IMPORTANCEVertebral compression fracture (VCF) is a potential adverse effect following treatment with stereotactic body radiation therapy (SBRT) for spinal metastases.OBJECTIVE To develop and assess a risk stratification model for VCF after SBRT. DESIGN, SETTING, AND PARTICIPANTSThis retrospective cohort study conducted at a high-volume referral center included 331 patients who had undergone 464 spine SBRT treatments from December 2007 through October 2019. Data analysis was conducted from November 1, 2020, to August 17, 2021. Exclusions included proton therapy, prior surgical intervention, vertebroplasty, or missing data.EXPOSURES One and 3 fraction spine SBRT treatments were most commonly delivered. Single-fraction treatments generally involved prescribed doses of 16 to 24 Gy (median, 20 Gy; range, 16-30 Gy) to gross disease compared with multifraction treatment that delivered a median of 30 Gy (range, 21-50 Gy). MAIN OUTCOMES AND MEASURESThe VCF and radiography components of the spinal instability neoplastic score were determined by a radiologist. Recursive partitioning analysis was conducted using separate training (70%), internal validation (15%), and test (15%) sets. The log-rank test was the criterion for node splitting. RESULTSOf the 331 participants, 88 were women (27%), and the mean (IQR) age was 63 (59-72) years. With a median follow-up of 21 months (IQR, 11-39 months), we identified 84 VCFs (18%), including 65 (77%) de novo and 19 (23%) progressive fractures. There was a median of 9 months (IQR, 3-21 months) to developing a VCF. From 15 candidate variables, 6 were identified using the backward selection method, feature importance testing, and a correlation heatmap. Four were selected via recursive partitioning analysis: epidural tumor extension, lumbar location, gross tumor volume of more than 10 cc, and a spinal instability neoplastic score of more than 6. One point was assigned to each variable, and the resulting multivariable Cox model had a concordance of 0.760. The hazard ratio per 1-point increase for VCF was 1.93 (95% CI, 1.62-2.30; P < .001). The cumulative incidence of VCF at 2 years (with death as a competing risk) was 6.7% (95% CI, 4.2%-10.7%) for low-risk (score, 0-1; 273 [58.3%]), 17.0% (95% CI, 10.8%-26.7%) for intermediate-risk (score, 2; 99 [21.3%]), and 35.4% (95% CI, 26.7%-46.9%) for high-risk cases (score, 3-4; 92 [19.8%]) (P < .001). Similar results were observed for freedom from VCF using stratification. CONCLUSIONS AND RELEVANCEThe results of this cohort study identify a subgroup of patients with high risk for VCF following treatment with SBRT who may potentially benefit from undergoing prophylactic spinal stabilization or vertebroplasty.

Patients with Fanconi anemia have higher incidences of ectopic neurohypophysis, adenohypophysis hypoplasia, platybasia and other midline central nervous system skull base posterior fossa abnormalities than age- and sex-matched controls. Patients with posterior fossa abnormalities, including pontocerebellar hypoplasia, are more likely to have biallelic BRCA2 mutations.

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The definition of oligometastatic (OM) disease has largely focused on the number of metastatic lesions. Here, we investigate the total volumetric burden of metastases at initial OM presentation as an independent prognostic factor for distant progression free survival (DPFS), widespread progression (WSP, i.e., > 5 new lesions), and overall survival (OS) in patients treated with SBRT. Materials/Methods: Patients with oligometastatic cancer treated with SBRT at 6 international institutions from 2007 − 2016 were retrospectively reviewed. Patients were included if they had 1) five or fewer metastases, 2) no history of brain metastases, 3) curative treatment for primary disease, and 4) SBRT to all known metastases. Multivariable Cox regression models were used to determine the relationship between DPFS and OS with the total planning target volume (PTV) at initial OM presentation. The relationship between WSP and total PTV was determined using multivariable competing risks regression. All models were adjusted for the potential confounders of histology, pre-SBRT systemic therapy, osseousonly vs. visceral lesions, and number of metastases. Results: In total, 961 OM patients were included. The median follow-up was 24.4mo (IQR: 13.8-37.5). The most common primary histologies were NSCLC (25.9%), colorectal (22.0%), prostate (13.3%), and breast (7.9%). The majority of patients (59.4%) had a solitary oligometastasis, while 22.6%, 9.6%, 5.5%, and 2.9% had 2, 3, 4, or 5 lesions, respectively. Twothirds (65.8%) did not have pre-SBRT systemic therapy, and 28.3% had only osseous lesions. The median total PTV was 40.0cc (IQR: 19.7-85.0). The median DPFS, time to WSP, and OS were 15.1, 43.5, and 44.7mo, respectively. Modeling total PTV using restricted cubic splines revealed significant non-linear effects, and log-transformation was optimal to account for this non-linearity. Total PTV had a significant effect on DPFS in the first 18mo after SBRT and this was most profound in the first 6mo, when each doubling of total PTV conferred a 40.6% increased risk of distant progression (P < 0.001). Similarly, each total PTV doubling increased the risk of WSP by 45.4% in the first 6mo (P < 0.001). Total PTV had a significant effect on OS in the first 2yrs after SBRT, with each PTV doubling increasing the risk of death by 60.7% during the first 6mo (P < 0.001) and by 34.6 % thereafter (P < 0.001). Exploratory GTV analysis, where complete data was available for 76.1% of patients due to variability in contouring GTV vs. CTV, confirmed the PTV-based observations. Conclusion: This large multi-institutional series demonstrates the strong impact of total volumetric burden of metastases at initial OM presentation on the risk of distant and widespread progression and OS. We propose that total volume of metastatic lesions may have prognostic merit beyond number of metastases in identifying OM patients who would benefit most from systemic therapy in addition to local metastasis-directed therapy.

