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Purposes: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Hippo‐avoidance prophylactic cranial irradiation (HA‐PCI) requires a hippocampal avoidance zone expanded from hippocampus to ensure dose fall‐off and compensate for setup errors. Most studies recommend a 5‐mm margin, while it could be optimized to a 2‐mm expansion. Here, we showed the details of optimized HA‐PCI for limited‐stage small cell lung cancer (LS‐SCLC).This cohort study reviewed patients with LS‐SCLC receiving optimized HA‐PCI from August 2014 to June 2020 in the National Cancer Center of China. The hippo‐related dose parameters were summarized. The comparison of the Hopkins Verbal Learning Test—Revised (HVLT‐R) scores in different time points was conducted. The Kaplan–Meier method was used to calculate the survival rates.A total of 112 patients were included. The average doses of hippocampus and hippocampal avoidance zone were 6.80 Gy (IQR: 6.40–7.44) and 7.63 Gy (IQR: 7.14–8.39). No differences were observed in the two radiation techniques (tomotherapy [TOMO] vs. volumetric‐modulated arc therapy [VMAT]). The decline of HVLT‐R score remained in a low level and not significant in assessable patients (p = 0.095). With a median follow‐up of 52 months (95% CI: 47.2–56.7), the 2‐year overall survival and progression‐free survival were 74.1% and 50.0%, respectively. Two intracranial recurrence lesions (2.3%) located <2 mm from the hippocampus.Optimized HA‐PCI could achieve similar dose limitation by TOMO and VMAT techniques with favorable efficacy and minor toxicity. [ABSTRACT FROM AUTHOR]

Abstract Purposes 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. Methods 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. Results 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. Conclusions 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.

Abstract Background and purpose 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). Methods 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. Results 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. Conclusion 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.

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

Background and purpose: 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). Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Simple Summary: 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 issues of screening in asymptomatic patients, prophylactic strategies with radiation and secondary chemoprevention with targeted agents are discussed. 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. [ABSTRACT FROM AUTHOR]

Abstract Background Prophylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged. Methods A multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited-stage is defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum and supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4–6 weeks after the completion of chemo-radiotherapy. Eligible patients will be randomly assigned to two arms: (1) PCI and brain MRI surveillance arm, receiving PCI (2.5 Gy qd to a total dose of 25 Gy in two weeks) followed by brain MRI surveillance once every three months for two years; (2) brain MRI surveillance alone arm, undergoing brain MRI surveillance once every three months for two years. The primary objective is to compare the 2-year brain metastasis-free survival (BMFS) rates between the two arms. Secondary objectives include 2-year overall survival (OS) rates, intra-cranial failure patterns, 2-year progression-free survival rates and neurotoxicity. In case of brain metastasis (BM) detect during follow-up, stereotactic radiosurgery (SRS) will be recommended if patients meet the eligibility criteria. Discussion Based on our post-hoc analysis of a prospective study, we hypothesize that in limited-stage SCLC patients with CR after definitive chemoradiotherapy, and ruling out of BM by MRI, it would be feasible to use brain MRI surveillance and omit PCI in these patients. If BM is detected during follow-up, treatment with SRS or whole brain radiotherapy does not appear to have a detrimental effect on OS. Additionally, this approach may reduce potential neurotoxicity associated with PCI.

Background: Prophylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged. Methods: A multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited-stage is defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum and supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4–6 weeks after the completion of chemo-radiotherapy. Eligible patients will be randomly assigned to two arms: (1) PCI and brain MRI surveillance arm, receiving PCI (2.5 Gy qd to a total dose of 25 Gy in two weeks) followed by brain MRI surveillance once every three months for two years; (2) brain MRI surveillance alone arm, undergoing brain MRI surveillance once every three months for two years. The primary objective is to compare the 2-year brain metastasis-free survival (BMFS) rates between the two arms. Secondary objectives include 2-year overall survival (OS) rates, intra-cranial failure patterns, 2-year progression-free survival rates and neurotoxicity. In case of brain metastasis (BM) detect during follow-up, stereotactic radiosurgery (SRS) will be recommended if patients meet the eligibility criteria. Discussion: Based on our post-hoc analysis of a prospective study, we hypothesize that in limited-stage SCLC patients with CR after definitive chemoradiotherapy, and ruling out of BM by MRI, it would be feasible to use brain MRI surveillance and omit PCI in these patients. If BM is detected during follow-up, treatment with SRS or whole brain radiotherapy does not appear to have a detrimental effect on OS. Additionally, this approach may reduce potential neurotoxicity associated with PCI. [ABSTRACT FROM AUTHOR]

Introduction: Small cell lung cancer (SCLC) is a highly aggressive lung cancer variant known for its elevated risk of brain metastases (BM). While earlier meta‐analyses supported the use of prophylactic cranial irradiation (PCI) to reduce BM incidence and enhance overall survival, modern MRI capabilities raise questions about PCI's universal benefit for limited‐stage SCLC (LS‐SCLC) patients. As a response, we have created a predictive model for BM, aiming to identify low‐risk individuals who may not require PCI. Methods: A total of 194 LS‐SCLC patients without PCI treated between 2009 and 2021 were included. We conducted both univariate and multivariate analyses to pinpoint the factors associated with the development of BM. A nomogram for predicting the 2‐ and 3‐year probabilities of BM was then constructed. Results: Univariate and multivariate analyses revealed several significant independent risk factors for the development of BM. These factors include TNM stage, the number of chemotherapy (ChT) cycles, Ki‐67 expression level, pretreatment serum lactate dehydrogenase (LDH) levels, and haemoglobin (HGB) levels. These findings underscore their respective roles as independent predictors of BM. Based on the results of the final multivariable analysis, a nomogram model was created. In the training cohort, the nomogram yielded an area under the receiver operating characteristic curve (AUC) of 0.870 at 2 years and 0.828 at 3 years. In the validation cohort, the AUC values were 0.897 at 2 years and 0.789 at 3 years. The calibration curve demonstrated good agreement between the predicted and observed probabilities of BM. Conclusions: A novel nomogram has been developed to forecast the likelihood of BM in patients diagnosed with LS‐SCLC. This tool holds the potential to assist healthcare professionals in formulating more informed and tailored treatment plans. [ABSTRACT FROM AUTHOR]

Abstract Small‐cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor that is prone to spread extensively. Compared to non‐small‐cell lung cancer (NSCLC), SCLC treatment progresses slowly. Although SCLC is highly sensitive to chemotherapy during the initial treatment, most patients still experience resistance and recurrence after receiving chemotherapy. A meta‐analysis demonstrated that thoracic radiotherapy (TRT) improves overall survival in SCLC. The results of the CALGB and CONVERT trials provide evidence for the efficacy of once‐daily high‐dose TRT. TRT at 60 Gy administered twice daily significantly improved survival without increasing toxicity. The long‐standing debate over the optimal timing of radiotherapy has not been fully resolved. SBRT has excellent local control rates and is a safe and effective treatment option for patients with stage I or II SCLC. Prophylactic cranial irradiation (PCI) is used to reduce treatment‐related neurotoxicity to the extent that there has been a recent discussion on whether magnetic resonance imaging (MRI) monitoring can replace PCI. Radiotherapy combined with immunotherapy significantly improves the survival rate of patients with NSCLC; however, its clinical effectiveness has not been systematically explored in patients with SCLC. Therefore, we summarize the evolving therapeutic strategies, (TRT for limited stage‐SCLC and consolidative TRT for extensive stage‐SCLC) and improved radiotherapy techniques (role of SBRT in stage I or II node‐negative SCLC, progress of PCI, and stereotactic radiosurgery), and discuss the possibilities and prospects of radiotherapy combined with immunotherapy for SCLC.

