinical trials." The research data extracted from above studies was analyzed by Review Manager 5.3 and Stata12.0 software. The outcomes included development of brain metastases (BMs), overall survival (OS), disease-free survival (DFS), BMs for different diagnoses, toxicity, quality of life (QoL). Fifteen trials (nine RCTs and six non-RCTs) involving 2418 NSCLC patients met the inclusion criteria. There was a significant reduction in the risk of developing BM in patients who received PCI compared with those who did not (95% CI, 0.20-0.37; P<0.00001). PCI significantly reduced the BM of squamous cell carcinoma (P=0.02), but not for adenocarcinoma (P=0.07) and other pathological types (P=0.29). There was a significant increase in DFS for the PCI compared to the non-PCI group (P=0.006); however, OS did not significantly differ (P=0.15). In addition, fatigue significantly increased in the PCI group (P=0.0002). Cognitive disturbance showed no significant difference between PCI and non-PCI groups (P=0.06). This study showed that, compared with non-PCI, PCI significantly decreased the incidence of NSCLC BM and improved the DFS of patients, and reduced the BM rate from squamous cell carcinoma. However, it showed no effect on OS and the BM rate of adenocarcinoma and other pathological types of tumors. There were limited data concerning PCI-related toxicity and QoL.

Rates of Overall Survival and Intracranial Control in the Magnetic Resonance Imaging Era for Patients With Limited-Stage Small Cell Lung Cancer With and Without Prophylactic Cranial Irradiation

Historical data suggest that there is an overall survival benefit associated with prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC). However, as the fidelity of magnetic resonance imaging (MRI) of the brain continues to improve, this idea is now being questioned, with recent research showing no survival benefit associated with PCI in extensive-stage SCLC; however, the role for PCI is not clear in patients with limited-stage SCLC (LS-SCLC). To report the overall survival and rates of intracranial control for patients with LS-SCLC, all staged with MRI, who either did or did not undergo PCI. This cohort study included 297 patients with LS-SCLC at a large US academic cancer center. Patients were treated with thoracic radiation; 205 also underwent PCI and 92 did not. All patients underwent at least baseline MRI, with restaging brain MRI and/or computed tomography; they did not have disease progression after thoracic radiation treatment. A propensity score-matching analysis was undertaken in an attempt to adjust for potential bias. Of the 297 patients who met the inclusion criteria, the propensity score was calculated for 295 patients, using patient, tumor, and treatment characteristics. Data were analyzed in October 2019. Prophylactic cranial irradiation in patients with LS-SCLC. The rate of overall survival and intracranial control. Of the 297 patients, 162 (54.5%) were men. The median age was 62.2 years (range, 27.0-85.0 years) for patients who underwent PCI and 68.6 years (range, 40.0-86.0 years) for those who did not undergo PCI. The 3-year cumulative incidence rate of brain metastases was higher in the no-PCI group vs the PCI group, when counting death as a competing risk, but the difference was not statistically significant (20.40% [95% CI, 12.45%-29.67%] vs 11.20% [95% CI, 5.40%-19.20%]; P = .10). The use of PCI was not associated with a difference in overall survival between the patient groups (hazard ratio, 0.844; 95% CI, 0.604-1.180; P = .32). These findings suggest that patients with LS-SCLC staged with MRI who undergo PCI after thoracic radiation treatment were not associated with a decreased risk of developing new brain metastases compared with patients who do not undergo PCI. The use of PCI was not associated with an overall survival benefit for such patients.

Meta-analysis of prophylactic cranial irradiation or not in treatment of extensive-stage small-cell lung cancer: The dilemma remains

PurposeThe role of prophylactic cranial irradiation (PCI) in treatment of extensive-stage small-cell lung cancer (SCLC) is controversial. The aim of this study was to systematically evaluate the efficacy and safety of using PCI in the treatment of extensive-stage SCLC. In the present study, we examined whether PCI was essential for the optimal treatment of extensive-disease small-cell lung cancer. Material and methodsWe searched the PubMed, Embase, Medline, and China National Knowledge Infrastructure databases to identify articles that assessed the efficacy of PCI in treating extensive-stage small-cell lung cancer patients. ResultsWe identified 8 studies that involved a total of 982 patients who received PCI (PCI group) and a total of 4509 patients who did not receive PCI (control group). The results showed that PCI significantly improved the 1-year overall survival rate (HR=1.50; 95% CI: 1.23–1.82; I2=67%; P<0.0001) and reduced the incidence of brain metastasis (HR=0.46; 95% CI: 0.37–0.58; I2=6%; P<0.00001). ConclusionPCI improves the 1-year overall survival rate and reduces the risk of brain metastasis in patients with extensive-stage SCLC.

