Completion Of Stereotactic Body Radiation Therapy Research Articles

Liver Stereotactic Body Radiation Therapy (SBRT) to Downstage Patients with Hepatocellular Carcinoma prior to Liver Transplant

Orthotopic liver transplantation (OLT) marks the most successful treatment for hepatocellular carcinoma (HCC) patients meeting Milan criteria. The process of reducing the disease burden of HCC patients not currently meeting criteria for OLT with local therapy is referred to as "downstaging" and has proven to be a feasible approach. RTOG 1112 recently demonstrated the efficacy and acceptable toxicity of liver SBRT for treating HCC. However, limited data currently exists describing the efficacy of SBRT for downstaging HCC patients and facilitating OLT. A single institution IRB approved prospective liver SBRT registry was surveyed for all patients outside of Milan criteria (1 lesion >5 cm; 2-3 lesions >3 cm) without vascular invasion or extrahepatic disease. Patients felt least likely to become OLT candidates with downstaging (age >80, >4 lesions, lesion >12 cm) were excluded. The primary endpoints were downstaging and OLT. Secondary endpoints were time to transplant, local control (LC), recurrence free survival (RFS) and overall survival (OS). A total of 38 HCC patients with a median age of 65 years (range 28 - 80) met inclusion criteria. Median follow up was 14 months (IQR 3 - 35). At baseline, median KPS was 80 (range 60 - 100) with 16 Child-Pugh (CP) A (42%), 13 CP B (34%), and 9 CP C patients (24%). All patients were outside of Milan criteria and 25 patients (66%) were outside of UCSF criteria at time of SBRT. No patients had extrahepatic disease or vascular invasion. Median number of lesions, largest tumor size, and total sum of lesions were 2 (range 1 - 4), 5.0 cm (IQR, 4.0 - 6.5), and 6.6 cm (IQR 5.9 - 9.2), respectively. Prior to SBRT, 22 patients (58%) had received non-SBRT local therapy. At time of SBRT a variety of dose fractionation schedules were selected with a median BED10 of 78 (IQR 62 - 100). Concurrent sorafenib was used in 2 patients (8%). Following completion of SBRT, 21 patients (55%) were successfully downstaged at a median 3.0 months (IQR 1.9 - 6.1) after treatment, most frequently secondary to decrease in size of the largest lesion (86%). Twelve patients (32%) proceeded to undergo OLT at a median 7 months (IQR 3 - 14) after SBRT and 105 days (IQR 18 - 344) following successful downstaging. Of the 25 patients initially exceeding UCSF criteria, 7 (28%) underwent OLT. Among those receiving OLT, 5 patients (42%) remain alive without evidence of disease, 3 patients (25%) have recurred, 3 patients (33%) died within 2 years from transplant complications, and 1 patient (8%) died from an unrelated cause. LC at 2 years was 83%. Median RFS and OS for the overall cohort were 7 months (95% CI 0 - 21) and 24 months (95% CI 11 - 36), respectively. Among the transplant recipients, the median OS was 37 months (95% CI 30 - 44) compared to 15 months (95% CI 6 - 23) among those not receiving transplant. With careful patient selection, liver SBRT serves as a feasible downstaging method to facilitate OLT in HCC patients.

Utilization of the Triangle Volume in Patients with Localized PDAC Undergoing Pre-Operative SBRT: Report of Early Outcomes

In patients with borderline resectable or locally advanced pancreatic adenocarcinoma (BRPC/LAPC), advances in neoadjuvant therapy have led to an increased proportion of patients undergoing margin negative resection. Nevertheless, locoregional recurrence rates remain high. We have previously reported that the location of locoregional recurrences in this setting map to the "Triangle Volume (TV)," the anatomical space between the celiac artery, superior mesenteric artery, common hepatic artery, and portal vein, which is enriched in extrapancreatic perineural tracts at risk for microscopic residual disease after resection. At the beginning of 2021, we systematically changed our target volume to include the TV, in addition to gross disease and involved vasculature. Herein, we report early locoregional failure outcomes after resection in the setting of BRPC or LAPC treated with pre-operative stereotactic body radiation therapy (SBRT) to the TV, as compared to historical rates. Patients who received a diagnosis of BRPC or LAPC and who were treated at our institution with neoadjuvant chemotherapy (CTX) and SBRT between 2016 and 2022 were retrospectively reviewed. Between 2016 and 2020, the SBRT clinical tumor volume (CTV) included gross disease and full circumference of involved vasculature at the level of involvement. From 2021 onward, the CTV also included the TV. Survival was estimated using the Kaplan-Meier method. Statistical analyses were performed using scientific 2-D graphing and statistics software. From January 2016 to December 2022, 204 patients with localized PDAC underwent neoadjuvant CTX followed by SBRT. After completion of SBRT, all patients proceeded with surgical exploration. Of these patients, 111 (54%) had LAPC and 92 (45%) had BRPC disease. All patients were treated with induction CTX, mostly commonly with FOLFIRINOX (N = 166, 81%). Following CTX, the most frequently used SBRT regimen was 33 Gy in 5 fractions (N = 191, 94%). 155 (67%) patients were treated between 2016 and 2020 to the traditional CTV, while 49 (24%) patients were treated after 2020 to a CTV that included the TV. The 2-year local progression free survival rate of patients treated with SBRT using the TV was 77.6% as compared to 47.5% in patients treated with the traditional CTV. Over a median follow up of 15.7 months (range: 1 to 78.2 months), 47% (N = 73 out of 155) of patients who underwent SBRT with the traditional CTV developed locoregional recurrence, but only 12% (N = 6 out of 49) treated with SBRT to the TV have thus far developed locoregional recurrence (p<0.0001). In patients with localized PDAC who undergo pre-operative SBRT for BRPC/LAPC, targeting the TV may help reduce locoregional recurrence. More data and longer follow-up are needed to verify these findings and inform whether the TV may serve as a new standard for target volume delineation in this setting.

