Role Of Prophylactic Cranial Irradiation Research Articles

Stereotactic radiosurgery in patients with small cell lung cancer and 1-10 brain metastases: A multi-institutional, phase II, prospective clinical trial.

2020 Background: Stereotactic radiosurgery (SRS) as opposed to whole brain radiation (WBRT) represents the standard of care for patients with a limited number of brain metastases. Brain metastases from small cell lung cancer (SCLC), however, represent an exception to this dogma, given that prior trials evaluating SRS in lieu of WBRT excluded patients with SCLC due to the historical role of prophylactic cranial irradiation (PCI) and concerns relating to neurologic decline and death when WBRT is omitted from upfront management. We conducted a prospective, multi-center, phase II trial of SRS in patients with SCLC and 1-10 brain metastases to determine how rates of neurologic death compared to historical controls managed with WBRT. Methods: Following approval from the Dana-Farber/Harvard Cancer Center IRB, we opened a single-arm, multi-center, phase II trial to investigate SRS in patients with SCLC and 1-10 brain metastases naïve to prior brain-directed radiation including PCI (NCT03391362). Prior resection of a brain metastasis was permitted. Patients with leptomeningeal disease were excluded. Metastases <2cm in maximal size were generally managed with SRS to 20 Gy; larger tumors, or those near sensitive structures, were dose reduced to 16-19 Gy or managed with fractioned SRS (SRT) to 30 Gy in 5 fractions. Gross totally resected brain metastases received SRT to 25 Gy in 5 fractions. We sought to determine, as the primary endpoint, whether or not use of SRS in lieu of WBRT would lead to meaningfully higher rates of neurologic death (HR 1.61, corresponding to a 1-year event rate of 26.7% relative to a historical 1-year rate of 17.5% in patients previously managed with WBRT at our center), with 90% power and a one-sided alpha error of 5%. Neurologic death was defined as marked, progressive, radiographic brain progression accompanied by corresponding neurologic symptomatology without systemic disease progression / systemic symptoms of a life-threatening nature and was assessed by a panel of 2-3 neuro-radiation oncologists. Results: Between 3/2018 – 4/2023, 100 patients were enrolled across 4 centers. The median age was 68 years (IQR 63 – 74 years). The median number of brain metastases was 2 (IQR 1 – 3); 16 (16%) of patients underwent prior neurosurgical resection. On study, 66 (66%) patients were treated with SRS alone while 32 (32%) were treated with SRT to at least 1 site; 2 patients died of systemic disease progression before study treatment. The median overall survival was 10.3 months. In total, 19 neurologic deaths were observed, relative to 62 systemic deaths. The neurologic death rate at 1 year was 11.0% (95% CI 4.8% – 17.2%). Conclusions: Our prospective, multi-institutional study demonstrated modest rates of neurologic death when SRS as opposed to WBRT is used in patients with SCLC and 1-10 brain metastases and represents the largest prospective experience to date. Clinical trial information: NCT03391362 .

Prophylactic Cranial Irradiation in Limited-Stage Small Cell Lung Cancer: A Meta-Analysis.

The role of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC) has been questioned in the era of magnetic resonance imaging (MRI). The purpose of this study was to re-evaluate the efficacy of PCI in patients with LS-SCLC. Three electronic databases were searched, including PubMed, Embase, and the Cochrane Library from January 2012 to April 2022.All relevant publications were included based on the inclusion criteria, and survival data and brain metastasis (BM) rates were extracted and pooled. Ten studies were selected which involved 532 patients who received PCI and 613 patients who did not receive PCI. In pooled estimates, PCI significantly improved overall survival (OS) and progression-free survival (PFS) [hazard ratio (HR) = 0.71, 95% confidence interval (CI): 0.61-0.82, p <0.001; HR = 0.68, 95% CI: 0.48-0.97, p = 0.03, respectively]. Additionally, the use of PCI was associated with a significant reduction in the risk of brain metastasis (BM, risk ratio = 0.64, 95% CI: 0.46-0.90, p = 0.009). In subgroup analyses. The authors found that the PCI effects on OS were independent of region and the use of brain imaging after initial treatment. These findings demonstrate that PCI improves OS and PFS while decreasing the risk of BM in patients with LS-SCLC, implying that PCI remains necessary even in the MRI era. Key Words: Prophylactic cranial irradiation, Small cell lung cancer, Magnetic resonance imaging, Brain metastasis.

