To evaluate the value of prophylactic cranial irradiation (PCI) in patients with limited-stage small cell lung cancer (LS-SCLC) at different risks of brain metastasis (BM).

A retrospective study included 498 LS-SCLC patients from three centers who achieved complete or partial response (CR/PR) after radical chemoradiotherapy. A nomogram was developed using significant factors associated with BM, identified through univariate and multivariate analyses. Patients were stratified into high- and low-risk groups based on risk scores. The incidence of BM was compared between patients with and without PCI in different risk-stratified populations using the log-rank test.

The nomogram included age, start of treatment to the end of radiotherapy (SER), hemoglobin, prognostic nutritional index (PNI), ProGRP, and NSE. The area under the receiver operating characteristics (AUC) of the nomogram for predicting the 2-year probability of intracranial progression-free survival (IPFS) were 0.738, 0.811, and 0.726 in the training, internal validation, and external validation cohorts, respectively. In the low-risk group, no significant differences were observed in BM incidence (p = 0.220), OS (p = 0.679), or PFS (p = 0.616) between PCI and non-PCI groups. In the high-risk group, PCI significantly reduced BM incidence (p < 0.0001) and improved PFS (p = 0.032), while no significant differences were found in OS (p = 0.778). Propensity score-matching analysis showed similar results.

PCI did not improve OS in patients regardless of high or low risk of BM. However, PCI did significantly reduce the incidence of BM and prolong PFS in patients at a high risk of BM.

Patients with extensive-stage small cell lung cancer (ES-SCLC) have a high risk of brain metastasis (BM). However, to the best of our knowledge, the risk factors for BM remain unclear. The present study aimed to investigate the risk factors and establish a prediction model for BM in patients with ES-SCLC. A total of 156 patients with ES-SCLC who had no BM and achieved a partial or complete response between January 2020 and March 2023 were included. Patients were randomly divided into training (n=109) and validation (n=47) cohorts. Factors associated with BM were assessed in the training cohort. Univariate and Cox multivariate analyses were performed to evaluate patients with ES-SCLC. Cox multivariate analysis identified oligometastasis [hazard ratio (HR), 0.35; 95% CI, 0.14-0.85; P=0.021], sex (HR, 2.48; 95% CI, 1.05-5.85; P=0.038) and baseline adrenal metastasis (HR, 2.85; 95% CI, 1.54-5.21; P<0.001) as independent risk factors for BM. A nomogram model was constructed to predict intracranial progression-free survival (iPFS). The areas under the receiver operating characteristic curves for the 9-, 12- and 18-month iPFS in the training cohort were 0.77, 0.74 and 0.75, respectively. The nomogram prediction and actual validation cohorts demonstrated good agreement. Among the high-risk factors for BM, the overall survival analysis demonstrated that non-oligometastasis and baseline adrenal metastasis were unfavorable prognostic factors. The present nomogram may aid risk assessment for BM in patients with ES-SCLC and guide prophylactic cranial irradiation.

Small cell lung cancer (SCLC) remains a challenge prognostically. A clinically silent early stage and predilection for early metastasis leads to over half of patients presenting with metastatic disease at the time of diagnosis. Akin to many other cancers, once SCLC metastasizes, current therapies begin to lose their effectiveness. The future of SCLC rests in innovative treatments aimed at improving patient outcomes. Chemotherapy and radiation remain the backbone treatment for SCLC. Most patients diagnosed with SCLC begin treatment with combination chemotherapy consisting of a platinum analog and topoisomerase inhibitor with or without concurrent radiation. Disease progression or recurrence warrants new treatment approaches. New chemotherapy combinations and advances in radiation precision offer patients novel approaches using the same backbone of treatment used in many other cancers. The introduction of newer therapeutic approaches, such as immune checkpoint inhibitors, small molecule targeted therapies, bispecific antibodies, and antibody-drug conjugates offer a bright future for patients with SCLC who fail first-line therapy. This review will focus on advancing treatment paradigms for SCLC in the era of precision medicine. Such a study might be helpful for pulmonologists and oncologists to manage precisely patients with SCLC.

Chemoimmunotherapy has emerged as the standard first-line treatment for extensive-stage small cell lung cancer (ES-SCLC), improving survival outcomes. However, the role of prophylactic cranial irradiation (PCI) in the context of chemoimmunotherapy remains undefined.

This study aimed to evaluate the impact of PCI on overall survival (OS) in patients with ES-SCLC after chemoimmunotherapy administration.

Retrospective study.

This retrospective analysis included 261 patients with ES-SCLC treated with first-line chemoimmunotherapy between January 2019 and December 2023. All patients underwent MRI scans to confirm the absence of brain metastases. After 1:2 propensity score matching (PSM), 46 and 81 patients were assigned to the PCI and observation groups, respectively. The primary endpoint was OS, with additional exploration of progression-free survival (PFS), the cumulative incidence of intracranial metastases, and intracranial progression-free survival (iPFS).

After PSM, the two groups were well-balanced in baseline characteristics. Survival analysis showed a median OS of 19.9 months (95% confidence interval (CI): 11.8-28.0) in the PCI group and 15.6 months (12.3-18.9) in the observation group, without a significant difference (hazard ratio (HR) = 0.763 (95% CI: 0.484-1.206), log-rank p = 0.265). PCI significantly reduced the risk of brain metastasis (Fine-Gray p = 0.002), with 1-year cumulative incidence rates of 13.8% (3.4%-24.2%) in the PCI group and 53.4% (41.3%-65.6%) in the observation group. Subgroup analysis showed that for ES-SCLC patients achieving a partial response to initial chemoimmunotherapy, the PCI group had longer median OS (25.7 months (95% CI: 15.4-36.1) vs 19.4 months (15.4-23.4); HR = 0.502 (0.284-0.886); log-rank p = 0.021).

PCI did not improve OS in ES-SCLC patients receiving first-line chemoimmunotherapy, while it may confer a survival benefit for patients who achieve remission following chemoimmunotherapy. In addition, PCI significantly reduced the incidence of brain metastases. These findings warrant further randomized studies for verification.