Abstract Objective The 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. Methods Patients 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. Results In 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). Conclusion Compared 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.

Abstract Introduction Small cell lung cancer (SCLC) is a highly aggressive lung cancer variant known for its elevated risk of brain metastases (BM). While earlier meta‐analyses supported the use of prophylactic cranial irradiation (PCI) to reduce BM incidence and enhance overall survival, modern MRI capabilities raise questions about PCI's universal benefit for limited‐stage SCLC (LS‐SCLC) patients. As a response, we have created a predictive model for BM, aiming to identify low‐risk individuals who may not require PCI. Methods A total of 194 LS‐SCLC patients without PCI treated between 2009 and 2021 were included. We conducted both univariate and multivariate analyses to pinpoint the factors associated with the development of BM. A nomogram for predicting the 2‐ and 3‐year probabilities of BM was then constructed. Results Univariate and multivariate analyses revealed several significant independent risk factors for the development of BM. These factors include TNM stage, the number of chemotherapy (ChT) cycles, Ki‐67 expression level, pretreatment serum lactate dehydrogenase (LDH) levels, and haemoglobin (HGB) levels. These findings underscore their respective roles as independent predictors of BM. Based on the results of the final multivariable analysis, a nomogram model was created. In the training cohort, the nomogram yielded an area under the receiver operating characteristic curve (AUC) of 0.870 at 2 years and 0.828 at 3 years. In the validation cohort, the AUC values were 0.897 at 2 years and 0.789 at 3 years. The calibration curve demonstrated good agreement between the predicted and observed probabilities of BM. Conclusions A novel nomogram has been developed to forecast the likelihood of BM in patients diagnosed with LS‐SCLC. This tool holds the potential to assist healthcare professionals in formulating more informed and tailored treatment plans.

Summary: Background: Patients with small cell lung cancer (SCLC) are at high risk for brain metastases. Prophylactic cranial irradiation (PCI) is recommended in this population to reduce the incidence of brain metastases and prolong survival. We aimed to assesses the efficacy of PCI in this population in the era of routine brain imaging. To our knowledge, this is the first systematic review and meta-analysis to examine the use among patients who were radiographically confirmed not to have brain metastases after completion of first-line therapy. Methods: In this systematic review and meta-analysis, cohort studies and controlled trials reporting on the use of PCI for patients SCLC were identified in EMBASE, MEDLINE, CENTRAL, and grey literature sources. The literature search was conducted on November 12, 2023. Summary data were extracted. Random-effects meta-analyses pooled hazard ratios (HR) for the primary outcome of overall survival between PCI and no intervention groups. This study is registered with the Open Science Framework, DOI:10.17605/OSF.IO/BC359, and PROSPERO, CRD42021249466. Findings: Of 4318 identified records, 223 were eligible for inclusion. 109 reported on overall survival in formats amenable to meta-analysis; PCI was associated with longer survival in all patients with SCLC (HR 0.59; 95% CI, 0.55–0.63; p

Background: The role of cranial radiation therapy with hippocampus avoidance (HA-CRT) in neurocognitive function (NCF), brain metastasis (BM), and overall survival (OS) in lung cancer remains unclear. Methods: A meta-analysis was conducted to evaluate the impact of HA-CRT in lung cancer. Data from studies on hippocampal-avoidance prophylactic cranial irradiation (HA-PCI) and whole brain radiotherapy (HA-WBRT) were pooled. Results: A total of 14 studies, including 5 randomized controlled trials, were included. The focus of NCF was mainly via the Hopkins Verbal Learning Test—Revised or the Free and Cued Selective Reminding Test. At 6 months post-radiotherapy, the pooled proportion of participants with decline in the performance of total recall, delayed recall, and discrimination in neurocognitive tests were 0.22 (95% CI 0.15, 0.29), 0.20 (95% CI 0.13, 0.27), and 0.14 (95% CI 0.05, 0.24) respectively. After 12 months, the proportion were 0.16 (95% CI 0.08, 0.23), 0.10 (95% CI 0.04, 0.16), and 0.04 (95% CI 0, 0.09) respectively. For HA zone relapse, the RR of HA-CRT versus CRT was 2.72 (95% CI 0.53, 13.87), and for 2-year BM, it was 1.20 (95% CI 0.82, 1.75). Regarding HA-PCI in SCLC, the 1-year BM rate was 0.12 (95% CI 0.07, 0.17), and the 2-year BM rate was 0.20 (95% CI 0.16, 0.25). For HA-WBRT in NSCLC with BM, the 2-year intracranial progression rate was 0.38 (95% CI 0.13, 0.62). There was no significant difference in OS between HA-CRT and CRT. Conclusions: HA-CRT appears to be safe in lung cancer, but it may not outperform conventional CRT. Larger RCTs comparing HA-CRT and CRT are warranted. [ABSTRACT FROM AUTHOR]

Background: Prophylactic cerebral irradiation (PCI) is the standard of care for patients with limited small cell lung cancer (SCLC). Cerebral irradiation is associated with the deterioration of the quality of life in terms of cognitive function, in which the hippocampus plays a critical role. Protection of the hippocampus during PCI aims to reduce the adverse effects of ionizing radiation on neurocognitive function, which may be important for optimal quality of life. To date, subjective psychological tests have been used as a methodical assessment of cognitive function in patients after PCI. Patients and methods: In 20 patients with SCLC, it was attempted to evaluate the effect of hippocampal sparing during PCI on the preservation of cognitive functions in these patients, using two diagnostic and screening tests: Mini-Mental State Examination (MMSE) Short Scale and Montreal Cognitive Assessment (MoCA) Scale. The assessment was made at three time points: before the start of radiation, immediately after completion of irradiation and 3 months after radiation therapy. Results: The results indicate that after radiation therapy there is a deterioration in cognitive functions. Additionally, it was found that the results of both tests after radiation therapy differed significantly according to the gender and education of patients. Conclusions: Following PCI, cognitive functions deteriorate in SCLC patients, even when radiation doses are reduced in the hippocampal area. This trend persists for at least 3 months after the end of brain irradiation. [ABSTRACT FROM AUTHOR]