Longitudinal assessment of hepatocellular carcinoma response to stereotactic body radiation using gadoxetate-enhanced MRI: A case series

PurposeTo describe the longitudinal response in patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT) and who underwent liver transplant (LT) using gadoxetate-enhanced MRI. MethodsFive men (median age 61y, range 57–64y) with 6 HCCs treated with SBRT (median dose 50 Gy) who subsequently underwent LT were included in this retrospective study. Patients underwent gadoxetate-enhanced MRI before and after SBRT over a period of 3–18 months. Response was assessed using RECIST1.1, mRECIST, LI-RADS and image subtraction, by 2 observers in consensus. Percentage of pathologic tumor necrosis was evaluated. ResultsLT was performed 278 days (IQR, 148–418d) after completion of SBRT and 48d after the last MRI. Histopathology demonstrated tumor necrosis of 48 ± 42% (range, 10–100%). Mean tumor size at baseline and last post-treatment MRIs pre-LT were 2.6 ± 0.8 cm and 2.4 ± 0.9 cm. Enhancing tumor component size at baseline MRI and last post-treatment MRI pre-LT were 1.6 ± 0.8 cm and 0.9 ± 1.0 cm. Responses assessed at the last LRI pre-LT were: partial response (PR, n = 3), stable disease (SD, n = 3) using RECIST1.1; complete response (CR, n = 2), partial response (PR, n = 2), stable disease (SD, n = 2) using mRECIST; and LR-TR viable (n = 4), LR-TR non-viable (n = 2) using LI-RADS. At the last MRI pre-LT, per-lesion features of arterial phase hyperenhancement (APHE, 4/6), portal venous washout (3/6) and capsule (3/6) were observed. 5/6 lesions displayed a hypointense perilesional halo on hepatobiliary phase with a mean delay of 3.1 months post-SBRT. ConclusionsThis case-series showed decreased size, persistent APHE, and incomplete pathologic necrosis in most HCCs treated with SBRT undergoing transplant.

Prostate Stereotactic Body Radiation Therapy With a Focal Simultaneous Integrated Boost: 5-Year Toxicity and Biochemical Recurrence Results From a Prospective Trial

Stereotactic body radiation therapy (SBRT) is increasingly used as a definitive treatment option for patients with prostate adenocarcinoma. The aim of this study was to assess the late toxicity, patient-reported quality of life outcomes, and biochemical recurrence rates after prostate SBRT with simultaneous integrated boost (SIB) targeting lesions defined by magnetic resonance imaging (MRI). Patients were eligible if they had biopsy-proven low- or intermediate-risk prostate adenocarcinoma, one or more focal lesions on MRI, and an MRI-defined total prostate volume of <120 mL. All patients received SBRT delivered to the entire prostate to a dose of 36.25 Gy in 5 fractions with an SIB to the lesions seen on MRI to 40 Gy in 5 fractions. Late toxicity was defined as any possible treatment-related adverse event occurring after 3 months from the completion of SBRT. Patient-reported quality of life was ascertained using standardized patient surveys. A total of 26 patients were enrolled. Six patients (23.1%) had low-risk disease and 20 patients had intermediate-risk disease (76.9%). Seven patients (26.9%) received androgen deprivation therapy. Median follow-up was 59.5 months. No biochemical failures were observed. Three patients (11.5%) experienced late grade 2 genitourinary (GU) toxicity requiring cystoscopy, and 7 patients (26.9%) had late grade 2 GU toxicity requiring oral medications. Three patients (11.5%) had late grade 2 gastrointestinal toxicity characterized by hematochezia requiring colonoscopy and steroids per rectum. There were no grade 3 or higher toxicity events observed. The patient-reported quality-of-life metrics at the time of last follow-up were not significantly different than the pre-treatment baseline. The results of this study support that SBRT to the entire prostate to a dose of 36.25 Gy in 5 fractions with focal SIB to 40 Gy in 5 fractions has excellent biochemical control and is not associated with undue late gastrointestinal or GU toxicity or long-term quality of life decrement. Focal dose escalation with an SIB planning approach may be an opportunity to improve biochemical control while limiting dose to nearby organs at risk.

Stereotactic Body Radiation Therapy is Safe and Feasible for the Treatment of Locally Recurrent Pancreatic Adenocarcinoma after Curative Resection