From the late 1980s to 2000, SCLC represented a decreasing proportion of lung cancer cases in the United States. Nevertheless, survival outcomes in SCLC did not improve, reflecting the paucity of treatment advances. We sought to determine whether these trends continued into more recent decades, before the Food and Drug Administration approval of immunotherapy for SCLC in 2019, by evaluating the incidence and survival of SCLC from 2000 to 2019 in the United States population, with attention to variance across gender and racial subgroups.

Using the United States Surveillance, Epidemiology, and End Results 17 database, we evaluated the incidence of SCLC and NSCLC from 2000 to 2019. Demographic, staging, and survival data were collected for patients with SCLC by comparing the incidence and outcomes across groups.

The percentage of SCLC among all newly diagnosed lung cancer cases decreased from 14.5% in 2000 to 11.8% in 2019. A decrease in SCLC incidence was observed in all sex and racial subgroups but was earlier and steeper in men than in women. This has resulted in a shift in the male-to-female ratio from 1.14:1 in 2000 to 0.93:1 in 2019. Among the racial subgroups, the incidence of SCLC declined most slowly in non-Hispanic Whites and most rapidly in non-Hispanic Asians and Pacific Islanders. There was a decline in limited-stage SCLC at diagnosis, from 31.1% in 2000 to 26.4% in 2019. Minimal improvement was observed in survival regardless of patient characteristics or stage.

In the preimmunotherapy era of 2000 to 2019, the incidence of SCLC continued to decline in both sexes and all racial subgroups. The male-to-female ratio continued to narrow with women outnumbering men in the most recent years. The proportion of patients with limited-stage disease continues to decline, likely because of improved staging procedures. The outcomes improved slightly but remained poor, highlighting the need for more effective treatment strategies.

Small cell lung cancer (SCLC) is a high-grade neuroendocrine carcinoma with an incidence of 4.7 cases per 100 000 individuals in 2021 in the US and a 5-year overall survival of 12% to 30%.

Cigarette smoking is the primary risk factor for development of SCLC, as 95% of patients diagnosed with SCLC have a history of tobacco use. Patients with SCLC may present with respiratory symptoms such as cough (40%), shortness of breath (34%), hemoptysis (10%), or metastases with corresponding local symptoms (30%) such as pleuritis or bone pain; approximately 60% of patients with SCLC may be asymptomatic at diagnosis. Chest imaging may demonstrate central hilar (85%) or mediastinal lymphadenopathy (75%). At diagnosis, approximately 15% of patients have brain metastases, which may present as headache or focal weakness. Diagnosis is confirmed by biopsy of a primary lung mass, thoracic lymph node, or metastatic lesion. Small cell lung cancer is classified into limited stage (LS-SCLC; 30%) vs extensive stage (ES-SCLC; 70%) based on whether the disease can be treated within a radiation field that is typically confined to 1 hemithorax but may include contralateral mediastinal and supraclavicular nodes. For patients with LS-SCLC, surgery or concurrent chemotherapy with platinum-etoposide and radiotherapy is potentially curative in 30% of patients. More recently, median survival for LS-SCLC has reached up to 55.9 months with the addition of durvalumab, an immunotherapy. First-line treatment for ES-SCLC is combined treatment with platinum-etoposide chemotherapy and immunotherapy with the programmed cell death 1 ligand 1 (PD-L1) inhibitors durvalumab or atezolizumab followed by maintenance immunotherapy until disease progression or toxicity. Although initial rates of tumor shrinkage are 60% to 70% with platinum-etoposide and immunotherapy treatment, the median overall survival of patients treated for ES-SCLC is approximately 12 to 13 months, with 60% of patients relapsing within 3 months. Second-line therapy for patients with ES-SCLC includes the DNA-alkylating agent lurbinectedin (35% overall response rate; median progression-free survival, 3.7 months) and a bispecific T-cell engager against delta-like ligand 3, tarlatamab (40% overall response rate; median progression-free survival, 4.9 months).

Small cell lung cancer is a smoking-related malignancy that presents at an advanced stage in 70% of patients. Three-year overall survival is approximately 56.5% for LS-SCLC and 17.6% for ES-SCLC. First-line treatment for LS-SCLC is radiation targeting the tumor given concurrently with chemotherapy and followed by consolidation immunotherapy. For ES-SCLC, first-line treatment is chemotherapy and immunotherapy followed by maintenance immunotherapy.

With the application of immune checkpoint inhibitors (ICIs) and the discovery of the synergistic effect of radiotherapy and immunotherapy, the intracranial benefit of thoracic radiotherapy (TRT) is receiving signiffcant clinical attention. The purpose of this study was to analyze the cranial benefits of ICIs and TRT in patients with extensive-stage small cell lung cancer (ES-SCLC) without baseline brain metastases (BMs).

From August 2019 to August 2022, data from patients diagnosed with ES-SCLC without baseline BMs were retroactively recorded. The Kaplan‒Meier method was used to calculate overall survival (OS), progression-free survival (PFS), and brain metastasis-free survival (BMFS), and the differences between the treatment groups were compared with the log-rank test. Risk factors associated with OS were analyzed via the Cox regression model.

A total of 216 patients were included, with a median follow-up of 24.73 months. Among these patients, 137 (63.4%) received first-line ICIs combined with chemotherapy (ChT), including 32 patients treated with anti-programmed death 1 antibody (αPD-1) and 105 patients treated with anti-programmed death-ligand 1 antibody (αPD-L1), and 79 patients (36.6%) received first-line ChT alone. Compared with the ChT-alone group, the ICI + ChT group demonstrated significantly improved PFS (8.07 vs. 6.87 months; p < 0.001) and OS (19.83 vs. 13.80 months; p = 0.001). The addition of ICIs to the ChT regimen did not significantly delay the onset of BMs compared to that with ChT alone (16.93 vs. 12.67 months; p = 0.379). Notably, the addition of TRT to the αPD-L1 + ChT regimen significantly prolonged BMFS compared to that without TRT (20.27 vs. 8.80 months; p = 0.045).

In patients with ES-SCLC without baseline BMs, first-line chemoimmunotherapy significantly improves PFS and OS. However, it does not delay intracranial metastasis. The addition of TRT to αPD-L1 + ChT therapy significant delays the development of BMs.

