Dose-Escalated Stereotactic Body Radiation Research Articles

Potential benefit of dose-escalated stereotactic body radiation therapy using CyberKnife for early-stage primary lung cancer.

The study aimed to evaluate the efficacy and safety of dose-escalated stereotactic body radiotherapy (SBRT) for primary lung cancer. Patients with peripherally located T1-2N0M0 primary lung cancer who underwent SBRT from April 2013 to December 2019 were included. Group A received 60Gy in five fractions with CyberKnife prescribed at 99% gross tumor volume. Group B received 48Gy in four fractions by a gantry-mounted linear accelerator, with isocenter prescription. Cumulative incidence of local failure (LF), progression free survival (PFS), overall survival (OS), and toxicity were retrospectively compared. Groups A and B comprised 39 and 36 patients, respectively. Group A had more patients without histological confirmation (p<.001) and showed lower V20 of bilateral lungs (p=.025). The median follow-up duration of Group A and B was 22.0 and 21.5 months, respectively, and the 2-year cumulative incidence of LF, PFS, and OS were .0%versus 11.6% (p=.065), 66.2%versus 62.7% (p=.694), 84.1%versus 81.1% (p=.827), respectively. There was no difference in Grade ≥ 2 toxicity rate between Groups A and B (7.7%vs. 11.1%; p=.704). Dose-escalated SBRT using CyberKnife showed reduced lung dose and potential benefits for improved local control with comparable toxicity.

Stereotactic body radiation therapy (SBRT) versus conventionally fractionated external beam radiation therapy in unfavorable intermediate-risk prostate cancer: An inverse propensity matched analysis.

e17054 Background: Conventionally fractionated radiotherapy (CFRT) or moderately hypofractionated radiotherapy (MFRT) ± short-course androgen deprivation therapy (ADT) is commonly employed for unfavorable intermediate-risk (UIR) prostate cancer. Stereotactic body radiation therapy (SBRT) has not been widely adopted, but may have radiobiologic advantages over more conventionally fractionated treatments. We hypothesized that radiotherapy dose-escalation with SBRT (35-40Gy in ≤5 fractions) is associated with improved overall survival (OS) relative to biologically equivalent doses of CFRT (72-86.4Gy in 1.8-2.0Gy/fraction) or MFRT (≥60Gy in 2.4-3.2Gy/fraction) ± ADT. Methods: The National Cancer Database (NCDB) was used to identify 28,028 men with UIR prostate cancer who received CFRT with (n = 12,872) or without ADT (n = 12,984), MFRT with (n = 251) or without ADT (n = 281), and SBRT with (n = 212) or without ADT (n = 1,428). SBRT+ADT patients were excluded due to low patient numbers. Inverse probability of treatment weighting was used to balance measured confounders. Unweighted- and weighted- multivariable analysis (MVA) using Cox regression was used to compare OS hazard ratios. Results: Relative to CFRT without ADT, CFRT+ADT (Hazard Ratio (HR): 0.92, [95% Confidence Interval: 0.87-0.97], P = .002) and SBRT without ADT (HR: 0.74 [0.61-0.89], P = .002) were both associated with improved OS on MVA. Relative to CFRT+ADT, SBRT without ADT correlated with improved OS on MVA (HR: 0.81 [0.67-0.99], P = .04). Weight-adjusted MVA demonstrated that SBRT (HR: 0.80 [0.65-0.98], P = .036) and ADT (HR: 0.91 [0.86-0.97], P = .002) correlated with improved OS. SBRT was not associated with improved OS relative to MFRT. Conclusions: Using inverse propensity treatment weighting, we adjusted for age, comorbidity score, and tumor factors, and observed a significant overall survival benefit in favor of administering dose-escalated SBRT over CFRT+ADT. To our knowledge, this is the first study to show that SBRT is associated with improved OS relative to CFRT for men with UIR prostate cancer. Together, this suggests that SBRT offers a cheaper and shorter course of therapy that mitigates COVID-19 exposure, which also is associated with improved OS relative to CFRT for UIR prostate cancer and may obviate the need for ADT in this population. While we await results from several ongoing clinical trials, we believe this study lends support to the use of SBRT in men with UIR prostate cancer.

