Cranial Irradiation In Patients Research Articles

Usefulness of pro-gastrin-releasing peptide as a predictor of the incidence of brain metastasis and effect of prophylactic cranial irradiation in patients with limited-stage small-cell lung cancer

Prophylactic cranial irradiation (PCI) is recommended for patients with limited-stage small-cell lung cancer (LS-SCLC) who respond well to initial treatment. However, PCI is often omitted because of its potential neurotoxicity in the era of modern diagnostic imaging devices. In the present study, we aimed to investigate the risk factors for brain metastasis (BM) in patients eligible for PCI and who may benefit more from it. Patients with LS-SCLC who responded well to definitive thoracic chemoradiotherapy were included in the present study. Competing risk regression was used to identify factors associated with BM, and the Kaplan–Meier method was used to assess overall survival (OS). Between 2004 and 2017, 62 patients were eligible for PCI and were analyzed. Of these, 38 (61.3%) underwent PCI. Overall, 17 patients (27.4%) developed BM, with a 2-year cumulative incidence of 22.8%. Multivariate analysis (MVA) revealed that pretreatment elevated pro-gastrin-releasing peptide (ProGRP) levels were associated with an increased risk for BM (HR, 7.96, P = 0.0091). PCI tended to reduce the risk of BM (HR, 0.33; P = 0.051). The use of PCI was associated with improved OS in patients with ProGRP levels > 410 pg/mL (P = 0.008), but not in those with ProGRP ≤ 410 pg/mL (P = 0.9). Pretreatment ProGRP levels may be useful in predicting the development of BM in patients with LS-SCLC who achieved a good response to initial therapy and to determine which patients should undergo PCI.

Outcomes of prophylactic cranial irradiation in patients with small cell lung cancer in the modern era of baseline magnetic resonance imaging of the brain

Background For decades many patients with small cell lung cancer (SCLC) have been offered prophylactic cranial irradiation (PCI) to prevent brain metastases (BM). However, the role of PCI is debated in the modern era of increased brain magnetic resonance imaging (MRI) availability. BM in SCLC patients may respond to chemotherapy, and if a negative MRI is used in the decision to use of PCI in the treatment strategy, the timing of brain MRI may be crucial when evaluating the effect of PCI. This retrospective study investigates the impact of PCI outcomes in patients with SCLC staged with brain MRI prior to chemotherapy. Materials and methods This study included 245 patients diagnosed SCLC/mixed NSCLC-SCLC treated between 2012 and 2019. The population was analyzed separately for limited disease (LS-SCLC) and extensive disease (ES-SCLC). Patients were divided into groups based on baseline brain MRI prior to chemotherapy and PCI. The primary endpoint was time to symptomatic BM. Secondary endpoints were overall survival (OS), and progression-free survival (PFS). Results In patients with LS-SCLC staged with brain MRI the probability of developing symptomatic BM at one year was 4% vs. 22% (p < 0.05), median OS was 55 vs. 24 months (p < 0.05), and median PFS was 30 vs. 10 months (p < 0.05) with and without PCI, respectively. No differences in probability of symptomatic BM and survival outcomes were observed in ES-SCLC. In a multivariate regression analysis, no variables were statistically significant associated with the risk of developing symptomatic BM in patients with LS-SCLC and ES-SCLC. For patients with ES-SCLC staged with brain MRI, PS (HR = 3.33, CI; 1.41–7.89, p < 0.05) was associated with poor survival. Conclusion This study found that PCI in LS-SCLC patients staged with brain MRI had lower incidence of symptomatic BM and improved survival outcomes suggesting PCI as standard of care. Similar benefit of PCI in patients with ES-SCLC was not found.

