Median Biological Effective Dose Research Articles

1133 Biologically Effective Dose and Prediction of Obliteration of Arteriovenous Malformations in Pediatric Patients Treated by Gamma Knife Radiosurgery

INTRODUCTION: Stereotactic radiosurgery (SRS) represents an effective treatment for pediatric arteriovenous malformations (AVMs). Biologic effective dose (BED) is recognized as a predictive variable for outcomes in the adult population, but its role has never been studied in pediatric outcomes. METHODS: Retrospective data for = 18 years old patients treated with single-session SRS for AVM was collected from 1989 – 2019. BED calculations were performed using an a/b ratio of 2.47. Kaplan-Meier analysis was used to evaluate obliteration, new hemorrhage, and radiation-induced changes (RIC). Cox-regression analysis was used for obliteration prediction using two models (margin dose versus BED). RESULTS: One-hundred-ninety-seven patients [median age = 13.1 years, Interquartile range (IQR) = 5.2] were included; 72.6% presented initially with spontaneous hemorrhage. A median margin dose of 22 Gy (IQ = 4.0) with a median BED of 183.2Gy (IQR = 70.54) was used to treat AVMs with a median volume of 2.8 cm3 (IQR = 2.9). Following SRS, obliteration was confirmed in 115 patients (58.4%) using MRI and angiography at a median follow-up of 2.85 years (IQR = 2.26). The cumulative obliteration probability was 43.6% (95% CI = 36.1-50.3), 60.5% (95% CI+=2.2-67.4), 66.0% (95% CI= 56.0-73.7) at 3, 5 and 10 years respectively. In multivariate analysis, a BED >180 Gy [HR = 2.11, 95% CI=1.30-3.40, p = 0.002] in model 1, and a margin dose >20 Gy [HR = 1.90, 95% CI = 1.15-3.13, p = 0.019] in model 2, were associated with obliteration. An AVM nidus volume >4 cm3 was associated with lower obliteration rates in both models. The probability of symptomatic RIC at 10 years was 8.6% (95% CI = 3.5-13.4). Neither BED nor margin dose were associated with RIC occurrence, with the only predictive factor being deep AVM location [HR = 3, 95% CI = 1-9.1, p = 0.048]. CONCLUSIONS: This study confirms BED as a predictor for pediatric AVM obliteration. Optimization of BED in pediatric AVM SRS planning may improve cumulative obliteration rates.

The dosimetric parameters impact on local recurrence in stereotactic radiotherapy for brain metastases.

Stereotactic radiotherapy (SRT) for brain metastases (BM) allows very good local control (LC). However, approximately 20%-30% of these lesions will recur. The objective of this retrospective study was to evaluate the impact of dosimetric parameters on LC in cerebral SRT. Patients treated with SRT for 1-3 BM between January 2015 and December 2018 were retrospectively included. A total of 349 patients with 538 lesions were included. The median gross tumour volume (GTV) was 2 cm3 (IQR, 0-7). The median biological effective dose with α/β = 10 (BED10) was 60 Gy (IQR, 32-82). The median prescription isodose was 71% (IQR, 70-80). Correlations with LC were examined using the Cox regression model. The median follow-up period was 55 months (min-max, 7-85). Median overall survival was 17.8 months (IQR, 15.2-21.9). There were 95 recurrences and LC at 1 and 2 years was 87.1% (95% CI, 84-90) and 78.1% (95% CI, 73.9-82.4), respectively. Univariate analysis showed that systemic treatment, dose to 2% and 50% of the planning target volume (PTV), BED10 > 50 Gy, and low PTV and GTV volume were significantly correlated with better LC. In the multivariate analysis, GTV volume, isodose, and BED10 were significantly associated with LC. These results show the importance of a BED10 > 50 Gy associated with a prescription isodose <80% to optimize LC during SRT for BM. Isodose, BED, and GTV volume were significantly associated with LC. A low isodose improves LC without increasing the risk of radionecrosis.

Short-term pain control after palliative radiotherapy for uncomplicated bone metastases: a prospective cohort study.

This study aimed at evaluating the efficacy of different radiotherapy (RT) fractionation regimens in managing uncomplicated painful bone metastases (BM) and identifying predictive factors for pain control. Patients with 1 to 4 symptomatic BM from any primary solid tumors and a life expectancy exceeding 3months were included in the study and received palliative RT, with SBRT restricted in the context of oligometastatic disease or in patients with good prognosis. Pain analysis using the Brief Pain Inventory (BPI) tool was conducted at baseline, 1 and 3months after RT. Analgesic intake was recorded as morphine-equivalent doses (OME). Pain response was assessed using the International Consensus on Palliative Radiotherapy Endpoint (ICPRE). Multivariate logistic regression analyzed patient-related, tumor-related, and treatment-related factors predicting BM pain control at 3months post-RT. From Feb 2022 to Feb 2023, 44 patients with 65 symptomatic BM were investigated. Breast (32%) and lung (24%) tumors were the most common primary tumors. Treatment plans included 3DCRT (60%) and VMAT (40%), with a median biological effective dose for tumors (BED) of 29Gy [14-108]. All patients completed the 3-month follow-up. Pain response rates were 62% at 1month and 60% at 3months. Responders had better PS ECOG scores (67%; P = 0.008) and received active systemic therapies (67%: P = 0.036). Non-responders had lower pretreatment BPI (mean: 13.7 vs. 58.2; P = 0.032), with significantly higher values after 1month (mean: 9.1 vs. 5.3, P = 0.033). Baseline BPI (OR: 1.17; 95% CI: 1.032-1.327; P = 0.014) and BPI at 1month (OR: 0.83; 95% CI: 0.698-0.976; P = 0.025) were independent predictors of pain response at 3months. Our findings show that palliative RT ensured short-term pain control in patients with BM, regardless of tumor type and dose-fractionation regimen. A larger sample size and a longer follow-up could potentially identify which patients are likely to benefit most from RT, and which fractionation might be indicated for achieving a durable pain relief. A multidisciplinary approach is paramount to provide a better care to BM patients.