Outcomes of a Dose-Escalated Stereotactic Body Radiation Phase 1 Trial for Patients With Low- and Intermediate-Risk Prostate Cancer

This study presents a prospective phase 1, institutional review board-approved dose-escalated stereotactic body radiation therapy trial for prostate cancer (CaP) to assess the impact of dose level on quality of life, toxicity, and clinical outcomes. From 2011 to 2016, 26 patients with low- and intermediate-risk CaP received 40, 45, and 50Gy in 5 fractions to the prostate in cohorts of 9, 10, and 7 patients. Self-reported quality of life was prospectively measured from the Expanded Prostate Cancer Index Composite and American Urological Association. Common Terminology Criteria for Adverse Events (version 4.03) data were collected to observe acute and late toxicities. The Phoenix definition was used to calculate outcome. No patients received androgen deprivation therapy. Median follow-up was 67.2months (range, 71-230months). There was an increase in Expanded Prostate Cancer Index Composite and American Urological Association scores followed by a return to baseline over 2years for all cohorts. There were no grade 3 or higher toxicities or significant differences in toxicity between treatment arms. The prostate-specific antigen (PSA) nadir was significantly lower in the 45-Gy and 50-Gy cohorts when compared with the 40-Gy cohort (P<.05). Two biochemical failures were observed in the 40-Gy arm after 43 and 62months, resulting in a freedom from biochemical failure rate of 92%. PSA survival was 100%, and actuarial overall survival was 96%. PSA nadir was 0.6, 0.1, and 0.1ng/mL, in the 40-Gy, 45-Gy, and 50-Gy cohorts, respectively. This prospective, phase 1 dose-escalation study of stereotactic body radiation therapy for CaP identified acceptable genitourinary and gastrointestinal toxicity for each dose level of 40, 45, and 50Gy. Although there was no difference in biochemical failure between the groups, we showed that higher doses of 45 and 50Gy are associated with improved PSA nadir. The results of this study will be used to develop a larger prospective study to confirm the findings.

Dose-Escalated Stereotactic Body Radiation Improves Outcomes in Patients with Low- and Intermediate-Risk Prostate Cancer

Dose-Escalated Stereotactic Body Radiation Improves Outcomes in Patients with Low- and Intermediate-Risk Prostate Cancer

Multicenter Trial of Stereotactic Body Radiation Therapy for Low- and Intermediate-Risk Prostate Cancer: Survival and Toxicity Endpoints

The radiobiology of prostate cancer may favor the extreme hypofractionation inherent in stereotactic body radiation therapy (SBRT); however, data from a large multicenter study are lacking. We therefore examined the hypothesis that dose-escalated SBRT can be safely administered across multiple institutions, with favorable 5-year disease-free survival (DFS) rates compared with historical controls. Twenty-one centers enrolled 309 patients with prostate adenocarcinoma: 172 with low-risk (LR) and 137 with intermediate-risk (IR) disease. All were treated with a non-coplanar robotic SBRT platform using real-time tracking of implanted fiducials. The prostate was prescribed 40 Gy in 5 fractions of 8 Gy. We assessed toxicities using Common Terminology Criteria for Adverse Events (CTCAE) version 3 and biochemical failure using the "nadir + 2" definition. The study population yielded 90% power to identify excessive (>10%) rates of grade ≥3 genitourinary (GU) or gastrointestinal toxicities and, in the LR group, 80% power to show superiority in DFS over a 93% historical comparison rate. At a median follow-up of 61 months, 2 LR patients (1.2%) and 2 IR patients (1.5%) experienced grade 3 GU toxicities, far below the 10% toxicity rate deemed excessive (upper limits of 95% confidence interval, 3.5% and 4.3%, respectively). No grade 4 or 5 toxicities occurred. All grade 3 toxicities were GU, occurring 11 to 51 months after treatment. For the entire group, the actuarial 5-year overall survival rate was 95.6% and the DFS rate was 97.1%. The 5-year DFS rate was 97.3% for LR patients (superior to the 93% DFS rate for historical controls; P = .0008; lower limit of 95% confidence interval, 94.6%) and 97.1% for IR patients. Dose-escalated prostate SBRT was administered with minimal toxicity in this multi-institutional study. Relapse rates compared favorably with historical controls. SBRT is a suitable option for LR and IR prostate cancer.

Decreased PSA nadir as a result of dose-escalated stereotactic body radiation for patients with low- and intermediate-risk prostate cancer.

e17076Background: Prostate cancer (CaP) is characterized by a low a/b ratio relative to surrounding normal tissue, and consequently a therapeutic gain could be achieved with dose escalation. The pu...