<h3>Purpose/Objective(s)</h3> Locoregional relapse rates following surgical resection of pancreatic cancer can be as high as 45-50%. The majority of these patients are not candidates for re-resection due to co-morbidities and/or technically unresectable disease, highlighting the role of non-invasive options such as radiation therapy. The purpose of this study was to report on a cohort of radiation-naïve patients who developed isolated local recurrence following surgical resection and were subsequently treated with stereotactic body radiation therapy (SBRT). <h3>Materials/Methods</h3> Patients who were treated with SBRT for locally recurrent pancreatic cancer after initial curative resection were retrospectively reviewed. Clinical outcomes were calculated from completion of SBRT and included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS). Univariate and multivariate analyses were performed to identify variables associated with clinical outcomes. Kaplan-Meier analysis was performed for survival outcomes. Toxicity was assessed using the Common Terminology Criteria for Adverse Events version 4.0. <h3>Results</h3> From September 2012 to November 2018, a total of 19 patients were treated with SBRT for locally recurrent pancreatic cancer after initial surgical resection. No patients had prior radiation. The most common SBRT dose/fractionation was 33 Gy in 5 fractions (12/19, 63.1 %), followed by 25 Gy in 5 fractions (4/19, 21.0%), 28 Gy in 5 fractions (1/19, 5.3%), 27 Gy in 4 fractions (1/19, 5.3%), and 26.4 Gy in 4 fractions (1/19, 5.3%). Peri-SBRT chemotherapy was administered to 10 patients, in the pre-SBRT (3/19, 15.7%) and/or post-SBRT (8/19, 42.1%) setting. Median OS was 17.1 months, with 6-month and 1-year OS rates of 94.4% and 69.6%, respectively. A total of 9 patients (47.4%) developed local failure after SBRT. Pattern of first failure after SBRT was distant in 7 patients (46.7%), local in 5 patients (33.3%), and synchronous distant and local in 3 patients (20.0%). One patient developed local failure after developing distant disease first. Of the 9 local failures, 3 (33.3%) were out-of-field, involving the porta hepatis (n=1), pancreaticojejunostomy (n=1), and pancreatic remnant (n=1). Median LPFS was 22.2 months, with 6-month and 1-year LPFS rates of 86.9% and 63.2%, respectively. A biologically effective dose (BED₁₀) < 54.8 Gy was associated with inferior LPFS (1-year LPFS, 25.0% vs 80.2%, p<0.009). Median DMFS and PFS were 15.6 months. There was 1 case (5.3 %) of grade 3 gastric perforation. There were no cases of grade 4-5 toxicity events. <h3>Conclusion</h3> Stereotactic body radiation therapy for local recurrence after initial curative resection is safe and feasible. A BED₁₀ < 54.8 Gy was significantly associated with inferior local control, and one-third of local failures were out-of-field. Further studies investigating dose escalation and optimal treatment volumes in the locally recurrent setting are warranted.

Tislelizumab Rechallenge for Recurrent or Metastatic Nasopharyngeal Carcinoma (RM-NPC) Previously Treated with Another Anti-PD1 Antibody

<h3>Purpose/Objective(s)</h3> To explore the ORR and PFS of Tislelizumab rechallenge in combination with chemotherapy or stereotactic body radiation therapy (SBRT) for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) previously treated with another anti-PD1 antibody. <h3>Materials/Methods</h3> This was part of a prospective study. RM-NPC patients who showed no response to or progressed after PD-1 blockade were rechallenged with Tislelizumab plus chemotherapy or SBRT. Tislelizumab was given at a fixed dose of 200 mg, repeated every three weeks. Chemotherapy regimen was low dose gemcitabine plus metronomic capecitabine. SBRT was given 4 Gy to 6 Gy in three or five fractions depending on the tumor site. Tislelizumab was delivered one day after the completion of SBRT. The primary endpoint was the ORR. The secondary endpoints included PFS, duration of response (DoR), and safety. Dynamic assessment of T lymphocytes, B lymphocytes, natural killer (NK) cells (TBNK), and regulatory T cells (Tregs) from peripheral blood mononuclear cells (PBMCs) was performed by flow cytometry every 2-3 months in order to analyze the change patterns following PD-1 blockade. <h3>Results</h3> From March 2019 to February 2022, 25 patients were enrolled in this study. All have previously received high dose platinum-based chemotherapy and PD-1 blockade. The salvage regimen was Tislelizumab rechallenge plus chemotherapy in 21 cases, and Tislelizumab plus SBRT in 4 cases. Altogether, there were 5 (20%) complete response (CR) and 12 (48%) partial response (PR), respectively. Stable disease (SD) and progressive disease (PD) were defined in 5 (20%) and 3 (12%) cases, respectively. The ORR was 17 out of 25 (68%). The disease control rate (DCR) was 22 out of 25 (88%). With a median follow-up of 12 months (4–26 months), three patients terminated immunotherapy due to disease progression, and the remaining 22 patients were still under treatment. The 1-year PFS was 78%, neither the median PFS nor the median DoR has been reached. Of the 12 patients who had regular TBNK and Treg surveillance in PBMCs, all showed an increasing trend in Treg accompanying with tumor progression. On the contrary, responders to Tislelizumab rechallenge demonstrated decrease of Treg in PBMCs. However, no specific regularity could be defined in TBNK. All observed adverse events during Tislelizumab rechallenge were defined as ≤ Grade 2. <h3>Conclusion</h3> Tislelizumab rechallenge combined with chemotherapy or SBRT displayed promising anti-tumor activity in RM-NPC previously undergone PD-1 blockade, with a low toxicity profile. The increase of Treg in PBMCs is always associated with immune tolerance after PD-1 blockade and the decrease of Treg is correlated with benefit from Tislelizumab rechallenge.

Predictors of Pneumonitis in Combined Thoracic Stereotactic Body Radiation Therapy and Immunotherapy

