Stereotactic central/core ablative radiation therapy: results of a phase I study of a novel strategy to treat bulky tumor.

Purpose: Bulky tumor remains as a challenge to surgery, chemotherapy and conventional radiation therapy. Hence, in efforts to overcome this challenge, we designed a novel therapeutic paradigm via strategy of Stereotactic Central/Core Ablative Radiation Therapy (SCART).), which is based on the principles of SBRT (stereotactic body radiation therapy and spatially fractionated radiation therapy (SFRT). We intend to safely deliver an ablative dose to the core of the tumor and with a low dose at tumor edge. The purpose of the phase 1 study was to determine dose-limiting toxicities (DLT)s and the Maximum Tolerated Dose (MTD) of SCART. Methods and materials: We defined a SCART-plan volume inside the tumor, which is proportional to the dimension of tumor. VMAT/Cyberknife technique was adopted. In the current clinical trial; Patients with biopsy proven recurrent or metastatic bulky cancers were enrolled. The five dose levels were 15 Gy X1, 15Gy X3, 18GyX3, 21GyX3 and 24GyX3, while keeping the whole tumor GTV's border dose at 5Gy each fraction. There was no restriction on concurrent systemic chemotherapy agents. Results: 21 patients were enrolled and underwent SCART. All 21 patients have eligible data for study follow-up. Radiotherapy was well tolerated with all treatment completed as scheduled. The dose was escalated for two patients to 24GyX3. No grade 3 or higher toxicity was observed in any of the enrolled patients. The average age of patients was 66 years (range: 14-85) and 13 (62%) patients were male. The median SCART dose was 18Gy (range: 15 - 24). Six out of the 18 patients with data for overall survival (OS) died, and the median time to death was 16.3 months (range: 1 - 25.6). The mean percent change for tumor shrinkage between first visit volumes and post-SCART volumes was 49.5% (SD: 40.89, p-value:0.009). Conclusion: SCART was safely escalated to 24 GyX 3 fractions, which is the maximum Tolerated Dose (MTD) for SCART. This regimen will be used in future phase II trials.

No Oncology Patient Left Behind: Challenges and Solutions in Rural Radiation Oncology.

Health inequities and decreasing median American lifespan, potentiated by the worldwide COVID 19 crisis, have taken centre stage in the public consciousness. Specifically, for this discourse, rural radiation oncology challenges external to the pandemic and unique to the rural American radiation oncology care delivery result from a confluence of the following: a) increased incidence of cancer in the United States;1 b) recent legislative emphasis on rural healthcare equity initiatives;2 c) pandemic-associated delays in cancer screening, diagnosis, and treatment3 , 4 with resultant presentation of advanced oncologic stages; d) social spotlight on healthcare equity and inclusion for disenfranchised populations.5We will attempt to delineate these issues and propose widely applicable common-sense solutions. We will review what has transpired at the University of Kentucky over the last two decades, specifically at radiation oncology centre in Morehead, a clinic in eastern Kentucky in the Appalachian foothills. While much more work remains ahead, this clinic has successfully applied many of the initiatives discussed. Funding: No relevant funding of any research was involved in the preparation of data or the manuscript.

Evaluating the clinical acceptability of deep learning contours of prostate and organs-at-risk in an automated prostate treatment planning process.