Currently, chemoimmunotherapy is the first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, only 0.8%–2.5% of the patients presented complete response after chemoimmunotherapy. Considering that ES-SCLC is highly sensitive to radiotherapy, the addition of radiotherapy after first-line treatment for ES-SCLC could further improve local control, which may be beneficial for patients’ survival. Prior studies have shown that consolidative thoracic radiotherapy (cTRT) can decrease disease progression and improve overall survival in patients with ES-SCLC who respond well to chemotherapy. However, the efficacy and safety of cTRT in the immunotherapy era remain unclear owing to a lack of prospective studies. Prophylactic cranial irradiation (PCI) has been shown to decrease brain metastasis (BM) and prolong survival in patients with limited-stage SCLC in previous reports. However, according to current guidelines, PCI is not commonly recommended for ES-SCLC. Immunotherapy has the potential to reduce the incidence of BM. Whether PCI can be replaced with regular magnetic resonance imaging surveillance for ES-SCLC in the era of immunotherapy remains controversial. Whole brain radiation therapy (WBRT) is the standard treatment for BM in SCLC patients. Stereotactic radiosurgery (SRS) has shown promise in the treatment of limited BM. Considering the potential of immunotherapy to decrease BM, it is controversial whether SRS can replace WBRT for limited BM in the immunotherapy era. Additionally, with the addition of immunotherapy, the role of palliative radiotherapy may be weakened in patients with asymptomatic metastatic lesions. However, it is still indispensable and urgent for patients with obvious symptoms of metastatic disease, such as spinal cord compression, superior vena cava syndrome, lobar obstruction, and weight-bearing metastases, which may critically damage the quality of life and prognosis. To improve the outcome of ES-SCLC, we discuss the feasibility of radiotherapy, including cTRT, PCI, WBRT/SRS, and palliative radiotherapy with immunotherapy based on existing evidence, which may offer specific prospects for further randomized trials and clinical applications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Small‐cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor that is prone to spread extensively. Compared to non‐small‐cell lung cancer (NSCLC), SCLC treatment progresses slowly. Although SCLC is highly sensitive to chemotherapy during the initial treatment, most patients still experience resistance and recurrence after receiving chemotherapy. A meta‐analysis demonstrated that thoracic radiotherapy (TRT) improves overall survival in SCLC. The results of the CALGB and CONVERT trials provide evidence for the efficacy of once‐daily high‐dose TRT. TRT at 60 Gy administered twice daily significantly improved survival without increasing toxicity. The long‐standing debate over the optimal timing of radiotherapy has not been fully resolved. SBRT has excellent local control rates and is a safe and effective treatment option for patients with stage I or II SCLC. Prophylactic cranial irradiation (PCI) is used to reduce treatment‐related neurotoxicity to the extent that there has been a recent discussion on whether magnetic resonance imaging (MRI) monitoring can replace PCI. Radiotherapy combined with immunotherapy significantly improves the survival rate of patients with NSCLC; however, its clinical effectiveness has not been systematically explored in patients with SCLC. Therefore, we summarize the evolving therapeutic strategies, (TRT for limited stage‐SCLC and consolidative TRT for extensive stage‐SCLC) and improved radiotherapy techniques (role of SBRT in stage I or II node‐negative SCLC, progress of PCI, and stereotactic radiosurgery), and discuss the possibilities and prospects of radiotherapy combined with immunotherapy for SCLC. [ABSTRACT FROM AUTHOR]

Purpose We aimed to evaluate the effectiveness of prophylactic cranial irradiation (PCI) for "early brain metastasis", which occurs before extracranial recurrence (ECR), and "late brain metastasis", which occurs after ECR, in limited-stage small cell lung cancer (LS-SCLC). Materials and Methods We retrospectively analyzed 271 LS-SCLC patients who underwent definitive chemoradiation. All patients were initially staged with brain magnetic resonance imaging and positron emission tomography. Intracranial recurrence (ICR), ECR, progression-free rate (PFR), and overall survival (OS) were analyzed as clinical endpoints. The competing risk of the first recurrence with ICR (ICRfirst) was evaluated. Significantly associated variables in multivariate analysis of ECR were considered as ECR risk factors. Patients were stratified according to the number of ECR risk factors. Results The application of PCI was associated with higher PFR (p=0.008) and OS (p=0.045). However, PCI was not associated with any of the clinical endpoints in multivariate analysis. The competing risk of ICRfirst was significantly decreased with the application of PCI (hazard ratio, 0.476; 95% confidence interval, 0.243 to 0.931; p=0.030). Stage III disease, sequential, and stable disease after thoracic radiation were selected as ECR risk factors. For patients without these risk factors, the application of PCI was significantly associated with increased OS (p=0.048) and a decreased risk of ICRfirst (p=0.026). Conclusion PCI may play a role in preventing early brain metastasis rather than late brain metastasis after ECR, suggesting that only patients with a low risk of ECR may currently benefit from PCI. [ABSTRACT FROM AUTHOR]

Background: The management of small-cell lung cancer shows differences, particularly with regard to the use of radio- (RT), chemo-, and immunotherapy. We performed a survey among German radiation oncologists to assess the management of small-cell lung cancer (SCLC). Methods: A 34-question online survey was created and sent out by e‑mail to radiation oncologists throughout Germany. The survey period extended from August 2020 to January 2021. The questions addressed indications for RT, planning techniques, dosing/fractionation, target volume definition for consolidative thoracic irradiation, and the use of prophylactic cranial irradiation (PCI). At the same time, we surveyed the use of atezolizumab. The survey addressed the treatment practice for limited-stage SCLC (LS-SCLC) and extensive-stage SCLC (ES-SCLC). Results: We received 74 responses. In LS-SCLC, treatment is planned predominantly based on diagnostic information from computed tomography (CT) of the thorax/abdomen/pelvis (88%), PET-CT (86%), and pulmonary function testing (88%). In LS-SCLC, 99% of respondents perform radiation concurrently with chemotherapy, preferably starting with cycle one or two (71%) of chemotherapy. The most common dose and fractionation schedule was 60–66 Gy in 30–33 fractions (once daily: 62% of all respondents). In ES-SCLC, 30 Gy in 10 fractions (once daily: 33% of all respondents) was the most commonly used regimen in consolidative thoracic irradiation. Only 25% use chemosensitization with RT. The inclusion criteria for PCI were similar for limited and extensive disease, with Karnofsky index (78% and 75%) being the most important decision factor. Respondents use a schedule of 30 Gy in 15 fractions most frequently in both stages (68% limited stage [LS], 60% extensive stage [ES]). Immunotherapy was used regularly or occasionally in LS-SCLC by 45% of respondents, with reduced lung function (37%), cardiac comorbidities (30%), and hepatic insufficiency (30%) being the most commonly mentioned exclusion criteria for this form of therapy. In ES-SCLC, atezolizumab use was reported in 78% of all questionnaires. Half of the respondents (49%) administer it simultaneously with cranial irradiation. Conclusion: Our survey showed variability in the management of SCLC. Results from future studies might help to clarify open questions regarding the optimal treatment paradigms. In addition, new treatment modalities, such as immunotherapy, might change practices in the near future. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: The 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. Methods: Patients 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. Results: In 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). Conclusion: Compared 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. [ABSTRACT FROM AUTHOR]

Abstract Background The recommendation of PCI for limited-stage small cell lung cancer (LS-SCLC) is primarily based on evidence from the pre-magnetic resonance imaging (MRI) era. However, as MRI accuracy improves and stereotactic radiosurgery advances, the role of PCI for LS-SCLC has become uncertain. This study aims to compare the contemporary survival outcomes of patients with LS-SCLC treated with PCI versus active surveillance. Methods We conducted a retrospective cohort study in which 1068 patients with LS-SCLC who achieved a good response to first-line chemoradiotherapy were consecutively enrolled from 5 tertiary medical centres between June 2009 and June 2019. Of these patients, 440 received PCI, while 628 received surveillance without PCI. Propensity score matching with a 1:1 ratio was performed to balance the baseline characteristics of the two cohorts. The endpoints were overall survival (OS) and the incidence of brain metastasis (BM). Results In total, 648 patients were matched. The baseline characteristics were generally well balanced. At a median follow-up of 64.5 months (range 2–190), patients who underwent PCI had a significantly lower risk for BM than those who underwent surveillance. The 3-year cumulative incidence rate of BM was 28.2% (95% CI 22.5–33.8%) in the PCI cohort and 38.5% (32.6–44.5%) in the surveillance cohort (Gray’s p = 0.002). However, the lower incidence of BM in the PCI cohort did not translate into a significant extension of OS. The median OS was 35.8 months (95% CI 27.6–44.0 months) in the PCI cohort versus 32 months (26.4–37.6 months) in the surveillance cohort (HR 0.90, 95% CI 0.74–1.10, p = 0.29). Multivariable analysis showed that disease stage, chemoradiotherapy sequence, and response to chemoradiotherapy were independent prognostic factors for BM or OS. Conclusions Overall, PCI reduces the risk for BM but does not substantially prolong OS compared with active surveillance. A phase 3, prospective clinical trial (NCT04829708) we initiated is currently underway, which is expected to corroborate our results.