Not applicable.

Prophylactic cranial irradiation (PCI) has long been used for SCLC to reduce the risk of brain metastases and potentially improve overall survival. Nevertheless, recent immunotherapy trials have provided limited data on its impact, as few patients were treated with PCI. The ADRIATIC trial reported improved outcomes with consolidation immunotherapy in limited-stage SCLC, and PCI was a stratification factor. Notably, patients receiving PCI in both arms had better outcomes than those who did not. Ongoing studies, such as EORTC-1901 PRIMALung (NCT04790253) and SWOG 1827-MAVERICK (NCT04155034), are further investigating PCI's role in the era of immunotherapy, highlighting its potential importance in evolving treatment strategies.

Small cell lung cancer (SCLC) is a highly aggressive disease, often diagnosed at an advanced stage and with limited treatment options. In recent years, immunotherapy has been approved in combination with chemotherapy in the first line setting of extensive stage disease (ES-SCLC). However, only 10-15 % of patients with ES-SCLC treated with chemoimmunotherapy (CT-IO) experience a long-term benefit. In addition, patients are often clinically frail due to advanced age, comorbidities, and disease-related symptoms, making SCLC a challenging condition. Real-world evidence (RWE) becomes particularly valuable in this scenario, not only to confirm the results of pivotal trials, but also to evaluate the outcomes of CT-IO in populations that are generally excluded from clinical trials. RWE could also define the role of integrative treatments such as thoracic consolidation radiotherapy and prophylactic cranial irradiation, which are used in selected patients in the clinical practice but were scarcely applied in pivotal trials. In this review, we focused on RWE in ES-SCLC, with the aim of improving clinical decision making. Notably, real-world data have largely confirmed the efficacy and safety of CT-IO observed in pivotal clinical trials, with a possible benefit even in more fragile patients. However, these studies also highlight that a significant proportion of the ES-SCLC population remains untreated due to poor clinical conditions.

The combination of atezolizumab with etoposide and carboplatin (AECb) has become a new standard of care for extensive-stage small-cell lung cancer (ES-SCLC). This study evaluates its impact on central nervous system (CNS) progression, specifically brain metastases.

We analyzed the outcomes of 550 ES-SCLC patients who received first-line therapy between 2016 and 2022, focusing on time to intracranial progression (TTicP), progression-free survival (PFS), and overall survival (OS).

Of the 550 patients, 247 (44.9 %) received AECb, while 303 (55.1 %) received conventional chemotherapy (CTx). Intracranial progression occurred in 179 patients (32.5 %), with the AECb group showing a significantly prolonged TTicP compared to the CTx group (median 24.4 vs. 14.3 months; p = 0.038). In patients without brain metastasis at diagnosis (n = 408), TTicP was also longer in the AECb group (27.2 vs. 15.3 months; p = 0.016). This benefit persisted even after excluding patients who underwent prophylactic cranial irradiation (PCI) (27.2 vs. 15.2 months; p = 0.02) (n = 394). These findings remained consistent after adjusting for age, initial metastatic site, and PCI. Additionally, the AECb group showed improved PFS (5.0 vs. 4.7 months; p = 0.004) and OS (11.1 vs. 9.8 months; p = 0.003).

Our findings suggest that the AECb regimen is superior to conventional chemotherapy in delaying CNS progression and controlling systemic disease in ES-SCLC. These results support the AECb regimen as the new standard of care. Further research is needed to explore the mechanisms behind these improved CNS outcomes and to reassess the necessity of PCI in this treatment era.

The role of prophylactic cranial irradiation (PCI) is not well-defined in extensive-stage SCLC (ES-SCLC), with conflicting results from randomized trials and a lack of relevant data for patients who received consolidative thoracic radiotherapy (CTRT). We sought to evaluate the impact of PCI on the outcomes of ES-SCLC patients who were all treated with CTRT.

A retrospective analysis of ES-SCLC patients without brain metastases who were all treated with CTRT between 2013-2021 at our institution was conducted. Overall survival (OS) and incidence of brain failure (BFR) were estimated using Kaplan-Meier estimation and cumulative incidence function. Multivariable Cox or Fine-Gray's proportional hazard regression analysis (MVA) were performed to determine association between PCI and OS.

47 patients met inclusion criteria and were theoretically eligible for PCI, 27 (57.4 %) received PCI and CTRT while 20 (42.6 %) received CTRT alone. Baseline characteristics were similar except for age, where patients receiving PCI were younger (median age 62) compared to patients who did not receive PCI (median age 72). Median OS with PCI was 19.2 months, compared to 10.8 months without PCI (P = 0.0334). This improved OS remained apparent in patients who received post-chemotherapy MRI restaging (P = 0.0245). BFR was reduced with PCI (HR = 0.22 [0.09-0.52], P = 0.0004). On MVA, PCI was significantly and independently associated with improved OS (HR = 0.39 [0.19-0.80], P = 0.01) and reduced BFR (HR = 0.20 [0.09-0.44], P = < 0.001).

This real-world study found PCI was independently associated with improved OS and reduced BFR in ES-SCLC patients treated with CTRT compared to patients treated with CTRT not receiving PCI, including after post-chemotherapy brain MRI. The role of PCI with CTRT should be evaluated in prospective studies.