BACKGROUND: Radiation treatment is considered an effective and the most common treatment option for prostate cancer. The treatment planning process requires accurate and precise segmentation of the prostate and organs at risk (OARs), which is laborious and time-consuming when contoured manually. Artificial intelligence (AI)-based auto-segmentation has the potential to significantly accelerate the radiation therapy treatment planning process; however, the accuracy of auto-segmentation needs to be validated before its full clinical adoption. PURPOSE: A commercial AI-based contouring model was trained to provide segmentation of the prostate and surrounding OARs. The segmented structures were input to a commercial auto-planning module for automated prostate treatment planning. This study comprehensively evaluates the performance of this contouring model in the automated prostate treatment planning process. METHODS AND MATERIALS: A 3D U-Net-based model (INTContour, Carina AI) was trained and validated on 84 computed tomography (CT) scans and tested on an additional 23 CT scans from patients treated in our local institution. Prostate and OARs contours generated by the AI model (AI contour) were geometrically evaluated against reference contours. The prostate contours were further evaluated against AI, reference, and two additional observer contours for comparison using inter-observer variation (IOV) and 3D boundaries discrepancy analyses. A blinded evaluation was introduced to assess subjectively the clinical acceptability of the AI contours. Finally, treatment plans were created from an automated prostate planning workflow using the AI contours and were evaluated for their clinical acceptability following the Radiation Therapy Oncology Group-0815 protocol. RESULTS: The AI contours demonstrated good geometric accuracy on OARs and prostate contours, with average Dice similarity coefficients (DSC) for bladder, rectum, femoral heads, seminal vesicles, and penile bulb of 0.93, 0.85, 0.96, 0.72, and 0.53, respectively. The DSC, 95% directed Hausdorff distance (HD95), and mean surface distance for the prostate were 0.83 ± 0.05, 6.07 ± 1.87 mm, and 2.07 ± 0.73 mm, respectively. No significant differences were found when comparing with IOV. In the double-blinded evaluation, 95.7% of the AI contours were scored as either "perfect" (34.8%) or "acceptable" (60.9%), while only one case (4.3%) was scored as "unacceptable with minor changes required." In total, 69.6% of the AI contours were considered equal to or better than the reference contours by an independent radiation oncologist. Automated treatment plans created from the AI contours produced similar and clinically acceptable dosimetric distributions as those from plans created from reference contours. CONCLUSIONS: The investigated AI-based commercial model for prostate segmentation demonstrated good performance in clinical practice. Using this model, the implementation of an automated prostate treatment planning process is clinically feasible.

The future of radiation-induced abscopal response: beyond conventional radiotherapy approaches.

Advances in the immunological pharmaceuticals, such as checkpoint inhibitors and agonists, have positive implications for the future of the radiotherapy abscopal response. A once rare phenomenon, whereby distant nonirradiated tumor sites regressed after radiotherapy alone, may become more common when combined with the immune modulating agents. Radiotherapy can increase neoantigen expression, increased tumor PD-L1 expression, increase MHC class I expression, reverse exhausted CD8 T cells and increase tumor-infiltrating tumors within the tumor microenvironment. These changes in the tumor and the tumor microenvironment after radiotherapy could potentiate responses to anti-CTL-4, anti-PD-L1/PD-1 and other immunotherapy agents. Thus, advances in checkpoint inhibitors have increased interest in re-evaluation of the role of conventional radiotherapy approaches on the immune system. We reviewed newer nonconventional approaches such as SBRT-PATHY, GRID, FLASH, carbon ion and proton therapy and their role in eliciting immune responses. We believe that combining these novel radiation methods may enhance the outcome with the newly US FDA approved immune modulating agents.

Post-mastectomy and post-breast conservation surgery pain syndrome: a review of etiologies, risk prediction, and trends in management.

Postmastectomy pain syndrome (PMPS) or breast conservation surgery (BCS) pain syndrome could be long-term and lead to disability and impairment on body and social function. The pain syndromes are not uncommon in breast cancer patients. It can affect social, psychological, physical and behavioral aspects of a patient. Surgery, radiation, chemotherapy and psychological factors can all contribute to the development of pain syndromes. Axillary dissection is a strong predictor for pain development. Pain medications, ganglion blocks are typically given to the patient for management. Integrative medicine such as acupuncture and psychological management methods are promising modalities in the management arsenal. In this study, we summarized the up-to-date literature to elucidate the etiology, risk factors and management strategies for PMPS.

Mono-institutional phase 2 study of innovative Stereotactic Body RadioTherapy targeting PArtial Tumor HYpoxic (SBRT-PATHY) clonogenic cells in unresectable bulky non-small cell lung cancer: profound non-targeted effects by sparing peri-tumoral immune microenvironment.

