OBJECTIVE: Hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) planning can present challenges. This study examines the influence of head tilt angles on the dosimetric characteristics of target and organs at risk (OARs), aiming to identify the optimal tilt angle that yields optimal dosimetric outcomes using tomotherapy (TOMO).
METHODS: Eight patients diagnosed with brain metastases underwent CT scans at five tilt angles: [0°, 10°), [10°, 20°), [20°, 30°), [30°, 40°), and [40°, 45°]. Treatment plans were generated using TOMO and volumetric modulated arc therapy (VMAT). Dosimetric parameters including conformity index (CI), homogeneity index (HI), D2cc, D98%, and Dmean of PTV, as well as Dmax, and Dmean of OARs were analyzed. Furthermore, a comparison was made between the dosimetric parameters of TOMO and VMAT plans. Finally, delivery efficiency of TOMO plans were assessed.
RESULTS: For the PTV, [40°, 45°] tilt angle demonstrated significantly better conformity, homogeneity, lower D2cc, and lower Dmean for the PTV. Regarding the OARs, the [40°, 45°] head tilt angle demonstrated significantly lower Dmax and Dmean in hippocampus, eyes, optic chiasm, and optic nerves. The [40°, 45°] tilt angle also showed significantly lower Dmax for brainstem and cochleas, as well as a lower Dmean for lens. In the [40°,45°] tilt angle for HA-WBRT, TOMO showed superior performance over VMAT for the PTV. TOMO achieved lower Dmax for brainstem, cochleas, optic nerves, and optic chiasm, as well as a lower Dmean for hippocampus. Furthermore, a significant correlation was found between delivery time and the PTV projection length in the sagittal plane.
CONCLUSIONS: The TOMO plan utilizing a tilt angle range of [40°, 45°] demonstrated superior PTV conformity and uniformity, along with enhanced OARs sparing. Furthermore, it exhibited a dosimetric advantage over VMAT for PTV and most OARs at the same angle range.

OBJECTIVE: 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.
CONCLUSIONS: 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.

BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: HA-WBRT-SIB is of efficiency and cognitive-conserving in treating Chinese lung cancer BM.
BACKGROUND: This study was retrospectively registered on ClinicalTrials.gov in 24th Feb, 2024. The ClinicalTrials.gov ID is NCT06289023.

UNASSIGNED: The effect of whole-brain radiation therapy (WBRT) plus simultaneous integrated boost (SIB) in brain metastasis from breast cancers has not been demonstrated.
UNASSIGNED: In this single-center retrospective study, we reviewed consecutive breast cancer patients who developed brain metastasis and were treated with hypofractionated radiation therapy plus WBRT using intensity-modulated radiation therapy (IMRT)-SIB approaches. We analyzed clinical outcomes, prognostic factors and patterns of treatment failure.
UNASSIGNED: A total of 27 patients were eligible for analysis. Four (14.8%) patients achieved clinical complete response and 14 (51.9%) had partial response of brain lesions. The other nine patients were not evaluated for brain tumor response. The median brain progression-free survival was 8.60 (95% CI [6.43-13.33]) months and the median overall survival was 16.8 (95% CI [13.3-27.7]) months. Three patients had in-field failure, five had out-field failure and two had in-field and out-field failure.
UNASSIGNED: WBRT plus SIB led to improved tumor control and clinical outcome in breast cancer patients with brain metastasis.

All known randomized trials of stereotactic radiotherapy (SRT) versus whole brain radiotherapy (WBRT) for brain metastases (BMs) comprise mixed histologies. The phase III HYBRID trial (NCT02882984) attempted to evaluate the non-inferiority of SRT vs. WBRT specifically for EGFR-mutated non-small cell lung cancer (EGFRm NSCLC) BMs.
Inclusion criteria were ≤ 5 BMs (any size) from treatment-naïve EGFRm NSCLC. All patients started a first-generation tyrosine kinase inhibitor on the first day of WBRT (37.5 Gy/15 fractions) or SRT (25-40 Gy/5 fractions per tumor volume). The primary endpoint was 18-month intracranial progression-free survival (iPFS; intention-to-treat).
The trial commenced in June 2015 and was closed in April 2021 after screening 208 patients but enrolling 85 (n = 41 WBRT, n = 44 SRT; median follow-up 31 and 36 months, respectively). Respectively, 9.5 % vs. 10.2 % of patients experienced intracranial progression at 18 months, and the median iPFS was 21.4 vs. 22.3 months (p > 0.05 for all). The SRT arm experienced higher overall survival and cognitive preservation (p < 0.05 for all). The most notable reason for low enrollment was patients not wishing to risk neurocognitive decline from WBRT.
Although this phase III trial was underpowered, there was no evidence that SRT yielded outcome detriments compared to WBRT for EGFRm NSCLC BMs. Lessons from prematurely closed trials are valuable, as they often provide important experiential perspectives for investigators designing/executing future trials. In the current era, randomized trials involving WBRT without cognitive sparing measures may be at high risk of underaccrual; trial investigators are encouraged to carefully consider our experience when attempting to design such trials. However, trials of molecular-/biologically-stratified patients are highly recommended as the notion of \"individualized medicine/oncology\" continues to expand.

