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Objective:To analyze the prognosis and risk factors for brain metastases (BM) in patients with limited-stage small cell lung cancer (LS-SCLC) after complete resection, aiming to identify those most likely to benefit from prophylactic cranial irradiation (PCI).Methods:Clinical data of 94 patients with LS-SCLC treated in Cangzhou Integrated Traditional Chinese and Western Medicine Hospital from January 2005 to December 2018 who underwent complete resection were retrospectively analyzed, including 31 cases treated with PCI and 63 without PCI. Prognostic factors and risk factors of BM were analyzed by Kaplan-Meier method. The differences between two groups were analyzed by log-rank test. Independent risk factors of overall survival (OS) and BM were assessed by multivariate Cox regression model.Results:The 2-year and 5-year OS rates were 80.6% and 61.3% in the PCI group, and 61.9% and 46.0% in the non-PCI group, respectively ( P=0.001). The 2-year and 5-year brain metastasis-free survival (BMFS) rates were 80.6% and 54.8% in the PCI group, and 57.1% and 42.9% in the non-PCI group, respectively ( P=0.045). The 2-year and 5-year progression-free survival (PFS) rates were 71.0% and 48.4% in the PCI group, and 49.2% and 34.9% in the non-PCI group, respectively ( P=0.016). PCI could improve OS in patients with pII/III stage LS-SCLC ( P=0.039, P=0.013), but the OS benefit in patients with pI stage LS-SCLC was not significant ( P=0.167). BM occurred in 3 patients (9.7%) in the PCI group, which was significantly lower than that in the non-PCI group ( n=17, 27.0%; P=0.044); there was no significant difference in the BM rate of patients with pI and pII stage LS-SCLC between PCI and non-PCI groups ( P=0.285, P=0.468); and the BM rate of patients with pIII stage LS-SCLC in the PCI group was significantly lower than that in the non-PCI group ( P=0.041). Multivariate analysis showed age ≥60 ( HR=2.803, P=0.001), BM ( HR=2.239, P=0.022), no PCI ( HR=0.341, P=0.004) and pathological stage pII/III ( HR=4.963, P=0.002) were the independent high-risk factors affecting OS; and pathological stage pII/III ( HR=11.665, P=0.007) was an independent high-risk factor affecting BM. Conclusions:LS-SCLC patients with pII-III stage have a higher risk of developing BM and poor prognosis after complete resection, and should receive PCI treatment. However, LS-SCLC patients with pI stage may not benefit significantly.
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Objective:To investigate the role of prophylactic cranial irradiation (PCI) in non-small cell lung cancer (NSCLC) by meta-analysis.Methods:Studies published from January 1, 1980 to August 30, 2021 were searched systematically in PubMed, Embase, Cochrane Systematic Review database and China National Knowledge Infrastructure Database. The searching keywords included "non-small cell lung cancer", "randomized controlled trial", "prophylactic cranial irradiation" and "clinical trial". The data extracted from the above studies were analyzed using Review Manager 5.3 and Stata 12.0 software. Outcomes included the development of brain metastases (BM), overall survival (OS), disease-free survival (DFS), toxicity, and quality of life (QoL).Results:Ten trials, including 2005 NSCLC patients, met the inclusion criteria. Patients who underwent PCI had a significantly lower risk of BM than those who did not ( OR=0.29, 95% CI: 0.22-0.40, P<0.001). Compared with non-PCI group, DFS in PCI group was significantly increased ( HR=0.75, 95% CI: 0.63-0.89, P=0.001). However, there was no significant difference in OS ( OR=0.90, 95% CI: 0.69-1.18, P=0.45). In addition, the incidence of fatigue was significantly increased in the PCI group ( OR=2.64, 95% CI: 1.58-4.40, P<0.001). There was no significant difference in cognitive impairment between the PCI and non-PCI groups ( OR=3.60, 95% CI: 0.97-13.32, P=0.06). Conclusions:PCI is the standard treatment for NSCLC. Compared with non-PCI, PCI significantly reduces the incidence of BM and prolongs the DFS of NSCLC patients. The effect of PCI-related toxicity on the QoL and long-term OS needs further study.