The role of prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (LS-SCLC) remains controversial in the era of magnetic resonance imaging (MRI). The present study aimed to evaluate the effectiveness of PCI in the treatment of LS-SCLC in the era of MRI. The PubMed, EMBASE and Cochrane Library databases were searched from the time of database creation until May 24, 2023, to identify clinical studies that evaluated the effectiveness of PCI in patients with LS-SCLC in the MRI era. The references of the obtained studies were also reviewed to identify clinical studies that were not discovered in the initial search. All studies were screened in accordance with the inclusion criteria, and the data were extracted and subjected to meta-analysis using STATA17.0. In total, 21 studies were included in the analysis. Notably, 10 studies only used brain MRI at baseline to confirm the absence of brain metastases (BMs; pre-chemoradiotherapy MRI group), 7 studies used brain MRI prior to PCI to confirm the absence of BMs (pre-PCI MRI group) and 4 studies used active surveillance in the form of brain MRI following PCI (MRI surveillance group). The results of the meta-analysis demonstrated that for all included patients, PCI was associated with a significant improvement in overall survival time [OS; hazard ratio (HR), 0.61; confidence interval (CI), 0.53-0.70] and progression-free survival (HR, 0.69; CI, 0.61-0.79), as well as a significant decrease in the rate of BM (HR, 0.59; CI, 0.50-0.70). Subgroup analyses revealed that PCI remained effective in improving OS and reducing the rate of BM in patients with LS-SCLC who did not have BMs confirmed via brain MRI performed at baseline or prior to PCI. However, in the MRI surveillance group, PCI failed to significantly improve the OS (HR, 0.65; CI, 0.41-1.05), despite significantly reducing the BM rate (HR, 0.6; CI, 0.45-0.8) of LS-SCLC. Collectively, the results of the present study demonstrated that PCI remained effective in improving OS and reducing the rate of BM in patients with LS-SCLC who had the absence of BM confirmed via brain MRI at baseline or prior to PCI. Additionally, in patients with LS-SCLC who had undergone active surveillance using brain MRI following PCI, the incidence of BM was reduced, while the OS was not significantly improved. However, additional randomized controlled clinical studies are required to verify these findings.

The median overall survival (OS) is approximately 10 months when chemotherapy alone is the first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). The approval of the two PD-L1 inhibitors, atezolizumab and durvalumab, marked the beginning of the immunotherapy era for ES-SCLC. Serplulimab, as the first PD-1 inhibitor to achieve success in the first-line treatment of ES-SCLC, has not only demonstrated significant improvements in patient survival outcomes but also ushered in a new era for PD-1 inhibitors in the treatment of ES-SCLC. Recently, antiangiogenic agents with chemo-immunotherapy have achieved breakthroughs in first-line ES-SCLC treatment. Improving the clinical benefits of individualized treatment for patients with ES-SCLC remains challenging. Challenges include identifying biomarkers for targeted therapy, exploring new treatments, developing new medicines, and classifying SCLC molecular subtypes. This review provides an in-depth analysis of research on first-line ES-SCLC treatment. Additionally, it discusses advances in ES-SCLC treatment.

Small cell lung cancer (SCLC) is an aggressive tumor that presents in most cases as a metastatic disease. The prognosis is poor, but the advent of immunotherapy has rekindled hopes for outcomes. Radiotherapy plays a crucial role in this oncological scenario, and there are still many open questions on the correct application of radiotherapy and its integration with chemotherapy and immunotherapy. These issues are of great interest to the oncology community; among these, in particular, there are the choice of optimal fractionation and total dose for thoracic radiotherapy in limited SCLC and its biological implications, the role of prophylactic cranial irradiation and thoracic consolidation in the context of modern treatments with chemoimmunotherapy in extensive SCLC, the role and indications of stereotactic radiotherapy in oligometastatic scenario and finally the complex clinical and multidisciplinary management of SCLC. This perspective article aims to describe the strengths and limitations of the role of radiotherapy in SCLC, highlighting the critical role of radiotherapy and the radiation oncologist, with the need to implement specific knowledge and skills on SCLC.

Purpose Small cell carcinoma of the lung (SCLC) often presents with brain metastases, with most patients developing them within a few years of diagnosis. Prophylactic cranial irradiation (PCI) is commonly recommended. Extrapulmonary small cell carcinoma (EPSCC) is rare, and its metastatic pattern is not well understood. This study reviews brain metastases in EPSCC patients at a single institution, focusing on management and overall survival (OS). Materials We identified EPSCC patients and analyzed their characteristics, treatment, and outcomes. Brain metastases were assessed through diagnostic imaging. Extracranial progression-free survival (ePFS) was defined as the time from diagnosis to progression outside the brain, while OS was defined as the time from diagnosis to death from any cause. Kaplan-Meier methods and log-rank tests were used for time-to-event analyses, and the cumulative incidence of brain metastasis was estimated with the competing risk of death. Statistical significance was set at p < 0.05. Results Of the 68 EPSCC patients with a median follow-up of 7.1 months, 66% were male with a median age of 68 years old. Common primary sites included genitourinary (32%) and gastrointestinal/hepatobiliary (22%). Brain metastases occurred in 12 patients (18%): five at diagnosis and seven during follow-up. The treatment of brain metastases varied, with four patients receiving whole-brain radiotherapy (WBRT), two receiving stereotactic radiosurgery (SRS), and one receiving both WBRT and SRS. The median OS was 10.0 months, with no significant survival difference between patients with (10.8 months) and without (9.4 months) brain metastases (p = 0.89). Conclusion EPSCC has a lower incidence of brain metastases than SCLC, and brain metastases do not significantly impact OS. Further research on brain imaging, PCI, and management strategies is warranted.

Small cell lung cancer (SCLC) is an aggressive disease with a poor prognosis, whereas its metastatic capacity carries a predilection for the brain. Although prophylactic cranial irradiation (PCI) has been used to address this problem, upcoming alternatives might necessitate reflection of its application in SCLC treatment.

The addition of immunotherapy to treatment guidelines has provided a new strategy for the management of brain metastases. Complementation of immunotherapy with active MRI surveillance could potentially replace PCI and avoid irradiation-related cognitive side effects. SCLC's molecular profile is heterogeneous, with differential response to treatment modalities between subgroups. Investigation of these variances might be essential to improve therapeutic outcomes in SCLC patients.

The role of PCI in SCLC treatment must be examined in light of immunotherapy. We summarize recent results, bearing SCLC subtypes and therapeutic vulnerabilities in mind, to derive tailored treatment strategies for SCLC patients in future settings.

The role of consolidative thoracic and prophylactic brain radiation for extensive stage small cell lung cancer patients is controversial. We investigated the factors associated with the use of any radiation therapy (RT) and whether RT has a benefit to overall survival (OS) in patients receiving any systemic therapy and whether this benefit is the same if Chemotherapy (CT) or chemo-immunotherapy (CT-IO) is used.