BACKGROUND: Radiotherapy-induced lymphopenia may be limiting the success of therapy and could also negatively affect the ability of immune system in mediating the bystander (BE) and abscopal effects (AE). A novel SBRT-based PArtial Tumor irradiation of HYpoxic clonogenic cells (SBRT-PATHY) for induction of the tumoricidal BE and AE by sparing the peritumoral immune microenvironment and regional circulating lymphocytes has been developed to enhance the radiotherapy therapeutic ratio of advanced lung cancer. The aim of this retrospective review of prospectively collected mono-institutional phase 2 study was to compare the outcomes between unconventional SBRT-PATHY and standard of care in unresectable stage IIIB/IV bulky NSCLC. MATERIALS AND METHODS: Sixty patients considered inoperable or unsuitable for radical radio-chemotherapy were enrolled and treated using the following 3 regimens: SBRT-PATHY (group I, n = 20 patients), recommended standard of care chemotherapy (group II, n = 20 patients), and institutional conventional palliative radiotherapy (group III, n = 20 patients). RESULTS: Median follow-up was 13 months. The 1-year overall survival was 75, 60, and 20% in groups 1, 2 and 3, respectively (p = 0.099). The 1-year cancer specific survival was 90, 60, and 20% in groups 1, 2, and 3, respectively (p = 0.049). Bulky tumor control rate was 95% for SBRT-PATHY compared with 20% in the other two groups. BE and AE were seen by SBRT-PATHY in 95 and 45% of patients, respectively. Multi-variate analysis for cancer specific survival was significant for treatment effect with SBRT-PATHY (p < 0.001) independent of age, sex, performance status, histology, stage, treated bulky site and tumor diameter. SBRT-PATHY resulted in lower toxicity (p = 0.026), and improved symptom control (p = 0.018) when compared to other two treatment options. CONCLUSION: SBRT-PATHY improved treatment outcomes in unresectable NSCLC and should be investigated in larger trials. Present study has been retrospectively registered on 8th of August 2019 by the ethic committee for Austrian region "Kärnten "in Klagenfurt (AUT), under study number A 31/19.

Radiation, Immune Checkpoint Blockade and the Abscopal Effect: A Critical Review on Timing, Dose and Fractionation.

The combination of radiation and immunotherapy is currently an exciting avenue of pre-clinical and clinical investigation. The synergy between these two treatment modalities has the potential to expand the role of radiation from a purely local therapy, to a role in advanced and metastatic disease. Tumor regression outside of the irradiated field, known as the abscopal effect, is a recognized phenomenon mediated by lymphocytes and enhanced by checkpoint blockade. In this review, we summarize the known mechanistic data behind the immunostimulatory effects of radiation and how this is enhanced by immunotherapy. We also provide pre-clinical data supporting specific radiation timing and optimal dose/fractionation for induction of a robust anti-tumor immune response with or without checkpoint blockade. Importantly, these data are placed in a larger context of understanding T-cell exhaustion and the impact of immunotherapy on this phenotype. We also include relevant pre-clinical studies done in non-tumor systems. We discuss the published clinical trials and briefly summarize salient case reports evaluating the abscopal effect. Much of the data discussed here remains at the preliminary stage, and a number of interesting avenues of research remain under investigation.

Reliable Radiation Technique to Minimize Ovarian Dose During Radiation Prophylaxis of Heterotopic Ossification.

BACKGROUND/AIM: Scattered radiation during radiotherapy (RT) directed at the hip joint poses concerns about ovarian function in patients of reproductive age. Here, we report the impact of using a split-beam technique (SBT) and different photon energies on the total ovary dose during radiation prophylaxis of heterotopic ossification (HO). PATIENTS AND METHODS: This was a single-institution, retrospective study of 32-patients with traumatic acetabular fractures (TAF). All underwent surgery followed by CT-based-RT within 72 h in a single fraction of 700 cGy. Ipsilateral (IL) and contralateral (CL) ovaries (OV) were contoured separately and dose volume histograms (DVH) generated. Additional planning trials were created for each patient by utilizing a SBT medially and by using different photon energies (6-18 MV) to investigate the difference in ovary dose among these maneuvers. RESULTS: The median Mean-dose delivered to ILOV was 59 cGy and the median Max-dose was 177 cGy. CLOV median Mean-dose was 6 cGy and median Max-dose was 10 cGy. SBT at the medial edge of the field led to a 27% and 22% dose reduction in the median Mean and Max. doses, respectively, to ILOV; 9% and 5% reduction was seen in the median Mean and Max. doses, respectively, to CLOV. Higher photon energies (10-18 MV) led to an additional 28% and 16 % reduction in median Mean and Max. doses, respectively, to ILOV when compared to those from 6 MV. The CLOV median Mean dose was reduced by 18% and the Max. dose was reduced by 12%. CONCLUSION: A biologically significant radiation dose is delivered to the ovaries during HO radiation prophylaxis at the hip joints. Ipsilateral ovarian dose could be reduced by half and contralateral by one-quarter by using CT-based treatment planning with a medial SBT and photon energies above 6 MV. We suggest using no more than 10 MV to minimize neutron contamination. Those techniques should be the standard of care as it provides a reliable method for minimizing the radiation dose to the ovaries, consequently, maximizing female fertility preservation during HO radiation prophylaxis. All female patients in childbearing age should be fully informed about ovarian radiation exposure and possible temporary alteration in ova production and morphology.

Management of Metastatic Spinal Cord Compression.