(P20) Decreased PSA Nadir as a Result of Dose-Escalated Stereotactic Body Radiation for Patients With Low- and Intermediate-Risk Prostate Cancer

Prostate cancer (CaP) is characterized by a low a/b ratio relative to surrounding normal tissue, and consequently a therapeutic gain could be achieved with dose escalation. While potentially ablative PSA nadirs have been demonstrated following LDR brachytherapy, the ability to achieve ablation following stereotactic body radiation therapy (SBRT) remains unclear. The purpose of this study was to report the clinical outcomes, PSA kinetics, and toxicities in patients with low and intermediate-risk CaP treated on a prospective, Phase I/II, IRB approved dose-escalated SBRT trial. From 2011 to 2016, 26 patients with low and intermediate-risk CaP received 40, 45, and 50 Gy in five fractions to the prostate and seminal vesicles in cohorts of 9, 10, and 7 patients (pts). Self-reported QOL was prospectively measured from the Expanded Prostate Cancer Index Composite (EPIC) and International Prostate Symptom Score (IPSS) at baseline and intervals of every 3 months for the first two years followed by every 6 months thereafter. Common Toxicity Criteria for Adverse Events v. 4.03, data was collected to observe acute and late toxicities. No pts received androgen deprivation therapy. Median follow-up was 4.8 years. A PSA nadir <0.5 ng/ml was seen in 22%, 80%, and 71% of patients receiving 40, 45, and 50 Gy, and <0.2 ng/ml in 11%, 50%, and 71% of patients after 3 years. After 5 years, a PSA nadir <0.5 ng/ml was achieved in 100% of patients receiving 45 Gy compared to 33% receiving 40 Gy. PSA nadir was significantly reduced when comparing cohorts receiving 45 or 50 Gy to 40 Gy one to five years following treatment (p<0.02). PSA velocity was not significantly different among treatment groups, demonstrating a sharp initial decline followed by gradual reduction at -1.394, -0.706, -0.330, -0.160, -0.104, -0.070, and -0.050 ng/mL/month, after 3 months, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years. A benign PSA bounce was observed in 8 patients (32%) at a median bounce height of 0.72 ng/ml after 18 months, demonstrating a trend towards an increased bounce height with increasing fractional dose. There was an acute increase in EPIC and IPSS scores followed by a return to baseline over two years. Acute Grade 2 urinary toxicity occurred in 10 pts with no significant difference among treatment arms. The three patients experiencing late Grade 2 toxicity were in the 45 or 50 Gy cohort. There were no Grade 3 or higher toxicities. Univariate analysis revealed that Grade 2 toxicity was associated with prostate size >60 cc (p<.01). One biochemical failure was observed in the 40 Gy arm after 3.6 years resulting in a freedom from biochemical failure rate of 96% at 5 years. Prostate cancer specific survival was 100% and actuarial overall survival was 96%. This small prospective dose-escalation study identified that higher doses of 45 and 50 Gy, respectively are associated with improved PSA nadir without increased risk of GU or GI toxicity. Further follow-up is needed to assess PSA freedom from recurrence and late toxicity.

(OA18) Outcomes of a Dose-Escalated Stereotactic Body Radiation Phase I/II Trial for Patients With Low- and Intermediate-Risk Prostate Cancer

(OA18) Outcomes of a Dose-Escalated Stereotactic Body Radiation Phase I/II Trial for Patients With Low- and Intermediate-Risk Prostate Cancer

Dose-Escalated Stereotactic Body Radiation Therapy for Prostate Cancer: Quality-of-Life Comparison of Two Prospective Trials.

The optimal prostate stereotactic body radiation therapy (SBRT) dose-fractionation scheme is controversial. This study compares long-term quality of life (QOL) from two prospective trials of prostate SBRT to investigate the effect of increasing dose (NCT01578902 and NCT01146340). Patients with localized prostate cancer received SBRT 35 or 40 Gy delivered in five fractions, once per week. QOL was measured using the Expanded Prostate Cancer Index Composite at baseline and every 6 months. Fisher's exact test and generalized estimating equations were used to analyze proportions of patients with clinically significant change and longitudinal changes in QOL. One hundred fourteen patients were included, 84 treated with 35 Gy and 30 treated with 40 Gy. Median QOL follow-up was 56 months [interquartile range (IQR) 46-60] and 38 months (IQR 32-42), respectively. The proportion of patients reporting clinically significant declines in average urinary, bowel, and sexual scores were not significantly different between dose levels, and were 20.5 vs. 24.1% (p = 0.60), 26.8 vs. 41.4% (p = 0.16), and 42.9 vs. 38.5% (p = 0.82), respectively. Similarly, longitudinal analysis did not identify significant differences in QOL between treatment groups. Dose-escalated prostate SBRT from 35 to 40 Gy in five fractions was not associated with significant decline in long-term QOL.