Survival and Toxicity in Patients With Unresectable or Inoperable Biliary Tract Cancers With Ablative Radiation Therapy Versus Nonablative Chemoradiation

Conventional chemoradiation (CCRT) is inadequately effective for the treatment of unresectable or inoperable biliary tract cancers (UIBC). Ablative radiation therapy (AR), typically defined as a biologically effective dose (BED) ≥80.5 Gy, has shown some promise in terms of local control and survival in these patients. We compare the efficacy and toxicity of AR to non-AR in UIBC patients. Patients with UIBC treated with stereotactic body radiation therapy (SBRT; n = 18) or CCRT (n = 28) between 2006 and 2021 were retrospectively analyzed. The associations of treatment, BED groups, selected characteristics with overall survival (OS), progression-free survival (PFS), and local control were estimated separately using Cox proportional hazards regression. Toxicity was scored using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Median dose fractionation was 60 Gy in 5 fractions (median BED, 127 Gy) for SBRT and 50 Gy in 25 fractions (median BED, 64 Gy) for CCRT. The median follow-up of the entire cohort was 11.5 months. The 1-year OS rate was 62% for BED <80.5 versus 66% for BED ≥80.5 (P = .069). The 1-year PFS rate was 24% for BED <80.5 and 29% for BED ≥80.5 (P = .050). The 1-year local control rate was 20% for BED <80.5 and 41% for BED ≥80.5 (P = .097). BED as a continuous variable (P = .013), BED ≥100 Gy (P = .044), and race (white versus nonwhite) (P = .037) were associated with improved overall mortality. BED ≥80.5 Gy (P = .046), smaller tumor size (<5 cm; P = .038) and N0 disease (P <.0001) were associated with improved disease progression rates. Local control was improved in patients with N0 disease compared with N1 disease (P <.0001). Both treatments were well tolerated; there was no difference in acute and late toxicity between AR and non-AR. In this review, there was improved PFS with BED ≥80.5 Gy with a trend toward OS benefit. BED ≥80.5 Gy was achieved mostly through SBRT and was well tolerated. AR could be considered a more effective treatment modality than CCRT in patients with UIBC.

Biologically Effective Dose and Prediction of Obliteration of Arteriovenous Malformations in Pediatric Patients Treated by Gamma Knife Radiosurgery.

Stereotactic radiosurgery (SRS) represents an effective treatment for pediatric arteriovenous malformations (AVMs). Biological effective dose (BED) has shown promising results in 2 previous studies as a predictive variable for outcomes in adults, but its role has never been studied in pediatric outcomes. Retrospective data for patients 18 years or younger treated with a single-session SRS for AVMs were collected from 1989 to 2019. BED calculations were performed using an α/β ratio of 2.47. Kaplan-Meier analysis was used to evaluate obliteration, new hemorrhage, and radiation-induced changes (RIC). Cox-regression analysis was used for obliteration prediction using 2 models (margin dose vs BED). One hundred ninety-seven patients (median age = 13.1 years, IQR = 5.2) were included; 72.6% (143/197) of them presented initially with spontaneous hemorrhage. A median margin dose of 22 Gy (IQR = 4.0) with a median BED of 183.2 Gy (IQR = 70.54) was used to treat AVM with a median volume of 2.8 cm 3 (IQR = 2.9). After SRS, obliteration was confirmed in 115/197 patients (58.4%) using magnetic resonance imaging and angiography at a median follow-up of 2.85 years (IQR = 2.26). The cumulative obliteration probability was 43.6% (95% CI = 36.1-50.3), 60.5% (95% CI+ = 2.2-67.4), and 66.0% (95% CI = 56.0-73.7) at 3, 5, and 10 years, respectively. In Cox multivariate analysis, a BED >180 Gy (hazard ratio [HR] = 2.11, 95% CI = 1.30-3.40, P = .002) in model 1 and a margin dose >20 Gy (HR = 1.90, 95% CI = 1.15-3.13, P = .019) in model 2 were associated with obliteration. An AVM nidus volume >4 cm 3 was associated with lower obliteration rates in both models. The probability of symptomatic RIC at 10 years was 8.6% (95% CI = 3.5-13.4). Neither BED nor margin dose was associated with RIC occurrence, with the only predictive factor being deep AVM location (HR = 3, 95% CI = 1-9.1, P = .048). This study confirms BED as a predictor for pediatric AVM obliteration. Optimization of BED in pediatric AVM SRS planning may improve cumulative obliteration rates.

Long-Term Safety and Efficacy of SAbR for Metastatic RCC.

Metastasis-directed stereotactic ablative radiation (SAbR) in metastatic renal cell carcinoma (mRCC) has been shown to prolong time to systemic therapy start/change. However, there is a paucity of data on the durability of local control by SAbR and long-term side effects, limiting its investigation in prospective trials. Here we report the long-term local control rates of SAbR for mRCC, focusing on factors that lead to local failure where dose escalation may be beneficial. We retrospectively reviewed 354 metastatic RCC patients who received SAbR to 902 lesions between 2005 and September 2021. Acute and late adverse events and their Common Terminal Criteria for Adverse Events (CTCAE) v. 5.0 grades were collected. RECIST v. 1.1 was used to evaluate treatment response. LC was estimated using the cumulative incidence function, with death as a competing risk. Local control (LC) was calculated using the Kaplan-Meier method. Lesions were followed for a median of 16 months; 136 lesions had >36 months of follow-up. The most common radiation prescription was 36 Gy in 3 fractions, and the median biological effective dose was 72 Gy10. 3-year local control was 80% (95% CI 75, 83). 3-year LC differed according to lesion location, ranging from 65% (95% CI 52, 75) in the spine to 93% (95% CI 80, 98) in the lungs. Radiation-induced adverse events were experienced by 101 patients: 79 had an acute (≤90 days of SAbR) grade 1-2 toxicity; 20 had an acute grade 3-4 toxicity; 59 had a late grade 1-2 toxicity; 15 had a late grade 3-4 toxicity. The most common acute grade 1-2 toxicity was pain (n = 32), followed by nausea (n = 22) and fatigue (n = 16). There were 7 occurrences of acute grade 3-4 pain, 4 of nausea, and 2 fractures. The most common late grade 1-2 toxicity was fracture (n = 16), followed by pain (n = 15) and pneumonitis (n = 12). Hyperglycemia was the only late grade 3-4 toxicity that occurred more than once (n = 2). SAbR offers durable LC of mRCC lesions with an acceptable toxicity profile. LC was affected by treated lesion location, with bone (including long bones and ribs) and spine locations experiencing less durable LC, corresponding to locations that received lower-BED treatments.