Background This study was aimed at developing and validating a decision‐making tool predictive of overall survival (OS) for patients receiving stereotactic body radiation therapy (SBRT) for spinal metastases. Methods Three hundred sixty‐one patients at one institution were used for the training set, and 182 at a second institution were used for external validation. Treatments most commonly involved one or three fractions of spine SBRT. Exclusion criteria included proton therapy and benign histologies. Results The final model consisted of the following variables and scores: Spinal Instability Neoplastic Score (SINS) ≥ 6 (1), time from primary diagnosis < 21 months (1), Eastern Cooperative Oncology Group (ECOG) performance status = 1 (1) or ECOG performance status > 1 (2), and >1 organ system involved (1). Each variable was an independent predictor of OS (p < .001), and each 1‐point increase in the score was associated with a hazard ratio of 2.01 (95% confidence interval [CI], 1.79–2.25; p < .0001). The concordance value was 0.75 (95% CI, 0.71–0.78). The scores were discretized into three groups—favorable (score = 0–1), intermediate (score = 2), and poor survival (score = 3–5)—with 2‐year OS rates of 84% (95% CI, 79%–90%), 46% (95% CI, 36%–59%), and 21% (95% CI, 14%–32%), respectively (p < .0001 for each). In the external validation set (182 patients), the score was also predictive of OS (p < .0001). Increasing SINS was predictive of decreased OS as a continuous variable (p < .0001). Conclusions This novel score is proposed as a decision‐making tool to help to optimize patient selection for spine SBRT. SINS may be an independent predictor of OS.

PURPOSE Vertebral compression fracture (VCF) is a potential adverse effect following stereotactic body radiation therapy (SBRT) for spinal metastases. In this analysis, we developed and internally validated a risk stratification model for VCF. METHODS From an initial set of 680 treatments, we excluded those with proton therapy, prior surgical intervention, or missing data. The final dataset had 464 treatments in 313 patients. Delineations of VCF and all radiographic components of the spinal instability neoplastic score (SINS) were determined by a radiologist. Recursive partitioning analysis (RPA) was conducted using separate training (70%), internal validation (15%), and test (15%) sets. The log-rank test was used as the criterion for node splitting. RESULTS With a median follow-up of 21 months, we identified 84 VCF (18%), including 65 (77%) de novo and 19 (23%) progressive fractures. There was a median 9 months (IQR: 3 – 21) to VCF. From an initial set of 15 candidate variables, six were identified using the backwards selection method, feature importance testing, and a correlation heatmap. Four were then selected in the highest-fidelity RPA models: epidural tumor extension, lumbar location, gross tumor volume &gt; 10 cc, and SINS &gt; 6. One point was assigned to each variable, and the resulting multivariate Cox model had a concordance of 0.760. Each one point increase in score was associated with increasing rates of VCF. Low-risk lesions (score: 0-1, n=273) had 2-year freedom from VCF of 92%, compared to 80% for intermediate-risk (score: 2, n=99) and 56% (score: 3-4, n=92) for high-risk lesions (p &lt; 0.0001). Cumulative incidence curves with death as a competing risk showed increased VCF with higher scores via Gray’s test (p &lt; 0.001). CONCLUSIONS Our internally-validated model identifies a subgroup of patients with high risk for VCF who may benefit from prophylactic surgical stabilization or vertebroplasty.

To investigate the relationship between tumor volume and survival in breast cancer liver metastasis (BCLM) patients treated with stereotactic radiotherapy. Materials/Methods: 39 biopsy proven breast cancer patients whom liver metastasis was treated with stereotactic radiotherapy (SRT) were retrospectively investigated. Patient characteristics, survival and their relation with tumor volume were analyzed. Results: Median age was 47 years (range; 27-78 years). Median tumor size was 1.8 AE 1.1 cm. Median gross tumor volume (GTV) and planning tumor volume (PTV) were 6.8 cc (range, 0.7-55.2 cc) and 38.7 cc (range; 9.3-163.8 cc), respectively. SRT dose prescription was 3 fr x 18 Gy in 37 patients (96%), 3 fr x 20 Gy in 1 patient (2%) and 3 fr x 16 Gy in 1 patient (2%). 13 patients (33%) had solitary liver metastasis while 26 patients (67%) also had other organ metastases beyond liver. Median follow-up for entire cohort was 15.4 months (range; 1-49 months). At last visit 26 patients (67%) had disease progression. Among these patients 25 patients (64%) had distant metastasis while 2 patients (5%) had isolated local recurrence. The 1-and 2-years overall survival (OS) rates were %79.1 and %46.0, respectively. Median OS was 23.8 months (95% CI: 13.3-34.3 months). 1 and 2-years progression-free survival (PFS) rates were 38.1% and 11.5%, respectively. Median PFS was 8.7 months (95%CI: 5.6-11.8 months). 1 and 2-years of local control (LC) per tumor were 92.9% and 85%, respectively. Patients were divided into two groups according to tumor volume £30 cc or >30 cc. 1-year OS was 100% for patients with tumor volume £30 cc while 1-year OS was 34% for patients with tumor volume > 30 cc (p Z 0.04). 4 patients developed grad 3 late toxicity. Among them 1 had duodenal ulcer, received medical treatment without any surgical intervention and 3 of them had rib fracture treated with symptomatic medical treatment. Conclusion: SRT is an efficient treatment with optimal LC and low toxicity profile in BCLM patients. Tumor volume of £30 cc had better survival.