PD-0842 Prophylactic cranial irradiation in patients with small cell lung cancer in the Netherlands

PD-0842 Prophylactic cranial irradiation in patients with small cell lung cancer in the Netherlands

Prophylactic cranial irradiation in patients with small cell lung cancer in The Netherlands: A population-based study

IntroductionControversy has arisen regarding the benefit of prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC), particularly since the 2017 Takahashi trial publication that supports MRI surveillance in extensive-stage (ES-)SCLC. The primary aim of this study was to assess trends and determinants in PCI use over the years 2010–2018. A secondary aim was to determine contemporary practice considerations among radiation oncologists (ROs). MethodsA nationwide population-based cohort study was conducted using the Netherlands Cancer Registry data on all newly diagnosed SCLC patients (2010–2018). The change in PCI frequency over the years and determinants for PCI were analyzed using logistic regression models. Second, an online survey was performed among Dutch lung cancer ROs in 2020. ResultsAmong 10,264 eligible patients, 4,894 (47%) received PCI. Compared to 2010–2014, PCI use significantly decreased in 2017–2018 in ES-SCLC (OR 0.68, 95%CI 0.60–0.77) and LS-SCLC (OR 0.56, 95%CI 0.47–0.67). Incidence year, age, performance status, and thoracic radiotherapy were independent determinants for PCI. Among 41 survey participants, PCI was recommended always/sometimes/never by 22%/71%/7% in ES-SCLC and 54%/44%/2% in LS-SCLC. For ES-SCLC and LS-SCLC, 63% and 25% of ROs, respectively, confirmed influence of the Takahashi trial on PCI recommendations. Denial of such influence was associated with insufficient institutional MRI capacity. ConclusionsA significant declining trend of PCI use in both ES-SCLC and LS-SCLC was observed in The Netherlands since 2017. The Takahashi trial seems an explanation for this trend even in LS-SCLC, with differential influence of the trial depending on institutional MRI capacity. An alarming increase in practice variation regarding PCI was found which stresses the importance of ongoing trials.

Prophylactic cranial irradiation for patients with limited-stage small cell lung cancer

Prophylactic cranial irradiation for patients with limited-stage small cell lung cancer

Use of prophylactic cranial irradiation in patients with extensive-stage small cell lung cancer receiving immunotherapy.

e19309 Background: Prophylactic cranial irradiation (PCI) use is controversial in extensive-stage small cell lung cancer (ES-SCLC). In addition to lack of survival benefit of PCI compared to close MRI surveillance in a 2017 published trial, the role of PCI is being further challenged in the modern immune-oncology (IO) era. The IMpower133 trial reporting a survival benefit to atezolizumab for ES-SCLC published in 2018 did not require PCI use. Contemporary practice patterns of PCI in relation to immunotherapy are unknown. Methods: We performed a retrospective cohort analysis of patients with ES-SCLC diagnosed between January 1, 2013 to September 31, 2019 from the nationwide Flatiron Health electronic health record-derived de-identified database. First-line chemotherapy (Chemo) was defined as Chemo given alone, while first-line IO therapy was IO alone or combined with chemotherapy as initial systemic therapy. Results: The cohort included 3047 ES-SCLC patients who received first-line Chemo, and 324 patients who received first-line IO. For first-line IO patients, 268 (82.7%) received first-line atezolizumab. The use of first-line IO increased from 1.2% of patients diagnosed in 2013 to 11.3% of patients diagnosed in 2018 (p &lt; 0.001), and 54.5% of patients diagnosed in 2019 (p &lt; 0.001). Overall documented PCI for patients receiving either first-line IO or first-line Chemo decreased from 14.7% in 2013 to 7.0% in 2018-2019 (p &lt; 0.001). For first-line IO patients, 23 (7.1%) had documented PCI over our study period, with 5.3% of patients diagnosed in 2018-2019 having received PCI. In contrast, for first-line Chemo patients, 428 (14.0%) received PCI over our study period, and PCI use significantly decreased from 14.8% in 2013 to 7.9% in 2018-2019 (p = 0.001). In 2018-2019, use of PCI was not significantly different between patients receiving first-line IO compared to first-line Chemo (5.3% vs 7.9%, p = 0.163). Conclusions: The use of first-line IO has significantly increased in ES-SCLC. Overall PCI rates for ES-SCLC patients decreased significantly over the study period, although documented PCI use rates do not differ between patients receiving upfront IO or Chemo in 2018-2019. Further investigation is warranted regarding effectiveness of PCI in the modern IO era.

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.

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.