An Analysis of Patients Treated with Stereotactic Body Radiotherapy for Metastatic Urinary Tract Tumors to Identify Predictors of Response.

To identify selection criteria linked to outcomes in patients treated with stereotactic body radiotherapy (SBRT) for metastatic tumors of the urinary tract (UT). Single institution retrospective analysis of SBRT treated patients for oligometastatic/progressive UT tumors from 2006-2022. Charts were queried for M1 status at diagnosis or during disease course, treatment details (surgery, SBRT, systemic therapy), metabolic status (diabetes [DM], BMI) and outcomes. A linear quadratic formula was used to calculate the biologically effective dose (BED) using an α/β of 10 for tumor. Descriptive statistics portrayed the cohort, and analyses were done at patient and site level. Time-to-event analyses, including overall survival (OS) and progression-free survival (PFS) from SBRT, were assessed by the Kaplan-Meier method. Cox regression was used for univariable (UVA) and multivariable analyses (MVA) to identify predictors of outcomes. A total of 35 patients were treated at 44 metastatic sites, including: bone (25%), node (36.4%), lung (20.5%), soft tissue (13.6%) and liver (4.5%). Most were male (74.3%) with a median age of 70 (range: 51-89), without DM (60%) having a median BMI of 29.8, and ECOG <2 (97.1%) at time of SBRT. Six (17.1%) patients were M1 at diagnosis. Of the 29 non-M1 patients, 86.2% received definitive local therapy (LT), 58.6% had at least T3/N+ disease, 75.8% received systemic therapy with a median of 2 agents (range: 1-6) prior to SBRT. Sixteen (45.7%) received immunotherapy (IO) with most receiving this before (75%) and after (56.2%) SBRT. Six patients had positive PD-L1 status (n = 10). The median RT dose, fractionation and BED was 40 Gy (range: 14-46), 5 fractions, and 72 (range: 28-132), respectively. At a median follow-up of 34.8, the median OS was 18.4 m (range: 9.3-27.4) with a 2-year OS of 35.9%. At patient level, 62.8% recurred after SBRT. The median PFS after SBRT was 5.3 m (range: 1.8-8.7) with a 2-yr PFS of 29.3%. Patient-level PFS was improved with LT (6.7 vs 1.4 m; p = 0.001) and DM (NR vs 2.9 m; p = 0.015), whereas improved OS was related with LT (18.9 vs 6.6 m; p = 0.03), DM (p = 0.04), ECOG (p = 0.004), and no relapse after SBRT (NR vs 9.8 m; p <0.001). Exposure to < 3 systemic agents prior to SBRT portended better PFS (6.7 vs 2.6 m; p = 0.04) without any impact by IO. At site level, 20.4% of sites had local relapse with 4 being the first event. Site was related with PFS (p = 0.009) with order of increased relapse risk being liver > bone > soft tissue > node > lung. No dosimetric feature was related with recurrence risk. On MVA, both DM (p = 0.02) and LT (p = 0.002) were predictive for PFS. Only recurrence after SBRT predicted for OS on MVA (HR: 6.7, 95% CI: 1.4-31; p = 0.014). In the IO subset, median PFS was 5.3 m and OS was 9.4 m, with no difference seen with IO-SBRT sequence or PDL1 status. Optimized selection criteria for metastasis-directed therapy in patients with UT tumors is unclear, notably with IO. Future studies may benefit by assessing circulating tumor markers prior to SBRT.

Validation of the Prognostic Index for Spine Metastasis (PRISM) Score for Stratifying Survival in Patients Treated with Spinal Stereotactic Radiosurgery

Stereotactic spinal radiosurgery (SSRS) has been increasingly utilized as a first-line treatment for the management of spine metastases due to its ability to prolong survival and improve symptom control. Studies have shown that SSRS is helpful for select patients; however, there is no universal scoring system utilized to predict patient response to treatment. The Prognostic Index for Spinal Metastases (PRISM) score was shown to predict the likelihood of patients benefiting from SSRS. We sought to further demonstrate its generalizability by performing validation with a large dataset from a second high-volume institution. We performed a retrospective review from 2017-2019 of 424 patients treated with SSRS at a single institution. Patients were stratified on the previously described PRISM criteria: Female sex (+2), solitary bone disease (+3), performance status (0 through +3.5), prior surgery at the SSRS site (+1), number of other metastatic sites (-N), prior radiation at the SSRS site (-1), and latency to treatment ≥ 5 months (+3). Patients were grouped based on PRISM scores: >7, Group 1; 4-7, Group 2; 1-3, Group 3; <1 Group 4. There were 89, 188, 88, and 59 patients in Groups 1, 2, 3, and 4, respectively. Most patients were male (70%) with a performance status of 0 (53%). The most common tumor histologies were prostate (34%), renal (18%), and lung (11%). The median biological effective dose (BED10) was 60 Gy (interquartile range [IQR], 60-82). We performed Cox proportional hazards analysis on overall survival (OS) based on PRISM score and patient and tumor characteristics. Concordance indices created from PRISM criteria and the multivariate Cox proportional analysis were compared. The median follow-up time was 50.5 months (95% confidence interval [CI], 45.8-54.7) with a median overall survival of 30.3 months (95% CI, 27.3-38.4). The median overall survivals for PRISM Groups 1, 2, 3, and 4 were 57.1, 37, 23.7, and 8.8 months, respectively. There were significant differences in overall survival among PRISM groups with hazard ratios of 0.49 (95% CI, 0.35-0.69; P<0.001) for Group 1, 0.71 (95% CI, 0.55-0.91); P<0.007) for Group 2, 1,45 (95% CI, 1.08-1.94); P = 0.010) for Group 3, and 3.47 (95% CI, 2.56-4.70; P<0.001) for Group 4. Multivariable Cox analysis for patient and tumor characteristics revealed only the number of organs involved and performance status as significant clinicopathologic prognostic attributes. However, the C-index using the PRISM criteria was 0.76, which was superior to the C-index when using the significant clinicopathologic attributes by themselves (0.71). These data demonstrate robust validation of the PRISM score to stratify OS in patients treated with SSRS and may help guide optimal treatment selection in prospective trials and clinical settings.