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Objective:To investigate the predictive value of enhanced CT-based radiomics for brain metastasis (BM) and selective use of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC).Methods:Clinical data of 97 patients diagnosed with LS-SCLC confirmed by pathological and imaging examination in Shanxi Provincial Cancer Hospital from January 2012 to December 2018 were retrospectively analyzed. The least absolute shrinkage and selection operator (LASSO) Cox and Spearman correlation tests were used to select the radiomics features significantly associated with the incidence of BM and calculate the radiomics score. The calibration curve, the area under the receiver operating characteristic (ROC) curve (AUC), 5-fold cross-validation, decision curve analysis (DCA), and integrated Brier score (IBS) were employed to evaluate the predictive power and clinical benefits of the radiomics score. Kaplan-Meier method and log-rank test were adopted to draw survival curves and assess differences between two groups.Results:A total of 1272 radiomics features were extracted from enhanced CT. After the LASSO Cox regression and Spearman correlation tests, 8 radiomics features associated with the incidence of BM were used to calculate the radiomics score. The AUCs of radiomics scores to predict 1-year and 2-year BM were 0.845 (95% CI=0.746-0.943) and 0.878 (95% CI=0.774-0.983), respectively. The 5-fold cross validation, calibration curve, DCA and IBS also demonstrated that the radiomics model yielded good predictive performance and net clinical benefit. Patients were divided into the high-risk and low-risk cohorts based on the radiomics score. For patients at high risk, the 1-year and 2-year cumulative incidence rates of BM were 0% and 18.2% in the PCI group, and 61.8% and 75.4% in the non-PCI group, respectively ( P<0.001). In the PCI group, the 1-year and 2-year overall survival rates were 92.9% and 78.6%, and 85.3% and 36.8% in the non-PCI group, respectively ( P=0.023). For patients at low risk, the 1-year and 2-year cumulative incidence rates of BM were 0% and 0% in the PCI group, and 10.0% and 20.2% in the non-PCI group, respectively ( P=0.062). In the PCI group, the 1-year and 2-year overall survival rates were 100% and 77.0%, and 96.7% and 79.3% in the non-PCI group, respectively ( P=0.670). Conclusion:The radiomics model based on enhanced CT images yields excellent performance for predicting BM and individualized PCI.
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Small cell lung cancer (SCLC) is highly malignant, aggressive and prone to brain metastasis. Several guidelines recommend prophylactic cranial irradiation (PCI) as the standard treatment for SCLC patients who have achieved complete remission after initial systemic treatment. However, in the modern era, magnetic resonance imaging (MRI) has been commonly applied in the diagnosis of brain metastasis, while radiotherapy combined with immunotherapy and molecular targeted therapy are widely adopted in the treatment of lung cancer. The value of PCI in SCLC has been questioned and challenged. In addition, the application of hippocampal avoidance and drugs to reduce the damage of neurocognitive function after PCI has also become a research hotspot. In this article, the research progress on PCI was reviewed with the latest literature, aiming to provide reference for selecting the most suitable individualized treatment for patients receiving PCI.
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The incidence of brain metastases in patients with non-small cell lung cancer (NSCLC) has increased as a result of improved local control rate and survival rate. Prophylactic cranial irradiation (PCI) has been proven to reduce the incidence of brain metastases and improve survival rate in patients with NSCLC. However, the value of PCI for NSCLC is still controversial. This paper reviews the progress of the efficacy and adverse reactions after PCI treatment for patients with NSCLC.
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Small cell lung cancer (SCLC) has the biological characteristics of high recurrence and metastasis. The brain is the common site of SCLC extrapulmonary metastasis. Prophylactic cranial irradiation (PCI) can effectively reduce the incidence of brain metastasis and prolong the overall survival of patients with limited SCLC. Nevertheless, nearly one third of patients develop brain metastases after PCI. This article reviews the risk factors of brain metastasis after PCI, aiming to determine which subgroup of patients with limited SCLC can benefit from PCI and provide reference for the clinical application of PCI.