SEOM clinical guidelines for the treatment of small-cell lung cancer (SCLC) (2019)

Small-cell lung cancer (SCLC) accounts for 15% of lung cancers. Only one-third of patients are diagnosed at limited stage. The median survival remains to be around 15–20 months without significative changes in the strategies of treatment for many years. In stage I and IIA, the standard treatment is the surgery followed by adjuvant therapy with platinum–etoposide. In stage IIB–IIIC, the recommended treatment is early concurrent chemotherapy with platinum–etoposide plus thoracic radiotherapy followed by prophylactic cranial irradiation in patients without progression. However, in the extensive stage, significant advances have been observed adding immunotherapy to platinum–etoposide chemotherapy to obtain a significant increase in overall survival, constituting the new recommended standard of care. In the second-line treatment, topotecan remains as the standard treatment. Reinduction with platinum–etoposide is the recommended regimen in patients with sensitive relapse (≥ 3 months) and new drugs such as lurbinectedin and immunotherapy are new treatment options. New biomarkers and new clinical trials designed according to the new classification of SCLC subtypes defined by distinct gene expression profiles are necessary.

Efficacy and Failure Patterns of Prophylactic Cranial Irradiation in Patients with Limited-stage Small Cell Lung Cancer Who Were Estimated by Modern Brain Imaging and Treated with Standard Chemoradiotherapy

Efficacy and Failure Patterns of Prophylactic Cranial Irradiation in Patients with Limited-stage Small Cell Lung Cancer Who Were Estimated by Modern Brain Imaging and Treated with Standard Chemoradiotherapy

Risk Stratification of Symptomatic Brain Metastases By Clinical and FDG PET Parameters for the Selective Use of Prophylactic Cranial Irradiation in Patients with Extensive Disease of Small Cell Lung Cancer

The role of prophylactic cranial irradiation (PCI) remains controversial in extensive disease small cell lung cancer (ED-SCLC). This study is performed to identify the risk factors of symptomatic brain metastasis and to evaluate the impact of PCI on brain metastasis-free survival (BMFS) and overall survival (OS) according to the risk of symptomatic brain metastasis in ED-SCLC. From 2006 to 2017, a total of 190 patients diagnosed with ED-SCLC who underwent FDG-PET and brain MRI prior to treatment were enrolled in this retrospective study. Among these patients, 53 (27.9%) received PCI and 137 (72.1%) did not. Prognostic index predicting a high risk of symptomatic brain metastasis was calculated in the observation group (137/190) on Cox regression model and the prognostic index was generated by summating significant factors weighted by a hazard ratio of each. The role of PCI in each risk group was analyzed by using Kaplan-Meier survival analysis. Median follow-up time was 10.6 months. 1-year and 2-year symptomatic BMFS were 86.9% and 49.8%, and 1-year and 2-year OS were 52.5% and 12.7%, respectively. Multivariate Cox regression analysis showed that 4 risk factors were associated with high risk of symptomatic brain metastasis: presence of extrathoracic metastases (P = 0.005) and hypermetabolism of bone marrow (BM) or spleen (P < 0.001) on FDG PET, as well as progressive disease (PD) after chemotherapy (P = 0.010) and high hemoglobin (Hb) level (P = 0.006). The prognostic index significantly divided patients into two subgroups of high and low-risk of symptomatic brain metastasis (P < 0.001). PCI significantly improved BMFS in high-risk patients (P = 0.002, 1-year rate 95.5% vs. 61.8%), but not in low-risk patients (P = 0.522, 1-year rate 100.0% vs. 91.9%). However, PCI did not improve OS in patients at high risk for symptomatic brain metastasis (P = 0.801, 1-year rate 45.0% vs. 50.0%). Four prognostic factors are associated with a high risk of symptomatic brain metastasis in ED-SCLC: the presence of extrathoracic metastases, hypermetabolism of BM or spleen from FDG PET parameters, PD after chemotherapy and high Hb level. PCI was beneficial for patients at high risk of symptomatic brain metastasis in terms of BMFS, but not OS. Thus, selective use of PCI in ED-SCLC according to the risk stratification by the prognostic factors from FDG PET and clinical parameters may be recommended, after the completion of a further validation study with a prospective manner.

Cranial Irradiation for Patients with Epidermal Growth Factor Receptor (EGFR) Mutant Lung Cancer Who Have Brain Metastases in the Era of a New Generation of EGFR Inhibitors.

