Search Results (17)

Small cell lung cancer (SCLC) is an aggressive malignancy with a high incidence of brain metastases. Prophylactic cranial irradiation (PCI) was developed to reduce central nervous system (CNS) relapses and has been shown to improve survival, particularly in limited-stage disease. The pivotal Auperin meta-analysis and subsequent studies confirmed its role in patients achieving a complete response to initial therapy. In extensive-stage SCLC, earlier trials demonstrated reduced brain metastases and modest survival gains, but more recent studies incorporating routine magnetic resonance imaging (MRI) surveillance failed to show overall survival benefits, supporting MRI monitoring with salvage therapy as an alternative. Neurocognitive toxicity remains the major limitation of PCI, especially in older adults. Common effects include memory impairment, cognitive changes, and a reduced quality of life. Advances such as hippocampal avoidance PCI and neuroprotective strategies like memantine have shown the ability to mitigate long-term decline. Modern radiotherapy techniques, including intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), enable the precise sparing of critical structures while maintaining intracranial control. The integration of immunotherapy has shifted treatment paradigms in SCLC. While checkpoint inhibitors have improved systemic outcomes, their impact on brain relapses and interactions with PCI remain uncertain. This review provides an overview of the evolution of PCI in SCLC, while emphasizing current challenges and future directions. Full article

Background: Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine malignancy characterized by rapid growth, early metastatic dissemination, and a dismal prognosis. For decades, treatment paradigms remained largely stagnant, particularly for extensive-stage disease (ES-SCLC). However, the last five years have witnessed a significant evolution in the therapeutic landscape. Methods: The information for this article was gathered by synthesizing data from several key sources. This article synthesizes the evidence supporting current standards of care for both limited-stage (LS-SCLC) and ES-SCLC, incorporating data from pivotal clinical trials, a network meta-analysis of first-line chemoimmunotherapy regimens, and a critical appraisal of international treatment guidelines, and a critical analysis of international treatment guidelines from prominent organizations like the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO). This comprehensive approach allows for a robust and well-supported summary of the current therapeutic landscape. Results: For limited-stage SCLC (LS-SCLC), concurrent chemoradiotherapy (cCRT) remains the curative-intent standard, but its efficacy is now being augmented by consolidative immunotherapy, as demonstrated by the landmark ADRIATIC trial. The role of prophylactic cranial irradiation (PCI) in LS-SCLC is being re-evaluated in the era of high-sensitivity brain imaging and concerns over neurotoxicity. For ES-SCLC, the treatment paradigm has been fundamentally transformed by the integration of immune checkpoint inhibitors (ICIs) with platinum–etoposide chemotherapy, establishing a new standard of care that offers a modest but consistent survival benefit. Conclusions: The treatment of SCLC has been significantly advanced by the integration of immunotherapy, particularly for extensive-stage disease, which has established a new standard of care and improved patient outcomes. Looking to the future, the quest for predictive biomarkers and the development of novel therapeutic classes, such as Bi-specific T-cell Engagers (BiTEs) and antibody–drug conjugates, promise to build upon recent progress and offer new hope for improving the dismal prognosis associated with this disease. Full article

Background: Prophylactic cranial irradiation (PCI) is recommended to decrease the incidence of brain metastases (BM) in extensive-stage small-cell lung cancer (ESSCLC) without BM after response to chemotherapy. However, PCI is associated with significant neurocognitive effects, and new studies are debating its benefits. Moreover, the introduction of immunotherapy in the management of the disease has raised new questions, and there is a lack of data on PCI and immunotherapy. We report a single-center retrospective study evaluating the impact of omitting PCI from real-life treatment, including immunotherapy, of patients with ES-SCLC. Methods: We identified patients followed at APHM between January 2014 and January 2021 for ES-SCLC without BM with an indication for PCI. The main assessment criteria considered in this study were overall survival (OS) and brain metastasis-free survival (BMFS) between patients who received PCI and those who did not. Results: 56 patients were included, 25 receiving PCI and 31 without PCI. The median follow-up was 16 months. Eighteen patients received immunotherapy, mostly in the group without PCI (p = 0.024). The median OS and BMFS were, respectively, 11.7 and 13.4 months in patients with PCI, and 20.3 and 10.7 months in patients without PCI, without any significant statistical difference (p = 0.412, p = 0.336). The prognostic factors highlighted in multivariate analysis were initial performance status (PS) < 2 for OS (HR = 2.74 (IC95% [1.23; 6.13])) and monocyte lymphocyte ratio (MLR) < 0.12 for BMFS (HR = 1.21 (IC95% [1.01; 1.45])). A recursive partitioning analysis (RPA) found PS, immunotherapy, and age to be influential factors for OS but not PCI. Conclusions: The clinical results of our study showed no benefit of PCI in terms of OS and BMFS for patients with ES-SCLC. This can be explained by the lack of benefit of PCI or by the introduction of immunotherapy. Full article