Thoracic stereotactic body radiation therapy (SBRT) is associated with high rates of local control but carries a risk of pneumonitis. Immunotherapy is a standard treatment for patients with metastatic disease but can also cause pneumonitis. To evaluate the feasibility and safety of thoracic SBRT with systemic immunotherapy, clinical outcomes of patients treated with immune checkpoint blockade (ICB) and SBRT on prospective trials were reviewed. Three consecutive phase 1 trials of combination SBRT and ICB conducted between 2016 to 2020 for widely metastatic solid tumors were reviewed. The protocols mandated adherence to NRG BR001/BR002 organs at risk constraints, resulting in <100% coverage of some target volumes. ICB was administered either sequentially (within 7 days after completion of SBRT) or concurrently (before or at the start of SBRT), depending on protocol. End points included pneumonitis, dose-volume constraints, local failure, and overall survival. The cumulative incidence estimator and Kaplan-Meier method were used. In the study, 123 patients met eligibility with 311 metastases irradiated. The most common histologies included non-small cell lung cancer (33%) and colorectal cancer (12%). Median follow-up was 12 months. The overall rate of grade 3+ pneumonitis was 8.1%; 1-year local failure was 3.6%. Established dosimetric parameters were significantly associated with the development of pneumonitis (P < .05). In most patients, the lungs were not challenged with high doses of radiation, defined as receiving ≥75% of the maximum for a given lung dose-volume constraint. Patients who were challenged were not found to have a significantly higher risk of pneumonitis. In the largest series of thoracic SBRT and immunotherapy, local control was excellent with acceptable toxicity and support the conclusion that established dose-volume constraints for the lung are safe. However, these results highlight the potential value in reporting of organs at risk being challenged with doses approaching protocol specified limits.

Stereotactic body radiation therapy for the treatment of locally recurrent pancreatic cancer after surgical resection.

To report on a cohort of radiation-naïve patients with pancreatic cancer who developed isolated local recurrence following surgical resection and were subsequently treated with stereotactic body radiation therapy (SBRT). Patients with pancreatic cancer who were treated with SBRT for isolated local recurrence after surgical resection were retrospectively reviewed. Clinical outcomes were calculated from completion of SBRT and included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS). Univariate (UVA) analysis was performed to identify variables associated with clinical outcomes. Kaplan-Meier method was used for survival outcomes. Toxicity was assessed using the Common Terminology Criteria for Adverse Events version 4.0. From September 2012 to November 2018, a total of 19 patients with localized pancreatic cancer were treated with SBRT for isolated local recurrence after initial surgical resection. No patients had prior radiation. The median biologically effective dose (BED10) was 54.8 Gy (range, 37.5-54.8 Gy). Median OS was 17.1 months, with 6-month and 1-year OS rates of 94.4% and 69.6%, respectively. Nine patients (47.4%) developed local failure after SBRT. Pattern of first failure after SBRT was distant in 7 patients (46.7%), local in 5 patients (33.3%), and synchronous distant and local in 3 patients (20.0%). One patient developed local failure after developing distant disease first. Of the 9 local failures, 3 (33.3%) were out-of-field. Median LPFS was 22.2 months, with 6-month and 1-year LPFS rates of 86.9% and 63.2%, respectively. A BED10 <54.8 Gy was associated with inferior LPFS (1-year, 25.0% vs. 80.2%, P<0.009). Median DMFS and PFS were 15.6 months. There was 1 case (5.3 %) of grade 3 gastric perforation. There were no cases of grade 4-5 toxicity events. SBRT for locally recurrent pancreatic cancer after initial curative resection is safe and feasible. A BED10 <54.8 Gy was significantly associated with inferior local control. Further studies investigating dose escalation and optimal treatment volumes in the locally recurrent setting are warranted.

Transcriptomic profiling identifies genomic markers associated with benefit from stereotactic body radiation therapy (SBRT) in oligoprogressive metastatic renal cell carcinoma (mRCC).

4555 Background: Addition of SBRT to systemic therapy in oligoprogressive mRCC has been shown to prolong the duration of systemic treatment (Cheung et al Eur Urol 2021; De et al BJUI 2021). To date, the genomic predictors of benefit are unknown. We hypothesized that hypoxia-related genes would be associated with lesser benefit from SBRT. Methods: We retrospectively identified patients (pts) with mRCC who had oligoprogressive disease (progression of &lt; 5 sites) while on systemic treatment and received SBRT without any systemic treatment change or interruption. Clinicopathologic characteristics, whole exome and transcriptome sequencing (Ashion Analytics) data were collected. Duration of systemic therapy (DOT) was quantified as systemic treatment duration prior to oligoprogression (DOT[P]) and after completion of SBRT (DOT[S]). The ratio of DOT[S]/DOT[P] was calculated and patients with a ratio ≥ 1.0 were considered to derive greater benefit from SBRT. The frequency of specific DNA alterations and RNA expression of pts above and below a DOT[S]/DOT[P] threshold of 1.0 was compared using a two-tailed Fischer’s exact and student’s t-test, respectively. Results: In this study, 23 mRCC pts who had oligoprogression during systemic treatment and received SBRT were identified. Within this cohort 16 pts (69.6%; M:F, 12:4) had available genomic data. Median age was 70 years and the most common histology was clear cell (87.5%). At the time of oligoprogression 11 pts (68.8%) were on immunotherapy, 4 pts (25.0%) were on targeted therapy. Median DOT[S] and DOT[P] were 12.6 months (range,0.7-46.3) and 13.4 months (range, 0.5-26.9), respectively, with a median DOT[S]/DOT[P] ratio of 1.4 (range,0.01-3.8). The most commonly mutated genes were VHL (56.3%), PBRM1 (37.5%), and SETD2 (37.5%). Alterations in VHL, PBRM1 and SETD2 were seen in 66.7% vs 42.9%, 33.3% vs 43.9%, and 44.4% vs 28.6% in patients with greater vs lesser benefit from SBRT, respectively (p≥0.05for each). Transcriptomic analysis was available in 9 pts and 1580 genes were noted to be differentially expressed between the groups (p &lt; 0.05). Limiting scope to cancer genes in the COSMIC database, pts with lesser benefit from SBRT had higher expression of CDKN1B, CNBP, and FOXO3 whereas pts with greater benefit had higher expression of RNF43, POLD1 and PBRM1 (p &lt; 0.05 for each). Gene set enrichment analysis showed a trend towards increased expression of hypoxia related genes in pts with lesser benefit. Conclusions: Our data align with existing studies supporting the role of SBRT in oligoprogressive mRCC. In addition, while clinical benefit from SBRT appears to be independent of DNA-level alterations, transcriptomic analysis revealed significant differences in gene expression. Hypoxia-associated signatures may be associated with lesser benefit from radiotherapy.

