Pre-stereotactic radiosurgery neutrophil-to-lymphocyte ratio predicts post-stereotactic radiosurgery survival of patients with brain metastases concurrently treated with immune checkpoint inhibitors.

OBJECTIVE: Treatment with immune checkpoint inhibitors (ICIs) has shown clinical benefit for a wide range of cancer types. The neutrophil-to-lymphocyte ratio (NLR) reportedly correlates with survival time or progression-free survival in patients treated with ICIs. However, NLR has not yet been assessed in patients with brain metastases (BMs) receiving stereotactic radiosurgery (SRS) combined with concurrent ICIs. The authors investigated the predictive impact of NLR on the survival data of patients with BMs who received SRS with concurrent ICIs. METHODS: The clinical records of patients who had undergone SRS with concurrent ICIs for BMs between January 2015 and August 2023 were retrospectively analyzed. NLR was calculated using the data obtained from the last examination prior to SRS. The optimal NLR cutoff value was identified by receiver operating characteristic (ROC) curve analysis for time-to-event data (overall survival [OS] ≤ 18 months). OS and intracranial disease progression-free survival (IC-PFS) rates were compared between the two NLR groups. RESULTS: Of the 185 eligible patients included, 132 were male. The median (IQR) patient age was 69 (61-75) years. The primary cancers were lung, genitourinary, skin, breast, gastrointestinal, and others in 132, 23, 22, 2, 2, and 4 patients, respectively. The post-SRS median OS and IC-PFS times for the entire cohort were 18.4 (95% CI 14.0-23.1) months and 9.2 (95% CI 6.9-10.8) months, respectively. ROC curve analysis identified the optimal NLR cutoff value for 18-month OS to be 5.0 (area under the curve 0.64, Youden index 0.31). Kaplan-Meier analysis revealed that patients with high NLR (> 5) had a significantly shorter OS (median survival time 10.9 months for 48 patients vs 22.2 months for 137 patients, HR 2.0, 95% CI 1.3-3.0, p < 0.001). Similarly, a significant difference in median IC-PFS was noted: 4.8 months with high NLR versus 10.7 months with low NLR (HR 1.7, 95% CI 1.2-2.5, p = 0.003). CONCLUSIONS: The authors found elevated pre-SRS NLR (> 5) to be associated with shorter OS and IC-PFS after SRS with concurrent ICIs for BMs. NLR is a simple, cost-effective, and widely accessible biomarker, which can thus be used for managing patients with BMs receiving SRS concurrently with ICIs. Further investigation in other large datasets is, however, required to validate these findings.

Long-Term Patient-Reported Outcomes of Stereotactic Radiosurgery for Trigeminal Neuralgia.

BACKGROUND: We aimed to evaluate patient-reported outcomes (PROs) of stereotactic radiosurgery (SRS) for TN in terms of treatment efficacy and toxicity. METHODS: We retrospectively analyzed patients who underwent Gamma Knife SRS for idiopathic or classic TN between January 2013 and February 2022. Questionnaires regarding pain relief, treatment toxicity, and post-SRS treatment were sent between late 2022 and early 2023, and the responses received were analyzed. The Faces Pain Scale (FPS, 0: best, 5: worst) was used for quantitative evaluation. RESULTS: Responses were received from 51 patients (76%). The mean pre-SRS FPS score was 4.1 (standard deviation (SD) 1.1). Forty-three patients (83%) reported initial pain relief and the best post-SRS FPS score was 1.1 (SD 1.5) (P < 0.001). At a median follow-up of 50 months, the FPS score was still 1.1 (SD 1.6) (P < 0.001). Analysis of factors contributing to durable pain relief showed neurovascular compression to be associated with FPS score improvement (Odds ratio 5.7, 95% CI 1.1-29.7, P = 0.038). Facial dysesthesia had a mean pre-SRS FPS score of 1.7 (SD 2.0) and a mean score of 1.4 (SD 1.7) at the last follow-up (P = 0.32). Eight patients (15%) received post-SRS interventions and 21 (40%) no longer required pharmacotherapy without post-SRS intervention. Forty-four patients (85%) reported being satisfied with SRS. CONCLUSIONS: We analyzed PROs of SRS for TN using the FPS and showed SRS to be a safe and effective treatment modality achieving long lasting pain relief.

