Hippocampal avoidance whole-brain radiotherapy with simultaneous integrated boost in lung cancer brain metastases and utility of the Hopkins verbal learning test for testing cognitive impairment in Chinese patients: a prospective phase II study.

This study aimed to evaluate the efficiency of hippocampal avoidance whole-brain radiotherapy with a simultaneous integrated boost (HA-WBRT-SIB) treating brain metastases (BM) and utility of the Hopkins Verbal Learning Test-Revised (HVLT-R) (Chinese version) in Chinese lung cancer patients. Lung cancer patients with BM undergone HA-WBRT-SIB at our center were enrolled. Brain magnetic resonance imaging, The HVLT total learning score, and side effects were evaluated before radiotherapy and 1, 3, 6, and 12 months after radiotherapy. This study analyzed the overall survival rate, progression-free survival rate, and changes in HVLT-R immediate recall scores. Forty patients were enrolled between Jan 2016 and Jan 2020. The median follow-up time was 14.2 months. The median survival, progression-free survival, and intracranial progression-free survival of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis indicated that male sex and newly diagnosed stage IV disease were associated with poor overall survival and progression-free survival, respectively. HVLT-R scores at baseline and 1, 3, and 6 months after radiotherapy were 21.94 ± 2.99, 20.88 ± 3.12, 20.03 ± 3.14, and 19.78 ± 2.98, respectively. The HVLT-R scores at 6 months after radiotherapy decreased by approximately 9.8% compared with those at baseline. No grade 3 toxicities occurred in the entire cohort. HA-WBRT-SIB is of efficiency and cognitive-conserving in treating Chinese lung cancer BM. This study was retrospectively registered on ClinicalTrials.gov in 24th Feb, 2024. The ClinicalTrials.gov ID is NCT06289023.

Li Z ，Wang J ，Deng L ，Zhai Y ，Zhang T ，Bi N ，Wang J ，Wang X ，Liu W ，Xiao Z ，Chen D ，Lv J ，Feng Q ，Wang W ，Zhou Z ... -  《BMC CANCER》

Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.

Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided. (1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS? Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses. Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS. Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments. Level III, diagnostic study.

Lee CC ，Chen CW ，Yen HK ，Lin YP ，Lai CY ，Wang JL ，Groot OQ ，Janssen SJ ，Schwab JH ，Hsu FM ，Lin WH ... -  《-》

A phase II study of anlotinib plus whole brain radiation therapy for patients with NSCLC with multiple brain metastases.

Gu D ，Yu H ，Ding N ，Xu J ，Qian P ，Zhu J ，Jiang M ，Tao H ，Zhu X ... -  《-》

Brain radiotherapy combined with camrelizumab and platinum-doublet chemotherapy for previously untreated advanced non-small-cell lung cancer with brain metastases (C-Brain): a multicentre, single-arm, phase 2 trial.

Brain metastases are a common complication in patients with non-small-cell lung cancer (NSCLC) lacking actionable driver mutations, with limited treatment options and poor prognosis. We aimed to investigate the efficacy and safety of brain radiotherapy combined with camrelizumab and platinum-doublet chemotherapy in patients with newly diagnosed advanced NSCLC and brain metastases. This multicentre, single-arm, phase 2 trial was done across nine tertiary hospitals in China. Eligible patients were aged 18 years or older, had newly diagnosed brain metastases from NSCLC with no actionable driver mutations (EGFR, ALK, or ROS1), and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible patients were treated with stereotactic radiosurgery or whole-brain radiotherapy combined with camrelizumab (200 mg intravenously once every 3 weeks) and investigator-selected platinum-doublet chemotherapy (pemetrexed 500 mg/m2 plus platinum [carboplatin, area under curve (AUC) of 5, or cis-platinum 75 mg/m2] for non-squamous NSCLC, and nab-paclitaxel 260 mg/m2 plus platinum [carboplatin AUC 5, or cis-platinum 75 mg/m2] for squamous NSCLC) for four to six cycles. Patients with controlled disease then received maintenance treatment with camrelizumab alone (200 mg intravenously once every 3 weeks; for squamous NSCLC) or camrelizumab plus pemetrexed (500 mg/m2 every 3 weeks; for non-squamous NSCLC). The primary endpoint was 6-month progression-free survival rate in the full analysis set, which included all patients who received at least one dose of study treatment regardless of whether they had measurable brain lesions per RECIST 1.1. The trial was registered with ClinicalTrials.gov, NCT04291092, and is ongoing. Between May 6, 2020, and Jan 30, 2023, 67 patients were assessed for eligibility. Two patients were excluded (brain lesions less than 5 mm) and 65 patients were enrolled and treated. Median age was 66 years (IQR 62-70). 60 (92%) of 65 patients were male and five (8%) were female. All 65 patients were Han Chinese. 50 (77%) of 65 patients had non-squamous NSCLC and 46 (71%) were symptomatic. The 6-month progression-free survival rate was 71·7% (95% CI 58·9-81·1) during the median follow-up of 14·1 months (IQR 9·0-20·3; data cutoff Dec 13, 2023). The most common grade 3-4 treatment-related adverse events were decreased neutrophil count (14 [22%] of 65 patients), decreased white blood cell count (ten [15%]), decreased platelet count (ten [15%]), and decreased lymphocyte count (nine [14%]). Neurological toxic effects of grade 3 occurred in three (5%) of 65 patients. Radiation necrosis occurred in three (5%) of 65 patients; all were grade 1 or 2. There were no treatment-related deaths. Brain radiotherapy combined with camrelizumab and platinum-doublet chemotherapy shows promising efficacy and manageable toxicity and could be a potential treatment option for patients with brain metastases from NSCLC. Randomised controlled trials will be required to confirm these findings. Beijing Xisike Clinical Oncology Research Foundation and Jiangsu Hengrui Pharmaceuticals. For the Chinese translation of the abstract see Supplementary Materials section.

Xu Y ，Chen K ，Xu Y ，Li H ，Huang Z ，Lu H ，Huang D ，Yu S ，Han N ，Gong L ，Qin J ，Chen J ，Xie F ，Hong W ，Lin X ，Cheng F ，Luo X ，Fan Y ... -  《-》

Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001.

Brown PD ，Gondi V ，Pugh S ，Tome WA ，Wefel JS ，Armstrong TS ，Bovi JA ，Robinson C ，Konski A ，Khuntia D ，Grosshans D ，Benzinger TLS ，Bruner D ，Gilbert MR ，Roberge D ，Kundapur V ，Devisetty K ，Shah S ，Usuki K ，Anderson BM ，Stea B ，Yoon H ，Li J ，Laack NN ，Kruser TJ ，Chmura SJ ，Shi W ，Deshmukh S ，Mehta MP ，Kachnic LA ，for NRG Oncology ... -  《-》