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Treatment of arteriovenous malformations (AVM) with stereotactic radiosurgery (SRS) has been shown to lead to complete response in short-interval time series. The long-term outcomes for these patients have remained a clinical question. Here we present the long-term outcomes of LINAC-based SRS treatments at a high-volume single institution academic center. Consecutive patients treated with LINAC-based SRS treatments with a diagnosis of AVM between 1989 and 2023 were identified. Clinical and dosimetric data were retrospectively collected. Kaplan Meier analysis was utilized to calculate time to complete response (CR). Multivariate linear regression was performed to identify prognostics indicators for disease response. One-hundred and forty patients were identified. Seven patients did not have adequate follow-up imaging to assess disease response, leaving 133 patients evaluable for this study. 70 patients had a reported CR to SRS treatment. An additional 48 patients had a partial response (PR), 11 had stable disease (SD), and 4 had progressive disease (PD). The Kaplan Meier plot estimate probability for CR at 10 years was 56.5% (95% CI = 0.47, 0.68). Median Kaplan Meier estimate of CR achievement was 13.2 years. Of the patients who did not achieve CR (n = 63), median follow-up imaging was 7.2 years. Nineteen patients (14%) of patients did experience a bleed after SRS treatment, with median time reported of 30 months. Multivariate analysis demonstrated the Spetzler-Martin grade (p = 0.01), treatment dose (p = 0.009) and target volume (p = 0.026) were significantly associated with CR rates. LINAC-based stereotactic radiosurgery in the setting of arteriovenous malformations appears to maintain long-term efficacy and safety. Spetzler-Martin grade, dose and treatment volumes are strong predictors for long-term efficacy of SRS for CR in these patients. [ABSTRACT FROM AUTHOR]

We previously reported disease outcomes on patients treated with moderately hypofractionated salvage RT (65-70 Gy in 26-28 fractions using imaging guided IMRT) with >13 years of follow-up. The rate of all late surgical/radiation/disease related grade 3-5 toxicities was 27%, which were documented at a median of 8.7 years after the end of radiation. Here we performed an analysis to attempt to identify factors associated with these toxicities. A total of 161 patients were analyzed; 44 patients experienced 58 late grade ≥3 toxicities. These were analyzed in several groups which included: all (n = 44), GU (n = 40), GU excluding incontinence (n = 35), stricture/fistula related (n = 28), hematuria related (n = 7), and grade 4 stricture/fistula related (n = 8). We investigated patient factors (age, preRT IPSS), surgical factors (clip volume, approach, margin status), and disease factors (stage, Gleason group, PSA nadir, preRT PSA, surgery to RT time). Surgical clip volume was contoured on CT and recorded in cc. Significance was determined using Mann-Whitney U test for continuous variables and Fisher's Exact test for binary variables. A higher volume of surgical clips in the prostate fossa was found to be significantly related to eventual grade ≥3 stricture/fistula related event (p = 0.05). The mean surgical clip volume was found to be 2.30 cc in those with a documented grade ≥3 stricture/fistula compared to 1.23 cc in those without. Patients with a positive margin had a 30.0% rate of grade ≥3 GU toxicity compared to 16.2% in those with a negative margin (p = 0.03). Surgical clip volume was not found to be significantly related to pathologic stage, nor to eventual biochemical failure (p = 0.799/0.897). A positive margin was associated with a lower rate of biochemical failure after salvage (p = 0.04). Grade 3 events were documented at a median of 7.7 years and grade 4 events at 12.0 years after the end of radiation. Our previous study found a high rate of grade ≥3 toxicities at time points for which there is a paucity of data both in conventional and hypofractionated regimens, particularly in the era of modern surgical and radiation techniques. We also found late toxicities can occur with increasing severity for many years after salvage radiotherapy. This analysis suggests that margin positivity and volume of surgical clips might identify patients at higher risk for late grade ≥3 toxicities, although the etiologies of these toxicities, whether surgery or radiation-related, are uncertain. [ABSTRACT FROM AUTHOR]