Clinical Efficacy and Safety of Once-Weekly Fractionation in Stereotactic Body Radiotherapy for Pulmonary Oligometastatic Lesions

As the oligometastatic disease paradigm has become more widely accepted, further investigation is needed to risk-stratify patients within this spectrum of disease and define optimal treatment methods. Stereotactic Body Radiotherapy (SBRT) has emerged as an efficacious and safe modality to control individual lesions and improve clinical outcomes in the setting of oligometastatic disease. There is scant literature describing ideal SBRT inter-fraction time intervals or their impact on clinical outcomes, especially for treating pulmonary oligometastases. Most institutions appear to offer treatments on consecutive days or every other day. In this abstract, we sought to evaluate the efficacy and safety of delivering SBRT treatments in a once-weekly fractionation scheme. The study was undertaken via retrospective review at a single institution. We included patients with pulmonary metastatic lesions treated with SBRT at our institution between 2015 and 2019. Patients with oligometastatic disease were included, defined as patients with 5 or fewer total metastatic lesions. Treatments were delivered between 3 and 5 fractions and using at least 5 Gy per fraction. Per institutional protocol, all treatments were delivered 7 days apart. From a single institution, 204 lesions from 111 patients were included. Median follow-up was 16.5 months [IQR 7 - 36.3]. Median dose was 40 Gy [IQR 30 - 50], median BED was 80 Gy [IQR 60-100], median dose per fraction was 10 Gy [IQR 8-11]. Median internal target volume (ITV) was 18.5 cc [IQR 9.3 - 45.8]. The most common tumor histologies were lung adenocarcinoma (38.2%), colorectal adenocarcinoma (15.6%), lung squamous cell carcinoma (12.7%), renal cell carcinoma (5.9%), breast invasive ductal carcinoma (5.4%), small cell lung cancer (3.9%), and melanoma (2.9%). 2-year local control (LC) rate was 85.7% and 5-year LC rate was 84.3%. 2-year regional control (RC) rate was 53.9% and 5-year RC was 49%. Median overall survival (OS) was 20 months [IQR 9 - 37.3]. Cox regression analysis revealed biologically effective dose (BED) (HR 0.99 [0.98 - 0.99] p = 0.001) as well as dose per fraction (HR 0.92 [0.86 - 0.97] p = 0.003) were both associated with improved OS. Longest tumor dimension was associated with worse OS independent of BED and dose per fraction (HR 1.26 [1.1 - 1.4] p = 0.001). Total toxicity incidence was 7.3%, which consisted only of G1-G2 cough, dyspnea, and fatigue. Treatment of pulmonary oligometastatic lesions with SBRT delivered via once-weekly fractionation is associated with excellent local control and minimal toxicity. Larger studies are warranted to directly compare clinical outcomes of weekly SBRT fractionation to other conventional SBRT treatment schedules.

The Effect of Stereotactic Body Radiotherapy (SBRT) Dose-Fraction (fx) Schema on Non-Small Cell Lung Cancer (NSCLC)

Stereotactic body radiotherapy (SBRT) dose-fraction (fx) schema for non-small cell lung cancer (NSCLC) varies at different centers and commonly involves 3 to 5 fx. Additionally, the frequency of treatment per week, or treatment schedules (TS), can also differ. We sought to evaluate and compare the effect of different dose-fx schemas on overall survival (OS). We retrieved data from the National Cancer Database. Patient eligibility included early-stage NSCLC with cT1-2 N0M0 disease treated with SBRT using 3-5f x regimens. Demographics and clinical characteristics were identified. Biologically effective dose (BED) and total dose (TD) were calculated. TD included following: 45-60 Gy for 3 fx, 48-60 Gy for 4 fx, and 50-60 Gy for 5 fx. TS was classified as one of the following: daily, every other day, twice per week, or prolonged (less frequently than twice weekly). Non-prolonged TS was defined as daily, every other day, and twice per week. OS was calculated from the date of end of RT to the date of death and censored at the date of last contact. Kaplan Meier method was used to estimate OS and log-rank tests were used to compare the difference between groups. TS was compared pairwise within each individual fx-group. Univariable Cox proportional models with robust standard errors to account for within institution correlations were used to investigate the association between BED, TD, TS, fx-group and OS. Within each fx-group, BED was also assessed and compared. A total of 3244 patients were identified, with median age 73. 48% were males and 52% females. 601 (19%) patients received 3 fx, 884 (27%) received 4 fx, and 1759 (54%) received 5 fx treatments. For the overall cohort, median and mean BEDs were 112 and 119, respectively. TS did not show a difference in OS among each individual fx group. Overall, prolonged vs non-prolonged schedules also did not show a difference in OS (p = 0.64). OS was superior in the 3 fx group compared to 4 and 5 fx groups, with median survival times of 61.5 vs 53.7 vs 52.6 months, respectively (p = 0.046). Overall, an increase in BED reduced risk of death (HR = 0.97 per 10-units, CI: 0.94-0.99, p = 0.04). When stratified by fx, each 10 unit rise in BED for those treated with 5 fx reduced the risk of death by 8% (HR = 0.92, CI: 0.87-0.97, p<0.01). However, increasing BED was not associated with change in OS for 3 fx (HR = 1.00, CI: 0.93-1.08, p = 0.93) and 4 fx (HR = 1.08, p = 0.08) regimens. Patients who received BED greater than the median (BED>112) had improved OS compared to those receiving BED£112 (HR = 0.86, p = 0.047). When evaluating the 5 fx-group individually, BED >100 (median of 5fx group) had superior OS compared to £100 (HR = 0.80, p = 0.02). Three-fraction regimens have superior OS compared to 4 and 5 fx regimens. Higher BED improves OS in 5 fx regimens. Treatment schedule variations among individual fx-groups does not impact OS.

Efficacy and Dose-Response Relationship of Stereotactic Body Radiotherapy for Abdominal Lymph Node Metastases from Hepatocellular Carcinoma.