Lung cancer, both non-small cell and small cell, harbors a high propensity for spreading to the central nervous system. Radiation therapy remains the backbone of the management of brain metastases. Recent advances in stereotactic radiosurgery have expanded its indications and ongoing studies seek to elucidate optimal fractionation and coordination with systemic therapies, especially targeted inhibitors with intracranial efficacy. Efforts in whole-brain radiotherapy aim to preserve neurocognition and to investigate the need for prophylactic cranial irradiation. As novel combinatorial strategies are tested and prognostic/predictive biomarkers are identified and tested, the management of brain metastases in lung cancer will become increasingly personalized to optimally balance intracranial efficacy with preserving neurocognitive function and patient values. Full article

Background: Extensive-stage small-cell lung cancer (ES-SCLC) treatment has recently been revolutionized by the advent of immune checkpoint inhibitors. This survey was conducted to evaluate the current pattern of care among Italian clinicians, in particular about the integration with radiation therapy (RT). Methods: In June 2023, 225 Italian cancer care professionals were invited to complete a 21-question web-based survey about ES-SCLC management through personal contacts and the Italian Association for Radiotherapy and Clinical Oncology (AIRO) network. Results: We received 90 responses; the majority were radiation oncologists (89%) with more than 10 years of experience (51%). The preferred management of ES-SCLC in patients with a good performance status was concomitant chemo-immunotherapy (84%). Almost all respondents recommended prophylactic cranial irradiation (PCI) (85%), taking into account age and thoracic response; PCI was performed mainly between the end of chemotherapy and before starting immunotherapy (37%), with a three-dimensional conformal technique (46%). Furthermore, 83% of respondents choose to deliver thoracic RT in the case of both an intrathoracic and extrathoracic response, with an RT schedule of 30 Gy/10 fractions. Stereotactic RT is increasingly being used in oligoprogressions. Conclusions: Our analysis showed the variability of real-world management of ES-SCLC. Future clinical trials and developments are needed to improve the multidisciplinary treatment of these patients. Full article

This review discusses the topic of prevention of brain metastases from the most frequent solid tumor types, i.e., lung cancer, breast cancer and melanoma. Within each tumor type, the risk of brain metastasis is related to disease status and molecular subtype (i.e., EGFR-mutant non-small cell lung cancer, HER2-positive and triple-negative breast cancer, BRAF and NRAF-mutant melanoma). Prophylactic cranial irradiation is the standard of care in patients in small cell lung cancer responsive to chemotherapy but at the price of late neurocognitive decline. More recently, several molecular agents with the capability to target molecular alterations driving tumor growth have proven as effective in the prevention of secondary relapse into the brain in clinical trials. This is the case for EGFR-mutant or ALK-rearranged non-small cell lung cancer inhibitors, tucatinib and trastuzumab–deruxtecan for HER2-positive breast cancer and BRAF inhibitors for melanoma. The need for screening with an MRI in asymptomatic patients at risk of brain metastases is emphasized. Full article

In this study, we investigated the outcomes and factors influencing treatment efficacy in 93 patients with limited disease small cell lung cancer (LD-SCLC), with a median age of 64 years. We focused on the impact of chemotherapy regimens, prophylactic cranial irradiation (PCI), and patient-related variables. The median follow-up for OS was 17.3 months. We observed a statistically significant difference in PFS between LD-SCLC patients treated with cisplatin and etoposide (EP) and those treated with carboplatin and etoposide (CP) (PFS: EP 13.63 months vs. CP 6.54 months, p < 0.01). Patients treated with EP had better overall survival (OS) than CP-treated patients (OS: EP 26.9 months vs. CP 16.16 months, p < 0.01). Concomitant chemotherapy was associated with improved PFS (p = 0.003) and OS (p = 0.002). Patients receiving PCI showed superior OS (p = 0.05) and a trend towards improved PFS (p = 0.057). Female gender was associated with better OS (p = 0.025). Most patients had an ECOG performance status of 0 (71%). This real-world study underscores the importance of multidisciplinary LD-SCLC management, emphasizing the roles of chemotherapy, radiotherapy, and PCI. These findings inform personalized treatment strategies and emphasize the need for prospective trials to validate these results and optimize LD-SCLC treatment. Full article