Development and Validation of a Nomogram for Patients with Lung Large Cell Neuroendocrine Carcinoma

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rarely high-grade neuroendocrine carcinoma of the lung with features of both small cell and non-small cell lung cancer. We aim to construct a prognostic nomogram combined with the clinical features and treatment options to predict disease-specific survival (DSS), meanwhile, evaluating the role of prophylactic cranial irradiation (PCI) in LCNEC by subgroup analysis. A total of 713 patients diagnosed with LCNEC from the US National Cancer Institute's Surveillance Epidemiology and End Results (SEER) registry between 2010 and 2016. Cox proportional hazards analysis was conducted to choose the significant predictors of DSS. External validation was performed using 77 patients with LCNEC in the West China Hospital Sichuan University between 2010 and 2018, subgroup analysis was carried out for the whole brain radiotherapy (WBRT) and PCI population. The predictive accuracy and discriminative capability were estimated by the concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve. The clinical applicability of the nomogram was verified through the decision curve analysis (DCA). Six independent risk factors for DSS were identified and integrated into the nomogram. The nomogram achieved good C- indexes of 0.803 and 0.767 in the training and validation group respectively. Moreover, the calibration curves of both cohorts for the probability of survival showed good agreement between prediction by nomogram and actual observation in 1-, 3- and 5-year DSS. The ROC curves demonstrated the prediction accuracy of the established nomogram (all AUC>0.8). DCA confirmed the better potential clinical practicality of the nomogram in the prediction of LCNEC survival than AJCC staging. A risk classification system was built which could perfectly classify LCNEC patients into high- and low-risk groups(p<0.001). Subgroup analysis showed that WBRT did not bring survival benefits, PCI appeared to have survival benefits in LCNEC patients without brain metastases (p>0.05). The prognostic nomogram developed in this study has certain prognostic value and clinical practicality for LCNEC patients. PCI might be investigated as a means of improving prognosis.

What is the current role of prophylactic cranial irradiation in the treatment algorithm for small cell lung cancer?

Prophylactic cranial irradiation (PCI) is considered an important technological advance made in oncology in an effort to reduce the incidence of brain metastases (BM) and improve overall survival (OS) of patients with small cell lung cancer (SCLC). Although it is often reported that PCI improves the therapeutic potential in limited-stage (LS) SCLC, no randomised trial has ever conclusively confirmed this. Nevertheless, PCI has been considered the standard of care for LS-SCLC since the late 1990s. The data supporting the use of PCI in LS-SCLC are based on an analysis of work performed prior to the current approach to staging [brain magnetic resonance imaging (MRI), positron emission tomography (PET)/computed tomography (CT)]. The evidence for the rationale and feasibility of this approach in the modern diagnostic era should be demonstrated. The situation with extensive stage (ES) SCLC is seemingly easier because, unlike LS-SCLC, we have data from two randomised trials. Unfortunately, their results are in direct conflict with each other. Although it is generally assumed that good control of brain disease leads to better quality of life, this has never been prospectively demonstrated. In fact, PCI is associated not only with increased treatment costs and some patient discomfort, but also with non-negligible potential toxicity. For this reason, efforts have been made to preserve cognitive function by sparing the hippocampus. This concept is called hippocampal avoidance. The optimal fractionation regimen is currently less controversial than the optimal integration of PCI into the treatment algorithm. A dose of 25 Gy administered in 10 fractions should remain the standard for the eventual use of PCI in patients with SCLC. In summary, PCI is not a conditio sine qua non in any indication. Neither in patients with LS-SCLC nor in patients with ES-SCLC has a clear improvement in OS been demonstrated at follow-up using current imaging modalities.

Prophylactic cranial irradiation effect on survival in patients with small cell lung cancer: a comprehensive systematic review and meta-analysis.