The histologic effects of neoadjuvant stereotactic body radiation therapy (SBRT) followed by pulmonary metastasectomy-rationale and protocol design for the Post SBRT Pulmonary Metastasectomy (PSPM) trial.

BackgroundFor the local management of pulmonary malignancies, surgical resection and stereotactic body radiation therapy (SBRT) are mutually exclusive treatments. This study aims to assess the effectiveness of SBRT on reducing tumor viability at a histologic level in the context of pulmonary metastases.MethodsThis protocol describes an open-label unblinded single-arm prospective Phase 2 trial to determine the effects of dual treatment of pulmonary metastasis amenable to curative resection using neoadjuvant SBRT followed by surgical resection, the Post SBRT Pulmonary Metastasectomy (PSPM) trial. Sample size require 39 patients, with an anticipated study duration of 30–36 months. Following completion of SBRT, eligible patients will be assessed at the 4–6-week mark by the treating radiation oncologist and thoracic surgeon with a post-treatment computed tomography (CT) of the chest. Patients with no disease progression will undergo scheduled surgical resection of all metastatic tumors at 8–12 weeks post SBRT. Patients will then be evaluated postoperatively at 30 days, and every 6 months for a total of 36 months with surveillance CT scans. Patients will also undergo sequential serologic evaluation of circulating tumor DNA (ctDNA) levels throughout their respective treatment pathway. The primary outcome of this study is the rate of complete pathologic response (pCR) following SBRT, assess using the International Association for the Study of Lung Cancer (IASLC) multidisciplinary recommendations for pathologic assessment of lung cancer resection specimens after neoadjuvant therapy. Secondary outcomes include overall survival (OS), disease free survival (DFS), local recurrence rates, cancer histology effects on pCR and treatment related complications, and treatment effect on ctDNA levels. Primary and secondary outcomes will be analyzed using Fisher’s Exact test and Student’s t-test based on data type. Cox-proportional hazard ratios will be used to evaluate OS and DFS, using the log rank test.DiscussionIn evaluating the effect of SBRT on pulmonary metastasis at a histologic level, this trial may increase the use of this modality in selected patients who would otherwise only undergo surgery for disease that has already metastasized. Also, the trial provides secondary benefits of evaluating the abscopal effects of radiation on pulmonary metastatic disease, and serves as a platform for more comprehensive large-scale research in this field.Trial RegistrationClinicalTrials.gov identifier: NCT04160143 (HiREB: 7925).

Phase I Dose Escalation Clinical Trial of Stereotactic Body Radiation Therapy (SBRT) for Limited Locoregional Recurrences of Ovarian Cancer

Radiation therapy is infrequently used in the treatment of advanced ovarian cancer due to the propensity for peritoneal spread and the dose limitations of large field techniques. However, for patients with limited sites of recurrence, advanced radiation techniques such as Stereotactic Body Radiation Therapy (SBRT) may offer an effective treatment option. There are many clinical trials supporting the safety and efficacy of SBRT for lung and liver tumors, but the role for abdominopelvic targets adjacent to gastrointestinal mucosa remains largely investigational, especially in this often heavily pretreated patient population.A single institution Phase I dose escalation study was conducted to determine the maximum tolerated dose (MTD) of SBRT for patients with limited (≤ 3 sites) abdominopelvic recurrences of ovarian cancer. We utilized a 3+3 design with 3 dose levels: 8 Gy x 3 fractions (DL1), 9 Gy x 3 fractions (DL2), and 10 Gy x 3 fractions (DL3). Dose limiting toxicity (DLT) was defined as treatment-related grade 3 or higher adverse events and the DLT monitoring period was 12 weeks after completion of SBRT prior to escalating to the next dose level. Secondary endpoints included toxicity, one-year local control (LC), progression-free survival (PFS), overall survival (OS), and quality of life (QOL) utilizing the EORTC QLQ-C30 assessment tool. Patients underwent tumor perfusion imaging as an exploratory endpoint. The median of each perfusion metric in the gross tumor volume (GTV) was computed at baseline, immediately following fraction one, and six weeks after completion of SBRT, and compared with a paired t-test.Sixteen patients were enrolled; 9 in the initial dose escalation and 7 in an expansion cohort. The initial dose escalation cohort has completed 12-month follow-up. Patients were enrolled according to the 3+3 design, with a safety break between levels, and the dose was safely escalated to DL3 with no DLT. There were no serious adverse events or any Grade 2 or higher SBRT-related toxicities, including bowel complications or bowel surgery. One-year LC, PFS, and OS were 92%, 44%, and 100%, respectively. The majority of patients received SBRT on study in lieu of systemic therapy (67%), and one-half of these patients remained off systemic therapy at one-year follow-up. At one year after completion of SBRT, global health status/QOL patient reported outcomes were maintained from baseline values. In perfusion imaging, we observed increases in GTV median permeability (P < 0.01) and blood flow (P = 0.03) after delivery of the first fraction of SBRT, and decreases in blood volume (P = 0.01) six weeks after treatment.This Phase I clinical trial offers preliminary evidence that SBRT can be delivered safely and can be effective in controlling limited locoregional recurrences of ovarian cancer, while maintaining quality of life. SBRT offers another potential tool in the armamentarium of treatments for gynecologic cancers with limited site recurrences.