Objective: To investigate the prognosis of patients with LS-SCLC who responded to chest chemoradiotherapy but did not receive PCI. Methods: A retrospective analysis was conducted on LS-SCLC patients who had achieved complete remission (CR) or partial remission (PR) after definitive chemoradiotherapy but did not receive PCI. The survival rates were calculated using Kaplan-Meier method. The prognosis was analyzed using Cox proportional hazard regression model. The main endpoint was OS. Results: Of the 500 patients with LS-SCLC admitted between June 2002 and January 2018, 327 achieved CR or PR after definitive chest chemoradiotherapy, 103 did not receive PCI, and 63 of them developed brain metastases (BM). The 1-year and 3-year OS rates in PCI group were 87.5% and 42.3% respectively, versus 70.4% and 20.9% for non-PCI group(P=0.002). The median survival time after BM was 8.7 months (range: 0.3-48.7), and 3-year OS rate was 15.0%, the median survival time of patients without BM was 20.1 months (range: 2.9-79.4), and 3-year OS was 33.4% (P=0.014). Patients with BM were subsequently treated with palliative therapy. Multivariate analysis showed that compared with no treatment, brain radiotherapy alone (HR: 0.131, 95%CI: 0.035-0.491, P=0.003) and radiotherapy combined with chemotherapy (HR: 0.039, 95%CI: 0.008-0.194, P<0.001) significantly reduced the risk of death. Multiple BM (HR: 2.391, 95%CI: 1.082-5.285, P=0.031) was an independent adverse prognostic factor for OS. Conclusion: LS-SCLC patients who achieved good response after chest chemoradiotherapy without receiving PCI were prone to develop BM and have a poor prognosis. Multiple BM was an independent adverse prognostic factor. PCI remains the standard of care for LS-SCLC patients. [ABSTRACT FROM AUTHOR]

Background: The purpose of the study was to evaluate the dosimetry of the Halcyon in prophylactic cranial irradiation (PCI) with volumetric modulated arc therapy (VMAT) and hippocampal-sparing for small cell lung cancer (SCLC). Methods: Five VMAT plans were designed on CT images of 15 patients diagnosed with SCLC and received PCI. Three plans with two full arcs were generated on the Trilogy and the TrueBeam accelerators, and flattening filter (FF) and flattening filter free (FFF) modes were used on TrueBeam. Two Halcyon plans with two and three full arcs were generated, referred to as H-2A and H-3A, respectively. The prescription dose was 25 Gy in 2.5-Gy fractions. The dose limit for hippocampus were D100 = 9Gy and Dmax = 16Gy. The Wilcoxon matched-paired signed-rank test was used to evaluate the significance of the observed differences between the five plans. Results: H-2A plans significantly increased the D2 of PTV, and H-3A plans showed comparable or even better target dosimetry (better conformity) compared to the three plans on C-arm accelerators. Compared to T and TB plans, the two Halcyon plans significantly reduced the D100 and mean doses of bilateral hippocampus, the mean doses of eyeballs, and the maximum doses of lenses. D100 of hippocampus was reduced in TrueBeam plans comparing to Trilogy plans. The FFF plans on TrueBeam also represented advantages in Dmean and D100 of hippocampas, Dmean and Dmax of eyeballs, and the Dmax of lenses compared to FF plans. Halcyon plans and TrueBeam plans with FFF mode increased the MUs compared to FF plans. Comparing to H-2A, the H-3A plans exhibited additional dosimetric advantages, including D2, CI and HI of PTV, as well as the maximum and mean doses of hippocampus and eyeballs, and the maximum doses of optic nerves and brainstem. The two Halcyon plans significantly reduced the delivery time and showed the higher gamma passing rate than the three plans of C-arm accelerators. Conclusions: Compared with the C-arm accelerators, the dose of hippocampus and the delivery times on Halcyon are relatively significantly reduced for hippocampal-sparing PCI. Three arcs are recommended for VMAT plans with the Halcyon in hippocampal-sparing PCI. [ABSTRACT FROM AUTHOR]

The use of prophylactic cranial irradiation (PCI) in patients suffering from limited-stage small-cell lung cancer (LS-SCLC) remains controversial in modern brain magnetic resonance imaging (MRI) staging. To this end, a systematic review with meta-analysis was hereby performed to investigate the overall survival (OS) in these patients. Relevant studies from the PubMed and EMBASE databases were reviewed, and pooled hazard risks were obtained using fixed-effects models. The PRISMA 2020 checklist was used. Fifteen retrospective studies were identified, with a total of 2,797 patients with LS-SCLC included in the analysis, 1,391 of which had received PCI. For all included patients, PCI was associated with improved OS [hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.58–0.70]. The combination of subgroup analysis and sensitivity analysis suggested that the effect of PCI on OS was independent of primary tumor treatment, proportion of complete response (CR), median age, PCI dose, publication years, etc. Additionally, the OS curve of 1,588 patients having undergone thoracic radiotherapy (TRT) as the primary tumor treatment from 8 studies were reconstructed, and the pooled 2-, 3- and 5-year OS rates of limited stage patients were 59% vs. 42%, 42% vs. 29% and 26% vs. 19% (HR: 0.69, 95% CI: 0.61–0.77) in the PCI group and the no PCI group, respectively. Another reconstructed OS curve of 339 patients having undergone radical surgery as the primary tumor treatment from 2 studies presented better results, and the pooled 2-, 3- and 5-year OS rates of in the PCI group and the no PCI group were 85% vs. 71%, 70% vs. 56% and 52% vs. 39% (HR: 0.59, 95% CI: 0.40–0.87), respectively. This meta-analysis demonstrates a significant beneficial effect of PCI on the OS in patients with LS-SCLC in modern pretreatment MRI staging. However, considering the absence of a strict follow-up of brain MRI recommended by the guideline for the control group from most of the included studies, the superiority of PCI to the treatment strategy of no PCI plus brain MRI surveillance remains unclear. [ABSTRACT FROM AUTHOR]

Introduction: In the randomized controlled trial in patients with SCLC comparing standard prophylactic cranial irradiation (PCI) with hippocampal avoidance PCI (HA-PCI), we did not observe beneficial effects of HA-PCI on tested cognition. Here, we report findings on self-reported cognitive functioning (SRCF) and quality of life (QoL). Methods: Patients with SCLC were randomized to receive PCI with or without HA (NCT01780675) and assessed at baseline (82 HA-PCI and 79 PCI patients) and at 4, 8, 12, 18, and 24 months of follow-up, using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and EORTC QLQ—brain cancer module (BN20). SRCF was assessed with the cognitive functioning scale of the EORTC QLQ-C30 and the Medical Outcomes Study questionnaire. A change of 10 points was used for minimal clinically important differences. Percentages of patients classified with having improved, stable, or deteriorated SRCF were compared between groups using chi-square tests. Changes in mean scores were analyzed using linear mixed models. Results: There was no significant difference in the percentage of patients with deteriorated, stable, or improved SRCF between the treatment arms. Depending on the evaluated time point, 31% to 46% and 29% to 43% of patients in the HA-PCI and PCI arm, respectively, reported a deteriorated SRCF on the basis of the EORTC QLQ-C30 and Medical Outcomes Study. QoL outcomes were not significantly different between the study arms, except for physical functioning at 12 months (p = 0.019) and motor dysfunction at 24 months (p = 0.020). Conclusions: Our trial did not find beneficial effects of HA-PCI over PCI on SRCF and QoL. The cognitive benefit of sparing the hippocampus in the context of PCI is still a subject of debate.