The objective of this study was to investigate the treatment efficacy of stereotactic body radiotherapy (SBRT) and evaluate the influence of radiation dose on local control and survival in patients with abdominal lymph node metastases (LNM) from hepatocellular carcinoma (HCC). Between 2010 and 2020, data of 148 patients with HCC with abdominal LNM, including 114 who underwent SBRT and 34 who received conventional fractionation radiation therapy (CFRT), were collected. A total radiation dose of 28-60 Gy was delivered in 3-30 fractions, with a median biologic effective dose (BED) of 60 Gy (range, 39-105 Gy). Freedom from local progression (FFLP) and overall survival (OS) rates were analyzed. With a median follow-up of 13.6 months (range, 0.4-96.0 months), the 2-year FFLP and OS rates of the entire cohort were 70.6% and 49.7%, respectively. Median OS of the SBRT group was longer than the CFRT group (29.7 vs. 9.9 months, P = .007). A dose-response relationship was observed between local control and BED in either the entire cohort or the SBRT subgroup. Patients who received SBRT with a BED ≥60 Gy had significantly higher 2-year FFLP and OS rates than those who received a BED <60 Gy (80.1% vs. 63.4%, P = .004; 68.3% vs. 33.0%, P < .001). On multivariate analysis, BED was an independent prognostic factor for both FFLP and OS. SBRT achieved satisfactory local control and survival with feasible toxicities in patients with HCC with abdominal LNM. Moreover, the findings of this large series suggest a dose-response relationship between local control and BED.

PD15-03 RADIATION DOSE REQUIRED TO CONTROL PROSTATE CANCER AS DETERMINED BY POST-TREATMENT BIOPSY: LONG TERM RESULTS

You have accessJournal of UrologyCME1 Apr 2023PD15-03 RADIATION DOSE REQUIRED TO CONTROL PROSTATE CANCER AS DETERMINED BY POST-TREATMENT BIOPSY: LONG TERM RESULTS Nelson Stone, Rendi Shue, Barry Rosenstein, and Richard Stock Nelson StoneNelson Stone More articles by this author , Rendi ShueRendi Shue More articles by this author , Barry RosensteinBarry Rosenstein More articles by this author , and Richard StockRichard Stock More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003262.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radiation therapy for prostate cancer is typically prescribed at a standard dose, 79-81 Gy for external beam irradiation (EBRT) and 145 Gy for iodine-125 brachytherapy (BT). Unlike prostatectomy where the gland is removed at the time of treatment successful radiation treatment relies on the death of all cancer cells in situ. However, the dose requirement for different Gleason grade groups or NCCN risk groups may also differ. We investigated the relationship between the biological effective dose (BED) and local control as determined by post-treatment biopsy (PB) in a large cohort of men who had BT +EBRT. METHODS: 545 men who had BT were followed a median of 11 years (range 2-26) and had PB a mean of 3.2 years (2-17) post-treatment. All PB were performed by one investigator (NNS) and routinely performed at 2 years or later for a rising PSA. Median age, PSA and BED were 66 years (41-85), 7.0 ng/ml (1-189) and 185.5 Gy (15-282). 295 (54.1%) received hormone therapy (HT) for a median of 6 months. Radiation doses were converted post-implant to the BED using an ꭤ/β of 2. Associations with grade, stage, PSA, NCCN status, HT use, BED were compared to the PB results and prostate cancer survival (PCS) using ANOVA, chi-square, linear regression, Kaplan Meier estimates with comparisons by log rank and Cox proportion hazards. RESULTS: 34 (6.2%) of the 545 men had a positive PB which occurred a mean of 5.9 years (range 2-17) after all treatment. BED (p<0.001), stage (p=0.004), PSA (p=0.038) and HT use (p=0.019) were associated with a positive PB but only BED (p<0.001) remained significant on regression analysis. Dichotomizing BED to <140, 160, 180, 200, 220 or greater yielded optimal local control (positive biopsy rate 2% or less) at 180 Gy for all 3 NCCN risk groups (Table). Men with a positive PB had a mean BED of 136.8 vs. 181.3 Gy for negative PB (p<0.001). At <180 Gy 24/229 (10.5%) had local failure compared to 5/392 (1.7%) for higher doses (p<0.001, OR 6.7, 95% CI 2.5-17.9). PCS at 15 and 20 years for negative PB was 94.5 and 94.5% vs. 74.4 and 46.5% for a positive one (p<0.001). PCS was associated with BED (p<0.001), PSA (p=0.028) and stage (p=0.018). CONCLUSIONS: This long-term investigation defined the radiation dose necessary to eradicate prostate cancer and should be considered as the minimal requirement when prescribing and delivering this treatment option. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e419 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nelson Stone More articles by this author Rendi Shue More articles by this author Barry Rosenstein More articles by this author Richard Stock More articles by this author Expand All Advertisement PDF downloadLoading ...

Gamma Knife Radiosurgery for Cushing’s Disease: Evaluation of Biological Effective Dose from a Single-Center Experience

Objective: Gamma knife radiosurgery (GKRS) has served as an adjunctive treatment in Cushing's disease (CD) for decades and has become a vital part of therapy in the management of CD. Biological effective dose (BED) is a radiobiological parameter with time correction, considering the cellular deoxyribonucleic acid repairment. We aimed to investigate the safety and efficacy of GKRS for CD and evaluate the association of BED and treatment outcome. Methods: A cohort study of 31 patients with CD received GKRS in West China Hospital between June 2010 and December 2021. Endocrine remission was defined as normalization of 24 h urinary free cortisol (UFC) or serum cortisol ≤ 50 nmol/L after a 1 mg dexamethasone suppression test. Result: The mean age was 38.6 years old, and females accounted for 77.4%. GKRS was the initial treatment for 21 patients (67.7%), and 32.3% of patients underwent GKRS after surgery due to residual disease and recurrence. The mean endocrine follow-up duration was 22 months. The median marginal dose was 28.0 Gy, and the median BED was 221.5 Gy2.47. Fourteen patients (45.1%) experienced control of hypercortisolism in the absence of pharmacological treatment, and the median duration to remission was 20.0 months. The cumulative rates of endocrine remission at 1, 2, and 3 years after GKRS were 18.9%, 55.3%, and 72.21%, respectively. The total complication rate was 25.8%, and the mean duration from GKRS to hypopituitary was 17.5 months. The new hypopituitary rate at 1, 2, and 3 years were 7.1%, 30.3%, and 48.4%, respectively. A high BED level (BED > 205 Gy2.47) was associated with better endocrine remission than a low BED level (BED ≤ 205 Gy2.47), while no significant differences were found between the BED level and hypopituitarism. Conclusions: GKRS was a second-line therapeutic option for CD with satisfactory safety and efficacy. BED should be considered during GKRS treatment planning, and optimization of BED is a potentially impactful avenue toward improving the efficacy of GKRS.