Small-cell neuroendocrine cervical carcinoma (SCNCC) is a rare yet aggressive gynecological malignancy associated with dismal clinical outcomes. Its rarity has led to a limited number of retrospective studies and an absence of prospective research, posing significant challenges for evidence-based treatment approaches. As a result, most gynecologic oncology centers have limited experience with this tumor, emphasizing the urgent need for a comprehensive review and summary. This article systematically reviews the pathogenesis, immunohistochemical and molecular characteristics, prognostic factors, and clinical management of gynecologic SCNCC. We specifically focused on reviewing the distinct genomic characteristics of SCNCC identified via next-generation sequencing technologies, including loss of heterozygosity (LOH), somatic mutations, structural variations (SVs), and microRNA alterations. The identification of these actionable genomic events offers promise for discovering new molecular targets for drug development and enhancing therapeutic outcomes. Additionally, we delve deeper into key clinical challenges, such as determining the optimal treatment modality between chemoradiation and surgery for International Federation of Gynecology and Obstetrics (FIGO) stage I phase patients within a precision stratification framework, as well as the role of targeted therapy within the homologous recombination (HR) pathway, immune checkpoint inhibitors (ICIs), and prophylactic cranial irradiation (PCI) in the management of SCNCC. Finally, we anticipate the utilization of multiple SCNCC models, including cancer tissue-originated spheroid (CTOS) lines and patient-derived xenografts (PDXs), to decipher driver events and develop individualized therapeutic strategies for clinical application. Full article

Backgrounds: 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. In this study, we aim to construct a prognostic nomogram that integrates the clinical features and treatment options to predict disease-specific survival (DSS). Methods: A total of 713 patients diagnosed with LCNEC were from the US National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) registry between 2010–2016. 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 2010–2018. 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). Additionally, we conducted a subgroup analysis of data available in the external cohort that may impact prognosis but was not recorded in the SEER database. Results: 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 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 Area Under Curve (AUC) > 0.8). DCA exhibited the favorable clinical applicability of the nomogram in the prediction of LCNEC survival. A risk classification system was built which could perfectly classify LCNEC patients into high-, medium- and low-risk groups (p < 0.001). The survival analysis conducted on the West China Hospital cohort indicated that whole brain radiation therapy (WBRT), prophylactic cranial irradiation (PCI), surgical procedures, tumor grade, Ki-67, and PD-L1 expression were not significantly associated with DSS. Conclusion: This study has effectively developed a prognostic nomogram and a corresponding risk stratification system, which demonstrate promising potential for predicting the DSS of patients with LCNEC. Full article

(1) Introduction: Small cell lung cancer (SCLC) is an aggressive tumor type, accounting for about 15% of all lung cancers. Radiotherapy (RT) plays a fundamental role in both early and advanced stages. Currently, in advanced disease, the use of consolidative chest RT should be recommended for patients with good response to platinum-based first-line chemotherapy, but its use has not yet been standardized. The present prospective study aims to evaluate the pattern of care of consolidative chest RT in patients with advanced stage SCLC, and its effectiveness in terms of disease control and tolerability. (2) Materials and methods: This study was a multicenter prospective observational trial, proposed and conducted within the AIRO lung study group to evaluate the pattern of care of consolidative chest RT after first-line chemotherapy in patients with advanced SCLC. The patient and tumor characteristics, doses, fractionation and volumes of thoracic RT and prophylactic cranial irradiation (PCI), as well as the thoracic and extrathoracic response to the treatment, toxicity and clinical outcomes, were collected and analyzed. (3) Results: From January 2017 to December 2019, sixty-four patients were enrolled. Median follow-up was 33 months. The median age was 68 years (range 42–81); 38 patients (59%) were male and 26 (41%) female. Carboplatin + etoposide for 6 cycles was the most commonly used first-line therapeutic scheme (42%). With regard to consolidative chest RT, 56% of patients (35) received 30 Gy in 10 factions and 16 patients (26%) received 45 Gy in 15 sessions. The modulated intensity technique was used in 84.5% of cases, and post-chemotherapy macroscopic residual disease was the target volume in 87.5% of patients. Forty-four patients (69%) also underwent PCI. At the last follow-up, over 60% of patients did not experience chest disease progression, while 67% showed extrathoracic progression. At the first radiological evaluation after RT, complete response and stable disease were recorded in 6% and 46% of the cases, respectively. Two patients had a long-term complete response to the combined treatment. The brain was the first site of extrathoracic progression in 28%. 1y and 2y OS and PFS were 67%, 19%, 28% and 6%, respectively. Consolidative chest RT was well-tolerated in the majority of patients; it was interrupted in three cases (due to G2 pulmonary toxicity, disease progression and clinical decay, respectively). Only 1 patient developed G3 asthenia. (4) Conclusions: Consolidative chest RT has been shown to be useful in reducing the risk of thoracic disease progression and is absolutely well-tolerated in patients with advanced stage SCLC with good response after first-line chemotherapy. Among the Italian centers that participated in this study, there is still variability in the choice of fractionation and target volumes, although the guidelines contain clear recommendations. The aim of future research should be to clarify the role and modalities of chest RT in the era of immunotherapy in advanced-stage SCLC. Full article