Cranial radiotherapy is a major treatment for leukemia and brain tumors. Our previous study found abscopal effects of cranial irradiation could cause spermatogenesis disorder in mice. However, the exact mechanisms are not yet fully understood. In the study, adult male C57BL/6 mice were administrated with 20 Gy X-ray cranial irradiation (5 Gy per day for 4 days consecutively) and sacrificed at 1, 2 and 4 weeks. Tandem Mass Tag (TMT) quantitative proteomics of testis was combined with bioinformatics analysis to identify key molecules and signal pathways related to spermatogenesis at 4 weeks after cranial irradiation. GO analysis showed that spermatogenesis was closely related to oxidative stress and inflammation. Severe oxidative stress occurred in testis, serum and brain, while serious inflammation also occurred in testis and serum. Additionally, the sex hormones related to hypothalamic-pituitary-gonadal (HPG) axis were disrupted. PI3K/Akt pathway was activated in testis, which upstream molecule SCF/C-Kit was significantly elevated. Furthermore, the proliferation and differentiation ability of spermatogonial stem cells (SSCs) were altered. These findings suggest that cranial irradiation can cause spermatogenesis disorder through brain-blood-testicular cascade oxidative stress, inflammation and the secretory dysfunction of HPG axis, and SCF/C-kit drive this process through activating PI3K/Akt pathway.

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.
CONCLUSIONS: 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.

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

Because of improved survival of cancer patients, more patients irradiated for brain metastases develop intracerebral recurrences requiring subsequent courses of radiotherapy. Five studies focused on reirradiation with whole-brain radiation therapy (WBRT) after initial WBRT for brain metastases. Following the second WBRT course, improvement of clinical symptoms was found in 31-68% of patients. Rates of neurotoxicity, such as encephalopathy or cognitive decline, were reported in two studies (1.4% and 32%). In another study, severe or unexpected adverse events were not observed. Survival following the second WBRT course was generally poor, with median survival times of 2.9-4.1 months. The survival prognosis of patients receiving two courses of WBRT can be estimated by a scoring tool considering five prognostic factors. Three studies investigated reirradiation with single-fraction stereotactic radiosurgery (SF-SRS) following primary WBRT. One-year local control rates were 74-91%, and median survival times ranged between 7.8 and 14 months. Rates of radiation necrosis (RN) after reirradiation were 0-6%. Seven studies were considered that investigated re-treatment with SF-SRS or fractionated stereotactic radiation therapy (FSRT) following initial SF-SRS or FSRT. One-year local control rates were 60-88%, and the median survival times ranged between 8.3 and 25 months. During follow-up after reirradiation, rates of overall (asymptomatic or symptomatic) RN ranged between 12.5% and 30.4%. Symptomatic RN occurred in 4.3% to 23.9% of cases (patients or lesions). The risk of RN associated with symptoms and/or requiring surgery or corticosteroids appears lower after reirradiation with FSRT when compared to SF-SRS. Other potential risk factors of RN include the volume of overlap of normal tissue receiving 12 Gy at the first course and 18 Gy at the second course of SF-SRS, maximum doses ≥40 Gy of the first or the second SF-SRS courses, V12 Gy >9 cm3 of the second course, initial treatment with SF-SRS, volume of normal brain receiving 5 Gy during reirradiation with FSRT, and systemic treatment. Cumulative EQD2 ≤100-120 Gy2 to brain, <100 Gy2 to brainstem, and <75 Gy2 to chiasm and optic nerves may be considered safe. Since most studies were retrospective in nature, prospective trials are required to better define safety and efficacy of reirradiation for recurrent or progressive brain metastases.

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.