The NCDB database was queried from years 2017-2019. Patients receiving systemic therapy- STX (CT or CT-IO) had to have at least 6 months of follow-up and have no brain metastases at diagnosis. All RT patients had to receive upfront systemic therapy, be treated 2-6 months from diagnosis, and if treated to the brain received 25 Gy in 10 fractions only. Multi-variable analyses (MVA) were used to determine factors associated with OS and selection for any radiation. Propensity matching for factors affecting OS were used to generate Kaplan-Meier OS curves. Log-rank tests were used to determine differences in Kaplan Meier survival curves for the effects of RT on OS.

The total number of patients receiving RT/STX or STX alone as well as their median follow-up (months) were (890, 17.0 mn) and (6898, 14.0mn). The median time to the start of STX and RT were 22.9 days and 152 days, respectively. MVA noted that RT had a greater effect on OS (Thorax, Brain, Both Brain/Thorax - HRs = 0.80, 0.77, 0.70) than other interventions including IO (HR 0.87) and palliative care without RT (HR 1.06). Selection for radiation depended significantly upon factors affecting OS (HR) including lack of liver metastases, females, age and Charlson co-morbidity index, but did not depend upon insurance status, race, or county income/high school graduation rates. Propensity-score matched OS curves noted the same significant effects of RT on OS in those receiving CT +/- IO, CT-IO, and CT alone with HRs of 0.68/0.68/0.68 for thoracic RT, 0.72/0.72/0.70 for brain RT, and 0.60/0.60/0.60 for brain/thoracic RT, respectively.

The patient with extensive stage small cell lung cancer who reach candidacy and receive RT may have a significant improvement in OS compared to the patients treated only with CT or CT-IO. Combined thoracic and prophylactic brain RT seems to be better than either one alone. The impact of radiation whether given to one or two sites may be more beneficial than immunotherapy added to chemotherapy.

SCLC is characterized by aggressiveness and limited treatment options, especially in extensive-stage SCLC (ES-SCLC). Immunotherapy added to the platinum-etoposide combination has recently become standard in this setting. This retrospective study aims to evaluate the real-world effectiveness of chemo-immunotherapy in patients with ES-SCLC, focusing on subpopulations excluded from clinical trials.

A retrospective binational multicenter study was conducted, involving consecutive patients with ES-SCLC from 10 British and 10 Swiss institutions. Patients received platinum-etoposide chemotherapy in combination with immunotherapy (atezolizumab or durvalumab). Patient, tumor, and treatment details were collected. Overall survival (OS), progression-free survival, objective response rate, and safety outcomes were analyzed.

A total of 436 patients were included. One hundred forty-two patients (32.6%) in our cohort would not have been eligible for the pivotal registrational trials owing to an Eastern Cooperative Oncology Group performance status of 2 or higher, autoimmune disease, active brain metastases, or steroid use. Most patients received carboplatin (96.8%) and atezolizumab (97.9%). The median progression-free survival was 5.5 months and the median OS was 9.3 months. The two-year OS was 14%. Patients with liver or bone metastases or an Eastern Cooperative Oncology Group performance status of 2 or higher had worse survival outcomes. Treatment-related adverse events were reported in 222 patients (51%) whereas immune-related adverse events occurred in 95 patients (22%). Three out of five grade 5 immune-related adverse events were caused by pneumonitis.

To our knowledge, this is the largest real-world cohort of patients treated with chemo-immunotherapy for ES-SCLC. Although one-third of patients would not have been eligible for pivotal trials, the survival outcomes in our cohort are similar to those in registrational trials. In particular, the number of long-term survivors and the safety data are comparable, supporting the use of chemo-immunotherapy as first-line treatment for ES-SCLC in daily clinical practice.

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.

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.

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.

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.

To construct a CT-based radiomics nomogram, enabling the estimation of overall survival (OS) in small cell lung cancer (SCLC) patients and facilitating the identification of prophylactic cranial irradiation (PCI) beneficiaries through risk stratification using the radiomics score (RS).

A retrospective recruitment of 375 patients with pathologically confirmed SCLC was conducted across three medical centers, followed by their division into different cohorts. To generate the RS, a series of analyses were performed, including Pearson correlation analysis, univariate Cox analysis, and least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Subsequently, patients were stratified into either the low RS or high RS group, determined by identifying the optimal RS cutoff value. Subsequently, a radiomics nomogram was constructed using the RS, followed by assessments of its discrimination, calibration, clinical utility and reclassification. Moreover, we evaluated the potential benefits of PCI following stratification by RS.

For the internal and external validation cohorts, the radiomics nomogram (concordance index [C-index]: 0.770, 0.763) outperformed clinical nomogram (C-index: 0.625, 0.570) in predicting OS. Besides, patients with high RS had survival benefit from PCI in both the limited and extensive stage (hazard ratio [HR]: 0.304, 95% confidence interval [CI]: 0.087-1.065, P = 0.003; HR: 0.481, 95% CI: 0.270-0.860, P = 0.019, respectively), while no significant association were observed in patients with low RS.

A radiomics nomogram based on CT shows potential in predicting OS for individuals with SCLC. The RS could assist in tailoring treatment plans to identify patients likely to benefit from PCI.

Recent advancements in magnetic resonance imaging (MRI) for staging have highlighted the critical question of the need for prophylactic cranial irradiation (PCI) in managing early to mid-stage small cell lung cancer (SCLC). This study assesses the impact of PCI on overall survival (OS) and intracranial control among patients with stage I-IIB SCLC.

Data from 148 stage I-IIB SCLC patients treated with thoracic radiation therapy (TRT) at two centers were examined. Patients were categorized based on PCI administration: 63 received PCI, while 85 did not. All underwent pretreatment MRI, achieving at least a partial response to therapy. A 1:1 propensity score matching analysis corrected for potential biases.

Propensity scores were generated to 116 patients, considering patient demographics, disease progression, and treatment methods. Death was included as a competing risk. The 3-year brain metastases (BM) occurrence rate was significantly higher in patients who did not receive PCI (30.0%) compared to those who did (14.8%), however, the difference was not statistically significant (No PCI vs. PCI, hazard ratio [HR]: 2.08, 95% CI [0.93-4.55], P = .07). No significant effect of PCI on OS was observed [PCI vs. No PCI, HR: 0.80, 95% CI (0.45-1.43), P = .45]. A subgroup analysis of stage IIB patients showed a significant increase in BM risk and mortality for those not receiving PCI (No PCI vs. PCI, BM risk HR: 5.85, 95% CI: 1.83-18.87, P = .003; mortality HR: 2.78, 95% CI: 1.14-6.67, P = .02), with less pronounced effects in stages I-IIA.