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Objective:To evaluate the risk and prognostic factors of brain metastasis (BM) after prophylactic cranial irradiation (PCI) in limited stage small cell lung cancer (LS-SCLC) patients with complete and partial remission (CR/PR) after radiochemotherapy.Methods:Baseline data of 550 patients with LS-SCLC who obtained CR/PR after chemoradiotherapy and received PCI in Zhejiang Cancer Hospital between 2002 and 2017 were collected. The risk of BM and clinical prognosis were retrospectively analyzed. The survival analysis was performed by Kaplan-Meier method. Multivariate prognostic analysis was conducted byCox models.Results:The overall BM rate after PCI was 15.6%(86/550), with 9%(4/43), 13%(7/52), and 16.5%(75/455) for stage Ⅰ, Ⅱ and Ⅲ patients, respectively. The median overall survival (OS) for the entire cohort was 27.9 months, and the 5-year OS rate was 31.0%. The OS was 24.9 and 30.2 months for patients with or without BM, and the 5-year OS rates were 8.9% and 36.1%( P<0.001). BM was an independent factor of OS ( P<0.001). Clinical staging remained the influencing factor of OS and BM-free survival ( P<0.001, P=0.027). Having tumors of ≥5 cm in diameter significantly increased the risk of BM ( P=0.034) rather than the OS ( P=0.182). The median OS of patients aged<60 years was significantly longer than those aged ≥60 years (34.9 months vs. 24.6 months, P=0.001). The median OS of patients irradiated with 2 times/d was 29.8 months, significantly longer than 24.5 months of those irradiated with 1 time/d ( P=0.013). Age, sex, radiotherapy fraction and efficacy of radiochemotherapy (CR/PR) were not associated with the incidence rate of BM (all P>0.05). Conclusions:SCLC patients with tumors of ≥5 cm in diameter may have a higher risk of developing BM after PCI. Patients aged<60 years achieve better OS compared with their counterparts aged ≥60 years.
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Brain metastasis of non-small cell lung cancer (NSCLC) is a common treatment failure mode, and the median survival time of NSCLC patients with brain metastasis is only 1 mon-2 mon. Prophylactic cranial irradiation (PCI) can delay the occurrence of brain metastasis, but the survival benefits of NSCLC patients are still controversial. It is particularly important to identify the patients who are most likely to benefit from PCI. This article reviews the high risk factors of brain metastasis in NSCLC. .
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Humans , Brain Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/pathology , Cranial Irradiation , Lung Neoplasms/pathology , Risk FactorsABSTRACT
Small cell lung cancer (SCLC), as a pathological type with high malignancy, presents a high risk of early brain metastasis. Prophylactic cranial irradiation (PCI) can reduce the risk of brain metastasis in patients with SCLC, however, the incidence of brain structural and functional damage caused by PCI is high, and their clinical symptoms are not typical. The existing treatment methods can relieve some clinical symptoms, but can not effectively reverse the process of brain injury, which reduces the survival benefit of patients. In-depth understanding the mechanisms of PCI neurotoxicity and exploring effective strategies for ptevention and treatment are of great value in improving prognosis of SCLC.
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Extensive-stage small cell lung cancer (ES-SCLC) accounts for approximately two-thirds of all SCLCs. Chemotherapy is still the main treatment, supplemented with radiotherapy and other comprehensive treatments. Although sensitive to chemotherapy and radiotherapy, almost all ES-SCLCs are vulnerable to treatment resistance and have high recurrence rates. Therefore, novel therapies are needed to improve treatment efficacy. The recent advances in radiotherapy for ES-SCLC include prophylactic cranial irradiation (PCI) and thoracic radiotherapy (TRT). Moreover, immunotherapy has shown good antitumor activity, and immune-checkpoint inhibi-tors may become an important breakthrough in SCLC treatment. This article briefly reviewed the clinical research on radiotherapy and immunotherapy for advanced-stage SCLC.