Two-institution results of Stereotactic Body Radiation Therapy (SBRT) for treating adrenal gland metastases from liver cancer

ObjectiveStereotactic Body Radiation Therapy (SBRT) has been found beneficial for adrenal gland metastases (AGMs) with a high local control rate and low toxicity. The role of SBRT for AGMs in patients with liver cancer has not been well-discussed before. We, therefore, report our two-institution experience to further elaborate on the feasibility and effectiveness of SBRT in the treatment of AGMs from liver cancer.MethodsA total of 23 liver cancer patients (19 males, 4 females) with 24 AGMs treated by SBRT from July 2006 to April 2021 were retrospectively included in this study. Toxicity was assessed based on clinical adverse events using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The effectiveness was assessed based on local control (LC), progression-free survival (PFS), and overall survival (OS), which were calculated using the Kaplan-Meier method. Univariate analyses were compared by log-rank test. The relevant covariates were evaluated using Cox proportional hazards models.ResultsThe median dose was 40 Gy in 5 fractions, with the corresponding median biological effective dose (BED10, α/β = 10 Gy) of 72 Gy. The median overall follow-up time was 15.4 months (range: 4.2–70.6 months). The complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) rates were 25.0%, 20.8%, 33.3%, and 20.8%, respectively. All 6 patients with AGMs accompanying symptoms had varying degrees of alleviation after SBRT. The 0.5-, 1-year and 2-year LC rates were 87.5%, 77.8%, and 77.8%, respectively. The 0.5-, 1-year and 2-year OS rates were 95.5%, 66.8%, and 41.1%, respectively. The treatments were all tolerated with only one patient reporting a grade-3 hepatic injury. The univariate analysis concluded that only gross tumor volume (GTV) < 34.5 ml (p = 0.039) was associated with a favorable LC rate. After multivariate analysis, favorable predictors correlated with OS were GTV < 34.5 ml (p = 0.043), systemic therapy (p = 0.017), and without additional organ metastasis after SBRT (p = 0.009).ConclusionOur results suggest that SBRT is a safe and effective technique to treat AGM from liver cancer, especially for small GTV (< 34.5ml). Moreover, the small metastatic lesion volume, fewer metastatic lesions, and intervention of systemic therapy are more likely to improve OS.

Angiotensin receptor blockade and stereotactic body radiation therapy for early stage lung cancer ARB & SBRT for early stage lung cancer

ABSTRACT Stereotactic body radiotherapy (SBRT) demonstrates excellent local control in early stage lung cancer, however a quarter of patients develop recurrence or distant metastasis. Transforming growth factor-beta (TGF-β) supports metastasis and treatment resistance, and angiotensin receptor blockade (ARB) indirectly suppresses TGF-β signaling. This study investigates whether patients taking ARBs while undergoing SBRT for early stage lung cancer exhibited improved overall survival (OS) or recurrence free survival (RFS) compared to patients not taking ARBs. This was a single institution retrospective analysis of 272 patients treated with SBRT for early stage lung cancer between 2009 and 2018. Patient health data was abstracted from the electronic medical record. OS and RFS were assessed using Kaplan–Meier method. Log-rank test was used to compare unadjusted survival between groups. Univariable and multivariable Cox proportional hazard regression models were used to estimate hazard ratios (HRs). Of 247 patients analyzed, 24 (10%) patients took ARBs for the duration of radiotherapy. There was no difference in mean age, median tumor diameter, or median biologic effective dose between patients taking ARBs or not. Patients taking ARBs exhibited increased OS (ARB = 96.7 mo.; no ARB = 43.3 mo.; HR = 0.25 [95% CI: 0.10 to 0.62, P = .003]) and increased RFS (median RFS, ARB = 64.3 mo.; No ARB = 35.1 mo.; HR = 0.26 [95% CI: 0.10 to 0.63, P = .003]). These effects were not seen in patients taking angiotensin converting enzyme inhibitors (ACEIs) or statins. ARB use while undergoing SBRT for early stage lung cancer may increase OS and RFS, but ACEI use does not show the same effect.

Role of biological effective dose for prediction of endocrine remission in acromegaly patients treated with stereotactic radiosurgery.

Stereotactic radiosurgery (SRS) can be used in acromegaly patients to achieve endocrine remission. In this study we evaluate the biological effective dose (BED) as a predictor of SRS outcomes for acromegaly. This retrospective, single-center study included patients treated with single-fraction SRS with growth hormone secreting pituitary adenomas and available endocrine follow-up. Kaplan-Meier analysis was used to study endocrine remission, new pituitary deficit, and tumor control. Cox analyses were performed using two models [margin dose (model 2) versus BED (model 1)]. Sixty-seven patients (53.7% male) with a median age of 46.8 years (IQR 21.2) were treated using a median dose of 25Gy (IQR 5), and a median BED of 171.9Gy2.47 (IQR 66.0). Five (7.5%) were treated without stopping antisecretory medication. The cumulative probability of maintained endocrine remission off suppressive medications was 62.5% [47.9-73.0] at 3 years and 76.5% [61.0-85.9] at 5 years. IGF1i > 1.5 was a predictor of treatment failure [Hazard ratio (HR) 0.40 (0.21-0.79) in model 1, p = 0.00783]. Margin dose > 22Gy [HR 2.33 (1.06-5.13), p = 0.03593] or a BED > 170Gy2.47 [HR 2.02 (1.06-3.86), p = 0.03370] were associated with endocrine remission. The cumulative probability of new hypopituitarism after SRS was 36.8% (CI 95% 22.4-45.9) at 3 years and 53.2% (CI 95% 35.6-66) at 5 years. BED or margin dose were not associated with new hypopituitarism. BED is a strong predictor of endocrine remission in patients treated with SRS. Dose planning and optimization of the BED to > 170Gy2.47 give a greater probability of endocrine remission in acromegalic patients.