Prophylactic cranial irradiation (PCI) is a companion treatment option for small cell lung cancer (SCLC) patients. However, its efficacy and associated risk factors have not been clearly defined. In this study, the authors aimed to systematically assess the effectiveness and role of PCI in the treatment plan of SCLC. The PubMed, Scopus, Web of Science, and Cochrane databases were searched using the following key terms and their equivalents: "brain," "radiotherapy," "metastases," "prophylactic," and "small cell lung cancer." Studies comparing overall survival (OS), progression-free survival (PFS), brain metastasis-free survival (BMFS), and incidence of brain metastases between patients receiving PCI and those not receiving it were considered eligible. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies-of Interventions (ROBINS-I) tool. Meta-analysis was conducted on the mentioned outcomes with subgrouping based on different factors. The authors identified 74 studies published between 1983 and 2022 with 31,551 SCLC patients, of whom 26.7% received PCI. The studies were a mix of prospective randomized and retrospective observational studies. Patients with limited-stage disease receiving PCI had better OS, PFS, and BMFS than those not receiving PCI. Patients receiving PCI also had significantly longer OS times and developed brain metastases significantly later. However, findings regarding extensive-stage SCLC were not as promising. PCI is an effective option for limited-stage SCLC patients. It improves OS and PFS, delays brain metastases, and reduces the incidence of brain metastases. However, it might not benefit patients with extensive-stage SCLC under adequate follow-up with MRI surveillance. Finally, the heterogeneity of the included studies and publication bias were the main limitations of this study.

Extensive‐stage small cell lung cancer: Is prophylactic cranial irradiation necessary in the era of immunotherapy with MRI surveillance?

AbstractObjectiveThe role of prophylactic cranial irradiation (PCI) in treating extensive‐stage small‐cell lung cancer (ES‐SCLC) has been controversial. This study aimed to comprehensively analyze the efficacy of PCI for the treatment of ES‐SCLC under active brain magnetic resonance imaging (MRI) surveillance.MethodsPatients with ES‐SCLC with no brain metastases (BM) confirmed by MRI at the time of diagnosis who responded well to first‐line chemoimmunotherapy at three general hospitals were retrospectively included. Overall survival (OS), progression‐free survival (PFS), and cumulative incidence of BM were compared between patients who underwent PCI and those who did not.ResultsIn total, 66 consecutive patients treated between March 2019 and December 2021 were included in our dataset. Seventeen patients underwent PCI (PCI group) and 49 patients did not (non‐PCI group). In comparison with the non‐PCI group, PCI did not provide OS (median OS: 18.53 vs. 17.35 months, p = 0.28) or PFS (median PFS: 8.61 vs. 7.56 months, p = 0.41) benefits. When death was counted as a competing risk, the difference in the cumulative incidence rate of BM was not statistically significant (1‐year: 12.79% vs. 38.09%; p = 0.14).ConclusionCompared to active MRI surveillance, first‐line chemoimmunotherapy followed by PCI did not improve the prognosis of patients with ES‐SCLC. Further studies are warranted to evaluate the therapeutic effects of PCI following chemoimmunotherapy.

Prophylactic cranial irradiation for limited-stage small-cell lung cancer in the magnetic resonance imaging era.

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.

Small cell carcinoma of the oesophagus: experience of an Indian Tertiary Cancer Centre