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PURPOSE: Prophylactic cranial irradiation (PCI) is a standard treatment for limited-stage small cell lung cancer (LS-SCLC) showing a response to initial treatment, but many patients do not receive PCI due to comorbidities or refusal. This study aims to define the patient group for whom PCI can be omitted with minimal risk. MATERIALS AND METHODS: Patients with LS-SCLC who underwent radiotherapy with curative aim at our institution between January 2004 and December 2015 were retrospectively reviewed. Patients who did not receive PCI were evaluated for brain metastasis-free survival (BMFS), progression-free survival (PFS), overall survival (OS), and prognostic factors for survival, and treatment outcomes were compared with a patient cohort who received PCI. RESULTS: A total of 350 patients achieved a response following thoracic radiotherapy, and 190 of these patients did not receive PCI. Stage I–II and a complete response (CR) to initial therapy were good prognostic factors for BMFS and OS on univariate analysis. Patients with both stage I–II and a CR who declined PCI showed comparable 2-year BMFS to those who received PCI (92% vs. 89%). In patients who achieved CR, PCI did not significantly improve OS or PFS. CONCLUSION: There should be less concern about omitting PCI in patients with comorbidities if they have stage I–II or a CR, with brain metastasis control being comparable to those patients who receive PCI.
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Humans , Brain , Cohort Studies , Comorbidity , Cranial Irradiation , Disease-Free Survival , Neoplasm Metastasis , Radiotherapy , Retrospective Studies , Small Cell Lung CarcinomaABSTRACT
Small cell lung cancer (SCLC) is a kind of highly invasive malignant neoplasm, which is characterized by short survival and high-risk cranial metastasis. Therefore, application of prophylactic cranial irradiation(PCI) is of clinical significance to reduce the incidence of brain metastasis and prolong the patients' survival on the basis of radio-and chemo-therapy. Nevertheless, the indications and clinical value of PCI have been controversial in recent years. These controversies mainly include the significance of PCI for extensive-stage SCLC,the indications of PCI for limited-stage SCLC and the alternative approaches for PCI. In this paper, the controversies and progresses of PCI applied in clinical practice are investigated and reviewed.
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The incidence of small cell lung cancer ( SCLC) is relatively low, which approximately accounts for 13％-20％ of all types of lung cancers. SCLC is characterized by high-degree malignancy and high metastasis and recurrence rates within a short period of time. Upon the confirmed diagnosis, limited-stage SCLC approximately accounted for 30％ of SCLC and merely 5％ of these patients were eligible for surgery. Over half of the patients who obtained complete remission after chemoradiotherapy presented with brain metastases. The postoperative incidence of brain metastases in patients with stageⅠ,ⅡandⅢSCLC was 6％-14％,13％-38％ and 11％-36％, respectively. Prophylactic cranial irradiation ( PCI) can enhance the overall survival rate of patients with complete remission after chemoradiotherapy and reduce the incidence of brain metastasis, which is a pivotal part of comprehensive treatment of limited-stage SCLC. However, the application of PCI remains controversial in clinical practice and the clinical efficacy for patients with surgically resected SCLC significantly varies. In this article, literature review was conducted and the research progress in this field was summarized.
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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.
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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.
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Objective To observe the impact of the prophylactic cranial irradiation (PCI) and its different interventional times on the prognosis of patients with limited-stage small cell lung cancer (LSCLC) who received comprehensive therapy of complete response (CR). Methods A total of 184 LSCLC patients who received radiotherapy and chemotherapy based on comprehensive treatment were retrospectively analyzed. Patients were divided into two groups based on with or without PCI intervention. There were 50 patients (27.2%) in the PCI group and 134 patients (72.8%) in the non PCI group. The PCI group was subdivided into two groups, PCI1 group (n=20) and PCI2 group (n=30), according to whether patients completed 4 cycles of chemotherapy. Chemotherapy regimen, irradiation method and dose were identical for two groups. Results The brain metastasis rates were 14.0%and 30.6%for PCI group and non PCI group. There was significant difference in brain metastasis rate between the two groups (P<0.05). The median survival times were 25 months (95%CI:21.487-28.513) and 17 months (95%CI:15.175-18.825) for PCI group and non PCI group (P<0.05). The 1, 2 and 3-year survival rates were 54%, 36%, 15% and 37%, 18%, 13% for the two groups. There were no significant differences in brain metastasis rates between PCI1 group and PCI2 group (10.0% and 16.7%). There was no significant difference in median survival time between the two subgroups. Conclusion PCI can reduce the incidence of SCLC brain metastases, and prolong the overall survival time. However, different intervention times of PCI have no significant influence on the prognosis of LSCLC.