Treatment of Thymic Oligometastastic or Oligoprogressive Lesions with Hypofractionated Radiation Therapy or Stereotactic Body Radiation Therapy

<h3>Purpose/Objective(s)</h3> Recent large clinical trials have demonstrated an improvement in local failure-free survival (LFFS) and progression free survival (PFS) with hypofractionated radiation therapy (HFRT) and stereotactic body radiation therapy (SBRT) in select patients with oligometastatic (OM) and oligoprogressive (OP) disease. However, little is known about the outcomes of HFRT and SBRT in patients with OM or OP disease from thymic malignancies. Therefore, the purpose of this analysis was to characterize the outcomes of such patients treated at our institution. <h3>Materials/Methods</h3> We retrospectively reviewed patients with OM or OP thymic malignancies treated with HFRT or SBRT between 2009-2021. We defined OM as 5 or fewer sites of metastatic disease at the time of RT and OP as 5 or fewer sites of metastatic disease increasing in radiological size. Patients treated with 20 or fewer fractions of radiation were included. Survival outcomes were defined from the end of RT. Analyses were done using the <i>lifelines</i> module in Python. <h3>Results</h3> We analyzed 48 patients treated to 81 lesions. The median age was 54 years old (range: 24-82 years), 63% were male and 79% were white. Patients had thymoma (54%), thymic carcinoma (38%), or atypical thymic carcinoid (8%). At the time of initial diagnosis, patients were stage I-II (21%), III (12.5%), IVA (23%) or IVB (42%). The majority of patients (65%) received systemic therapy prior to radiation therapy. Of the 81 lesions treated, 67 (83%) were OM lesions and 14 (17%) were polymetastatic, but OP lesions. Treatment sites included bone (37%), pleura (25%), lymph nodes (20%), lung (10%), brain (5%) and other (4%). Most patients were treated in 3 fractions (N=31; 8-10 Gy x 3 fractions), 5 fractions (N=28; 5-7 Gy x 5 fractions (N=20) or 8-10 Gy x 5 fractions (N=8)), or 15 fractions (N=11; 2.5-4 Gy x 15 fractions). The median biological effective dose (BED) was 51.3 Gy. Median follow up was 16 months. The 2-year/5-year rates of LFFS and PFS were 83%/76% and 32%/17%, respectively. The 2-year/5-year/10-year rates of overall survival (OS) were 92%/80%/61%. Patients with thymic carcinoma or atypical carcinoid had similar LFFS vs. those with thymoma (2-year LFFS: 85% vs. 82%, p=0.31), but they had shorter PFS (2-year PFS: 5% vs. 39%, p=0.01), and OS was not significantly different (2-year OS: 86% vs. 96%, p=0.25). Patients (N=14 patients treated to 19 lesions) treated with a BED > 60 Gy did not experience any local failure at 2 years (2-yr LFFS=100%). <h3>Conclusion</h3> Patients with OM or OP thymic malignancies treated with HFRT or SBRT had high rates of LFFS, PFS and OS. Despite having a more aggressive disease, patients with thymic carcinoma still experienced favorable LFFS with HFRT or SBRT. Patients treated with regimens with BED greater than 60 Gy had excellent LFFS. These results suggest that with long OS and PFS times, consideration should be given to SBRT/HFRT regimens to maximize local control in these patients with favorable prognoses.

Multi-Target Thoracic Stereotactic Body Radiotherapy – Toxicity and Efficacy Analysis

<h3>Purpose/Objective(s)</h3> With the increasing utilization of stereotactic body radiation therapy (SBRT) for primary and metastatic cancer, use of multi-target thoracic (MTT) SBRT is rising. Given the limited safety and efficacy data on MTT, the purpose of this study was to report the experience of this strategy from a large academic center. <h3>Materials/Methods</h3> Between 2012 and 2021, patients who received SBRT for ≥2 thoracic targets within 1 year were retrospectively reviewed. The primary endpoint was clinically significant radiation pneumonitis (CSRP) requiring steroids, oxygen, or intubation. Secondary endpoints included late grade ≥3 toxicity (Common Terminology Criteria for Adverse Events, version 5.0) apart from pneumonitis, local failure (LF), initiation or change of systemic therapy (ICST), progression-free survival (PFS), and overall survival (OS). Competing risk analysis was used to evaluate the cumulative incidence (CI) of CSRP, LF, and ICST. PFS and OS were estimated using the Kaplan-Meier method. Univariate analyses (UVA) and multivariable analyses (MVA) were performed to look for clinical and dosimetric predictive factors of CSRP. <h3>Results</h3> One-hundred and ninety patients (481 lesions) were treated with MTT SBRT with a median follow-up of 19.7 months. Primary histologies included colorectal (29.9%), lung (28.1%), kidney (17.5%), and breast (6.0%). Indications for SBRT were oligoprogression (n=180; 37.4%), oligometastases (n=164; 34.1%), curative intent (n=81; 16.9%), and control of dominant areas of progression (n=56; 11.6%). Thirty-two patients (16.8%) had systemic therapy within 3 months of SBRT. Number of irradiated tumors ranged from 2-7 and the majority of SBRT courses were delivered concurrently (88.2%). Of concurrent courses, 157 (62.3%) used multiple isocenters and 95 (37.7%) used a single isocenter. Median SBRT dose was 50 Gy (range: 25-60 Gy) delivered in 1-8 fractions, with a median biological effective dose of 105.6 Gy (range: 37.5-150 Gy). Overall, 14 patients (7.4%) had CSRP, with 5 cases requiring oxygen. The CI of CSRP at 6 and 12 months was 5.3% and 7.7%, respectively. Two other patients had late grade ≥3 toxicity: 1 grade 3 rib fracture and 1 grade 4 esophageal perforation. The CI of LF at 2 years was 10.5%. The CI of ICST at 2 years was 44.0%. Median PFS was 9.9 months and median OS was 47.4 months. On UVA, shorter time between SBRT treatments (HR=62.50; p<0.01), ≥3 tumor targets (HR=2.96; p=0.04), and a higher V35Gy (HR=2.60; p=0.02) were predictive for a higher risk of CSRP. On MVA, shorter time between SBRT treatments (HR=55.56; p<0.01) and a higher V35Gy (HR=2.58; p=0.02) remained as statistically significant predictors. <h3>Conclusion</h3> In one of the largest institutional series of MTT SBRT, rates of CSRP and LF were low. Increasing the time between SBRT treatments and optimizing plans to lower the V35Gy may decrease the risk of CSRP.