SBRT for the Treatment of Isolated Local Recurrence of Resected Pancreatic Cancer

<h3>Purpose/Objective(s)</h3> Following curative resection for pancreatic ductal adenocarcinoma (PDAC), there are high rates of local recurrence. The optimal treatment of patients with isolated local recurrence (ILR) – recurrence in the abdomen without distant metastases – is not known. This study evaluated stereotactic body radiation therapy (SBRT) as a treatment option for ILR. <h3>Materials/Methods</h3> A multi-institutional retrospective analysis was performed on patients with ILR of PDAC following oncologic surgical resection treated with SBRT. Patient demographics, tumor and prior treatment characteristics, details of recurrence, SBRT treatment design and dosimetry, and patient follow-up and toxicity data were recorded from the medical record. Progression and overall survival estimates were calculated using cumulative incidence and Kaplan-Meier models, respectively. <h3>Results</h3> Between January 2010 and December 2020, 34 patients (17 males and 17 females, median age 69 years) were treated at five institutions in the United States. At the time of initial resection, most patients had T3 tumors (71%) and involved lymph nodes (71%). 31 of 34 (91%) patients underwent a Whipple procedure and 3 (9%) had a distal pancreatectomy. The R0 resection rate was 68%. 29% and 85% received neoadjuvant or adjuvant chemotherapy, respectively; and 12% and 27% had prior neoadjuvant or adjuvant radiation courses around the time of initial surgical resection. Median time to ILR was 18.7mos. The most common location of recurrence was in the pancreatic remnant or near the superior mesenteric artery. All patients underwent 5-fraction photon (28 patients) or proton (6 patients) SBRT to a median dose of 3500cGy (range 3000-4000cGy) with a median BED of 5950cGy (α/β = 10). Median follow-up after SBRT was 3.05 years. The 1-year and 2-year cumulative incidence of cancer progression were 72% (95% CI 56-93%) and 92% (95% CI 76-100%). Distant metastasis was the most common site of first recurrence (15 of 23 recurrences, 65%). 6 patients (25%) had local failure as site of first recurrence. Prior radiation was not associated with increased risk of progression after SBRT (HR 1.31 95% CI 0.56-3.07, <i>P</i> = 0.54). 1-year and 2-year overall survival was 64% (95% CI 49-84%) and 40% (95% CI 25-64%), with a median survival of 1.2 years from time of SBRT. Four patients (12%) developed grade 3 toxicities within one year after completion of SBRT. There were no grade 4-5 toxicities. <h3>Conclusion</h3> For treatment of PDAC ILR after surgical resection, SBRT was well tolerated and offered high rates of local tumor control with low treatment-related toxicity.

The Utility of Stereotactic Body Radiotherapy for Pelvic Recurrences After Prior Radiation Therapy

Patients with locally recurrent colorectal cancer represent a particular clinical challenge as these patients often present with unresectable disease and a history of prior pelvic radiotherapy. While options are therefore limited, radiation is usually the only local therapy available. The purpose of this study was to analyze the efficacy and outcomes associated with treating recurrent colorectal cancer using stereotactic body radiation therapy (SBRT) in patients who have been previously irradiated to the pelvis.We identified 23 patients with recurrent rectal (n = 20, 87%) or colon (n = 3, 13%) adenocarcinoma who were treated with SBRT in the Department of Radiation Oncology at Stanford University from June 2009 to November 2019. In total, 11 males and 12 females were included in this study with a median age of 53 years old (range: 25-76). All 23 patients had a history of surgical resection and at least one course of radiation therapy to disease in the pelvis before SBRT treatment to the pelvis for recurrent cancer, of which 8 patients (35%) received two prior radiotherapy courses and 1 patient (4%) received three prior courses. Data collection included tumor staging and grading, radiation treatment details, and follow up information to determine toxicities and survival outcomes. Time to events were calculated from the completion of SBRT. Toxicities were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v.5.0.Median time to follow up was 91 months (range: 36-237). Median GTV and PTV volumes for tumor treated using SBRT were 79.9 and 136.5 cm3, respectively. Median SBRT dose was 40 Gy (range: 30 - 50). Median PTV mean dose was 41.8Gy. The median cumulative biological effective dose (BED) was 145 Gy (range: 72.0-254.4). Overall, 22 patients received 5 fractions of treatment and one patient received 4 of the 5 planned fractions due to deteriorating condition related to disease. Median time to overall survival (OS) was 125 months (range: 61-194) and median progression free survival (PFS) was 82 months (range: 57-142). The 3- and 5-year rate of local failure was 4.4% and 17.4%, respectively. Of the 23 patients in this cohort, there were 6 patients (26%) with grade 2 acute toxicities, including 3 patients (13%) with increased pain, and 6 patients (26%) with late grade 2 or 3 toxicities, including 3 patients (13%) with grade 3 neuropathy. There was no grade 3 or 4 acute, or grade 4 late toxicities reported. On univariate analysis, no factors were significantly predictive of OS, PFS, or toxicity.SBRT to previously irradiated areas of the pelvis was effective in controlling unresectable pelvic recurrences of colorectal cancer following previous radiation. While treatment was generally well-tolerated, pelvic pain was the most common acute toxicity, and neuropathy was the most common late toxicity. Further investigation is needed to improve the toxicity profile and optimize the therapeutic ratio.