Immediate whole brain radiation (WBRT) has been the standard for patients with lung cancer with brain metastases. The study aims to evaluate the effect of immediate cranial irradiation in patients with epidermal growth factor receptor (EGFR) mutant lung cancer in the era of a new generation of EGFR inhibitors. Medical records of 198 patients with EGFR mutant non-small cell lung cancer and brain metastases at initial metastatic diagnosis were reviewed. Patients were categorized into four groups: immediate WBRT, immediate cranial stereotactic radiosurgery (SRS), delayed radiation upon progression of cranial lesions (DRT), and never cranial irradiation (NRT). Overall survival (OS) and progression-free survival related to EGFR inhibitors were analyzed. The SRS group had the fewest brain metastases and fewest extracranial lesions, and the DRT and NRT groups had the smallest brain metastases. Median survival were 18.5, 55.7, 21.1, and 18.2 months for the WBRT, SRS, DRT, and NRT groups, respectively. Patients who had received EGFR T790M inhibitors survived longer (41.1 vs. 19.8 months). In multivariate analysis, the OS of patients in the SRS group was longer than that in the NRT group (adjusted hazard ratio [aHR]: 0.315). Patients who had fewer extracranial lesions and who had received EGFR T790M inhibitor treatments also survived longer (aHR: 0.442 and 0.357, respectively). Immediate stereotactic radiosurgery but not whole brain radiation was associated with longer survival. Because of patient heterogeneity and the introduction of EGFR T790M inhibitors, the timing and modality of cranial irradiation should be determined individually, and cranial irradiation may be omitted for selected patients. Immediate whole brain radiation has been the standard for patients with lung cancer with brain metastases. In this study, it was observed that, for patients with epidermal growth factor receptor (EGFR) mutant advanced lung cancer who had brain metastases, there was no difference in survival between patients who never received cranial irradiation and those who received whole brain radiation immediately. Patients who received immediate stereotactic radiosurgery or who had ever received EGFR T790M inhibitors survived longer. Patients who received immediate stereotactic radiosurgery have fewer brain metastases. These findings suggest that the timing and modality of cranial irradiation should be determined individually, and cranial irradiation may be omitted in selected patients.

Thoracic twice-daily radiotherapy and brain metastasis in patients with small cell lung cancer.

8560 Background: Although thoracic twice-daily radiotherapy (TDRT) is one of standards of care for small cell lung cancer, its impact on brain metastases remains unknown. This study aimed to compare TDRT with once-daily radiotherapy (ODRT) for the brain metastases rate after prophylactic cranial irradiation in patients with small cell lung cancer. Methods: Consecutive patients received TDRT (45Gy/30f)/ODRT(50-66Gy/25-33f), chemotherapy and prophylactic cranial irradiation were retrieved from eight hospitals’ databases between 2003 and 2016. The endpoints included brain metastases, progression-free survival and overall survival. Brain metastases rate was evaluated using competing risk analysis. A 1:1 propensity score matching approach was used to control confounding between these two groups. Confounding covariates included eight demographic variables and eight treatment related covariates. Results: Of the 778 eligible patients with median age of 55-year (IQR, 48-61), 204 (26.2%) were female. At a median follow-up time of 23.6 months (IQR, 14.2- 38.2), 131 (16.8%) experienced brain metastases. The rates in TDRT were significantly higher than ODRT (3-year, 26.0% vs. 16.9%; HR = 1.55, 95%CI 1.06-2.26, P = 0.03). Of the 338 matched patients (169 in ODRT vs. 169 in TDRT), 60 (17.8%) experienced brain metastases with 3-year rate of 14.9% in ODRT vs 26.0% in TDRT (HR = 1.71, 95%CI 1.02-2.88, P = 0.04). Progression-free survival was similar in both the whole cohort and the matched one. Overall survival in ODRT tended to be significantly longer after matching (median, 47.2 months in ODRT vs. 32.8 months in TDRT; HR = 1.41, 95%CI 0.99-2.01, P = 0.06). When jointly evaluated biologically effective dose (BED), start of any therapy to the end of radiotherapy (SER) and TDRT/ODRT in the multivariable analysis, the impact of ODRT/TDRT on overall survival become more significant (HR = 1.69, 95%CI 1.05-2.71, P = 0.03). Conclusions: Patients with small cell lung cancer who were treated with thoracic TDRT appeared to have higher risk of brain metastases than those with ODRT, which strongly supports the need for further prospective randomized clinical trials, especially in China or other parts of Asia.