Bone Only Oligometastatic Renal Cell Carcinoma Patients Treated with Stereotactic Body Radiotherapy: A MULTI-Institutional Study

<h3>Purpose/Objective(s)</h3> Previous studies demonstrated the efficacy of stereotactic-body radiotherapy (SBRT) for oligometastatic renal cell carcinoma (RCC) patients. However, it has not been well-studied in patients with bone-only metastatic RCC. This study aimed to analyze the prognostic factors associated with overall survival (OS) and progression-free survival (PFS) in patients with bone-only metastatic RCC who have five or fewer lesions treated with SBRT. <h3>Materials/Methods</h3> The clinical data of 54 patients with 70 bone metastases undergoing SBRT treated between 2013 and 2020 with a fraction dose of at least 6 Gy per fraction, and a biologically effective dose (BED) of at least 90 Gy was retrospectively evaluated. The prognostic factors associated with OS and PFS were assessed. <h3>Results</h3> The majority of lesions were located in the spine (57.4%), and had only one metastasis (64.8%). The median SBRT fraction and total doses were 10 Gy (range: 6–18 Gy) and 20 Gy (range: 12–40 Gy), and SBRT was administered with a median fraction of 3 (range, 1–5). The median BED of SBRT was 108.4 Gy (range: 90.0–202.2 Gy). After a median follow-up of 22.4 months, the 1- and 2-year OS rates were 84.6% and 67.3%, respectively, and median OS was 43.1 months. The 1- and 2-year PFS rate, and median PFS were 63.0%, 38.9%, and 15.3 months, respectively. After completion of metastasis-directed treatment (MDT), disease progression occurred in 26 patients (48.1%) at a median of 12.7 months (IQR 7.1–29.9 months). There were 22 (84.6%) with distant metastasis, one (3.8%) with in-field local recurrence, and three (11.6%) with both distant metastasis and local recurrence. In SBRT-treated lesions, only 4 patients (7.4%) experienced local recurrence, and the 1- and 2-year LC rates per lesion were 94.9% and 92.0% per lesion. Age, metastasis localization, and number of fractions for SBRT were significant prognostic factors for OS in univariate analysis. In multivariate analysis, patients with spine metastasis had a better OS [HR=3.1 (95% CI, 1.3–7.7; p = 0.001)] compared to their counterparts, and patients who received single fraction SBRT [HR=2.2 (95%, 1.2–4.2; p = 0.01)] had a better PFS than those who did not. No patient experienced acute or late toxicities of grade 3 or greater. <h3>Conclusion</h3> To the best of our knowledge, this is the first multicenter study of bone-only oligometastatic RCC patients treated with SBRT. Despite excellent LC at the oligometastatic site treated with SBRT, disease progression was observed in nearly half of patients 13 months after MDT, particularly as distant disease progression other than treated lesion, necessitating an effective systemic treatment to improve treatment outcomes. Prospective trials of SBRT for oligometastatic bone sites are warranted because they may shed light on disease control, survival, and quality of life after such therapy.

Biologically Effective Dose as a Predictor of Radiosurgery Treatment Outcomes for Pulmonary Metastases

<h3>Purpose/Objective(s)</h3> As targeted therapy for oligometastatic disease becomes more widely accepted, continued investigation is needed to characterize predictors of treatment outcomes and better inform clinical management. In this abstract we describe how biologically effective dose (BED) impacts local control (LC), regional control (RC) distant control (DC), and overall survival (OS) in a cohort of patients receiving stereotactic body radiotherapy (SBRT) for metastatic and recurrent pulmonary lesions. <h3>Materials/Methods</h3> The study was undertaken via retrospective review at a single institution. Lung lesions in patients who underwent SBRT to pulmonary metastases from distant primaries or recurrent tumors from previously treated lung cancer were included. Only patients who were treated between 2016 and 2019 were included. Patients with newly diagnosed primary lung cancer manifesting as single pulmonary lesions were excluded. A two-proportion z-test was employed for statistical analysis. <h3>Results</h3> From a single institution, 246 treated metastatic lesions from 75 patients were included. A subset of 114 treated metastatic lesions from 41 patients received a BED < 80 Gy. A subset of 132 treated metastatic lesions from 66 patients received a BED of ≥ 80 Gy. SBRT was performed at a median BED of 57.6Gy (interquartile range [IQR], (38.4,60)]) for lesions receiving BED < 80Gy and at a median BED of 100Gy (IQR, 80-112.5) for lesions receiving BED ≥ 80Gy. Two-year LC was 82.5% (94/114) for lesions with BED <80Gy and 90.9% (120/132) for lesions with BED ≥ 80Gy (p=0.048). Two-year RC was 51.8% (59/114) for lesions with BED <80Gy and 56.8% (75/132) for lesions with BED ≥ 80Gy (p=0.424). Two-year DC was 48.2% (55/114) for lesions with BED <80Gy and 59.1% (78/132) for lesions with BED ≥ 80Gy (p=0.089). Two-year OS was 33.3% (38/114) for lesions with BED <80Gy and 60.6% (80/132) for lesions with BED ≥ 80Gy (p<0.0001). <h3>Conclusion</h3> When treating oligometastatic pulmonary lesions with SBRT, a BED of greater than or equal to 80Gy is associated with improved two-year LC and two-year OS to a statistically significant degree. However, no significant difference in two-year RC and DC is noted when using a BED greater than or equal to 80Gy. These results suggest that higher radiation doses are more effective when using SBRT to treat oligometastatic pulmonary lesions, and that a goal BED of 80 Gy or more should be pursued.