A Phase II Trial of PD-1 Inhibitors Combined With Multisite Radiotherapy and GM-CSF (PRaG Regimen) for the Treatment of Chemo-Refractory Metastatic Solid Tumors

Advanced cancer patients refractory to chemotherapy have a poor prognosis and few therapeutic options. Evidences have shown that radiotherapy can induce a systemic anti-tumor immune response, which may potentially sensitize PD-1 inhibitors. Immunomodulatory cytokines such as granulocyte macrophage-colony stimulating factor (GM-CSF) may have a synergistic effect with radiotherapy or anti-PD-1 therapy. A phase Ⅱ trial was conducted to assess the clinical efficacy and safety of stereotactic body radiation therapy (SBRT) or hypofractionated radiotherapy (HFRT) combined with PD-1 inhibitor and GM-CSF (PRaG regimen) for the treatment of chemo-refractory solid tumor patients.Subjects with multi-metastatic solid tumors and progressed beyond at least first-line chemotherapy were enrolled. In a PRaG cycle, SBRT or HFRT (3 × 8 Gy or 3 × 5 Gy) was delivered for one metastatic site, GM-CSF 200 µg was subcutaneously injected daily for 2 weeks after radiotherapy, and sindilimab 200 mg or toripalimab 240 mg was intravenously administered once within one week after completion of SBRT or HFRT. PRaG was repeated every 21 days for at least 2 cycles. After discontinuation of PRaG and patient had no disease progression, sindilimab or toripalimab monotherapy was given until disease progression or unacceptable toxicity. The primary endpoint is progression-free survival (PFS). This trial is registered in chictr.org.cn (No. ChiCTR 1900020175).By February 2021, a total of 48 patients were enrolled. Forty-three patients (89.6%) completed at least two cycles of the triple-combination therapy, and the remaining five patients received one cycle of the triple therapy and continued treatment. Treatment-related adverse events (TRAE)of any grade occurred in 35 (72.9%) patients. The common adverse events were fatigue 52.1%, anorexia 47.9%, thyroid dysfunction 29.2%, liver dysfunction 18.8% and rash 14.6%. Two patients (4.2%) experienced Gr3 and higher TRAE. Both patients had lung lesions irradiated during PRaG and one patient experienced Gr3 pneumonia and another patient experienced Gr4 pneumonitis. Forty-one patients completed at least one efficacy evaluation, seven patients had confirmed partial response (PR), and the objective response rate (ORR) was 14.6% (RECIST 1.1). The median PFS was 5.2 months (95% CI, 4.3-6.1).The PRaG regimen is well tolerated with acceptable toxicity. Our data suggest that SBRT or HFRT can sensitize the anti-tumor effects of anti-PD-1 therapy and produce a great synergistic efficacy. The PRaG regimen could contribute to a promising salvage treatment for patients with chemotherapy-refractory metastatic solid tumor.

Prostate Stereotactic Body Radiation Therapy With a Focal Simultaneous Integrated Boost: Late Toxicity and Biochemical Recurrence Results From a Prospective Trial

<h3>Purpose/Objective(s)</h3> Stereotactic Body Radiation Therapy (SBRT) is increasingly utilized as a definitive treatment option for patients with prostate adenocarcinoma, especially in the low or intermediate risk setting. The aim of this study is to assess the late toxicity and biochemical recurrence rates of a single institution prospective clinical trial evaluating prostate SBRT with simultaneous integrated boost (SIB) targeting focal lesions as defined by magnetic resonance imaging (MRI). <h3>Materials/Methods</h3> Patients were eligible if they had biopsy-proven low or intermediate risk prostate adenocarcinoma with initial prostate specific antigen (PSA) values ≤20 ng/mL, clinical stage from T1c to T2c, and Gleason score ≤7. Patients also had to have one or more focal lesions on MRI and an MRI-defined total prostate volume of < 120 cm³. All patients received SBRT delivered to the entire prostate to a dose of 36.25 Gy in 5 fractions with an SIB to the lesions seen on MRI to 40 Gy in 5 fractions. Late toxicity was defined as any possible treatment-related adverse event occurring after three months from the completion of SBRT and graded according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). Biochemical recurrence was defined by the Phoenix definition of PSA increase of 2 ng/mL above the nadir. <h3>Results</h3> A total of 26 patients were enrolled, and all enrolled patients underwent planned SBRT. Six patients (23.1%) had low risk disease and twenty patients had intermediate risk disease (76.9%). Eight patients (30.8%) received androgen deprivation therapy. Median follow up was 40.5 months (range 12-64 months). No biochemical failures have yet been observed. Three patients (11.5%) experienced late grade 2 genitourinary (GU) toxicity requiring cystoscopy; two of these three patients experienced hematuria requiring cystoscopy and one patient experienced dysuria requiring cystoscopy. Six patients (23.1%) had late grade 2 GU toxicity requiring medications such as tamsulosin or oxybutynin. Two patients (7.7%) had late grade 2 gastrointestinal (GI) toxicity; both patients experienced hematochezia requiring colonoscopy and were found to have proctitis requiring steroids per rectum. There was no grade 3 or higher toxicity events observed. <h3>Conclusion</h3> The results of this study support that SBRT to the entire prostate to a dose of 36.25 Gy in 5 fractions with focal SIB to 40 Gy in 5 fractions is not associated with undue late GI or GU toxicity. Thus far, this regimen has excellent biochemical control. Focal dose escalation with an SIB planning approach may be an opportunity to improve biochemical control while limiting dose to nearby organs at risk.

Long-term outcomes of a prospective single institution study with multiagent chemotherapy and stereotactic body radiation therapy in locally advanced or recurrent pancreatic adenocarcinoma.