Cancer metastasis is a key event in tumor progression associated not only with mortality but also significant morbidity. Metastatic disease can promote end-organ dysfunction and even failure through mass effect compression of various vital organs including the spinal cord. In such cases, prompt medical attention is needed to restore neurological function, relieve pain, and prevent permanent damage. The three therapeutic approaches to managing metastatic spinal cord compression include corticosteroids, surgery, and radiation therapy. Although each may improve patients' symptoms, their combination has yielded the best outcome. In cancer patients with clinical suspicion of spinal cord compression, dexamethasone should be initiated followed by surgical decompression, when possible, and radiation. The latter becomes the preferred treatment in patients with inoperable disease.

Five-year outcomes of an oropharynx-directed treatment approach for unknown primary of the head and neck.

PURPOSE: Squamous cell carcinoma of unknown primary (SCCHNUP) is commonly treated with comprehensive radiation to the laryngopharynx and bilateral necks. In 1998, we established a departmental policy to treat SCCHNUP with radiation directed to the oropharynx and bilateral neck. METHODS: From 1998-2011, 60 patients were treated - N1: 18%, N2: 75% and N3: 7%. 82% underwent neck dissection. 55% received IMRT and 62% underwent concurrent chemoradiotherapy. RESULTS: At median follow-up of 54months, 5 patients failed regionally and 4 emerged with a primary (tongue base, hypopharynx and thoracic esophagus). Five-year rates of regional control, primary emergence, distant metastasis, disease-free survival and overall survival were 90%, 10%, 20%, 72% and 79%, respectively. The 5year rate of primary emergence in a non-oropharynx site was 3%. CONCLUSION: This is the first demonstration that an oropharynx-directed approach yields low rates of primary emergence in SCCHNUP with excellent oncologic outcomes.

Low rates of contralateral neck failure in unilaterally treated oropharyngeal squamous cell carcinoma with prospectively defined criteria of lateralization.

BACKGROUND: Unilateral radiotherapy (RT) of oropharyngeal carcinomas is accepted for patients with lateralized primary and low-volume nodal disease. Utilizing prospectively defined criteria of laterality and staging positron emission tomography (PET)/CT, we studied outcomes in patients with advanced-stage oropharyngeal cancer undergoing unilateral RT. METHODS: Thirty-seven patients with oropharyngeal tumors >1 cm from midline regardless of node status underwent unilateral RT and were followed prospectively. Patient characteristics: T1 = 11; T2 = 22; T3 = 4; N0 = 3; N1 = 9; N2a = 3; N2b = 21; and Nx = 1. Dosimetry were determined and weekly National Comprehensive Cancer Network (NCCN) distress thermometer data were collected. RESULTS: At median follow-up of 32 months, 3-year locoregional control, contralateral regional failure, distant metastasis-free survival, and disease-free survival were 96%, 0%, 7%, and 93%, respectively. CONCLUSION: Low rates of contralateral neck failure are demonstrated utilizing prospectively defined criteria for unilateral RT. The tolerances of contralateral organs are respected and patients report low to moderate levels of distress throughout treatment.

Testicular Dose During Prophylaxis of Heterotopic Ossification with Radiation Therapy.

AIM: A single-institution, retrospective study was performed to investigate potential techniques to minimize radiation exposure to the testicles during heterotopic ossification (HO) prophylaxis. We report the impact of split-beam technique (SBT) and different photon energies on the total dose of radiation received by the testicles during prophylaxis of HO. MATERIALS AND METHODS: Between 2008 and 2010, we identified 64 patients with traumatic acetabular fractures who underwent surgery followed by radiation therapy (RT) without testicular shielding. Postoperative RT was delivered within 72 h in a single fraction of 700 cGy using 6-18 MV photons, without testicular shielding due to patient refusal. All patients underwent 3-D RT planning in which the testicles were contoured as a region of interest and dose-volume histograms (DVH) were generated. Additional treatment planning trials were created for each patient by utilizing a SBT medially and by using different photon energies (6, 10 and 18 MV) to study the effects of these maneuvers on the delivered dose to the testicles. RESULTS: In reviewing the DVH, it was noted that the mean dose delivered to the testicles was 10 cGy (range=3-40). The maximum dose was 31 cGy (range=7-430). When SBT was utilized, a significant reduction in the mean (44%) and maximum (47%) doses delivered to the testicles was noted. Further reductions in the mean (26%) and maximum (14%) doses were achieved by using higher-energy (10-18 MV) beams. The radiation doses to the testicles from the CT simulation and the two portal images were estimated to be 4 and 1.5 cGy, respectively. CONCLUSION: Low-dose prophylactic RT to prevent HO around the hip causes a low, but likely biologically meaningful, radiation dose to be delivered to the testicles. This dose could be further reduced by using a medial SBT and photon energies above 6 MV. Testicular shielding should be offered to all male patients receiving such RT. In addition, all patients should be informed about the consequences of testicular radiation as part of their informed consent.