Synergistic effects of immune checkpoint inhibitors in combination with stereotactic radiosurgery for patients with lung cancer and brain metastases: a propensity score-matched analysis.

OBJECTIVE: Stereotactic radiosurgery (SRS) is the mainstay treatment for brain metastases (BMs) from lung cancer. In recent years, immune checkpoint inhibitors (ICIs) have been applied to metastatic lung cancer and have contributed to improved outcomes. The authors investigated whether SRS with concurrent ICIs for lung cancer BMs prolongs overall survival (OS), improves intracranial disease control, and raises safety concerns. METHODS: Patients who underwent SRS for lung cancer BMs at Aizawa Hospital between January 2015 and December 2021 were included. Concurrent use of ICIs was defined as no more than 3 months between SRS and ICI administration. The two treatment groups, which had a similar likelihood of receiving concurrent ICIs, were generated by propensity score matching (PSM; match ratio 1:1) based on 11 potential prognostic covariates. Patient survival and intracranial disease control were compared between the groups with and without concurrent ICIs (ICI + SRS vs SRS) by time-dependent analyses, taking into account competing events. RESULTS: Five hundred eighty-five patients with lung cancer BM (494 with non-small cell lung cancer and 91 with small cell lung cancer) were eligible. Of those patients, 93 (16%) received concurrent ICIs. Two groups, each with 89 patients (ICI + SRS group and SRS group), were generated by PSM. The 1-year survival rates of the ICI + SRS and SRS groups after the initial SRS were 65% and 50% and the median survival times were 16.9 and 12.0 months, respectively (HR 0.62, 95% CI 0.44-0.87, p = 0.006). The 2-year cumulative neurological mortality rates were 12% and 16%, respectively (HR 0.55, 95% CI 0.28-1.10, p = 0.091). The 1-year intracranial progression-free survival rates were 35% and 26% (HR 0.73, 95% CI 0.53-0.99, p = 0.047). The 2-year local failure rates were 12% and 18% (HR 0.72, 95% CI 0.32-1.61, p = 0.43) and the 2-year distant recurrence rates were 51% and 60% (HR 0.82, 95% CI 0.55-1.23, p = 0.34). Severe adverse radiation events (Common Terminology Criteria for Adverse Events [CTCAE] grade 4) occurred in 1 patient in each group, and CTCAE grade 3 toxicities were observed in 3 patients in the ICI + SRS group and in 5 in the SRS group (OR 1.53, 95% CI 0.35-7.7, p = 0.75). CONCLUSIONS: The present study found that SRS with concurrent ICIs for patients with lung cancer BMs was associated with longer survival and durable intracranial disease control, with no apparent increase in treatment-related adverse events.

Effectiveness of immune checkpoint inhibitors in combination with stereotactic radiosurgery for patients with brain metastases from renal cell carcinoma: inverse probability of treatment weighting using propensity scores.