IntroductionSmall cell carcinoma of the oesophagus (SCCE) is a rare and aggressive tumour with no established standard treatment.MethodsThis is a retrospective study of adult patients with histologically proven SCCE registered between February 2011 and March 2020 at Tata Memorial Hospital in Mumbai.ResultsThere were 56 patients, with 29 (51.8%) having limited-stage disease (LD) and 27 (48.2%) having extensive-stage disease (ED). The median age was 58 (interquartile range = 51–65) years; 57.1% were men; and 40% were smokers. Among LD-SCCE patients, 23 underwent local therapy, i.e., radiation (19, 65.5%) and surgery (4, 13.8%), and 27 received chemotherapy in neoadjuvant (23, 79.3%), concurrent (18, 62.1%) and adjuvant (4, 13.8%) settings. Totally, 19 ED-SCCE patients (70.4%) received chemotherapy. Prophylactic cranial irradiation (PCI) was delivered to 11 (37.9%) and 7 (25.9%) patients with LD-SCCE and ED-SCCE, respectively. Significant grade 3 or more chemotoxicities in patients with LD-SCCE and ED-SCCE included febrile neutropenia in 33.3% and 23.5%, anaemia in 9.5% and 17.6%, and dyselectrolytemia in 14.3% and 11.8%, respectively. The median overall survival (OS) in LD-SCCE and ED-SCCE was 22.9 (95% CI = 1.8–44.1) months and 11.8 (95% CI = 7.3–16.4) months, respectively. Age <60 years (p = 0.004) and tumour epicentre in the lower third oesophagus (p = 0.002) were independent good prognostic factors for OS in LD-SCCE and ED-SCCE patients, respectively. The incidence of brain metastasis was low, at both presentation (1/27, 3.7%) and relapse (5/56, 8.9%).ConclusionAlthough the survival of LD-SCCE is better than ED-SCCE, it is still under 2 years. Brain metastases are uncommon and the role of PCI is uncertain.

Role of Prophylactic Cranial Irradiation in Extensive-Stage Small Cell Lung Cancer.

Patients with small cell lung cancer (SCLC) are at significant risk of developing brain metastases during their disease course. Prophylactic cranial irradiation (PCI) has been incorporated into SCLC treatment guidelines to diminish the risk of developing brain metastases. In 2007, a randomized trial suggested that PCI decreases the incidence of brain metastases and prolongs overall survival (OS) in patients with extensive-stage SCLC (ES-SCLC) who have responded to initial therapy. However, this study did not include modern central nervous system imaging with CT or MRI prior to randomization. A more recent Japanese trial with MRI staging and surveillance demonstrated that PCI diminished the incidence of brain metastases but did not improve survival. This review examines the largest clinical studies, controversies, and future directions of PCI in patients with ES-SCLC.

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.

PO-1196 Role of prophylactic cranial irradiation in limited and extensive-stage small cell lung cancer

PO-1196 Role of prophylactic cranial irradiation in limited and extensive-stage small cell lung cancer

Role of Radiation in Extensive Stage Small Cell Lung Cancer: A National Cancer Database Registry Analysis

The role of prophylactic cranial irradiation (PCI) and thoracic radiation therapy (TRT) in extensive-stage small cell lung cancer remains controversial. The authors examined the National Cancer Database and identified patients with extensive-stage small cell lung cancer with no brain metastasis. Patients were excluded if they died 30 days from diagnosis, did not receive polychemotherapy, had other palliative radiation or had missing information. A propensity score-matched analysis was also performed. A total of 21,019 patients were identified. The majority of patients did not receive radiation (69%), whereas 10% received PCI and 21% received TRT. The addition of PCI and TRT improved median survival and survival at 1 and 2 years (p ≤ 0.05). The propensity score-matched analysis confirmed the same overall survival benefit with both PCI and TRT. This registry-based analysis of &gt;1500 accredited cancer programs shows that PCI and TRT are not commonly utilized for extensive-stage small cell lung cancer patients who are treated with multiagent chemotherapy. The addition of PCI and TRT significantly improves overall survival in this otherwise poor prognostic group. Further research is needed to confirm the role of PCI and TRT, especially in the era of improved systemic therapy.

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.

PN1 but not pN0/N2 predicts survival benefits of prophylactic cranial irradiation in small-cell lung cancer patients after surgery.