Patients with biochemical failure after prostatectomy are commonly treated with standard fractionation radiotherapy requiring 6.5-8 weeks of treatment. GU003 recently reported favorable short-term efficacy and acceptable toxicity using hypofractionated salvage radiotherapy after prostatectomy. However, follow-up for the study is short and questions remain regarding whether late toxicities will remain acceptable. Here, we report on long term outcomes of patients treated with a similar regimen. We evaluated a consecutive cohort of patients treated from 2003-2013 with salvage RT to 65-70 Gy in 25-28 fractions using image-guided IMRT. Freedom from biochemical recurrence (FFBR), prostate cancer specific survival (PCSS), and overall survival (OS) were assessed using Kaplan-Meier analysis. Factors associated with biochemical failure were assessed using Cox regression analysis (surgical margins, Gleason score ≥8, PSA nadir, time to detectable PSA, PSA doubling time, and presalvage PSA). Late GU toxicities were scored based on a modified LENT/RTOG grading system. A total of 160 patients were identified with a median follow-up of 155 months. Twenty-six patients (16.3%) received androgen deprivation therapy following surgery or concurrently with radiation and 20 patients (12.5%) had lymph nodes electively treated. FFBR was 63% at 5 years and 56% at 10 years; PCSS was 99% at 5 years and 93% at 10 years; OS was 97% at 5 years and 85% at 10 years. Factors associated with increased biochemical recurrence included negative surgical margin status and higher pre-salvage PSA (p =0.025, 0.050). Total incidence grade ≥3 late toxicities was 21.9% (n=35, 33 GU, 1 GI, 1 lymphovascular) which were observed a median of 101 months after the end of radiation. There were four late grade 4 toxicities and three observed deaths potentially associated with radiation (urothelial cancer, urosepsis related to a suprapubic catheter, and pelvic sarcoma). Prostate cancer has a long natural history as do many late RT toxicities. This cohort of patients with >10 years follow-up treated with hypofractionated salvage RT shows long-term control comparable to that seen in other salvage RT series with long-term follow-up. Although we do not have a comparator group treated with standard fractionation, these data illustrate the importance of long-term follow-up when considering toxicity from salvage RT. [ABSTRACT FROM AUTHOR]

Conventional whole brain radiotherapy (c-WBRT) has been a mainstay in the treatment of brain metastases, but is associated with significant long-term neurocognitive deficits in memory, problem-solving and executive function. WBRT with hippocampal avoidance (HA-WBRT) has been shown to better preserve cognitive function with no detriment in oncologic outcomes. Our group previously established using a magnetic resonance imaging (MRI) deep learning model that c-WBRT is associated with rapid, global brain aging based on anatomic surface morphology. Herein, we compare post-treatment brain aging between c-WBRT and HA-WBRT. We studied patients with brain metastases who underwent either c-WBRT or HA-WBRT (per NRG-CC001 guidelines) and examined MRI anatomic surface data before and after treatment. We implemented an established graph convolutional neural network model to estimate patient's brain age. We further developed a fixed-effects linear model to compare age of whole brain and substructures after WBRT, written as follows: ΔAge = φ + (1|patient); where for each patient, ΔAge = [model_predicted_age_post_treatment – actual_age_post_treatment], and φ = fixed-effect coefficient for type of WBRT (c-WBRT versus HA-WBRT respectively). φ > 0 corresponded to HA-WBRT being associated with less aging compared to c-WBRT, φ < 0 corresponded to HA-WBRT being associated with greater aging, and non-significant φ implied that the interventions were not different in terms of aging. Mann-Whitney (MW) test and Fisher exact (FE) test were used to compare variables between the groups. 54 patients were analyzed (37 patients with c-WBRT and 17 patients with HA-WBRT). The median age was 61.5 years versus 55 years for c-WBRT and HA-WBRT patients respectively (p =0.2001 MW test). For c-WBRT and HA-WBRT patients respectively, 75% versus 82% had five or more metastases (p =0.7251 FE test), and 78% versus 88% had prior systemic therapy (p =0.4668 FE test). Median dose was 30 Gy for both groups. 71% of HA-WBRT patients received concurrent memantine versus 31% of c-WBRT patients (p =0.0149 FE test). Results of aging analysis are presented in Table 1. Between c-WBRT and HA-WBRT, there was no difference in ΔAge for the whole brain, the cortex or subcortical structures; however, there was a statistically significant decrease in ΔAge of the hippocampus for HA-WBRT group (φ = 9.99, p =0.002). Based on median follow up of approximately 6 months, the hippocampus aged an additional 9.99 years in c-WBRT patients compared to HA-WBRT patients. Our results suggest that HA-WBRT with concurrent memantine confers focal brain aging protection that mirrors the long-term neurocognitive benefits seen when compared to c-WBRT. [ABSTRACT FROM AUTHOR]