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Small cell lung cancer ( SCLC ) is one common type of lung cancer in China. No remarkable progress has been made in systemic therapy for SCLC since the 90’ s. However, there are some advances in radiotherapy ( RT) for SCLC, which make it possible to improve treatment outcomes of SCLC. Those advances are mainly made in thoracic RT and prophylactic cranial irradiation for extensive?stage SCLC, radiation dose and technology of thoracic RT for limited?stage SCLC, and significance of prophylactic cranial irradiation for early?stage SCLC. The paper reviews the research advances in the East and West to provide some help and references for readers.
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At present,conventional whole brain radiotherapy is the standard treatment for brain metastases and prophylactic cranial irradiation,and it can improve patients' clinical symptoms and survival.However,whole brain radiotherapy may induce cognitive function impairment and affect patients' long-term quality of life.The newest radiotherapy technology can protect the hippocampal gyrus during whole brain radiotherapy and then protect cognitive function and improve quality of life.This article reviews the methods and clinical value of hippocampal gyrus protection in whole brain radiotherapy,as well as related advances.
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Objective To evaluate the high?risk factors for brain metastases after prophylactic cranial irradiation ( PCI), and to provide a basis for personalized treatment. Methods A retrospective analysis was performed in 188 patients with limited?stage small?cell lung cancer who received PCI in our hospital from 2005 to 2010. The Kaplan?Meier method was used to calculate the cumulative rate of brain metastases. The log?rank test and the Cox model were used for the univariate and multivariate analyses of the potential factors for the cumulative incidence of brain metastases, respectively. Results In the 188 patients, 31 ( 16?5%) had brain metastases. The 1?, 2?, and 3?year cumulative incidence rates of brain metastases were 4%, 15%, and 20%, respectively. The univariate analysis showed that staged Ⅲ disease before treatment, elevated levels of tumor markers, incomplete remission after chemoradiotherapy, and local?regional relapse were risk factors for high incidence of brain metastases ( P= 0?044, 0?037, 0?005, 0?007) . The multivariate analysis revealed that incomplete remission after chemoradiotherapy and local?regional relapse after chemoradiotherapy were risk factors for high incidence of brain metastases after PCI ( P= 0?003, 0?040 ) . Conclusions Patients with incomplete remission or local?regional relapse after chemoradiotherapy have high incidence of brain metastases after PCI. For those patients, a frequent follow?up of the central nervous system plus salvage cranial irradiation might provide an alternative to PCI.
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Objective To investigate the dosimetric characteristics of hippocampal?avoidance prophylactic cranial irradiation ( HA?PCI ) in fixed?field intensity?modulated radiotherapy ( IMRT ) and volumetric modulated arc therapy ( VMAT) and the feasibility and risks of hippocampal avoidance. Methods Prophylactic cranial irradiation (PCI) was performed for 16 patients with localized small cell lung cancer ( SCLC) who were treated in our hospital from January to August, 2014, and achieved complete response ( CR) after chemoradiotherapy, with a prescribed dose of 25 Gy in 10 fractions. CT localization image was fused with brain MRI image to contour the hippocampus on the fused image, and the boundary of the hippocampus was extended 5 mm outward to form the area for reduced dose. IMRT and VMAT plans with hippocampal avoidance were developed separately, and the dose distribution in the whole brain, the hippocampus, and the 5?mm area outside the hippocampus was evaluated for these two plans. Independent?samples t test was applied to evaluate the difference between the two groups. Results The mean hippocampal volume in the 16 patients was 2. 76 cm3 ( range 2. 56 ?3. 01 cm3 ) . The mean radiation dose ( Dmean ) in the hippocampus during IMRT and VMAT was 9. 04± 0. 20 Gy and 10. 32± 0. 28 Gy, respectively, reduced by 66. 0% and 61. 2%, respectively, compared with the prescribed dose ( P=0. 55);Dmean in the area for reduced dose during IMRT and VMAT was 13. 57± 0. 90 Gy and 14. 86± 0. 60 Gy, respectively, reduced by 49. 0% and 44. 1%, respectively, compared with the prescribed dose (P=0. 88). Conclusions HA?PCI in IMRT and VMAT meets the clinical requirements, and can reduce the dose in the hippocampus while ensuring the whole?brain radiation dose, and therefore can be applied in PCI and provide a technical support to protect the patient’ s neurocognitive function.