Association of Twice-Daily Radiotherapy With Subsequent Brain Metastases in Adults With Small Cell Lung Cancer

ImportanceAlthough thoracic twice-daily radiotherapy (TDRT) is one of the standards of care for small cell lung cancer, its association with brain metastases remains unknown.ObjectiveTo investigate the association of TDRT vs once-daily radiotherapy (ODRT) with brain metastases after prophylactic cranial irradiation in patients with small cell lung cancer.Design, Setting, and ParticipantsIn this multicenter cohort study, data on 778 consecutive patients with small cell lung cancer who had undergone thoracic radiotherapy (609 received ODRT and 169 received TDRT), chemotherapy, and prophylactic cranial irradiation were retrieved from the databases of 8 hospitals in China between July 1, 2003, and June 30, 2016. A 1:1 propensity score matching approach was used to control for confounding between the ODRT and TDRT groups. Confounding covariates included 8 demographic variables and 8 treatment-related covariates. Data analysis was conducted from November 1, 2017, to May 31, 2018, and reanalyzed for revision.ExposuresThe ODRT group received 50 to 66 Gy given in 25 to 33 fractions. The TDRT group received 45 Gy given in 30 fractions.Main Outcomes and MeasuresThe primary end point was brain metastases. Secondary end points included progression-free survival and overall survival.ResultsOf the 778 patients (median age, 55 years [interquartile range, 48-61 years]), 204 were women and 574 were men. At a median follow-up of 23.6 months (interquartile range, 14.2-38.2 months), 131 patients (16.8%) experienced brain metastases. The rate of brain metastasis at 3 years in the TDRT group was significantly higher than in the ODRT group (26.0% vs 16.9%; hazard ratio, 1.55; 95% CI, 1.06-2.26; P = .03). Of the 338 matched patients (169 in the ODRT group vs 169 in the TDRT group), 60 (17.8%) experienced brain metastases, with a rate at 3 years of 14.9% in the ODRT group vs 26.0% in the TDRT group (hazard ratio, 1.71; 95% CI, 1.02-2.88; P = .04). Progression-free survival was similar in both the whole cohort and the matched cohort. Median overall survival in the ODRT group tended to be significantly longer than in the TDRT group after matching (47.2 vs 32.8 months; hazard ratio, 1.41; 95% CI, 0.99-2.01; P = .06).Conclusions and RelevanceIn this study, patients with small cell lung cancer who received thoracic TDRT appeared to have a higher risk of brain metastases than those who received ODRT, which supports the need for further prospective randomized clinical trials, especially in China and other parts of Asia.

The retrospective evaluation of prophylactic cranial irradiation in patients treated for limited stage small-cell lung cancer — a single centre study

Introduction. The standard treatment for patients with LD SCLC (limited stage small-cell lung cancer) is combined modality therapy that includes chemotherapy (ChT) with platinum-based regimens and thoracic radiotherapy (RT), followed by prophylactic cranial irradiation (PCI) in patients with a response in the thorax. Objectives. The evaluation of PCI in patients with LD SCLC and the analysis of the effects of certain therapeutic factors on the frequency and occurrence of brain metastases. Materials and methods. Between 2002 and 2015, a total of 271 patients with LD SCLC received chemo-radiotherapy (concurrently in 122 pts — 45% and sequential in 149 pts — 55%). PCI was administered in 167 pts (61.6%) with total dose of 30 Gy given to the whole brain; 86 pts (51.1%) received PCI after completed chemo-radiotherapy and in 81 pts (48.9%) PCI was administered immediately after the end of thoracic irradiation. The following statistical methods were used: Kaplan-Meier method (evaluation of survival rates: overall survival — OS, and brain metastases-free survival — BMFS), log-rank test (for comparison of survival rates), Cox’ proportional hazard model (for multivariate analysis), Pearson chi2 test for independence (for categorized variables comparison) and variance analysis (for continuous variables comparison). All the calculations were performed using Statistica v. 13.3 software (TIBCO Software Inc.) and the significance level for all the statistical methods was p < 0.05. Results. Complete response in thorax was observed in 172 pts (63.5%) and remaining 99 pts (36.5%) developed partial response. During follow-up, 120 pts (44.3%) developed distant metastases from which brain metastases were most frequent (61 cases — 60.8%). The cumulative 5-year incidence of brain metastases amounted to 18.9% (when PCI was administered) and 45.9% (when PCI was omitted) and these differences were significant (p < 0.0001). PCI was an independent prognostic factor for BMFS and for OS. Omitted PCI is related with HR amounted: 6.25 for BMFS and 1.81 for OS. Conclusions. PCI significantly reduces the incidence of brain metastases and delays the development of brain metastases in patients treated for LD SCLC. PCI is a significant independent prognostic factor for brain metastases-free survival and overall survival. The development of brain metastases is the most common type of failure in patients with LD SCLC and 90% of such relapses occurred during the 24 months following the completion of chemo-radiotherapy.