Purpose: Design and evaluate a knowledge-based model using commercially available artificial intelligence tools for automated treatment planning to efficiently generate clinically acceptable hippocampal avoidance prophylactic cranial irradiation (HA-PCI) plans in patients with small-cell lung cancer. Materials and methods: Data from 44 patients with different grades of head flexion (range 45°) were used as the training datasets. A Rapid Plan knowledge-based planning (KB) routine was applied for a prescription of 25 Gy in 10 fractions using two volumetric modulated arc therapy (VMAT) arcs. The 9 plans used to validate the initial model were added to generate a second version of the RP model (Hippo-MARv2). Automated plans (AP) were compared with manual plans (MP) according to the dose-volume objectives of the PREMER trial. Optimization time and model quality were assessed using 10 patients who were not included in the first 44 datasets. Results: A 55% reduction in average optimization time was observed for AP compared to MP. (15 vs 33 min; p = 0.001).Statistically significant differences in favor of AP were found for D98% (22.6 vs 20.9 Gy), Homogeneity Index (17.6 vs 23.0) and Hippocampus D mean (11.0 vs 11.7 Gy). The AP met the proposed objectives without significant deviations, while in the case of the MP, significant deviations from the proposed target values were found in 2 cases. Conclusion: The KB model allows automated planning for HA-PCI. Automation of radiotherapy planning improves efficiency, safety, and quality and could facilitate access to new techniques. [ABSTRACT FROM AUTHOR]

Simple Summary: In this proof-of-concept study, we implemented Steven Paget's "seed-and-soil" theory and proposed that inter-individual differences exist in the brain's congeniality for developing brain metastasis (BM). Using a non-invasive radiomics method, we demonstrated that a seed-and-soil radiomics model developed from non-metastatic brain magnetic resonance (representing the soil) and primary tumor computed tomography (representing the seed) imaging features can predict BM development in NSCLC patients, which is first-in-class in metastasis prediction studies. Furthermore, a BM radiomics score was developed, and we have shown that this score was significantly correlated with BM-free survival. These results demonstrated that the intrinsic features of a non-metastatic host organ could exert a significant impact on metastasis development, and a host organ's congeniality for metastasis might be different across individuals, which provides new evidence for the "seed-and-soil" theory and indications for risk-stratified prophylactic cranial irradiation in NSCLC management. 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. [ABSTRACT FROM AUTHOR]

Brain metastasis of non-small cell lung cancer (NSCLC) is a common treatment failure mode, and the median survival time of NSCLC patients with brain metastasis is only 1 mon-2 mon. Prophylactic cranial irradiation (PCI) can delay the occurrence of brain metastasis, but the survival benefits of NSCLC patients are still controversial. It is particularly important to identify the patients who are most likely to benefit from PCI. This article reviews the high risk factors of brain metastasis in NSCLC.

• Limited treatment options for LS-SCLC result from insufficient molecular studies. • BM is still prevalent even after thoracic and cranial irradiation therapies. • Assessing clinical/genomic features for BM enhances understanding for interventions. • BM incidence correlates with smoking, PCI therapy, RB1 and FLT4 mutations. • Consolidation PCI provides limited benefits to patients with baseline RB1 mutations. Small-cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis. Limited-stage (LS)-SCLC comprises only one-third of SCLC cases, resulting in limited molecularly targeted therapies and treatment options. Despite advances in thoracic and cranial irradiation leading to improved outcomes, a notable proportion of patients develop brain metastasis (BM), highlighting the importance of identifying high-risk patients for tailored screening and treatment strategies. We analyzed baseline tumor biopsies from 180 LS-SCLC patients who received frontline definitive chemoradiotherapy (dCRT) using a 474-gene pan-cancer panel. The cumulative incidence of BM was calculated with death scored as a competing risk. Independent prognostic factors for BM risk were identified using the Fine-Gray model. Alterations in the cell cycle pathway, particularly RB1 mutations, were more common in patients with BM, while FLT4 mutations were more frequent in those without BM (P =0.002 and P =0.021, respectively). Significant risk factors for BM include smoking (subdistribution hazard ratio [SHR]: 1.73; 95 % confidence interval [CI]: 1.11–2.70; P =0.016), RB1 mutations (SHR: 2.19; 95 % CI: 1.27–3.81; P =0.005), and BCL3 amplification (SHR: 2.27; 95 % CI: 1.09–4.71; P =0.028). Conversely, prophylactic cranial irradiation (PCI) (SHR: 0.39; 95 % CI: 0.25–1.60; P <0.001), FLT4 mutations (SHR: 0.26; 95 % CI: 0.07–0.98; P =0.047), and NOTCH pathway alterations (SHR: 0.65; 95 % CI: 0.43–1.00; P =0.049) were associated with a lower incidence of BM in LS-SCLC. Notably, consolidation PCI therapy did not reduce the BM risk in patients with baseline RB1 mutations, with BM occurrence probabilities of 34.7 % at 20 months and 62.6 % at 40 months. Our study yields valuable insights into the genetic characteristics of LS-SCLC patients with and without BM, aiding the development of personalized treatment strategies. Identifying risk factors associated with the incidence and timing of BM, within the standard regimen of dCRT followed by PCI, may help optimize clinical decision-making for LS-SCLC. [ABSTRACT FROM AUTHOR]

Abstract Background In the modern era of magnetic resonance imaging (MRI) staging, the benefit of prophylactic cranial irradiation (PCI) in patients with small-cell lung cancer (SCLC) has been controversial. This study evaluated the prognostic impact of PCI in patients with limited- or extensive-stage SCLC who had no brain metastases at diagnosis according to MRI. Methods Data from newly diagnosed patients in 2014 from the Korean Association for Lung Cancer Registry database were used. Patients with limited- or extensive-stage SCLC who had no brain metastases according to MRI were identified. Univariate and multivariate survival analyses were conducted to assess the prognostic association of PCI. Results Of 107 and 122 patients with limited- and extensive-stage SCLC, 24% and 14% received PCI, respectively. In the limited-stage SCLC group, the 2-year overall survival (OS) rates of patients who received PCI and those who did not were 50% and 29% (P = 0.018), respectively. However, there was no significant difference in OS for patients with extensive-stage SCLC (P = 0.336). After adjusting for other covariates, PCI was found to be associated with improved OS in the limited-stage SCLC group (P = 0.005). Based on the time-course hazard rate function plots in the limited-stage SCLC group, the OS benefit of PCI was maximized within the first year of follow-up. Conclusions In the modern era of MRI staging, PCI might be beneficial for patients with limited-stage SCLC but not for those with extensive-stage SCLC. Further studies with a large sample size are needed to verify the prognostic association of PCI.