OBJECTIVE: Stereotactic radiosurgery (SRS) is the mainstay for treating brain metastases (BMs) from renal cell carcinoma (RCC). In recent years, immune checkpoint inhibitors (ICIs) have been applied to metastatic RCC and have contributed to improved outcomes. The authors investigated whether SRS with concurrent ICIs for RCC BM prolongs overall survival (OS) and improves intracranial disease control and whether there are any safety concerns. METHODS: Patients who underwent SRS for RCC BMs at the authors' institution between January 2010 and January 2021 were included. Concurrent use of ICIs was defined as no more than 3 months between SRS and ICI administration. The time-to-event analysis of OS and intracranial progression-free survival (IC-PFS) between the groups with and without ICIs (ICI+SRS and SRS, respectively) was performed using inverse probability of treatment weighting (IPTW) based on propensity scores (PSs) to control for selection bias. Four baseline covariates (Karnofsky Performance Scale score, extracranial metastases, hemoglobin, and number of BMs) were selected to calculate PSs. RESULTS: In total, 57 patients with 147 RCC BMs were eligible. The median OS for all patients was 9.1 months (95% CI 6.0-18.9 months), and the median IC-PFS was 4.4 months (95% CI 3.1-6.8 months). Twelve patients (21%) received concurrent ICIs. The IPTW-adjusted 1-year OS rates in the ICI+SRS and SRS groups were 66% and 38%, respectively (HR 0.30, 95% C 0.13-0.69; p = 0.005), and the IPTW-adjusted 1-year IC-PFS rates were 52% and 16%, respectively (HR 0.30, 95% CI 0.14-0.62; p = 0.001). Severe tumor hemorrhage (Common Terminology Criteria for Adverse Events [CTCAE] grade 4 or 5) occurred immediately after SRS in 2 patients in the SRS group. CTCAE grade 2 or 3 toxicity was observed in 2 patients in the ICI+SRS group and 5 patients in the SRS group. CONCLUSIONS: Although the patient number was small and the analysis preliminary, the present study found that SRS with concurrent ICIs for RCC BM patients prolonged survival and provided durable intracranial disease control, with no apparent increase in treatment-related adverse events.

Safety and efficacy of upfront stereotactic radiosurgery for brain metastases with high cumulative intracranial tumor volume (> 7 ml): analysis of 233 consecutive patients.

BACKGROUND: The cumulative intracranial tumor volume (CITV) has recently been suggested to be a more relevant predictive factor for patients with brain metastases (BM) treated with stereotactic radiosurgery (SRS). We aimed to investigate the feasibility of upfront SRS for patients with BM having a high CITV, i.e., exceeding 7 ml. METHODS: Two hundred thirty-three consecutive patients with BM having a CITV > 7 ml who underwent SRS as first-line treatment from 2011 to 2019 were retrospectively identified. The overall survival (OS) and intracranial disease control rates were analyzed. Multivariate proportional hazards models were used to identify prognostic factors associated with treatment outcome. Toxicity and salvage therapy were also investigated. RESULTS: The median OS was 8.7 months (95% confidence interval: 7.1-10.4), and 6-month and 1-year OS rates were 60 and 40%, respectively. Systemic anticancer therapy (hazard ratio (HR): 0.45, p < 0.001), female sex (HR: 0.61, p = 0.001), synchronous SRS (HR: 0.57, p = 0.003), number of BM (HR: 1.04, p = 0.008), controlled extracranial disease (HR: 0.56, p = 0.009), Karnofsky performance status (HR: 0.87, p = 0.015), and staged SRS (HR: 0.71, p = 0.037) were found to be factors independently associated with OS. Post-SRS toxicities of CTCAE grades 3, 4, and 5 were observed in 14, 5, and 1 patient, respectively. As salvage management, repeat SRS, whole brain radiotherapy, and surgical resection were required for 84, 16, and 10 patients, respectively, CONCLUSIONS: With vigilant surveillance and appropriate salvage management, upfront SRS alone can be considered as a relatively safe and effective treatment strategy even for BM with CITV > 7 ml.

Single- versus 2-session Gamma Knife surgery for symptomatic midsize brain metastases: a propensity score-matched analysis.

