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.
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SUBMITTER: Ge W
PROVIDER: S-EPMC6107943 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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
Project description:BackgroundProphylactic cranial irradiation (PCI) offers extensive-stage small-cell lung cancer (ES-SCLC) patients a lower chance of brain metastasis and slightly longer survival but is associated with a short-term decline in quality of life due to side-effects. This tradeoff between survival and quality of life makes PCI suitable for shared decision-making (SDM), where patients and clinicians make treatment decisions together based on clinical evidence and patient preferences. Despite recent clinical practice guidelines recommending SDM for PCI in ES-SCLC, as well as the heavy disease burden, research into SDM for lung cancer has been scarce. This exploratory study presents patients' experiences of the SDM process and decisional conflict for PCI.MethodsRadiation oncologists (n=7) trained in SDM applied it in making the PCI decision with ES-SCLC patients (n=25). We measured patients' preferred level of participation (Control Preferences Scale), the level of SDM according to both groups (SDM-Q-9 and SDM-Q-Doc), and patients' decisional conflict [decisional conflict scale (DCS)].ResultsSeventy-nine percent of patients preferred a collaborative role in decision-making, and median SDM scores given by patients and clinicians were 80 (IQR: 75.6-91.1) and 85.2 (IQR: 78.7-88.9) respectively, indicating satisfaction with the process. However, patients experienced considerable decisional conflict. Over 50% lacked clarity about which choice was suitable for them and were unsure what to choose. Sixty-four percent felt they did not know enough about the harms and benefits of PCI, and 60% felt unable to judge the importance of the harms/benefits in their life.ConclusionsES-SCLC patients prefer to be involved in their treatment choice for PCI but a substantial portion experiences decisional conflict. Better information provision and values clarification may support patients in making a choice that reflects their preferences.
| S-EPMC8350106 | biostudies-literature
Project description:Background and purposeThe 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 methodsPatients 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.ResultsOne 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.ConclusionUnder active brain MRI surveillance, PCI could be beneficial for patients with ES-SCLC who show good responses after first-line chemotherapy.
| S-EPMC7508717 | biostudies-literature
Project description:BackgroundThe recommendation of PCI for limited-stage small cell lung cancer (LS-SCLC) is primarily based on evidence from the pre-magnetic resonance imaging (MRI) era. However, as MRI accuracy improves and stereotactic radiosurgery advances, the role of PCI for LS-SCLC has become uncertain. This study aims to compare the contemporary survival outcomes of patients with LS-SCLC treated with PCI versus active surveillance.MethodsWe conducted a retrospective cohort study in which 1068 patients with LS-SCLC who achieved a good response to first-line chemoradiotherapy were consecutively enrolled from 5 tertiary medical centres between June 2009 and June 2019. Of these patients, 440 received PCI, while 628 received surveillance without PCI. Propensity score matching with a 1:1 ratio was performed to balance the baseline characteristics of the two cohorts. The endpoints were overall survival (OS) and the incidence of brain metastasis (BM).ResultsIn total, 648 patients were matched. The baseline characteristics were generally well balanced. At a median follow-up of 64.5 months (range 2-190), patients who underwent PCI had a significantly lower risk for BM than those who underwent surveillance. The 3-year cumulative incidence rate of BM was 28.2% (95% CI 22.5-33.8%) in the PCI cohort and 38.5% (32.6-44.5%) in the surveillance cohort (Gray's p = 0.002). However, the lower incidence of BM in the PCI cohort did not translate into a significant extension of OS. The median OS was 35.8 months (95% CI 27.6-44.0 months) in the PCI cohort versus 32 months (26.4-37.6 months) in the surveillance cohort (HR 0.90, 95% CI 0.74-1.10, p = 0.29). Multivariable analysis showed that disease stage, chemoradiotherapy sequence, and response to chemoradiotherapy were independent prognostic factors for BM or OS.ConclusionsOverall, PCI reduces the risk for BM but does not substantially prolong OS compared with active surveillance. A phase 3, prospective clinical trial (NCT04829708) we initiated is currently underway, which is expected to corroborate our results.