Introduction: Prophylactic cranial irradiation (PCI) increases survival in patients with small-cell lung cancer. Although the underlying pathophysiology is not fully understood, it has been associated with posttreatment neurocognitive impairment. Our study aims to show the brain's glucose metabolism change after PCI with 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). Materials and Methods: A total of 17 patients who underwent PET/CT before and after PCI were evaluated retrospectively. 18F-FDG PET images of the brain before and after PCI were compared visually and semi-quantitatively using MI-Neurology Software. The brain was automatically segmented into eleven regions by this software. The mean standard uptake values (SUVmean) of all brain regions were measured within the automatically drawn region of interest area, and standard uptake value ratio (SUVR) values were found for each region by taking the brainstem SUVmean value as a reference. SUVR values were calculated from PET/CT scannings taken before and after PCI for each patient. The P < 0.05 value was considered statistically significant in comparisons. Results: We found a significant decrease in 18F-FDG uptake and glucose metabolism of the brain after PCI when compared with PET/CT before PCI in all brain regions identified according to the Combined-AAL atlas (all P < 0.001). Similarly, a significant decrease was found in brain 18F-FDG uptake on PET/CT taken after PCI in the brainstem used to calculate SUVR (P = 0.039). Conclusion: 18F-FDG PET/CT neuroimaging may be a new metabolic imaging technique for diagnosing radiation-induced cognitive impairment in the metabolic imaging era.

Small cell lung cancer (SCLC) accounts for about 15% of all lung cancers. Chemotherapy, immunotherapy and radiotherapy all play important roles in the management of SCLC. The aim of this study was to provide a comprehensive overview of the role and evidence of radiotherapy in the cure and palliation of SCLC. The search strategy included a search of the PubMed database, hand searches, reference lists of relevant review articles and relevant published abstracts. ClinicalTrials.gov was also queried for relevant trials. Thoracic radiotherapy improves overall survival in limited stage SCLC, but the timing and dose remain controversial. The role of thoracic radiotherapy in extensive stage SCLC with immunotherapy is the subject of several ongoing trials. Current evidence supports the use of prophylactic cranial irradiation (PCI) for limited stage SCLC but the evidence is equivocal in extensive stage SCLC. Whole brain radiotherapy is well established for the treatment of brain metastases but evidence is rapidly accumulating for the use of stereotactic radiosurgery. Further studies will define the role of PCI, whole brain radiotherapy and hippocampal avoidant PCI in the immunotherapy era. Radiotherapy is an essential component in the multimodality management of SCLC. Technological advances have allowed safer delivery of radiotherapy with reduced toxicities. Discussion at multidisciplinary team meetings is important to ensure radiotherapy is considered and offered in appropriate patients. • Radiotherapy has an important role in both the cure and palliation of SCLC. • Technological advances allow safer delivery of thoracic radiotherapy with reduced toxicities. • Role of thoracic radiotherapy in the immunotherapy era is uncertain and is a subject of ongoing trials. • Hippocampal avoidance PCI in LS-SCLC may reduce neurotoxicity without compromising outcomes. • Shared decision making on PCI versus MRI surveillance in ES-SCLC is essential. [ABSTRACT FROM AUTHOR]

OBJECTIVE The aim of this study is to examine the survival outcomes in limited-stage small-cell lung cancer (SCLC) treated with definitive chemoradiotherapy and to evaluate the prognostic factors that may affect survival. METHODS 83 patients diagnosed with limited-stage SCLC were identified retrospectively. Demographic features, clinical information, hemoglobin level, lactate dehydrogenase, C-reactive protein, and albumin levels were recorded. Kaplan--Meier method was used to calculate overall survival (OS), progression-free survival (PFS), and local regional recurrence-free survival (LRRFS), and differences were assessed using the Log-rank test. The Cox proportional hazard regression model was performed to evaluate the potential prognostic variables. RESULTS Thoracic radiotherapy was given with 1st or 2nd chemotherapy in 68.7% of the patients. Prophylactic cranial irradiation (PCI) was applied to 45.9% of the patients. At a median follow-up of 14 (3--83) months, 5 of the patients were alive at the final follow-up. Disease recurrence was observed in 31 patients, distant metastases were detected in 51 patients. Median and 2-y OS, PFS and LRRFS were 16, 11, and 14 months and 31.8%, 20.5%, and 26.9%, respectively. Hypoalbuminemia was found to affect PFS and LRRFS in univariate analysis (p=0.033, p=0.044). In subgroup analysis, PCI was effective on OS (p=0.045). In multivariate regression analysis, no significant relationship was found between PCI and OS (p=0.055), hypoalbuminemia was statistically significant on PFS and LRRFS (p=0.022, p=0.032). CONCLUSION With the addition of PCI to the treatment, there was a tendency to improve in terms of OS. Low albumin level at the time of diagnosis was found to negatively affect PFS and LRRFS. [ABSTRACT FROM AUTHOR]

Background: The recommendation of PCI for limited-stage small cell lung cancer (LS-SCLC) is primarily based on evidence from the pre-magnetic resonance imaging (MRI) era. However, as MRI accuracy improves and stereotactic radiosurgery advances, the role of PCI for LS-SCLC has become uncertain. This study aims to compare the contemporary survival outcomes of patients with LS-SCLC treated with PCI versus active surveillance.Methods: We conducted a retrospective cohort study in which 1068 patients with LS-SCLC who achieved a good response to first-line chemoradiotherapy were consecutively enrolled from 5 tertiary medical centres between June 2009 and June 2019. Of these patients, 440 received PCI, while 628 received surveillance without PCI. Propensity score matching with a 1:1 ratio was performed to balance the baseline characteristics of the two cohorts. The endpoints were overall survival (OS) and the incidence of brain metastasis (BM).Results: In total, 648 patients were matched. The baseline characteristics were generally well balanced. At a median follow-up of 64.5 months (range 2-190), patients who underwent PCI had a significantly lower risk for BM than those who underwent surveillance. The 3-year cumulative incidence rate of BM was 28.2% (95% CI 22.5-33.8%) in the PCI cohort and 38.5% (32.6-44.5%) in the surveillance cohort (Gray's p = 0.002). However, the lower incidence of BM in the PCI cohort did not translate into a significant extension of OS. The median OS was 35.8 months (95% CI 27.6-44.0 months) in the PCI cohort versus 32 months (26.4-37.6 months) in the surveillance cohort (HR 0.90, 95% CI 0.74-1.10, p = 0.29). Multivariable analysis showed that disease stage, chemoradiotherapy sequence, and response to chemoradiotherapy were independent prognostic factors for BM or OS.Conclusions: Overall, PCI reduces the risk for BM but does not substantially prolong OS compared with active surveillance. A phase 3, prospective clinical trial (NCT04829708) we initiated is currently underway, which is expected to corroborate our results. [ABSTRACT FROM AUTHOR]