Prophylactic cranial irradiation has been shown to reduce brain metastases and provide survival benefits in small-cell lung cancer (SCLC). However, its role in limited-stage SCLC patients after surgery remains unclear. Further, it is unknown whether the effect of prophylactic cranial irradiation is generalizable in these patients with different pathological nodal (N0-N2) stages, a state indicating the presence of tumor metastases. We combined data from a single medical center and Surveillance, Epidemiology, and End Results database. Propensity score matching analyses were performed (1:2) to evaluate the role of prophylactic cranial irradiation in SCLC patients after surgery. Cox proportional hazards regression model was used to identify predictors of survival. 124 (18.7%) out of 664 surgically-treated SCLC patients received prophylactic cranial irradiation treatment. Within the entire cohort, multivariate Cox regression analysis identified dataset source, age, pathological T and N stages, adjuvant chemotherapy, resection type, and histology as independent prognostic factors for overall survival. Prophylactic cranial irradiation appeared to be associated with a better overall survival, but the difference is marginally significant (P=0.063). Further, we stratified patients based on the pathological N0-N2 stages using propensity score matching analyses, which showed that prophylactic cranial irradiation treatment was superior to non-prophylactic cranial irradiation treatment for surgically-treated SCLC patients with N1 stage only (univariate analysis: P=0.026; multivariate Cox: P=0.004), but not N0/N2 stage (univariate analysis: P=0.65 and P=0.28, respectively; multivariate Cox: P=0.99 and P=0.35, respectively). Prophylactic cranial irradiation provides survival benefits for SCLC patients with pN1 after surgery but not with pathological N0/N2 stage. Our findings may provide helpful stratifications for clinical decision-making of prophylactic cranial irradiation intervention in SCLC patients.

Association Between Prophylactic Cranial Irradiation and Improved Overall Survival in Small Cell Lung Cancer

While prior evidence had suggested that prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) may improve overall survival, a more recent trial did not demonstrate a survival benefit in patients with extensive-stage (ES)-SCLC. In light of conflicting evidence, the role of PCI in both limited-stage (LS) and ES-SCLC remains controversial. We therefore examine the use and outcomes of PCI in a large, curated, and contemporary cohort of patients with SCLC. We performed a retrospective cohort analysis of patients with LS-SCLC and ES-SCLC diagnosed between January 1, 2013 to September 30, 2019 from the nationwide Flatiron Health electronic health record-derived de-identified database. Receipt of radiation and PCI were chart-confirmed. Kaplan-Meier estimate, log-rank test, and multivariable Cox proportional hazards modeling (with forward selection of demographics, smoking history, practice type, cancer stage, and performance status variables with p<0.1 on univariate model) were used for time-to-event analysis. We performed sequential landmark analysis to account for immortal time bias. The landmark was chosen by increasing the required minimum length of survival for inclusion until the proportional hazards assumption was no longer violated. A total of 6,489 patients with SCLC were included in our cohort. Patients had a median age of 67 (IQR 60-74), 3,106 (47.9%) were male, 4,837 (74.5%) were white, 6,378 (98.3%) had a smoking history, and 6,066 (93.5%) were treated in a community setting. There were 2,091 (32.2%) limited-stage and 4,038 (62.2%) extensive-stage patients. Overall documented PCI use decreased from 24.2% of patients diagnosed in 2013 to 16.0% of patients diagnosed in 2018 (p<0.001). For limited-stage patients, documented PCI use decreased from 46.2% in 2013 to 35.2% in 2018 (p = 0.005), and for extensive-stage patients decreased from 13.9% in 2013 to 7.0% in 2018 (p<0.001). On multivariable analysis using a landmark of 256 days, documented PCI use was significantly associated with improved overall survival (HR 0.68, 95% CI 0.60-0.77, p<0.001; log-rank p<0.001). After restricting analysis to only extensive-stage patients, using the same landmark, documented use of PCI was still significantly associated with improved overall survival (HR 0.79, 95% CI 0.70-0.90, p<0.001; log-rank p<0.001). PCI is associated with improved overall survival for both LS-SCLC and ES-SCLC patients in the real-world setting, though further research is needed to determine how much of this effect is due to patient selection. Despite conflicting clinical trial results being demonstrated in the extensive-stage setting, documented PCI use has decreased significantly among both limited-stage and extensive-stage patients.

The Role of Prophylactic Cranial Irradiation in Limited Stage Small Cell Lung Cancer in the MRI Era

The Role of Prophylactic Cranial Irradiation in Limited Stage Small Cell Lung Cancer in the MRI Era

Radiosurgery for small-cell lung cancer brain metastases: a review.