542P - Prophylactic cranial irradiation in patients with extensive-stage small-cell lung cancer (ES-SCLC): An updated tertiary cancer centre experience

542P - Prophylactic cranial irradiation in patients with extensive-stage small-cell lung cancer (ES-SCLC): An updated tertiary cancer centre experience

Clinical efficacy of prophylactic cranial irradiation for patients with surgically resected small cell lung cancer

Objective To evaluate the clinical efficacy of prophylactic cranial irradiation (PCI) in the treatment of surgically resected small cell lung cancer (SCLC). Methods Clinical data of SCLC patients undergoing radical resection surgery in Zhejiang Cancer Hospital from 2003 to 2015 were retrospectively analyzed. According to the treatment modality, all patients were allocated into the PCI and non-PCI groups. A total of 52 patients were finally included, including 19 patients in the PCI group (5 cases of stage Ⅰ, 5 stage Ⅱ and 9 stage Ⅲ) and 33 in the non-PCI group (12 cases of stage Ⅰ, 5 stage Ⅱ and 16 stage Ⅲ). Kaplan-Meier method was utilized for survival analysis. Cox proportional hazards model was adopted to analyze clinical prognosis. Results The median survival time was 32.9 months in the PCI group, and 20.4 months in the non-PCI group. The 2-year overall survival rate was 72% in the PCI group, significantly higher than 38% in the non-PCI group (P=0.023). The median brain metastasis-free survival (BMFS) was 32.5 months in the PCI group, and 17.1 months in the non-PCI group. In the PCI group, the 2-year BMFS rate was 89%, significantly better than 53% in the non-PCI group (P=0.026). Subgroup analysis demonstrated that PCI could confer survival benefit to patients with p-stage Ⅲ(P=0.031) rather than p-stage Ⅰ(P=0.924) and Ⅱ(P=0.094) counterparts. Multivariate analysis revealed that PCI (HR=0.330, P=0.041) was an independent prognostic factor of the overall survival. Conclusions PCI can reduce thr risk of brain metastasis rate and improve the overall survival of patients with surgically resected SCLC. Key words: Carcinoma, small cell lung/surgery; Brain, neoplasms metastasis/prophylactic cranial irradiation; Prognosis

Phase II clinical trial of hippocampal-sparing prophylactic cranial irradiation in patients with small cell lung cancer

Objective To evaluate the dose distribution and clinical efficacy of hippocampal-sparing prophylactic cranial irradiation (HS-PCI) in patients with small cell lung cancer by using helical tomotherapy. Methods Clinical data of 49 patients with small cell lung cancer receiving HS-PCI using helical tomotherapy in Cancer Hospital between 2014 and 2017 were retrospectively analyzed. All patients received brain MRI to exclude the possibility of brain metastasis within 1 month after standard surgery or radio-and chemo-therapy. The prescription dose was 95% PTV, 25 Gy in 10 fractions. The adverse reactions and cognitive functions of patients were observed before, 6 months and 1 year after treatment, and the dose distribution in the hippocampal gyrus, survival rate and brain metastasis rate were analyzed. Results The median follow-up time was 16 months. The average dose in the hippocampal gyrus was 7.23 Gy and 8.46 Gy in the reduction region, which was reduced by 71.88% and 66.16% compared with the prescription dose. The maximum dose in the hippocampal gyrus was 10.66 Gy and 15.43 Gy in the reduction region. Among 49 patients, 8 died, the 1-year survival rate was 85.1% and the 2-year survival rate was 70.3%.Nine patients (18.3%) had brain metastases, and one of them with extensive multiple brain metastases (n=13) presented with metastasis adjacent to the hippocampal gyrus. The main adverse reactions included mild headache, dizziness and brain edema, whereas no ≥ grade 2 adverse reactions occurred. At 6 months after treatment, the HVLT-R score was significantly decreased, and declined by 6.78% at 12 months after treatment. The HVLT-R scores did not significantly differ in patients without brain metastasis before and 12 months after treatment (P>0.05). Conclusion Application of HS-PCI using helical tomotherapy meets the dose requirement, effectively protects the cognitive function and yields slight adverse reactions. Key words: Cancer, small cell lung, limited stage; Prophylactic cranial irradiation; Cognitive function