With modern MRI-based screening, PCI may markedly benefit stage IIB SCLC patients by reducing BM and improving OS after initial sensitive treatment. This benefit does not appear to extend to stage I-IIA patients.

Whole-brain radiotherapy (WBRT) is a standard and effective approach for brain metastases, but it is linked to neurocognitive complications, specifically issues related to the hippocampus. Innovative strategies are being explored to enhance outcomes. However, a consensus is yet to be reached in this field. Our aim is to investigate the efficacy and safety of WBRT combined with simultaneous integrated boost (SIB), memantine, and hippocampal avoidance (HA) techniques in treatment of brain metastases.

In this systematic review and meta-analysis, we comprehensively searched PubMed, MEDLINE, Embase, and Cochrane for studies reporting the efficacy and toxicity of WBRT-based combination therapies from inception to September 19, 2023. Data were pooled using random-effects models. Results were reported as risk ratios (RRs) and risk differences (RDs) for dichotomous outcomes, along with their 95% confidence intervals (CIs). Heterogeneity was evaluated using the I2 statistic.

Among 2175 articles, 29 studies involving 3460 patients were included. The meta-analysis revealed that compared to WBRT alone, combination therapies significantly mitigated neurocognitive function decline (RD = -0.09, 95% CI [-0.18-0.01]; P = 0.03) and intracranial control failure (RR = 0.86, 95% CI [0.52-1.44]; P = 0.02), without increasing the risk of hippocampal recurrence or high-grade toxicities. Notably, HA-WBRT + SIB/memantine demonstrated improved neurocognitive outcomes and survival benefits.

WBRT-based combination therapies demonstrate improved efficacy and comparable safety to WBRT alone, with specific emphasis on the effectiveness of HA-WBRT + Memantine and HA-WBRT + SIB in optimizing therapeutic outcomes for brain metastases.

Neuroendocrine carcinoma of the bladder (NEC-bladder) is a rare disease with poor outcomes and variable treatment approaches.

Patients with localized NEC-bladder treated with surgery or radiation between 2001-2021 were retrospectively identified. Rates of pathologic complete response (pCR) and downstaging were evaluated following NAC in surgically-treated patients. Progression-free survival (PFS) and overall survival (OS) were analyzed with univariable (log-rank) and multivariable (MVA; Cox regression) methods.

Sixty-five patients were identified having a median age of 73. The tumor histology distribution was small cell (64.6%) or urothelial with NE differentiation (35.4%). Most patients (69.2%) received NAC. Patients received local therapy by surgery (78.5%) or chemoradiation (21.5%). The majority (62.7%) of surgical patients had ≥ pT2 with 37.3% having nodal involvement (pN+). The pCR and downstaging rates were 21.6% and 35.1%, respectively. At a median follow-up of 60 months (m), the median PFS and OS were 16.4m and 25.9m, respectively. NAC improved PFS (p=0.04) and downstaging improved PFS (p=0.012) and OS (p<0.001). Patients receiving NAC with ypN0 vs. ypN+ had median OS of 69.9m vs 15.3m, respectively (p<0.001). MVA identified receipt of NAC and pN as predictors of PFS; pN was predictive of OS. No differences in PFS or OS were seen between histology of primary tumor. The brain metastasis rate was 10.8% with all patients having small cell histology.

Optimized therapy in NEC-bladder includes NAC followed by local consolidation. Ascertainment of ypN0 is associated with long term survival, while pN+ remains associated with poor outcomes.

Brain metastases (BMs) in extensive-stage small cell lung cancer (ES-SCLC) are often associated with poor survival rates and quality of life, making the timely identification of high-risk patients for BMs in ES-SCLC crucial. Patients diagnosed with ES-SCLC between 2010 and 2018 were screened from the Surveillance, Epidemiology, and End Results (SEER) database. Four different machine learning (ML) algorithms were used to create prediction models for BMs in ES-SCLC patients. The accuracy, sensitivity, specificity, AUROC, and AUPRC were compared among these models and traditional logistic regression (LR). The random forest (RF) model demonstrated the best performance and was chosen for further analysis. The AUROC and AUPRC were calculated and compared. The findings from the RF model were utilized to identify the risk factors linked to BMs in patients diagnosed with ES-SCLC. Examining 4,716 instances of ES-SCLC, the research conducted an analysis, with brain metastases arising in 1,900 cases. Through evaluation of the ROC curve and PRC concerning the RF Model, results depicted an AUROC of 0.896 (95% CI: 0.889-0.899) and AUPRC of 0.900 (95% CI: 0.895-0.904). Test accuracy measured at 0.810 (95% CI: 0.784-0.833), sensitivity at 0.797 (95% CI: 0.756-0.841), and specificity at 0.819 (95% CI: 0.754-0.879). Based on the SHAP analysis of the RF predictive model, the top 10 most relevant features were identified and ranked in order of relative importance: bone metastasis, liver metastasis, radiation, age, tumor size, primary tumor location, N-stage, race, T-stage, and chemotherapy. The research developed and validated a predictive RF model using clinical and pathological data to predict the risk of BMs in patients with ES-SCLC. This model may assist physicians in making clinical decisions that could delay the onset of BMs and improve patient survival rates.

To evaluate the impact of prophylactic cranial irradiation (PCI) on the prognosis of patients with limited-stage small cell lung cancer (SCLC) in the era of MRI surveillance.

Limited-stage SCLC patients with complete remission (CR) or partial remission (PR) of tumor after definitive chemo-radiotherapy (CRT) were retrospectively analyzed. Survival data were calculated by Kaplan-Meier methods, Cox proportional hazards model was applied for multivariate prognostic analysis.

