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Prophylactic cranial irradiation for extensive-stage small cell lung cancer: Analysis based on active brain MRI surveillance

ABSTRACT: Highlights • The value of PCI remains controversial in ES-SCLC.• Under the active brain MRI surveillance, PCI improve the PFS and BSS for ES-SCLC.• PCI reduce the incidence of BM for ES-SCLC. Background and purpose The value of prophylactic cranial irradiation (PCI) for extensive-stage small-cell lung cancer (ES-SCLC) has recently been challenged. This study was conducted to evaluate the role of PCI for ES-SCLC under active brain magnetic resonance imaging (MRI) surveillance. Materials and methods Patients with ES-SCLC who showed any responses after first-line chemotherapy and no initial brain metastasis (BM) were retrospectively included. Active brain MRI surveillance was performed for all patients. Progression-free survival (PFS) and overall survival (OS) were compared between PCI and non-PCI patients. The time-related hazard of BM was evaluated in non-PCI patients. Results One hundred and eighteen consecutive patients were included in the study. The median follow-up time was 26.5 months (3–72 months). The median PFS and OS were better in the PCI cohort than in the non-PCI group. Multivariate analyses revealed first-line chemotherapy cycles (> 4 vs. ? 4 cycles, HR: 0.29; 95% CI: 0.15–0.55, P < 0.01) and PCI (Yes vs. No, HR: 0.54; 95% CI: 0.29–0.99, P = 0.04) were independent prognostic factors for disease progression. In the non-PCI group, 47.4% (46/97) of the patients developed BM and the hazard of BM increased continuously in three-quarters of the first year since diagnosis. Conclusion Under active brain MRI surveillance, PCI could be beneficial for patients with ES-SCLC who show good responses after first-line chemotherapy.

SUBMITTER: Yu J

PROVIDER: S-EPMC7508717 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Prophylactic Cranial Irradiation for Extensive-Stage Small-Cell Lung Cancer: A Retrospective Analysis.

Project description:PURPOSE:Extensive-stage small-cell lung cancer (esSCLC) is an incurable disease and represents a therapeutic challenge because of its poor prognosis. Studies in prophylactic cranial irradiation (PCI) in esSCLC have shown a decreased incidence of symptomatic brain metastases in patients who respond to systemic chemotherapy. However, its effect on overall survival is debatable. We evaluated the benefit of PCI in patients with esSCLC in terms of overall survival, progression-free survival, incidence of brain metastases, recurrence rate, and exposure to postrecurrence therapies. MATERIALS AND METHODS:We retrospectively reviewed electronic charts from patients diagnosed with esSCLC from 2008 to 2014 at our institution. All patients had negative baseline brain imaging before chemotherapy and PCI and received at least 4 cycles of platinum-based chemotherapy in the first-line setting without progressive disease on follow-up. PCI was performed at the discretion of the treating physician. Analyses were based on descriptive statistics. Survival curves were calculated by Kaplan-Meier method. RESULTS:Among 46 eligible patients, 16 (35%) received PCI and 30 (65%) did not. Compared with no PCI, PCI led to improved progression-free survival (median, 10.32 v 7.66 months; hazard ratio, 0.4521; 95% CI, 0.2481 to 0.8237; P < .001) and overall survival (median, 20.94 v 11.05 months; hazard ratio, 0.2655; 95% CI, 0.1420 to 0.4964; P < .001) as well as lower incidence of brain metastases (19% v 53%; P = .0273) and higher exposure to second-line chemotherapy (87% v 57%; P = .0479). CONCLUSION:Careful patient selection for PCI can improve not only brain metastases control and higher second-line chemotherapy exposure but also patient survival.

| S-EPMC6181177 | biostudies-literature

Patterns of failure in limited-stage small cell lung cancer: Implications of TNM stage for prophylactic cranial irradiation.

Project description:Background and purposeThe relationship between tumor-node-metastasis (TNM) stage and patterns of failure in limited-stage small cell lung cancer (LS-SCLC) remains unclear. We hypothesized that TNM stage predicts brain metastasis risk, and could inform the use of prophylactic cranial irradiation.Material and methodsWe reviewed 283 patients with stage I-IIIB SCLC. Competing-risks regression was used to analyze local, distant, and brain failure. Multivariate analysis was used to evaluate the effect of treatment and clinical factors on failure and OS.ResultsPatients with stage I or II SCLC (35% of cohort) had significantly better survival and lower risk of distant and brain metastasis, compared with stage III patients. The 5-year cumulative incidence of brain metastasis for stage I/II and III were 12% and 26%, respectively. Stage had no correlation with local failure. On multivariate analysis, stage was independently prognostic for survival, distant metastasis risk, and brain metastasis risk.ConclusionsTNM staging predicts likelihood of distant metastasis, brain metastasis, and survival in LS-SCLC. This supports the routine use of TNM staging in clinical practice. The lower risk of brain metastasis in stage I and II SCLC suggests that prophylactic cranial irradiation could play a more limited role in treatment of early-stage disease.

| S-EPMC5643234 | biostudies-literature

Factors influencing the utilization of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer.