Simple Summary: The brain is a common metastasis site of small-cell lung cancer (SCLC), and up to 50% of SCLC patients are at risk of brain metastasis (BM) within 2 years. Prophylactic cranial irradiation (PCI), as an essential treatment for reducing the risk of BM, inevitably leads to neurotoxicity. Differentiating the risk of BM in patients and individualized PCI treatment decisions may play an essential role in reducing the occurrence of BM, prolonging the overall survival, and improving the quality of life. Our study constructed and validated a clinical model to predict the incidence of BM and risk stratification for individualized PCI decisions. PCI could reduce the incidence of BM and improve overall survival (OS) in patients with a high risk of BM, but there was no significant difference between PCI and non-PCI groups in patients within a low-risk cohort. 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. [ABSTRACT FROM AUTHOR]

We aimed to clarify whether prophylactic cranial irradiation (PCI) is associated with improved outcomes in limited-stage small-cell lung cancer (LS-SCLC) in the current era of magnetic resonance imaging (MRI). Data from patients with LS-SCLC who achieved a complete response to definitive chemoradiotherapy (CRT) at two medical centers were retrospectively reviewed. Propensity score-matching was performed in a 2:1 ratio to balance the baseline characteristics of the no-PCI and PCI groups. The endpoints were the incidence of brain metastasis (BM), neurological causes of death and overall survival (OS). Overall, 80% patients underwent head MRI during the initial staging and 75 patients (no-PCI, n = 50; PCI, n = 25) were matched. Their baseline characteristics were generally well-balanced except for age; patients in the no-PCI group tended to be older. The median follow-up period was 29 months. Although the incidence of BMs tended to be higher in the no-PCI group (1-year BM occurrence: 26% vs 17%, P = 0.22), the incidence of multiple BMs (defined as >4 metastases) was similar between groups (1-year multiple BMs occurrence: 8% vs 9%, P = 0.65). The 2-year neurological causes of death and OS rate did not significantly differ between the groups (6% and 9%; P = 0.85; and 70% and 79%; P = 0.36, respectively). The 1-year occurrence of multiple BMs did not increase, even without PCI, when modern imaging modalities were integrated into the initial diagnosis, suggesting that PCI could be omitted after CRT, if MRI was incorporated into the initial diagnosis and follow-up., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objectives: Small-cell lung carcinoma (SCLC) is usually a wide-spread, highly-lethal malignancy but occasionally presents as localized, limited stage cancer amenable to local treatment. We reviewed our experience using surgery or stereotactic body radiotherapy (SBRT) to assess safety, survival rates and treatment toxicity in clinical stage I SCLC patients., Materials and Methods: Electronic medical records of patients with clinical stage I lymph node-negative SCLC who underwent surgical resection or SBRT between 1996 and 2021 were retrospectively reviewed. A multivariable Cox Proportional Hazards model was constructed., Results: Of 96 patients meeting inclusion criteria, 77 underwent resection and 19 underwent SBRT. Surgical patients were younger (mean 68.4 ± 9.2 years surgery versus 74.3 ± 6.6 years SBRT, P = .005) and had better pulmonary function (81.5 ± 19.6 FEV1% of predicted surgery versus 44.0 ± 20.9% SBRT, P < .001). SBRT patients had significantly more comorbidities. For both cohorts, 59 tumors were pure SCLC and 37 were mixed SCLC/NSCLC histology. Median survivals were 21 months versus 31 months for SBRT and surgery patients respectively (P = .07). There were no treatment-related mortalities. Mean length of hospital stay for surgical patients was 5.4 ± 5.7 days. Survival was longer in lymph node-negative surgery patients (median 48 months node-negative versus 19 months node-positive, P = .04). For node-negative-surgery patients, the estimated 2- and 5-year survival rates are 60% and 48%., Conclusions: Our single-institutional experience over 25 years demonstrates that local treatment with surgery or SBRT for clinical stage I SCLC is safe and effective, with survivals lower than similar stage non-small-cell carcinoma patients. However, our results compare favorably with prior small-cell surgical series and far better than reported results of chemoradiotherapy for similar stage patients, thereby validating current recommendations for employing surgery or SBRT for stage I SCLC., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & purpose: Prophylactic cranial irradiation (PCI) is recommended for limited-stage small-cell lung cancer (LS-SCLC) patients with good response to concurrent chemoradiation. We report our institution’s 20-year experience with this patient population and associated clinical outcomes. Materials & methods: A retrospective cohort of consecutive LS-SCLC patients treated with curative intent chemoradiation at our institution (1997–2018) was reviewed. Overall survival (OS) was calculated using the Kaplan-Meier method, and significant covariates determined by the Cox proportional hazards model. Covariates predictive of PCI were determined using Fisher's exact test and the Mann-Whitney test. Brain failure risk (BFR) was calculated using the cumulative incidence method treating death as a competing event. Treatment cohorts (historic vs. contemporary) were stratified by the median year of diagnosis (2005). Results: A total of 369 patients with LS-SCLC were identified, of which 278 patients were notionally PCI eligible. PCI was given to 196 patients (71%). Younger age was associated with PCI utilization (p

The current standard treatment for limited-stage small-cell lung cancer (LS-SCLC) is chemotherapy with concurrent chemoradiotherapy (CCRT). In this single-arm phase II study, patients with LS-SCLC received four cycles of etoposide, cisplatin, and durvalumab every 3 weeks. Thoracic radiotherapy of 52.5 Gy in 25 once-daily fractions was started with the third cycle of chemoimmunotherapy. After CCRT plus durvalumab, patients received durvalumab consolidation therapy every 4 weeks for a maximum of 2 years after study enrolment. Prophylactic cranial irradiation (PCI) was recommended. Fifty-one patients were enrolled, and 50 were included in the full analysis set. With the median follow-up duration of 26.6 months, the median PFS was 14.4 months (95% confidence interval: 10.3–NA), and the 24-month PFS rate was 42.0%. The median overall survival was not reached with a 24-month overall survival rate of 67.8%. The positive PD-L1 group (n = 22) was not associated with longer PFS (hazard ratio, 0.70; 0.31–1.58) and overall survival (0.64; 0.22–1.84) compared with the negative PD-L1 group (n = 20). Among the 43 patients who were candidates for PCI treatment, the PCI group (n = 22) had significantly fewer events of brain metastasis as the first failure sites compared to the no PCI group (n = 21) (13.6% vs. 42.9%, P = 0.033). There were several grade 3 or 4 adverse events which were well managed with appropriate supportive care. Durvalumab with CCRT for LS-SCLC exhibited promising clinical efficacy with a tolerable safety profile, prompting its validation in a randomized study. NCT03585998. • Durvalumab with chemoradiotherapy demonstrates the promising efficacy in LS-SCLC. • Durvalumab administered concurrently with radiotherapy was tolerable. • Prophylactic cranial irradiation demonstrated lower brain metastases rate. • The predictive role value of PD-L1 expression was insufficient. [ABSTRACT FROM AUTHOR]

Introduction: Controversy has arisen regarding the benefit of prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC), particularly since the 2017 Takahashi trial publication that supports MRI surveillance in extensive-stage (ES-)SCLC. The primary aim of this study was to assess trends and determinants in PCI use over the years 2010–2018. A secondary aim was to determine contemporary practice considerations among radiation oncologists (ROs). Methods: A nationwide population-based cohort study was conducted using the Netherlands Cancer Registry data on all newly diagnosed SCLC patients (2010–2018). The change in PCI frequency over the years and determinants for PCI were analyzed using logistic regression models. Second, an online survey was performed among Dutch lung cancer ROs in 2020. Results: Among 10,264 eligible patients, 4,894 (47%) received PCI. Compared to 2010–2014, PCI use significantly decreased in 2017–2018 in ES-SCLC (OR 0.68, 95%CI 0.60–0.77) and LS-SCLC (OR 0.56, 95%CI 0.47–0.67). Incidence year, age, performance status, and thoracic radiotherapy were independent determinants for PCI. Among 41 survey participants, PCI was recommended always/sometimes/never by 22%/71%/7% in ES-SCLC and 54%/44%/2% in LS-SCLC. For ES-SCLC and LS-SCLC, 63% and 25% of ROs, respectively, confirmed influence of the Takahashi trial on PCI recommendations. Denial of such influence was associated with insufficient institutional MRI capacity. Conclusions: A significant declining trend of PCI use in both ES-SCLC and LS-SCLC was observed in The Netherlands since 2017. The Takahashi trial seems an explanation for this trend even in LS-SCLC, with differential influence of the trial depending on institutional MRI capacity. An alarming increase in practice variation regarding PCI was found which stresses the importance of ongoing trials.