First-line stereotactic radiosurgery (SRS) is now considered the preferred treatment over whole brain radiation therapy (WBRT) for limited brain metastases arising from most tumor histologies. This standard was reached following the consistent results of multiple phase III studies which demonstrated that, despite improved CNS control, the addition of WBRT to SRS does not improve overall survival (OS) and is associated with a reduction in cognitive function. Thus, it may be reasonable to consider the benchmark necessary to favor a paradigm of SRS alone over strategies incorporating WBRT as the demonstration of comparable OS in the context of decreased treatment-related side effects. However, patients with small-cell lung cancer (SCLC) brain metastases were excluded from the landmark trials that established SRS alone for limited brain metastases, largely due to concerns for short-interval CNS progression in SCLC as well the historic role of prophylactic cranial irradiation (PCI) in SCLC in the absence of known brain metastases. As a result, WBRT has remained the standard for SCLC for limited and even solitary brain lesions. With shifting SCLC care patterns including increased MRI surveillance, decreased PCI delivery, and emerging systemic agents, interest in first-line SRS for SCLC is likely to continue to increase over time. Herein we will review the emerging data for first-line SRS in the management of SCLC brain metastases and the potential for its increasing role in the setting of a greater utilization of MRI surveillance and improving systemic therapies.

Prophylactic cranial irradiation or MRI surveillance for extensive stage small cell lung cancer.

The treatment paradigm for extensive stage small cell lung cancer (ES-SCLC) is evolving. Prophylactic cranial irradiation (PCI) has long been considered a component of standard treatment in patients with extensive stage disease who respond to chemotherapy. However, in the modern era of magnetic resonance imaging, the role of PCI has become an area of controversy following conflicting level I evidence. Due to conflicting data and toxicity concerns, the routine use of PCI has declined. Recent improvements in systemic disease control with the use of immunotherapy and reductions in the toxicity attributable to PCI with hippocampal avoidance and memantine have reignited the discussion. As such, we present here a narrative review of PCI with a focus on historical milestones, randomized data, risk mitigation and future directions.

The Role of Prophylactic Cranial Irradiation in Limited Stage Small Cell Lung Cancer in the MRI Era

The Role of Prophylactic Cranial Irradiation in Limited Stage Small Cell Lung Cancer in the MRI Era

Treatment and toxic effects of prophylactic cranial irradiation in stage II-III non-small cell lung cancer: A meta-analysis.

To determine the role of prophylactic cranial irradiation (PCI) in non-small cell lung cancer (NSCLC) patients using meta-analysis. PubMed, Embase, the Cochrane Database of Systematic Review and the China National Knowledge Infrastructure databases were systematically searched for studies published between 1 January 1980 and 31 March 2019. Search terms included "non-small cell lung cancer," "prophylactic cranial irradiation" and "clinical trials." The research data extracted from above studies was analyzed by Review Manager 5.3 and Stata12.0 software. The outcomes included development of brain metastases (BMs), overall survival (OS), disease-free survival (DFS), BMs for different diagnoses, toxicity, quality of life (QoL). Fifteen trials (nine RCTs and six non-RCTs) involving 2418 NSCLC patients met the inclusion criteria. There was a significant reduction in the risk of developing BM in patients who received PCI compared with those who did not (95% CI, 0.20-0.37; P<0.00001). PCI significantly reduced the BM of squamous cell carcinoma (P=0.02), but not for adenocarcinoma (P=0.07) and other pathological types (P=0.29). There was a significant increase in DFS for the PCI compared to the non-PCI group (P=0.006); however, OS did not significantly differ (P=0.15). In addition, fatigue significantly increased in the PCI group (P=0.0002). Cognitive disturbance showed no significant difference between PCI and non-PCI groups (P=0.06). This study showed that, compared with non-PCI, PCI significantly decreased the incidence of NSCLC BM and improved the DFS of patients, and reduced the BM rate from squamous cell carcinoma. However, it showed no effect on OS and the BM rate of adenocarcinoma and other pathological types of tumors. There were limited data concerning PCI-related toxicity and QoL.