Management algorithm for HIV-associated parotid lymphoepithelial cysts.

We report an evidence-based management algorithm for benign lymphoepithelial cysts (BLEC) of the parotid glands in HIV patients based on long-term outcomes after radiation therapy. From 1987 to 2013, 72 HIV-positive patients with BLEC of the parotid glands treated at our institutions were identified and their medical records were reviewed and analyzed. The primary endpoint of our study was to determine a dose response in HIV patients with BLEC. In group A (≤18 Gy), which received a median dose of 10 Gy (8-18), overall response (OvR), complete response (CR), partial response (PR), and local failure (LF) was experienced by 7, 7, 0, and 93 %, respectively. In group B (≥22.5 Gy), which received a median dose of 24 Gy (22.5-30), OvR, CR, PR, and LF was experienced by 88, 65, 23, and 12 %. Logistic regression revealed that higher dose (≥22.5 Gy) predicted for cosmetic control (p = 0.0003). Multiple regression analysis revealed higher dose predicted for cosmetic control (p = 0.0001) after adjusting for confounding variables (age, gender, race, HAART use, BLEC duration, and fractionation size). No patients in either group experienced RTOG grade ≥3 toxicities. A radiation dose of 24 Gy delivered in 12-16 fractions of 1.5-2 Gy per fraction provides long-term cosmetic control in HIV-positive patients with BLEC of the parotid glands.

Is Breast Conserving Therapy a Safe Modality for Early-Stage Male Breast Cancer?

INTRODUCTION: Male breast cancer (MBC) is a rare disease and lacks data-based treatment guidelines. Most men are currently treated with modified radical mastectomy (MRM) or simple mastectomy (SM). We compared the oncologic treatment outcomes of early-stage MBC to determine whether breast conservation therapy (BCT) is appropriate. MATERIALS AND METHODS: We searched the Surveillance, Epidemiology, and End Results database for MBC cases. That cohort was narrowed to cases of stage I-II, T1-T2N0 MBC with surgical and radiation therapy (RT) data available. The patients had undergone MRM, SM, or breast conservation surgery (BCS) with or without postoperative RT. We calculated the actuarial 5-year cause-specific survival (CSS). RESULTS: We identified 6263 MBC cases and included 1777 men with stage I or II, T1-T2, node-negative disease, who had the required treatment information available. MRM without RT was the most common treatment (43%). Only 17% underwent BCS. Of the BCS patients, 46% received adjuvant RT to complete the traditional BCT. No deaths were recorded in the BCT group, regardless of stage, or in the 3 stage I surgical groups if the men had received RT. The actuarial 5-year CSS was 100% in each BCT group. MRM alone resulted in an actuarial 5-year CSS of 97.3% for stage 1% and 91.2% for stage 2. CONCLUSION: The results from our study suggest that BCT for early-stage MBC yields comparable survival compared with more invasive treatment modalities (ie, MRM or SM alone). This could shift the treatment paradigm to less-invasive interventions and might have the added benefit of increased functional and psychological outcomes. Further prospective studies are needed to confirm our conclusions.

Lhermitte's Sign following VMAT-Based Head and Neck Radiation-Insights into Mechanism.

PURPOSE/OBJECTIVES: We observed a number of patients who developed Lhermitte's sign (LS) following radiation to the head and neck (H/N), since instituting volumetric modulated arc therapy (VMAT). We aimed to investigate the incidence of LS following VMAT-based RT without chemotherapy, and determine the dosimetric parameters that predict its development. We explored whether the role of inhomogeneous dose distribution across the spinal cord, causing a "bath-and-shower" effect, explains this finding. METHODS AND MATERIALS: From 1/20/2010-12/9/2013, we identified 33 consecutive patients receiving adjuvant RT using VMAT to the H/N without chemotherapy at our institution. Patients' treatment plans were analyzed for dosimetric parameters, including dose gradients along the anterior, posterior, right, and left quadrants at each cervical spine level. Institutional Review Board approval was obtained. RESULTS: 5 out of 33 (15.2%) patients developed LS in our patient group, all of whom had RT to the ipsilateral neck only. LS patients had a steeper dose gradient between left and right quadrants across all cervical spine levels (repeated-measures ANOVA, p = 0.030). Within the unilateral treatment group, LS patients received a higher mean dose across all seven cervical spinal levels (repeated-measures ANOVA, p = 0.046). Dose gradients in the anterior-posterior direction and mean doses to the cord were not significant between LS and non-LS patients. CONCLUSIONS: Dose gradients along the axial plane of the spinal cord may contribute to LS development; however, a threshold dose within the high dose region of the cord may still be required. This is the first clinical study to suggest that inhomogeneous dose distributions in the cord may be relevant in humans. Further investigation is warranted to determine treatment-planning parameters associated with development of LS.