• First systematic review on (peri-)hippocampal brain metastasis (BM) incidence. • Forty trials included, encompassing 5,374 patients with over 32,570 BMs. • 4.4 % and 9.2 % had hippocampal and perihippocampal BMs, respectively. • 4.5 % failure rate after hippocampal-avoiding (HA) PCI or WBRT. • Hippocampal failure rate not increased in comparison with non-HA PCI or WBRT. In patients requiring prophylactic cranial irradiation (PCI) or whole-brain radiotherapy (WBRT) for brain metastases (BMs), hippocampal avoidance (HA) has been shown to preserve neurocognitive function and quality of life. Here, we aim to estimate the incidence of hippocampal and perihippocampal BMs and the subsequent risk of local undertreatment in patients undergoing hippocampal sparing radiotherapy. MEDLINE, Embase, and Scopus were searched with the terms " Hippocampus ", " Brain Neoplasms ", and related terms. Trials reporting on the incidence of hippocampal and/or perihippocampal BMs or hippocampal failure rate after PCI or WBRT were included. Forty records were included, encompassing a total of 5,374 patients with over 32,570 BMs. Most trials employed a 5 mm margin to define the HA zone. In trials reporting on BM incidence, 4.4 % (range 0 − 27 %) and 9.2 % (3 − 41 %) of patients had hippocampal and perihippocampal BMs, respectively. The most common risk factor for hippocampal BMs was the total number of BMs. The reported failure rate within the HA zone after HA-PCI or HA-WBRT was 4.5 % (0 − 13 %), salvageable with radiosurgery in most cases. SCLC histology was not associated with a higher risk of hippocampal failure (OR = 2.49; p = 0.23). In trials comparing with a conventional (non-HA) PCI or WBRT group, HA did not increase the hippocampal failure rate (OR = 1.90; p = 0.17). The overall incidence of hippocampal and perihippocampal BMs is considerably low, with a subsequent low risk of local undertreatment following HA-PCI or HA-WBRT. In patients without involvement, the hippocampus should be spared to preserve neurocognitive function and quality of life. [ABSTRACT FROM AUTHOR]

• A CT-based deep learning model for small-cell lung cancer was developed. • The deep learning model performed well in predicting overall survival. • The deep learning model was significantly superior to the clinical model. • High-risk patients had survival benefit from prophylactic cranial irradiation. To develop a computed tomography (CT)-based deep learning model to predict overall survival (OS) among small-cell lung cancer (SCLC) patients and identify patients who could benefit from prophylactic cranial irradiation (PCI) based on OS signature risk stratification. This study retrospectively included 556 SCLC patients from three medical centers. The training, internal validation, and external validation cohorts comprised 309, 133, and 114 patients, respectively. The OS signature was built using a unified fully connected neural network. A deep learning model was developed based on the OS signature. Clinical and combined models were developed and compared with a deep learning model. Additionally, the benefits of PCI were evaluated after stratification using an OS signature. Within the internal and external validation cohorts, the deep learning model (concordance index [C-index] 0.745, 0.733) was far superior to the clinical model (C-index: 0.635, 0.630) in predicting OS, but slightly worse than the combined model (C-index: 0.771, 0.770). Additionally, the deep learning model had excellent calibration, clinical usefulness, and improved accuracy in classifying survival outcomes. Remarkably, patients at high risk had a survival benefit from PCI in both the limited and extensive stages (all P < 0.05), whereas no significant association was observed in patients at low risk. The CT-based deep learning model exhibited promising performance in predicting the OS of SCLC patients. The OS signature may aid in individualized treatment planning to select patients who may benefit from PCI. [ABSTRACT FROM AUTHOR]

• The cost-effectiveness of PCI compared to no PCI was assessed in stage III NSCLC. • A cohort partitioned survival model was developed including five health states. • PCI was more effective (0.443 QALYs) and costly (€10,123) than no PCI. • The probability of PCI being cost-effective was 93%. In stage III non-small cell lung cancer (NSCLC), prophylactic cranial irradiation (PCI) reduces the brain metastases incidence and prolongs the progression-free survival without improving overall survival. PCI increases the risk of toxicity and is currently not adopted in routine care. Our objective was to assess the cost-effectiveness of PCI compared with no PCI in stage III NSCLC from a Dutch societal perspective. A cohort partitioned survival model was developed based on individual patient data from three randomized phase III trials (N = 670). Quality-adjusted life years (QALYs) and costs were estimated over a lifetime time horizon. A willingness-to-pay (WTP) threshold of €80,000 per QALY was adopted. Sensitivity and scenario analyses were performed to address parameter uncertainty and to explore what parameters had the greatest impact on the cost-effectiveness results. PCI was more effective and costly (0.443 QALYs, €10,123) than no PCI, resulting in an incremental cost-effectiveness ratio (ICER) of €22,843 per QALY gained. The probability of PCI being cost-effective at a WTP threshold of €80,000 per QALY was 93%. The probability of PCI gaining three and six additional months of life were 76% and 56%. The scenario analysis adding durvalumab increased the ICER to €35,159 per QALY gained. Using alternative survival distributions had little impact on the ICER. Assuming fewer PCI fractions and excluding indirect costs decreased the ICER to €18,263 and €5554 per QALY gained. PCI is cost-effective compared to no PCI in stage III NSCLC, and could therefore, from a cost-effectiveness perspective, be considered in routine care. [ABSTRACT FROM AUTHOR]

Purpose of reviewExtensive-stage small cell lung cancer (ES-SCLC) remains a disease with a dismal prognosis, with median survival of approximately 8-10 months. Despite many attempts to develop effective systemic therapies, very little progress has been made in the last several decades. Platinum-based combination chemotherapy remains the standard of care in the first-line setting and is associated with high response rates albeit short-lived. However, there have been recent advances in the use of radiation therapy, as well as new insights into the biology of SCLC.Recent findingsSome of the most appreciable advances in the last decade have involved the use of local radiation therapy. With the use of new laboratory techniques such as genomic sequencing, there remains promise of rationally targeted drug development. Circulating tumor cell research may also provide insights to SCLC biology and further refine treatment.SummarySystemic therapy for SCLC has changed little over the past 30 years with the most significant advances in ES-SCLC relating to radiotherapy rather than systemic therapy. The effectiveness of prophylactic cranial irradiation and thoracic radiotherapy has renewed interest in therapeutics focused on the modulation of DNA damage or repair. Recent developments in genomic sequencing and immunotherapy may translate to new treatment paradigms for SCLC.