Prophylactic Cranial Irradiation In Small-cell Lung Cancer Research Articles

Current dilemma and future directions over prophylactic cranial irradiation in SCLC: a systematic review in MRI and immunotherapy era

Small cell lung cancer (SCLC) is the most malignant pathological type of lung cancer with the highest mortality, and the incidence of brain metastasis (BM) is in high frequency. So far, prophylactic cranial irradiation (PCI) has been suggested as an effective treatment for preventing brain metastasis of SCLC. PCI has long been applied to limited-stage SCLC (LS-SCLC) patients who have achieved complete remission after radiotherapy and chemotherapy as a standard treatment. However, the neurocognitive decline is a major concern surrounding PCI. New therapeutic approaches targeting PCI-induced neurotoxicity, including hippocampal protection or memantine, have been increasingly incorporated into the therapeutic interventions of PCI. Helical tomotherapy, RapidArc, and Volumetric-modulated arc therapy (VMAT) with a head-tilting baseplate are recommended for hippocampal protection. Besides, in the MRI and immunotherapy era, the significance of PCI in SCLC patients is controversial. SCLC patients with PCI should be recruited in clinical trials since this is the only way to improve the existing standard of care. This review summarizes the current therapeutic strategy and dilemma over PCI for SCLC, providing a theoretical basis for clinical decision-making and suggestions for PCI practice in clinical.

Prophylactic cranial irradiation in SCLC.

Prophylactic cranial irradiation (PCI) has well established place in therapy for patients with limited-disease small cell lung cancer who responded to treatment. The data from randomized trials document that PCI reduces brain metastases rate from approximately 60% to 30%, and increases 3-year overall survival by approximately 5%. Currently, the dose of 25 Gy in 10 fractions is considered as standard. In attempt to reduce neuropsychological sequelae attributable to PCI hippocampal sparing techniques are employed. The existing studies suggest the benefit of hippocampal sparing in limiting memory and higher neurocognitive function losses, but with a risk of failures in the spared region. Ongoing studies will further validate the role of hippocampal sparing, both in terms of toxicity reduction and metastases prevention. PCI for patients who have undergone resection for stage I small cell lung cancer (SCLC) is not recommended, PCI may be, however, associated with a favourable outcome in SCLC patients who have undergone complete surgery in stages II−III. The role of PCI in extensive-disease (ED) SCLC has been evolving. Most recent evidence indicate that PCI is controversial in ED patients with response to initial chemotherapy and absence of brain metastases confirmed by contrast-enhanced MRI. The patients who do not receive PCI, must, however, receive periodic MRI examination during follow-up, i.e., remain under active surveillance with access to radiotherapy at brain relapse. The assessment of safety and effectiveness of hippocampal-sparing PCI, with or without drug neuroprotection in consideration of diverse combinations of radiotherapy, chemotherapy and immunotherapy create a background for future directions of research.

Clinical value of carcinoembryonic antigen for predicting the incidence of brain metastases and survival in small cell lung cancer patients treated with prophylactic cranial irradiation.

BackgroundAlthough the role of prophylactic cranial irradiation (PCI) in the treatment of small cell lung cancer (SCLC) has been confirmed, the occurrence of brain metastases (BM) in patients remains a major problem. We designed this study to evaluate the clinical value of carcinoembryonic antigen (CEA) for predicting the incidence of BM and survival in SCLC patients who received PCI.Materials and methodsThe records of 128 consecutive SCLC patients, who underwent PCI in our institute between 2005 and 2015, were analyzed. The collected data included clinicopathological features and the levels of CEA, neuron-specific enolase (NSE), cytokeratin 19 fragments (CYFRA21-1), and albumin. Kaplan–Meier and Cox regression analyses were used to determine the factors that affect BM and survival in SCLC patients after PCI.ResultsIn total, 128 patients were identified, with a median (range) age of 62 (30–83) years. Thirty-two patients developed BM at some time during follow-up. The median levels of CEA, NSE, CYFRA21-1, and albumin were 7.6 ng/mL, 44 ng/mL, 4.6 ng/mL, and 42.1 g/L, respectively. In the multivariate analysis, CEA level (HR: 2.479, 95% CI: 1.101–5.581; P=0.028), advanced clinical stage (HR: 2.929, 95% CI: 1.338–6.413; P=0.007), and NSE level (HR: 3.021, 95% CI: 1.226–7.442; P=0.016) were significantly correlated with BM. CEA (HR: 1.903, 95% CI: 1.133–3.195; P=0.015) and advanced clinical stage (HR: 2.002, 95% CI: 1.227–3.267; P=0.005) were independently associated with worse overall survival in SCLC patients.ConclusionCEA is an independent predictive factor for the incidence of BM after PCI in SCLC and can be used as a predictor of BM in SCLC. In addition, a high level of CEA indicates a poor prognosis in SCLC patients after PCI. Prospective randomized clinical studies are required to confirm these findings.