Short-term clinical outcome and dosimetric comparison of tandem and ring versus tandem and ovoids intracavitary applicators.

PURPOSE: To compare the short-term toxicity and dosimetry of tandem and ring (TR), and tandem and ovoid (TO) applicators in treatment of gynecologic malignancy. MATERIAL AND METHODS: Following pelvic external beam radiation therapy (EBRT), a total of 52 computed tomography-based plans from 13 patients with cervical cancer (FIGO IB2-IIIB) were evaluated for HDR brachytherapy. Prescription was 7 Gy to the ICRU point A for four weekly fractions. Gastrointestinal and genitourinary toxicities were evaluated. Clinical target volume (CTV) and organs at risk were delineated on CT scans. Bladder, rectum, and sigmoid mean doses and D2cc were calculated. Treatment time and irradiated tissue volume were compared. Percent of CTV receiving 100% (CTV100%) of the prescribed dose as well as the percent of the prescription dose covering 90% of the CTV (D90) were evaluated. RESULTS: Gastrointestinal and genitourinary toxicities were not different between TO and TR applicators. No significant differences in the dose to the right and left point A, or the left point B were observed. TO delivered a higher dose to right point B. Organs at risk doses were similar between the two applicators, except mean rectal dose was lower for TO applicator. Overall, TO treats a larger tissue volume than TR. Mean treatment time was shorter for TR. Tumor coverage (D90 and CTV100%) was equivalent between TO and TR applicators. CONCLUSION: Although TO treats a larger tissue volume than TR, short-term toxicities and tumor coverage are similar. Long-term clinical outcomes will be elucidated with longer follow up period.

Prostate-specific antigen decline during salvage radiation therapy following prostatectomy is associated with reduced biochemical failure.

PURPOSE: To evaluate the prognostic value of prostate-specific antigen (PSA) decline during salvage radiation therapy (SRT) after prostatectomy. METHODS AND MATERIALS: We reviewed an institutional database and identified all prostate cancer patients who were treated with SRT between the years 2003 and 2010, had at least 1 PSA measurement during their SRT course, and had no history of androgen deprivation therapy use prior to or during SRT. Disease characteristics, treatment information, and clinical outcomes data were tabulated for each patient. The PSA response during SRT was defined as a PSA decline of at least 0.2 ng/mL compared with the pretreatment PSA level. Bivariate and multivariate analyses using Cox proportional hazards modeling were performed to identify predictors of biochemical recurrence. RESULTS: Sixty-four patients met eligibility criteria for this analysis. Median PSA before SRT was 0.63 ng/mL (interquartile range: 0.42-1.00). With a median follow-up time of 70 months after SRT, 5-year actuarial rates for biochemical control and metastasis-free survival were 61% (95% confidence interval [CI], 48%-75%) and 88% (95% CI, 79%-97%), respectively. The median number of PSA measurements per patient during SRT was 3 (range, 1-5). On bivariate analysis, PSA response during SRT and positive surgical margins were significantly associated with a decreased risk of biochemical recurrence (BR), with hazard ratios of 0.160 (95% CI, 0.059-0.431, P < .001) and 0.396 (95% CI, 0.168-0.935, P = .035). On multivariate analysis, PSA response during SRT and positive surgical margin were independent, favorable predictors for BR, with hazard ratios of 0.171 (95% CI, 0.063-0.463, P < .001) and 0.411 (95% CI, 0.177-0.956, P = .039). The 5-year biochemical control rate for PSA responders was 81%, compared with 37% for nonresponders (P < .001). CONCLUSIONS: Prostate-specific antigen decline during SRT may be a valuable prognostic factor for subsequent clinical outcomes. Future studies should investigate the value of monitoring PSA during SRT and how PSA response may be used to personalize therapy.