There is a lack of consensus around the diagnosis, management and follow-up of radiation pneumonitis (RP). A Delphi consensus process was conducted in this area. In round 1, open questions were distributed to 31 clinicians treating thoracic malignancy. In round 2, participants rated agreement/disagreement with statements derived from round 1 answers using a 5-point Likert scale. Consensus was defined as >/=75% agreement. Statements which did not achieve consensus were modified and re-tested in round 3. Response rate was 74% in round 1 (n=23/31; 17 oncologists, 6 pulmonologists); 82% in round 2 (n=19/23; 15 oncologists, 4 respirologists); and 100% in round 3 (n=19/19). Thirty-eight of 64 round 2 statements achieved consensus; a further 11/26 statements achieved consensus in round 3. In round 2, there was agreement on risk stratification/mitigation accounting for patient factors; the importance of minimizing RP risk through treatment planning; the basis for diagnosis of RP; and that oncologists and respirologists should be involved in treatment. Treatment should involve oral steroids with consideration of gastroprotection, starting with 60mg PO prednisolone or equivalent for 2 weeks, followed by a weekly taper of 10 mg in the daily dose, or for severe pneumonitis, IV methylprednisolone for 3 days before PO. Key statements achieving consensus in round 3 were: "There is uncertainty about the clinical significance of whether pneumonitis is radiation- or drug-induced, and further research is needed to understand this area," and "Although there are guidelines for the review schedule of patients receiving immunotherapy, it is unclear how these could be modified for patients also receiving radiotherapy." Consensus was achieved on many aspects of RP diagnosis and management. Further research is needed, particularly on pneumonitis in those receiving both radiotherapy and immunotherapy. These data will inform the development of final consensus statements providing practical guidance on diagnosis and management of RP. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Recent autopsy data from patients with glioblastoma (GBM) has demonstrated that pronounced brainstem infiltration is now a common pattern of disease progression near the end of life. The present study evaluated the association of disease proximity to the brainstem on imaging, both at diagnosis and at recurrence, with overall survival (OS).Materials/methods: 140 patients with IDH wild-type GBM treated definitively with resection and adjuvant chemoradiation at a single institution from 2013-2019 were retrospectively analyzed. Disease proximity to brainstem was calculated from measurements made on T1 post-contrast MRI brain obtained at diagnosis postoperatively and at recurrence. Tumor volume was approximated by the resection cavity plus adjacent extrinsic enhancement, measured during target delineation at time of treatment delivery. The Kaplan-Meier method was used to estimate OS, and multivariable analysis was performed using the Cox proportional hazards model. Logistic regression was used to assess the effect of tumor volume on brainstem involvement, and the relationship between tumor volume and proximity to brainstem was assessed by the Spearman correlation.Results: Median distance of disease to brainstem was 22.4 mm (range 0-54) at diagnosis, with 2.1% (n = 3) having brainstem involvement. At 56-month median follow-up, 87% of patients had recurrence; 2-year OS was 38.6%. Median distance of disease to brainstem was 20.8 mm (range 0-63) at recurrence, with 5.7% (n = 8) having brainstem involvement at recurrence. Controlling for resection status, MGMT methylation, and Karnofsky performance status, there was no noted association of brainstem invasion (P = .60) or proximity at diagnosis (P = .14) with OS. However, at recurrence, distance from the brainstem was significantly associated with improved OS when measured continuously (HR: .97, 95% CI: .95-.99, P = 0.001) and when compared by group (20-40 mm vs. ≤20 mm: HR .59, 95% CI: .35-.99, P = 0.05; > 40 mm vs. ≤20 mm: HR .16, 95% CI: 0.05-.55, P = 0.003). While volume of tumor at diagnosis was not found to be independently associated with brainstem involvement (P = .99) or OS (P = .90) at recurrence, tumor volume at diagnosis was found to be significantly associated with disease proximity to brainstem at the time of recurrence (P = 0.037), with larger volume disease more likely to recur close to the brainstem.Conclusion: GBM proximity to the brainstem at diagnosis was not found to be prognostic, whereas disease proximity to the brainstem at recurrence was associated with worse OS. Tumor volume at diagnosis was found to be associated with disease proximity at recurrence, with higher volume disease at diagnosis associated with greater proximity to the brainstem at recurrence. These findings may have ramifications for upfront and salvage radiation treatment design.Author Disclosure: A. Bajaj: None. E.T. Benishay: None. I.B. Helenowski: None. R. Savoor: None. M.R. Drumm: None. N. Rammohan: None. S. Sachdev: None. C.M. Horbinski: None. T. Kruser: Employee; Northwestern Memorial Hospital. Honoraria; Elsevier, OncLive. Speaker's Bureau; AstraZeneca. Advisory Board; AstraZeneca. [ABSTRACT FROM AUTHOR]