Longitudinal Brain Changes Associated with Prophylactic Cranial Irradiation in Lung Cancer

IntroductionThe toxic effects of prophylactic cranial irradiation (PCI) and platinum-based chemotherapy on cognition in the lung cancer population have not yet been well established. In the present study we examined the longitudinal neuropsychological and brain structural changes observed in patients with lung cancer who were undergoing these treatments. MethodsTwenty-two patients with small cell lung cancer (SCLC) who underwent platinum-based chemotherapy and PCI were compared with two control groups: an age- and education-matched group of healthy controls (n = 21) and a group of patients with non-SCLC (NSCLC, n = 13) who underwent platinum-based chemotherapy. All groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging: T1-weighted and diffusion tensor imaging at baseline (before PCI for SCLC and chemotherapy for NSCLC) and at 3 months after treatment. T1 voxel-based morphometry and tract-based spatial statistics were used to analyze microstructural changes in gray matter (GM) and white matter (WM). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire—Core Questionnaire was also completed. ResultsPatients with SCLC exhibited cognitive deterioration in verbal fluency over time. Structural magnetic resonance imaging showed decreases in GM at 3 months in the right subcortical regions, bilateral insular cortex, and superior temporal gyrus in patients with SCLC compared with both control groups. Additionally, patients with SCLC showed decreases in GM over time in the aforementioned regions plus in the right parahippocampal gyrus and hippocampus, together with changes in the WM microstructure of the entire corpus callosum. These changes had a limited impact on responses to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire—Core Questionnaire, however. Patients with NSCLC showed no cognitive or brain structural differences after chemotherapy. ConclusionsThis longitudinal study documents moderate neuropsychological deficits together with notable brain-specific structural changes (in GM and WM) in patients with SCLC after chemotherapy and PCI, suggesting that chemotherapy and especially PCI are associated with the development of cognitive and structural brain toxic effects.

P2-001 - The Treatment Options of Recurred Brain Metastasis after Prophylactic Cranial Irradiation in Patients with Small-Cell Lung Cancer

ABSTRACT Background Even after prophylactic cranial irradiation (PCI), many small-cell lung cancer (SCLC) patients succumb to brain metastasis. Brain metastasis after PCI is an unsolved issue in SCLC in terms of its dismal prognosis and the limitation of further treatment options. Regarding the treatment option, it is not determined whether re-whole brain radiotherapy (re-WBRT) is safe or gamma-knife surgery (GKS) has its role in SCLC. We investigated which treatment option could be recommended as the up-front therapy to improve survival for SCLC patients with brain metastasis who were previously treated with PCI. Methods The medical records were reviewed for SCLC patients who experienced brain metastases after receiving PCI from 2000 to 2010. We compared overall survival according to the modality of up-front therapy. Overall survival was determined as time from brain metastasis to death due to any cause. Results In total, 245 patients had received PCI in a state of limited disease (n = 204) or extensive disease status (n = 41). Among them, 47 (19.2%) experienced brain metastases: 16.7% (34/204) in LD and 31.7% (13/41) in ED. At the time when brain metastasis developed, extracrainal disease was also on progressing state in 19 patients (40.4%). The modality of up-front therapy for brain metastasis was as follows: 17 (36.1%) got GKS, 14(29.8%) re-WBRT, 7 (14.9%) up-front chemotherapy without local therapy, and 9 (19.1%) did not receive any further treatment. The median overall survival after brain metastasis was 4.9 months. Among 31 patients who received GKS or re-WBRT, 10 patients received at least one subsequent chemotherapy in their lifetime after GKS (6/17, 35.3%) or re-WBRT (4/14, 28.6%). The median survival of GKS, re-WBRT and chemotherapy was 14.3, 3.9 and 6.0 months (P = 0.24), which showed the tendency favoring for up-front GKS. Although it failed to meet statistical significance. Conclusions The up-front GKS showed longer survival in patients who experienced brain metastasis after PCI for SCLC, compared with re-WBRT or chemotherapy only. However, the number of participants was too small to get confirmatory results requiring a prospective therapy to demonstrate the role of GKS in this setting.

Central pontine myelinolysis presented after prophylactic cranial irradiation in small cell lung cancer

Prophylactic cranial irradiation (PCI) should now be considered as a part of the standard treatment of patients with small cell lung cancer (SCLC) in complete remission. The PCI has been offered in SCLC to reduce the incidence of brain metastasis and increase survival. The complications of PCI were reported brain necrosis, seizure or dementia. The complications were more frequent when chemotherapy was given at the time of cranial irradiation, or large radiation fraction size was employed. It is established that the pathophysiological reaction to irradiation in the normal brain tissue is necrosis, demyelinization, and diffuse changes due to wall thickening of the vascular structures. However, central pontine myelinolysis (CPM) of low dose irradiation like PCI is very rare. We report a patient with the classical syndrome of CPM following PCI for SCLC. The diagnosis was supported by typical features on magnetic resonance imaging.

Models Support Prophylactic Cranial Irradiation

Models Support Prophylactic Cranial Irradiation

Should current management of small cell lung cancer include prophylactic cranial irradiation?

The literature on the use of prophylactic cranial irradiation (PCI) in the management of small cell lung cancer (SCLC) is reviewed, focusing on the ten randomized trials published until 1991. Eight out of ten randomized trials have shown some reduction in the frequency of CNS relapse in patients who have had PCI, whereas none have shown any survival benefit associated with PCI. Current data indicate that survival is exclusively dependent on an effect of PCI in only a very limited subgroup of patients (10% of complete responders). It is generally agreed that PCI is not justified in patients who are not in CR, but even in this situation it is unknown whether PCI is necessary. The current therapeutic potentials seem to leave comparable fractions of patients without sufficient palliation of their symptomatic brain metastases regardless of whether or not PCI is given. Data from sufficiently large randomized trials have to be matured and analyzed, before the role of PCI in SCLC can be defined.