Between June 2002 and January 2017, 620 patients with limited-stage SCLC were accrued in our study. After CRT, 228 (36.8%) patients achieved CR, of whom, 29 patients did not receive PCI, among the rest 199 patients, 172 (86.4%) received brain MRI to exclude brain metastasis (BM) before PCI. With a median follow-up time of 25.6 months, the cumulative BM rate was 17.1% and 37.9% in patients who received or did not receive PCI (P = 0.011). The median survival time was 30.2 months and 30.5 months, respectively and the 1 -, 3 -, 5-year survival rates were 93.7%, 42.9%, 35.8% and 83.4%, 46.5%, 41.9%, respectively (P = 0.98). Multivariate analysis indicated that baseline KPS ≥ 90 was a favorable independent prognostic factor for OS in CR patients (HR: 0.33, 95% CI: 0.23-0.46, P = 0.000). After CRT, 392 (63.2%) patients achieved PR, 53 cases did not receive PCI and 310 (91.4%) of the remaining 339 patients received brain MRI before PCI. With a median follow-up time of 15.5 months, the cumulative brain metastasis rate was 12.7% and 46.2% respectively (P = 0.000). The median survival time was 25.7 months and 18.6 months, respectively. The 1 -, 3 -, and 5-year survival rates were 87.6%, 40.2%, 29.2% and 75.7%, 16.7%, 10.3% (P = 0.000). Baseline KPS ≥ 90 (HR: 0.32, 95% CI: 0.25-0.41, P = 0.000) and PCI (HR: 0.57, 95% CI: 0.41-0.79, P = 0.001) were favorable prognostic factors for OS in PR patients.

In this study, PCI significantly reduced the incidence of BM in patients with limited-stage SCLC who were evaluated as CR and PR after CRT, but it has no significantly positive impact on overall survival in CR patients. Further prospective randomized studies were warranted.

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.

Patients with small cell lung cancer (SCLC) have historically been characterised by poor overall survival (OS) and high risk for brain metastasis (BM), but large-scale real-world evidence on clinical presentation and treatment in this population is lacking. Our aim was to describe the clinical characteristics and outcomes of patients with SCLC and BM in Ontario, Canada.

This population-based, retrospective cohort study included all patients in Ontario, Canada, who were diagnosed with SCLC between April 1, 2010, and March 31, 2018. Data were analysed between June 2, 2022, and December 20, 2023. Patients with second cancer diagnosis were excluded. Patients were identified and data retrieved from the Institute for Clinical Evaluative Sciences (ICES) databases. Kaplan-Meier and multivariable Cox regression analyses were performed to compare OS between patient cohorts stratified by disease stage, BM diagnosis, and intracranial treatment modality. Propensity score-matching based on age, disease stage, time to BM, and receipt of chemotherapy was performed to compare OS between intracranial treatment modalities.

8705 patients were included (male: 4433, female: 4272). Median age at diagnosis was 68 years (interquartile range, IQR, 61-75). Median OS of all patients was 7.46 months (95% confidence interval, CI, 7.23-7.69). 32% (n = 2686) of patients developed BM (synchronous, 43.7%; asynchronous, 56.3%) with median OS of 9.76 months (95% CI, 9.36-10.22). 102 (4%), 1654 (62%), and 930 (35%) patients received stereotactic radiosurgery (SRS), whole brain radiation therapy (WBRT), or no treatment, respectively, for their BM in the first-line setting or after prophylactic cranial irradiation (PCI). In propensity score-matched analyses, OS from time of BM diagnosis was non-inferior between SRS- and WBRT-treated cohorts among patients who did not receive PCI (hazard ratio, HR, 0.68, 95% CI, 0.44-1.06, p = 0.091, n = 86) and in favour of SRS for those who received PCI prior to BM development (HR, 0.47, 95% CI, 0.31-0.72, p = 0.0042, n = 112).

OS for patients with SCLC remains poor, and many patients present with BM. With careful selection, patients with SCLC and BM may benefit from SRS treatment. Future research should incorporate information on burden of intracranial disease and novel immunotherapies.

None.

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).

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.

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.

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.

Extensive-stage small cell lung cancer (ES-SCLC) is a notoriously aggressive malignancy frequently associated with brain metastases (BMs), presenting substantial therapeutic challenges. This study delves into the effectiveness of immunotherapy combined with diverse radiotherapy, especially the influence of brain radiotherapy (BRT) on survival outcomes in the immunotherapy era.

ES-SCLC patients treated at Xiangya Hospital and Xiangya Boai Hospital from February 2020 to June 2024 were retrospectively included. The study focused on patients receiving immune checkpoint inhibitors (ICIs). Metrics included overall survival (OS) and progression-free survival (PFS), employing univariate and multivariate Cox regression models for statistical analysis.

A total of 393 patients with ES-SCLC who received ICIs were included in the study. Within the entire cohort, the presence of baseline BMs did not statistically affect OS or PFS. However, thoracic radiotherapy (TRT) was identified as a favorable prognostic factor for both OS and PFS. BRT demonstrated a beneficial effect on OS across both the general cohort and the baseline_BMs subgroup. In patients from the baseline_BMs subgroup who had previously undergone TRT, ICIs plus BRT did not significantly improve OS compared to ICIs alone. Conversely, for patients who had not received prior TRT, adding BRT to ICIs significantly enhanced OS. Among the patients who underwent BRT, 71 received whole brain radiotherapy (WBRT) while 19 opted for stereotactic radiosurgery (SRS). No significant differences in OS and PFS were observed between the SRS and WBRT modalities. The sequence of ICIs relative to BRT was found to influence PFS adversely. Administering BRT before ICIs (RT-ICI) was associated with worse PFS compared to administering ICIs followed by BRT (ICI-RT). Additionally, no significant differences in OS and PFS were noted among the three subgroups defined by varying intervals between ICIs and BRT. For patients without baseline BMs, TRT and prophylactic cranial irradiation were associated with delayed onset of brain metastases.

Our study underscores the importance of optimizing treatment strategies and considering the timing and integration of radiotherapy and immunotherapy to improve outcomes for patients with ES-SCLC, particularly those at risk of or presenting with BMs.