OBJECTIVE: Two-session Gamma Knife surgery (GKS) has recently been demonstrated to be an effective and less-invasive alternative for large brain metastases not treatable by microsurgical resection. This raises the clinical question of whether the 2-session GKS strategy further improves treatment outcomes for patients with symptomatic midsize brain metastases (2-10 cm3) as compared to single-session GKS. The present study aimed to compare the local therapeutic effects and toxicities of single-session and 2-session GKS for treating these lesions. METHODS: Patients with focal neurological deficits attributable to midsize brain metastases who underwent upfront GKS during the period from 2010 to 2018 were retrospectively identified from an institutional database. Patients for whom both post-GKS imaging studies and neurological evaluations from outpatient visits were available were eligible. Using propensity score-matching (PSM) analysis, unique matched pairs which had a similar likelihood of receiving 2-session GKS were generated. The main outcome measure was a composite of imaging and/or neurological worsening of the lesion of interest. Functional improvement and overall survival (OS) were also compared between the 2 treatment arms. RESULTS: In total, 219 cancer patients with 252 symptomatic midsize brain metastases were eligible. Of these 252 tumors, 176 and 76 were treated with single- and 2-session GKS, respectively. After PSM, 68 pairs of tumors were obtained. The Gray test showed that 2-session GKS achieved a longer local progression-free interval than single-session GKS (1-year local control rate: 84% vs 53%; HR 0.31, 95% CI 0.16-0.63, p = 0.001). Two-session GKS was also associated with greater functional improvement in KPS scores (mean 18.3 ± 14.6 vs 12.8 ± 14.1, p = 0.040). The median OS did not differ significantly between single- and 2-session GKS (15.6 vs 24.7 months; HR 0.69, 95% CI 0.44-1.10, p = 0.11). CONCLUSIONS: Two-session GKS achieved more durable local tumor control and greater functional improvement than single-session GKS for patients with symptomatic midsize brain metastases, although there was no OS advantage.

Impacts of EGFR-mutation status and EGFR-TKI on the efficacy of stereotactic radiosurgery for brain metastases from non-small cell lung adenocarcinoma: A retrospective analysis of 133 consecutive patients.

OBJECTIVES: Recent advances in target therapies have prolonged overall survival (OS) for patients with epidermal growth factor receptor (EGFR)-mutant lung cancer. The impact of EGFR mutations on stereotactic radiosurgery (SRS) for brain metastases (BM) has yet to be determined. The present study sought to evaluate the efficacy and limitations of SRS, administered with EGFR-tyrosine kinase inhibitors (TKI), for BM from EGFR-mutant lung adenocarcinoma. MATERIALS AND METHODS: This retrospective observational study analyzed data from patients with BM arising from EGFR-mutant lung adenocarcinoma who received upfront Gamma Knife SRS between December 2010 and April 2016. OS and distant and local intracranial disease control rates were calculated. The prognostic factors for each event were also determined. RESULTS: One hundred thirty-three consecutive patients (47 males/86 females) were eligible. The median age was 69 years, and the median Karnofsky performance status (KPS) was 90. Sixty-six patients (50%) had no history of EGFR-TKI use at the time of SRS. EGFR-TKI were administered to 85% of EGFR-TKI naïve patients after SRS. One- and 2-year OS rates were 74% and 52%, respectively. One- and 2-year distant BM recurrence rates (per patient) after SRS were 34% and 53%, respectively. One- and 2-year rates of local tumor control (per lesion) were 97% and 95%, respectively. Multivariate proportional hazards analyses showed that being EGFR-TKI naïve was associated with longer OS (HR: 0.42, P < 0.001), a lower distant intracranial recurrence rate (HR: 0.61, P = 0.037) and a higher local tumor control rate (HR: 0.28, P = 0.001). CONCLUSIONS: The present study demonstrated the upfront SRS strategy to offer a minimally invasive and effective treatment option for EGFR-mutant lung adenocarcinoma patients with limited BM. EGFR-TKI naïve patients were found to be a distinct subgroup for which a longer survival time and durable intracranial disease control can be expected.

Stereotactic body radiotherapy for stage I lung cancer and small lung metastasis: evaluation of an immobilization system for suppression of respiratory tumor movement and preliminary results.