EP1.12-04 Can Prophylactic Cranial Irradiation Reduce Neurological Symptoms in Patients with Small Cell Lung Cancer?

The central nervous system is the usual site of metastasis in patients with small cell lung carcinoma (SCLC). Despite advances in combined treatment modalities, it’s the main cause of morbidity in these patients. High prevalence of brain metastases, combined with the poor intracranial penetration of most chemiotherapy regimens used, led to development of prophylactic cranial irradiation (PCI), a preventive radiotherapeutic treatment, which has been shown to be effective in reducing the incidence of brain metastases. Earlier studies showed that patients who had PCI, had reduced rate of symptomatic brain metastasis at one year (14.6% vs 40.4%) and had slightly better overall survival. In Institute for pulmonary diseases of Vojvodina, there are around 1200 newly diagnosed patients with lung cancer in each year, of which around 200 patients (14%) have SCLC. PCI is now routinely administered to patients with SCLC, after a complete/partial response to initial treatment. This was a retrospective study conducted at the Institute for Pulmonary Diseases of Vojvodina, Serbia, which included patients diagnosed with SCLC in this institution, between October 2015 - October 2017. The patients were divided into two groups, one who received PCI after complete/partial answer to systemic therapy and chest irradiation, total of 34 patients. The control group consisted of 30 patients, who also had good answer to systemic therapy and chest radiation therapy, but didn’t receive PCI. In this study, significantly higher percentage of patients in the PCI group (84.8% vs 40.0%) didn’t develop neurological symptoms (p= 0.000). In the group of patients who received PCI, only 5 out of 34 (14.7%) developed CNS symptoms, an average of 10 months after completing the PCI. In the control group, 60% (18/30) of patients experienced neurological symptoms, on average 11 months after diagnosis. Data analysis found that patients in PCI group were 8.4 times less likely to develop neurological symptoms. Also, it was confirmed that overall survival was better for patients who received PCI after systemic and irradiation treatment, the mean OS of patients in the PCI group was 19.0 months, compared to the control group where it was 15.4 months. The authors strongly believe that PCI should remain a standard of care for patients with SCLC, after response to initial treatment. If not only for prolonging the overall survival, but also because it improves the quality of life in these patients by reducing the neurological symptoms.

Prophylactic cranial irradiation in small cell lung cancer: a systematic review and meta-analysis

BackgroundThe efficacy of prophylactic cranial irradiation (PCI) in treating patients with small cell lung cancer (SCLC) has not been clear, and recent randomized studies have demonstrated conflicting results from previously published findings. The purpose of this study was to reevaluate the efficacy of PCI in patients with SCLC and to assess factors associated with its efficacy.MethodsWe conducted a quantitative meta-analysis to explore the efficacy of PCI in patients with SCLC. A literature search was performed using EMBASE, MEDLINE, Cochrane and ClinicalTrials.gov databases. We pooled the data and compared overall survival (OS) and brain metastasis (BM) between patients treated with PCI (PCI group) and patients without PCI treatment (observation group).ResultsOf the 1074 studies identified in our analysis, we selected seven studies including 2114 patients for the current meta-analysis. Our results showed that the PCI group showed decreased BM (HR = 0.45, 95% CI: 0.38–0.55, P < 0.001) and prolonged OS (HR = 0.81, 95% CI: 0.67–0.99, P < 0.001). However, in terms of OS, the pooled analysis showed a high heterogeneity (I2 = 74.1%, P = 0.001). In subgroup analyses of OS, we found that the heterogeneity mainly came from patients with brain imaging after initial chemoradiotherapy (HR = 0.94, 95% CI: 0.74–1.18, P = 0.59).ConclusionsThe results of this study showed that PCI has a significant effect on decreasing BM but little benefit in prolonging OS when brain imaging was introduced to confirm lack of BM after initial chemoradiotherapy and before irradiation.

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.