Background: Small cell lung cancer (SCLC) is a lethal form of lung cancer with few treatment options and a high rate of relapse. While SCLC is initially sensitive to first-line DNA-damaging chemo- and radiotherapy, relapse disease is almost universally therapy-resistant. As a result, there has been interest in understanding the mechanisms of therapeutic resistance in this disease. Conclusions: Progress has been made in elucidating these mechanisms, particularly as they relate to the DNA damage response and SCLC differentiation and transformation, leading to many clinical trials investigating new therapies and combinations. Yet there remain many gaps in our understanding, such as the effect of epigenetics or the tumor microenvironment on treatment response, and no single mechanism has been found to be ubiquitous, suggesting a significant heterogeneity in the mechanisms of acquired resistance. Nevertheless, the advancement of techniques in the laboratory and the clinic will improve our ability to study this disease, especially in patient populations, and identify methods to surmount therapeutic resistance.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3, has shown durable anticancer activity and manageable safety in previously treated small cell lung cancer (SCLC) in DeLLphi-300 phase I and DeLLphi-301 phase II trials. Here, we report extended follow-up of DeLLphi-300 (median follow-up, 12.1 months [range, 0.2-34.3]) in fully enrolled cohorts treated with tarlatamab ≥10 mg dose administered once every two weeks, once every three weeks, or once on day 1 and once on day 8 of a 21-day cycle (N = 152). Overall, the objective response rate (ORR) was 25.0%; the median duration of response (mDOR) was 11.2 months (95% CI, 6.6 to 22.3), and the median overall survival (mOS) was 17.5 months (95% CI, 11.4 to not estimable [NE]). Among 17 patients receiving 10 mg tarlatamab once every two weeks, the ORR was 35.3%, the mDOR was 14.9 months (95% CI, 3.0 to NE), the mOS was 20.3 months (95% CI, 5.1 to NE), and 29.4% had sustained disease control with time on treatment ≥52 weeks. No new safety signals were identified. In modified Response Assessment in Neuro-Oncology Brain Metastases analyses, CNS tumor shrinkage of ≥30% was observed in 62.5% of patients (10 of 16) who had a baseline CNS lesion of ≥10 mm, including in a subset of patients with tumor shrinkage long after previous brain radiotherapy. In DeLLphi-300 extended follow-up, tarlatamab demonstrated unprecedented survival and potential findings of intracranial activity in previously treated SCLC.

Lung cancer is one of the leading causes of death worldwide. It can broadly be divided into small cell lung cancer (SCLC) and nonsmall cell lung cancer. There have been many advances over the recent years in both fields. The purpose of this review is to provide a concise summary of SCLC for the general respiratory readership.

Small cell lung cancer (SCLC) is an aggressive malignancy with a high propensity for brain metastases (BM). Limited-stage SCLC (LS-SCLC) can be effectively treated with chemoradiotherapy and prophylactic cranial irradiation (PCI) to enhance patient outcomes. The aim of the present study was to assess the risk factors and prognostic significance of brain metastases (BM) in patients with limited-stage small cell lung cancer (LS-SCLC) who attained complete remission (CR) or partial remission (PR) following combined chemoradiotherapy and subsequent prophylactic cranial irradiation (PCI). Data for 290 patients diagnosed with LS-SCLC and treated at Chengde Central Hospital and Hebei Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine (Chengde, China), who achieved CR or PR and underwent PCI between 2015 and 2023, were retrospectively analyzed. BM rates and overall survival (OS) were estimated using the Kaplan-Meier method, whilst differences were assessed using the log-rank test. Risk factors affecting BM and OS were assessed using univariate and multivariate Cox regression analyses. The overall incidence of BM after PCI was 16.6% (48/290), with annual rates of 1.4, 6.6 and 12.8% at 1, 2 and 3 years, respectively. Multivariate Cox regression analysis identified an initial tumor size of >5 cm [hazard ratio (HR)=15.031; 95% confidence interval (CI): 5.610-40.270; P<0.001] as a significant independent risk factor for BM following PCI. The median OS was 28.8 months and the 5-year OS rate was 27.9%. The median OS for patients with and without BM at 27.55 and 32.5 months, respectively, and the corresponding 5-year OS rates were 8.3 and 31.8%, respectively (P=0.001). Median OS rates for stages I, II and III were 61.15, 48.5 and 28.4 months, respectively, with 5-year OS rates of 62.5, 47.1 and 21.6%, respectively (P<0.001). Further multivariate Cox regression analysis indicated that BM (HR=1.934; 95% CI: 1.358-2.764; P<0.001) and clinical stage (HR=1.741; 95% CI: 1.102-2.750; P=0.018; P=0.022) were significant independent risk factors associated with patient OS. In conclusion, a tumor size of >5 cm is a significant risk factor for BM following PCI in patients with LS-SCLS achieving CR or PR through radiotherapy and chemotherapy. Furthermore, BM and clinical staging independently influence OS.

In the context of the widespread availability of magnetic resonance imaging (MRI) and aggressive salvage irradiation techniques, there has been controversy surrounding the use of prophylactic cranial irradiation (PCI) for small-cell lung cancer (SCLC) patients. This study aimed to explore whether regular brain MRI plus salvage brain irradiation (SBI) is not inferior to PCI in patients with limited-stage SCLC (LS-SCLC).

This real-world multicenter study, which was conducted between January 2014 and September 2020 at three general hospitals, involved patients with LS-SCLC who had a good response to initial chemoradiotherapy and no brain metastasis confirmed by MRI. Overall survival (OS) was compared between patients who did not receive PCI for various reasons but chose regular MRI surveillance and followed salvage brain irradiation (SBI) when brain metastasis was detected and patients who received PCI.

120 patients met the inclusion criteria. 55 patients received regular brain MRI plus SBI (SBI group) and 65 patients received PCI (PCI group). There was no statistically significant difference in median OS between the two groups (27.14 versus 33.00 months; P = 0.18). In the SBI group, 32 patients underwent whole brain radiotherapy and 23 patients underwent whole brain radiotherapy + simultaneous integrated boost. On multivariate analysis, only extracranial metastasis was independently associated with poor OS in the SBI group.

The results of this real-world study showed that MRI surveillance plus SBI is not inferior to PCI in OS for LS-SCLC patients who had a good response to initial chemoradiotherapy.