Dose-Escalated Stereotactic Body Radiation Therapy for Patients With Intermediate- and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes

To report the short-term clinical outcomes and acute and late treatment-related genitourinary (GU) and gastrointestinal (GI) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy (SBRT). Between 2011 and 2014, 24 patients with prostate cancer were treated with SBRT to the prostate gland and proximal seminal vesicles. A high-dose avoidance zone (HDAZ) was created by a 3-mm expansion around the rectum, urethra, and bladder. Patients were treated to a minimum dose of 36.25Gy in 5 fractions, with a simultaneous dose escalation to a dose of 50Gy to the target volume away from the HDAZ. Acute and late GU and GI toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version4. The median follow-up was 25months (range, 18-45months). Nine patients (38%) experienced an acute grade 2 GU toxicity, which was medically managed, and no patients experienced an acute grade 2 GI toxicity. Two patients (8%) experienced late grade 2 GU toxicity, and 2 patients (8%) experienced late grade 2 GI toxicity. No acute or late grade ≥3 GU or GI toxicities were observed. The 24-month prostate-specific antigen relapse-free survival outcome for all patients was 95.8% (95% confidence interval 75.6%-99.4%), and both biochemical failures occurred in patients with high-risk disease. All patients are currently alive at the time of this analysis and continue to be followed. A heterogeneous prostate SBRT planning technique with differential treatment volumes (low dose: 36.25Gy; and high dose: 50Gy) with an HDAZ provides a safe method of dose escalation. Favorable rates of biochemical control and acceptably low rates of acute and long-term GU and GI toxicity can be achieved in patients with intermediate- and high-risk prostate cancer treated with SBRT.

Prospective Phase 2 Clinical Trial of Radiation Dose-Escalated Stereotactic Body Radiation Therapy (SBRT) for Centrally Located Lung Cancer: An Institutional Trial

Prospective Phase 2 Clinical Trial of Radiation Dose-Escalated Stereotactic Body Radiation Therapy (SBRT) for Centrally Located Lung Cancer: An Institutional Trial

Improved Local Control Associated With Dose-Escalated Stereotactic Body Radiation Therapy (SBRT) Indicates Dose-Response Relationship

To determine prognostic factors for local control of primary or metastatic tumors within the lung, liver, or other extracranial sites treated with SBRT within a single institution. The records of 152 consecutive patients treated with SBRT from October 1999 through August 2005 were retrospectively reviewed on an IRB-approved protocol. A total of 261 lesions in the lungs, liver, or other extracranial sites were treated; 18% (27/152) of patients were treated on formal prospective Phase I/II studies. Patients ineligible or unwilling to participate in the dose-escalation studies were treated with the highest safe dose established at the time of treatment. A nominal dose of ≥30 Gy was prescribed to 84% of the lesions, and 97% were treated in a 3 fraction course (Fig.). Local control was assessed via serial imaging with CT, MRI, and/or PET/CT. The equivalent uniform dose (EUD) was tabulated for each lesion from dose-volume histogram (DVH) data, and local control was evaluated according to both nominal dose and EUD. A multivariate analysis was performed to identify patient or treatment factors associated with improved local control. The local control rate of treated tumors improved with increased dose, expressed as either nominal dose or EUD. At a median follow-up of 8.4 months (18.3 months for living patients, 5.9 months deceased), lesions treated to a nominal dose of ≥54 Gy had a 3-year actuarial local control rate of 89.3%, whereas the values for those treated to 36.1–53.9 Gy and <36 Gy were 59.7% and 8.7%. Likewise, lesions treated with the highest third of EUD (>64.3 Gy) had a 3-year local control rate of 90.6%, compared to 56.0% in the middle third (43.5–64.3 Gy, p = 0.0047) and 9.9% in the lowest third (<43.5 Gy, p < 0.0001). On univariate and multivariate analysis, increased dose (nominal or EUD) and smaller GTV were statistically significant predictors of improved local control. Patient age, gender, tumor histology, primary site, treatment site, duration of treatment, and clinical context (primary v metastasis) did not predict for local control on either univariate or multivariate analysis. Treatment was well tolerated; 3.4% of patients experienced a grade ≥3 toxicity. These single institution results demonstrate a dose-response relationship within the range of SBRT doses applied. Severe toxicity was uncommon. Excellent local control rates are achieved with a nominal dose of 54–60 Gy, corresponding to an EUD of >64.3 Gy. These results support the use of aggressive, high-dose SBRT regimens when durable tumor control is the primary objective.