| S-EPMC9526908 | biostudies-literature
Project description:BackgroundProphylactic cranial irradiation (PCI) for limited-stage small-cell lung cancer (LS-SCLC) patients has become more controversial. Since the publication of the systematic review by Aupérin et al. in 1999, no randomized controlled trials regarding PCI in LS-SCLC have been completed. The aim of this study was to systematically review and meta-analyze the effect of PCI on overall survival (OS) in patients with LS-SCLC.MethodsA systematic search was conducted in the databases of MEDLINE (PubMed), Embase and the Cochrane library. Only studies that reported an adjusted hazard ratio (aHR), indicating the effect of PCI versus no PCI on OS (adjusted for confounders) in patients with LS-SCLC were included for critical appraisal and meta-analysis. A pooled aHR estimate was calculated using a random-effects model.ResultsPooling of 28 retrospective studies including a total of 18,575 patients demonstrated a significant beneficial effect of PCI versus no PCI on OS with a pooled aHR of 0.62 (95% CI: 0.57-0.69). Substantial heterogeneity of reported aHRs among studies was observed (I2 = 65.9%). Subgroup analyses revealed that this heterogeneity could partly be explained by study sample size. The pooled aHR among 7 versus 21 studies with a sample size of > 300 versus ≤ 300 patients was 0.79 (95% CI: 0.64-0.97) versus 0.56 (95% CI: 0.46-0.69; p < 0.001), respectively.ConclusionsThis meta-analysis demonstrates a significant beneficial effect of PCI on OS in patients with LS-SCLC. Larger studies reported a milder beneficial effect, possibly due to a decreased risk of model overfitting. Serious risk of selection and confounding bias were of concern due to the lack of prospective trials. These results support the role of PCI in standard clinical practice in patients with LS-SCLC while awaiting results of prospective trials on alternative strategies.
| S-EPMC8881197 | biostudies-literature
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
Project description:We investigated the role of prophylactic cranial irradiation (PCI) in limited-stage small-cell lung cancer (LS-SCLC) according to tumor response in the magnetic resonance imaging (MRI) era. We retrospectively evaluated patients with LS-SCLC without brain metastases (BMs) on MRI who achieved either complete response (CR) or partial response (PR) after initial chemoradiotherapy at our center from 2006 to 2017. This study comprised 116 patients (median age, 58 years; men, 92; women, 24). After initial chemoradiotherapy, 53 patients achieved CR, while 63 patients achieved PR. Eighty-three patients received PCI. Patients who received PCI had better overall survival (OS, 5-year: 52.5% vs. 35.1%; p = 0.012) and progression-free survival (PFS, 5-year: 45.0% vs. 28.2%; p = 0.001) and a lower incidence of BMs (5-year: 18.3% vs. 39.4%; p = 0.010). In the subgroup analysis, PCI improved OS (5-year: 67.8% vs. 46.7%, p = 0.005) and PFS (5-year: 65.2% vs. 35.0%, p = 0.021) and decreased BM risk (5-year: 12.1% vs. 52.4%, p = 0.002) for patients with CR. However, PCI had no benefit (5-year OS: 40.5% vs. 35.6%, p = 0.763; 5-year BMs: 24.6% vs. 31.9%, p = 0.561) for patients with PR. Tumor response remained an important factor for selecting patients for PCI in the MRI era. PCI should be recommended for patients with LS-SCLC who achieve CR after initial thoracic chemoradiotherapy.
| S-EPMC9939136 | biostudies-literature
Project description: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.
| S-EPMC8107729 | biostudies-literature
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
Project description:IntroductionSmall cell lung cancer (SCLC) is a highly aggressive lung cancer variant known for its elevated risk of brain metastases (BM). While earlier meta-analyses supported the use of prophylactic cranial irradiation (PCI) to reduce BM incidence and enhance overall survival, modern MRI capabilities raise questions about PCI's universal benefit for limited-stage SCLC (LS-SCLC) patients. As a response, we have created a predictive model for BM, aiming to identify low-risk individuals who may not require PCI.MethodsA total of 194 LS-SCLC patients without PCI treated between 2009 and 2021 were included. We conducted both univariate and multivariate analyses to pinpoint the factors associated with the development of BM. A nomogram for predicting the 2- and 3-year probabilities of BM was then constructed.ResultsUnivariate and multivariate analyses revealed several significant independent risk factors for the development of BM. These factors include TNM stage, the number of chemotherapy (ChT) cycles, Ki-67 expression level, pretreatment serum lactate dehydrogenase (LDH) levels, and haemoglobin (HGB) levels. These findings underscore their respective roles as independent predictors of BM. Based on the results of the final multivariable analysis, a nomogram model was created. In the training cohort, the nomogram yielded an area under the receiver operating characteristic curve (AUC) of 0.870 at 2 years and 0.828 at 3 years. In the validation cohort, the AUC values were 0.897 at 2 years and 0.789 at 3 years. The calibration curve demonstrated good agreement between the predicted and observed probabilities of BM.ConclusionsA novel nomogram has been developed to forecast the likelihood of BM in patients diagnosed with LS-SCLC. This tool holds the potential to assist healthcare professionals in formulating more informed and tailored treatment plans.
| S-EPMC10790059 | biostudies-literature