BACKGROUND: In stereotactic body radiotherapy (SBRT) for lung tumors, reducing tumor movement is necessary. In this study, we evaluated changes in tumor movement and percutaneous oxygen saturation (SpO2) levels, and preliminary clinical results of SBRT using the BodyFIX immobilization system. METHODS: Between 2004 and 2006, 53 consecutive patients were treated for 55 lesions; 42 were stage I non-small cell lung cancer (NSCLC), 10 were metastatic lung cancers, and 3 were local recurrences of NSCLC. Tumor movement was measured with fluoroscopy under breath holding, free breathing on a couch, and free breathing in the BodyFIX system. SpO2 levels were measured with a finger pulseoximeter under each condition. The delivered dose was 44, 48 or 52 Gy, depending on tumor diameter, in 4 fractions over 10 or 11 days. RESULTS: By using the BodyFIX system, respiratory tumor movements were significantly reduced compared with the free-breathing condition in both craniocaudal and lateral directions, although the amplitude of reduction in the craniocaudal direction was 3 mm or more in only 27% of the patients. The average SpO2 did not decrease by using the system. At 3 years, the local control rate was 80% for all lesions. Overall survival was 76%, cause-specific survival was 92%, and local progression-free survival was 76% at 3 years in primary NSCLC patients. Grade 2 radiation pneumonitis developed in 7 patients. CONCLUSION: Respiratory tumor movement was modestly suppressed by the BodyFIX system, while the SpO2 level did not decrease. It was considered a simple and effective method for SBRT of lung tumors. Preliminary results were encouraging.

Incidence of brain atrophy and decline in mini-mental state examination score after whole-brain radiotherapy in patients with brain metastases: a prospective study.

PURPOSE: To determine the incidence of brain atrophy and dementia after whole-brain radiotherapy (WBRT) in patients with brain metastases not undergoing surgery. METHODS AND MATERIALS: Eligible patients underwent WBRT to 40 Gy in 20 fractions with or without a 10-Gy boost. Brain magnetic resonance imaging or computed tomography and Mini-Mental State Examination (MMSE) were performed before and soon after radiotherapy, every 3 months for 18 months, and every 6 months thereafter. Brain atrophy was evaluated by change in cerebrospinal fluid-cranial ratio (CCR), and the atrophy index was defined as postradiation CCR divided by preradiation CCR. RESULTS: Of 101 patients (median age, 62 years) entering the study, 92 completed WBRT, and 45, 25, and 10 patients were assessable at 6, 12, and 18 months, respectively. Mean atrophy index was 1.24 +/- 0.39 (SD) at 6 months and 1.32 +/- 0.40 at 12 months, and 18% and 28% of the patients had an increase in the atrophy index by 30% or greater, respectively. No apparent decrease in mean MMSE score was observed after WBRT. Individually, MMSE scores decreased by four or more points in 11% at 6 months, 12% at 12 months, and 0% at 18 months. However, about half the decrease in MMSE scores was associated with a decrease in performance status caused by systemic disease progression. CONCLUSIONS: Brain atrophy developed in up to 30% of patients, but it was not necessarily accompanied by MMSE score decrease. Dementia after WBRT unaccompanied by tumor recurrence was infrequent.

Invasive thymoma: postoperative mediastinal irradiation, and low-dose entire hemithorax irradiation in patients with pleural dissemination.