Prophylactic Cranial Irradiation in Patients With Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

We systematically reviewed the literature for trials addressing the efficacy of prophylactic cranial irradiation (PCI) in patients with non-small-cell lung cancer (NSCLC) treated with a curative intent. Randomized controlled trials (RCT) comparing PCI to no PCI in patients with NSCLC treated with a curative intent were eligible for inclusion. We searched EMBASE, MEDLINE, PubMed, and CENTRAL between 1946 and July 2016. We also received continual search alerts from PubMed through September 2017. Search terms included "non-small-cell lung carcinoma," "cranial irradiation," and "randomized controlled trials." We conducted meta-analyses using random-effects models for relative measures of treatment effect for the incidence of brain metastasis, overall survival (OS), and disease-free survival (DFS). We used Parmar's methodology to derive hazard ratios (HR) when not explicitly stated in RCTs. We narratively synthesized data for the impact of PCI on quality of life (QoL) and neurocognitive function (NCF). We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. Out of 3,548 citations captured by the search strategy, we retained 8 papers and 1 abstract, reporting on 6 eligible trials. Patients who received PCI had a significant reduction in the risk of developing brain metastases as compared with patients who did not [relative risk (RR) = 0.37; 95% confidence interval (CI): 0.26-0.52; moderate quality evidence]. However, there was no OS benefit (HR = 1.08, 95% CI: 0.90-1.31; moderate quality evidence). Sensitivity analysis excluding older studies did not show substantively different findings. DFS was reported in the two most recent trials that included only stage III patients. There was significant improvement in DFS with PCI (HR = 0.67; 95% CI: 0.46-0.98; high quality evidence). Two studies that reported on QoL reported no statistically significant differences. There was no significant difference in NCF decline in the only study that reported on this outcome, except in immediate and delayed recall, as assessed by the Hopkins Verbal Learning Test. There is moderate quality evidence that the use of PCI in patients with NSCLC decreases the risk of brain metastases, but does not provide an OS benefit. However, data limited to stage III patients suggests that PCI improves DFS, with no effect on QoL.

Efficacy of prophylactic cranial irradiation in patients with limited-disease small-cell lung cancer who were confirmed to have no brain metastasis via magnetic resonance imaging after initial chemoradiotherapy.

BackgroundProphylactic cranial irradiation (PCI) is recommended for patients with limited-disease small-cell lung cancer (LD-SCLC) who achieved good response to definitive chemoradiotherapy. However, most clinical studies lacked brain imaging scans before PCI. Our study aimed to investigate whether PCI has a survival benefit in patients who have no brain metastases (BM) confirmed via magnetic resonance imaging (MRI) before PCI.ResultsEighty patients were included in this study. Sixty patients received PCI (PCI group) and 20 patients did not (non-PCI group). OS was not significantly different between the two groups. The median OS time was 4.3 years (95% CI: 2.6 years–8.6 years) in the PCI group and was not reached (NR) (95% CI: 1.9 years–NR) in the non-PCI group (p = 0.542). Moreover, no differences were observed in the 3-year rates of PFS (46.2% and 44.4%, p = 0.720) and cumulative incidence of BM (24.0% vs. 27%, p = 0.404).ConclusionsOur result suggests that PCI may not have a survival benefit in patients with LD-SCLC confirmed to have no BM after initial therapy, even if patients achieve a good response to definitive chemoradiotherapy.Patients and MethodsWe retrospectively evaluated patients with LD-SCLC who were confirmed to have no BM via MRI after initial chemoradiotherapy at the Shizuoka Cancer Center between September 2002 and August 2015. The overall survival (OS), progression-free survival (PFS), and cumulative incidence of BM were estimated using the Kaplan–Meier method between patients who received PCI and those who did not. Propensity score matching was used to balance baseline characteristics.