Project description:Brain metastases are common in patients with limited-stage small cell lung cancer (LS-SCLC) due to the inability of most chemotherapeutics to penetrate the blood-brain barrier. Prophylactic cranial irradiation (PCI) is therefore recommended for use in patients with a good response to concurrent chemoradiotherapy. However, PCI is not always delivered; therefore, we investigated the reasons for PCI omission in patients who underwent therapy with curative intent.We retrospectively reviewed all patients with LS-SCLC who were treated with curative intent at our institution. Overall survival and cumulative incidence of brain metastasis were estimated by the Kaplan-Meier method. The Pearson ?2 test and Mann-Whitney U test were used to examine factors associated with PCI use, and prognostic factors were analyzed with Cox proportional hazards modeling.We examined 208 patients who were treated for LS-SCLC at our institution. A total of 115 patients (55%) received PCI. The most common documented reason for PCI omission was patient refusal due to neurotoxicity concerns (38%). Physician assessment of being medically unfit (33%) and of advanced age (8%) were the second and third most common reasons, respectively. Karnofsky performance status and clinical American Joint Committee on Cancer stage but not PCI were significantly associated with overall survival. Only clinical stage remained an independent factor on multivariate analysis.Approximately half of patients with LS-SCLC ultimately receive PCI, generally for guideline-recommended reasons. The most common reason for PCI omission was patient concerns regarding neurotoxicity. Efforts to decrease PCI neurotoxicity, including hippocampal-sparing radiation and memantine use, may increase the use of this survival-improving intervention in eligible patients with LS-SCLC.

| S-EPMC5707415 | biostudies-other

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.

Project description:BACKGROUND:A 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. METHODS:PubMed, 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. RESULTS:A 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. CONCLUSION:PCI improves overall survival in extensive-stage SCLC. More randomized controlled trials are needed to verify our findings.

| S-EPMC6107943 | biostudies-literature

Prophylactic cranial irradiation in non-small cell lung cancer: evidence and future development.

Project description:In non-small cell lung cancer (NSCLC) brain metastases (BM) will affect up to 50% of patients during whole disease period. BM themselves impact heavily not only on patient's prognosis but also are a source of symptoms aggravating quality of life. Standard (pemetrexed), and non-standard chemotherapy (temozolomide) in patients with NSCLC failed to prevent them from BM. In terms of systemic treatment there are promising results showed when durvalumab (PACIFIC study), osimertinib (FLAURA trial) or alectinib (JALEX study) was used. However, those substances are effective only in small cohort with ALK or EGFR alterations. Prophylactic cranial irradiation (PCI) as a non-specific treatment has proven to be a powerful tool in preventing BM without affecting overall survival in neither way. That has been proved in nearly all earlier and all recent studies-NVALT11/DLCRG-02, RTOG 0214 update, Li et al. The positive effect of BM incidence reduction may draw fear form PCI usage due to potential cognitive toxicity the PCI may cause. Results of recent trials show that after PCI only mild cognitive disorders (MCD) may arise. Promising results in terms of reducing MCD are shown when memantine is used or/and hippocampal avoidance techniques are implemented. HA in PCI seem to be cost effective but calculations were made on small-cell lung cancer cohorts. Still even recent studies did not clarify finally which patients could benefit from PCI or other forms of preventing BM. It seems that new trials should focus on younger, fit and non-squamous histology patients and use the tests for mild cognitive disorders (MoCA, BHA) rather than screening tests for dementia (MMSE, HVLT, ADL). The main obstacle in performing new trials on PCI in NSCLC cohorts may be, however, patients' accrual, as a difficulty which occurred during latest trials.

| S-EPMC8182492 | biostudies-literature

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

Project description: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.

| S-EPMC6341615 | biostudies-literature

Patterns of relapse following hippocampal avoidance prophylactic cranial irradiation for small cell lung carcinoma

Project description:Background Hippocampal avoidance techniques are an evolving standard of care for patients undergoing cranial irradiation. Our aim was to assess the oncological outcomes and patterns of failure following hippocampal avoidance prophylactic cranial irradiation (HA-PCI) as a standard of care in unselected patients with both limited and extensive stage small cell lung carcinoma. Materials and methods Consecutive patients with small cell lung carcinoma with a complete (limited stage) or good partial (extensive stage) response following chemotherapy were eligible to receive HA-PCI, with a total dose of 25 Gray in 10 fractions. All patients had a negative baseline MRI brain scan with gadolinium prior to HA-PCI. Patients had baseline and follow up Common Toxicity Criteria Adverse Event assessments. Following completion of HA-PCI, all patients had three-monthly MRI brain scans with gadolinium until confirmation of intracranial relapse, as well as three-monthly CT of the chest, abdomen and pelvis. Overall and progression-free survival were calculated using the Kaplan-Meier method. Results A total of 17 consecutive patients, 9 men and 8 women, with a mean age of 70 years received HA-PCI between May 2016 and June 2020 after completion of their initial chemotherapy. There were no Grade 4 or greater adverse events. No patient had an isolated hippocampal avoidance zone relapse alone; three of 17 patients had multifocal relapses that included the hippocampal avoidance zone. Conclusion In our series, there were no hippocampal only relapses and we conclude that HA-PCI is a safe alternative to standard PCI in the setting of small cell lung cancer.