INTRODUCTION: We evaluated the results of postoperative mediastinal radiotherapy (MRT) for invasive thymoma and low-dose entire hemithorax radiotherapy (EHRT) for pleural dissemination. METHODS: Sixty patients were treated with a nearly uniform policy. Generally, we administered 30 to 40 Gy MRT after surgery at 2 Gy daily fractions for Masaoka stage II tumors or suspected residual diseases, and 50 to 55 Gy MRT for stage III tumors and for highly-suspected or macroscopic residual diseases. Since 1992, we have administered EHRT in patients with pleural dissemination, with 11.2 Gy in 7 fractions or 15 to 16 Gy in 10 fractions after removal of disseminated lesions in addition to MRT. We treated 52 patients with MRT alone and 8 with EHRT and MRT. In addition, we gave EHRT to four patients who developed pleural dissemination later. RESULTS: For all 60 patients, the overall and cause-specific survival and local and pleural-dissemination control rates at 5 years were 79, 87, 86, and 69%, respectively. Both Masaoka stage and tumor resectability were associated with prognosis. In stage IVa patients, pleural dissemination control rate was 71% at 3 years after EHRT, whereas it was 49% in patients receiving MRT alone (p = 0.38). Grade 2 or higher radiation pneumonitis was observed in only 3 of 52 patients (5.8%) undergoing MRT initially. In 12 patients who underwent EHRT, 3 patients (25%) experienced grade 2 or 4 pneumonitis. CONCLUSIONS: Postoperative MRT appeared to prevent local recurrence with acceptable toxicity. EHRT is generally safe and may contribute to control of pleural dissemination.

Stereotactic imaging for radiosurgery: localization accuracy of magnetic resonance imaging and positron emission tomography compared with computed tomography.

Computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) provide complementary information for treatment planning in stereotactic radiosurgery. We evaluated the localization accuracy of MRI and PET compared with CT. Two kinds of phantoms applicable to the Leksell G stereotactic skull frame (Elekta, Tokyo) were developed. Deviations of measured coordinates at target points (x = 50, 100, 150; y = 50, 100, 150) were determined on different axial planes (z = 30-140 for MRI and CT study and Z = 50-120 for PET and CT study). For MRI, the deviations were no more than 0.8 mm in each direction. For PET, the deviations were no more than 2.7 mm. For both imaging modalities studied, accuracy was at or below the imaging resolution (pixel size) and should be considered useful for clinical stereotactic planning purposes.

Stereotactic radiosurgery as a salvage treatment for recurrent epipharyngeal carcinoma.

Fourteen patients with recurrent epipharyngeal carcinoma (EPC) were treated by gamma knife stereotactic radiosurgery. The tumor volume ranged from 0.3 to 80 ml (median 18.9 ml). Treatment was done with a tumor margin dose of 10-27 Gy (median 15 Gy). The median follow-up period was 15 months (range 2-47 months). Ten patients were alive and 4 were dead at the end of the follow-up period. In 6 patients (43%), the tumor disappeared or decreased in size until the end of the follow-up period. In 2 (14%), the tumor remained unchanged in size. In 6 (43%), the tumor showed regression initially but was enlarged later. A second radiosurgery was performed in 4 of those 6 cases and the tumor decreased in size again in 3 of them. Thus, the overall control rate of local tumor was 79% (11/14). In selected patients with recurrent EPC, stereotactic radiosurgery can be considered as a salvage treatment producing local control.

Stereotactic radiosurgery as a salvage treatment for recurrent skull base adenoid cystic carcinoma.

Twelve patients (15 lesions) with recurrent skull base adenoid cystic carcinoma (ACC) were treated by Gamma Knife stereotactic radiosurgery (SRS). The tumor volume ranged from 2 to 103 ml (median 15 ml). Treatment was prescribed at the 40-60% isodose line and ranged from 10 to 18 Gy (median: 13.0 Gy). The median follow-up period was 18 months (range 3-55). Six patients were alive and 6 dead at the end of the follow-up period. Only 1 patient died from local tumor recurrence. Ten among 15 tumors treated by SRS decreased in size until the end of the follow-up period or the patients' death. Three remained unchanged in size. Two tumors initially regressed but then increased in size. In selected patients with recurrent skull base ACC, SRS can be considered as a salvage treatment with good local control.

Focal fibrosis as a cause of localized ground glass attenuation (GGA)--CT and MR findings.

We report a case of focal fibrosis that appeared as localized ground glass attenuation (GGA) on thin-section computed tomography (TSCT). The TSCT and MRI findings correlated well with the pathological results, corresponding to fibrous thickening of the alveolar septa with mild chronic inflammation.