Introduction: Brain is a major site of metastasis for lung cancer, and effective therapy for developed brain metastasis (BM) is limited. Prophylactic cranial irradiation (PCI) has been shown to reduce BM rate and improve survival in small cell lung cancer, but this result was not replicated in unselected non-small cell lung cancer (NSCLC) and had the risk of inducing neurocognitive dysfunctions. We aimed to develop a radiomics BM prediction model for BM risk stratification in NSCLC patients. Methods: 256 NSCLC patients with no BM at baseline brain magnetic resonance imaging (MRI) were selected; 128 patients developed BM within three years after diagnosis and 128 remained BM-free. For radiomics analysis, both the BM and non-BM groups were randomly distributed into training and testing datasets at an 70%:30% ratio. Both brain MRI (representing the soil) and chest computed tomography (CT, representing the seed) radiomic features were extracted to develop the BM prediction models. We first developed the radiomic models using the training dataset (89 non-BM and 90 BM cases) and subsequently validated the models in the testing dataset (39 non-BM and 38 BM cases). A radiomics BM score (RadBM score) was generated, and BM-free survival were compared between RadBM score-high and RadBM score-low groups. Results: The radiomics model developed from baseline brain MRI features alone can predict BM development in NSCLC patients. A fusion model integrating brain MRI features with primary tumor CT features (seed-and-soil model) provided synergetic effect and was more efficient in predicting BM (areas under the receiver operating characteristic curve 0.84 (95% confidence interval: 0.80–0.89) and 0.80 (95% confidence interval: 0.71–0.88) in the training and testing datasets, respectively). BM-free survival was significantly shorter in the RadBM score-high group versus the RadBM score-low group (Log-rank, p < 0.001). Hazard ratios for BM were 1.056 (95% confidence interval: 1.044–1.068) per 0.01 increment in RadBM score. Cumulative BM rates at three years were 75.8% and 24.2% for the RadBM score-high and RadBM score-low groups, respectively. Only 1.2% (7/565) of the BM lesions were located within the hippocampal avoidance region. Conclusion: The results demonstrated that intrinsic features of a non-metastatic brain exert a significant impact on BM development, which is first-in-class in metastasis prediction studies. A radiomics BM prediction model utilizing both primary tumor and pre-metastatic brain features might provide a useful tool for individualized PCI administration in NSCLC patients more prone to develop BM. Full article

Background: In the ATLANTIS study, second-line lurbinectedin/doxorubicin did not improve overall survival (OS), however patients with a chemotherapy-free interval (CTFI) of ≥180 days had an improved progression free survival (PFS). The objective of this retrospective study was to identify the proportion of real-world small cell lung cancer (SCLC) patients who are suitable for lurbinectedin-based therapy based on these criteria. Methods: A retrospective study of all SCLC referred to BC Cancer between 2012 and 2017 was conducted. Patient demographics, staging, treatment, and survival data were collected retrospectively. Baseline characteristics were compared using descriptive statistics. OS was calculated using Kaplan–Meier curves. Statistically significant p-value was <0.05. Results: A total of 1048 patients were identified. Baseline characteristics: median age 68 years, 47% male, 61% current smoking status, 68% extensive disease. Best supportive care was received by 22%. First-line systemic therapy was platinum doublet for 71% of the population. Second-line systemic therapy was delivered to 22%. Of the 219 patients who received second-line systemic therapy after platinum doublet, 183 patients had a CTFI of ≥90 days and 107 patients had a CTFI of ≥180 days. Patients originally treated as limited stage disease, received platinum doublet as second line, received thoracic radiation (RT) or prophylactic cranial irradiation (PCI) were more likely to have a CTFI of ≥90 and ≥180 days. Conclusion: In our real-world SCLC population, only 21% of the SCLC population received second-line therapy after platinum doublet with 17% achieving CTFI of ≥90 days and 10% CTFI of ≥180 days. Based on this retrospective review, only a small fraction of platinum-treated patients would be preferentially offered lurbinectedin in the second-line setting. Full article