| S-EPMC8726451 | biostudies-literature

Risk factors for brain metastases after prophylactic cranial irradiation in small cell lung cancer.

Project description:Despite administration of prophylactic cranial irradiation (PCI), some small cell lung cancer (SCLC) patients still suffer from brain metastases (BM) with unknown risk factors. We conducted this study to identify patients with higher BM risk after PCI and improve their outcome. The characteristics and survival of all the SCLC patients underwent PCI in our institute from 2003 to 2014 were analyzed. Kaplan-Meier method was applied to estimate BM free survival (BMFS) and overall survival (OS). Cox regression analyses were performed to explore risk factors for BM. A total of 175 patients with the median age of 55 years (range, 29-76) were eligible, among whom 36 (20.6%) developed BM with median follow-up of 42 months. Both univariate and multivariate analyses showed HART and TNM classification (p?<?0.05) were associated with BM. Two-stage system was not related with BMFS or OS (p?>?0.05). Stage IIIB-IV and HART were independent risk factors for BM after PCI in SCLC. TNM classification was more valuable on prognosis than two-stage system. Further large-scale studies are needed to confirm our findings.

| S-EPMC5311871 | biostudies-other

Patterns of brain metastasis immediately before prophylactic cranial irradiation (PCI): implications for PCI optimization in limited-stage small cell lung cancer.

Project description:BackgroundProphylactic cranial irradiation (PCI) is indicated for limited-stage small cell lung cancer (LS-SCLC) with good response to chemoradiotherapy (CRT). However, brain metastasis (BM) developed in LS-SCLC before PCI is not rare. In this study, we comprehensively investigated the features of pre-PCI BMs, aiming to explore the potential of PCI optimization for LS-SCLC.MethodsOne-hundred-ten LS-SCLC patients achieving clinical complete remission after definitive CRT with contrast-enhanced cranial magnetic resonance imaging (MRI) at baseline and immediately before PCI were included. The time trend and risk factors for pre-PCI BM were evaluated. Several radiological features, including numbers, sizes, and locations of pre-PCI BMs, were investigated to explore the technical feasibility of stereotactic radiotherapy and hippocampal-avoidance (HA) PCI.ResultsTwenty-four (21.8%) of the LS-SCLC patients harbored pre-PCI BM, all except one were asymptomatic. CRT duration (CRT-D) was the only independent risk factor for pre-PCI BM. The pre-PCI BM rate gradually increased in line with a growing time interval between treatment initiation and pre-PCI MRI. Pre-PCI BM and prolonged CRT-D were both correlated with worse overall survival. Of 129 pre-PCI intracranial lesions, 2 (1.5%) were in the HA region. Eight of the 24 (33.3%) pre-PCI BM patients were ineligible for stereotactic radiotherapy.ConclusionOur findings suggest that PCI is still of importance in LS-SCLC, and MRI evaluation before PCI is indispensable. Investigations are warranted to explore the possibility of moving PCI up to before CRT completion in LS-SCLC patients with prolonged CRT-D. HA-PCI could be considered to reduce neurotoxicity.

| S-EPMC6749639 | biostudies-literature

Prophylactic cranial irradiation in small-cell lung cancer: update on patient selection, efficacy and outcomes.

Project description:Over 10% of small-cell lung cancer (SCLC) patients have brain metastases (BM) at initial diagnosis; more than 50% will develop BM within 2 years. BM are detected in up to 80% of all patients at autopsy. After primary treatment, prophylactic cranial irradiation (PCI) has been established as standard of care in SCLC patients responding to initial therapy. Based on level I evidence, PCI significantly decreases the risk of intracranial relapse and shows a modest survival benefit after 3 years. However, the role of PCI in defined patient subgroups such as resected SCLC, elderly and extensive stage patients with access to magnetic resonance imaging surveillance and stereotactic radiotherapy is yet to be fully clarified. Furthermore, strategies to effective prevention of neurocognitive decline after PCI remain unclear. All these factors significantly impact treatment decision making and should be evaluated in prospective settings. New concepts such as hippocampal avoidance and drug neuroprotection prevent chronic neurocognitive effects reducing treatment-related side effects of PCI. The aim of this review is to present a summary and update of the latest evidence for patient selection, efficacy and outcome of PCI.

| S-EPMC6181088 | biostudies-literature

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