Prophylactic cranial irradiation (PCI), as an essential part of the treatment of limited-stage small-cell lung cancer (LS-SCLC), inevitably leads to neurotoxicity. This study aimed to construct a brain metastasis prediction model and identify low-risk patients to avoid PCI; 236 patients with LS-SCLC were retrospectively analyzed and divided into PCI (63 cases) and non-PCI groups (173 cases). The nomogram was developed based on variables determined by univariate and multivariate analyses in the non-PCI group. According to the cutoff nomogram score, all patients were divided into high- and low-risk cohorts. A log-rank test was used to compare the incidence of brain metastasis between patients with and without PCI in the low-risk and high-risk groups, respectively. The nomogram included five variables: chemotherapy cycles (ChT cycles), time to radiotherapy (RT), lactate dehydrogenase (LDH), pro-gastrin-releasing peptide precursor (ProGRP), and lymphocytes–monocytes ratio (LMR). The area under the receiver operating characteristics (AUC) of the nomogram was 0.763 and 0.782 at 1 year, and 0.759 and 0.732 at 2 years in the training and validation cohorts, respectively. Based on the nomogram, patients were divided into high- and low-risk groups with a cutoff value of 165. In the high-risk cohort, the incidence of brain metastasis in the non-PCI group was significantly higher than in the PCI group (p < 0.001), but there was no difference in the low-risk cohort (p = 0.160). Propensity score-matching (PSM) analysis showed similar results; the proposed nomogram showed reliable performance in assessing the individualized brain metastasis risk and has the potential to become a clinical tool to individualize PCI treatment for LS-SCLC. Full article

Limited-stage (LS) small-cell lung cancer (SCLC) is defined as disease confined to a tolerable radiation portal without extrathoracic metastases. Despite clinical research over two decades, the prognosis of LS-SCLC patients remains poor. The current standard of care for LS-SCLC patients is concurrent platinum-based chemotherapy with thoracic radiotherapy (RT). Widespread heterogeneity on the optimal radiation dose and fractionation regimen among physicians highlights the logistical challenges of administering BID regimens. Prophylactic cranial irradiation (PCI) is recommended to patients following a good initial response to chemoradiation due to improved overall survival from historical trials and the propensity for LS-SCLC to recur with brain metastases. However, PCI utilization is being debated due to the greater availability of magnetic resonance imaging (MRI) and data in extensive-stage SCLC regarding close MRI surveillance in lieu of PCI while spurring novel RT techniques, such as hippocampal-avoidance PCI. Additionally, novel treatment combinations incorporating targeted small molecule therapies and immunotherapies with or following radiation for LS-SCLC have seen recent interest and some concepts are being investigated in clinical trials. Here, we review the landscape of progress, limitations, and challenges for LS-SCLC including current standard of care, novel radiation techniques, and the integration of novel therapeutic strategies for LS-SCLC. Full article

Background: The management of small-cell lung cancer (SCLC) with radiotherapy (RT) varies, with many treatment regimens having been described in the literature. We created a survey to assess patterns of practice and clinical decision-making in the management of SCLC by Canadian radiation oncologists (ROS). Methods: A 35-item survey was sent by e-mail to Canadian ROS. The questions investigated the role of RT, the dose and timing of RT, target delineation, and use of prophylactic cranial irradiation (PCI) in limited-stage (LS) and extensive-stage (ES) SCLC. Results: Responses were received from 52 eligible ROS. For LS-SCLC, staging (98%) and simulation or dosimetric (96%) computed tomography imaging were key determinants of RT suitability. The most common dose and fractionation schedule was 40–45 Gy in 15 once-daily fractions (40%), with elective nodal irradiation performed by 31% of ROS. Preferred management of clinical T1/2aN0 SCLC favoured primary chemoradiotherapy (64%). For ES-SCLC, consolidative thoracic RT was frequently offered (88%), with a preferred dose and fractionation schedule of 30 Gy in 10 once-daily fractions (70%). Extrathoracic consolidative RT would not be offered by 23 ROS (44%). Prophylactic cranial irradiation was generally offered in LS-SCLC (100%) and ES-SCLC (98%) after response to initial treatment. Performance status, baseline cognition, and pre-PCI brain imaging were important patient factors assessed before an offer of PCI. Conclusions: Canadian ROS show practice variation in SCLC management. Future clinical trials and national treatment guidelines might reduce variability in the treatment of early-stage disease, optimization of dose and targeting in LS-SCLC, and definition of suitability for PCI or consolidative RT. Full article