440 Background: We previously reported a multi-center study in which gemcitabine and stereotactic body radiation therapy (SBRT) were shown to be safe with outcomes comparable to chemoradiation in locally advanced pancreatic cancer (LAPC). This prospective clinical trial was developed to evaluate the efficacy of adding SBRT to multi-agent chemotherapy in LAPC. Herein, we report on the long-term survival outcomes. Methods: From 2012 to 2015, 48 patients (pts) were prospectively enrolled after multidisciplinary evaluation at a single high-volume pancreatic center. Pts received multi-agent chemotherapy (CTX) with modified mFOLFIRINOX (mFFX) or gemcitabine/abraxane followed by 5 fractions of SBRT (median 33 Gy; range, 25-33 Gy). At the time of fiducial placement, biopsies were obtained and DNA extracted for targeted sequencing using MSK-IMPACT. Kaplan-Meier curves were generated to compare survival outcomes by sub-group. Multivariate analysis (MVA) was performed to identify factors prognostic for survival. Results: 44 pts (91.7%) had LAPC disease and 4 (8.3%) had locally recurrent disease. The median follow-up interval was 21.5 months (mo) from diagnosis. CTX consisted of mFFX in 25 pts (52.1%) with 24 pts (50.0%) receiving therapy for a duration ≥4 mo. Of 44 pts with LAPC, 15 (34.1%) were surgically explored, and 11 (73.3%) achieved a margin-negative resection. From diagnosis and after completion of SBRT, respectively, the median overall survival (OS) was 21.6 (95% CI 16-29.7 mo) and 14.6 mo (95% CI: 11.6-23.0 mo); median progression free survival (PFS) was 13.2 (95% CI 11.9-18.1mo) and 6.4 mo (95% CI: 5-12.7 mo); median local PFS (LPFS) was 23.9 (95% CI 18.9-56.9 mo) and 15.8 mo (95% CI: 12.9-27.6 mo); and median distant metastasis free survival (DMFS) was 18.4 (95% CI 12.6-29.3 mo) and 8.5 mo (95% CI: 6.3-17.2 mo). Resected pts experienced better DMFS at 1-year (78% vs. 34%, p= 0.004) with an improved trend for 1-year OS (73% vs. 52%, p= 0.331). If CTX duration was ≥4 mo, 1-year OS (75% vs. 42%, p= 0.018), PFS (50% vs. 21%, p= 0.022), and DMFS (72% vs. 29%, p= 0.031) were significantly improved. In 44 LAPC pts, MVA confirmed ≥4 mo duration of CTX was associated with OS, PFS, and DMFS. Surgical resection was associated with improved DMFS, and CA19-9 level prior to SBRT was associated with PFS and LPFS. The most common mutations detected from biopsy specimens were KRAS (64.3%) , TP53 (50%), and SMAD4 (16.7%). Conclusions: In a prospective trial of pts with LAPC receiving multiagent CTX and SBRT, clinical outcomes were improved with longer durations of CT ( &gt; 4 mo). A high proportion of LAPC pts underwent margin negative resection with favorable outcomes. Future studies should focus on which pts are most likely to benefit from SBRT and surgery following multiagent CTX. In pts who cannot undergo resection, escalated doses of SBRT may be indicated. Clinical trial information: NCT01781728.

Obstructive Uropathy after Prostate SBRT is Rare: Characterizing Clinical and Dosimetric Predictors From a Large Patient Cohort

Acute urinary obstruction is a known potential sequela of prostate radiation. Several series have characterized risk factors for patients undergoing brachytherapy. While preliminary data indicate a more favorable incidence of obstruction for patients receiving Stereotactic Body Radiation Therapy (SBRT), there is a paucity of long-term data to define risk factors in this cohort. Herein, we assess these risk factors after prostate SBRT and explore the related potential long-term outcomes in a large hospital experience. 3308 patients with prostate cancer were treated with non-coplanar SBRT at an academic institution from April 10, 2006 to November 25, 2019. Patients had NCCN low (22.3%), favorable intermediate (24.6%), unfavorable intermediate (35.5%) and high risk (17.6%) disease. 2945 (89.0%) treatments consisted of a 5-fraction regimen of 35.0-36.25 Gy while 363 (11.0%) involved pelvic irradiation (median dose 45Gy) followed by 3 fraction SBRT as boost (19.5-21Gy). ADT was prescribed in 774 (23.9%) cases. Acute obstruction was defined as requiring foley catheterization ≤6 months after treatment, with long-term toxicity scored as occurring ≥6 months from the completion of SBRT. Survival curves were calculated by the Kaplan-Meier method and multivariate analysis was assessed by Cox regression. 65 (2.0%) patients experienced acute urinary obstruction. These individuals were more likely to be older than age 70 (54.7% vs. 41.4%, p = .023), with a greater likelihood of taking 5-alpha reductase inhibitor medication (12.1% vs. 5.6%, p = .045). They were more likely to have prior history of TURP procedure (5.2% vs. 1.3%, p = .046) and to have prostate gland size ≥70cc’s (37.5% vs. 13.8%, p = .001). Patients treated with 5-fraction SBRT were more likely to experience acute obstruction if treated with consecutive vs. QOD fractionation (7.0% vs. 0%, p = .013) and if their Bladder V34 was ≥ 12cc’s (56% vs. 28.4%, p = .004). Pelvic irradiation and baseline patient EPIC questionnaires did not predict for acute obstruction. Those experiencing acute obstruction were more likely to undergo subsequent TURP procedure (4.9% vs. 0.5%, p = .023). They were more likely to experience 5-year cumulative grade 2+ (12.5% vs. 3.2%, p = .002) and grade 3+ (12.5% vs. 2.0%, p<.0001) genitourinary toxicity, with no difference in biochemical outcome. On MVA, prostate size ≥70cc’s (HR 9.25, CI 3.01-28.37, p<.001) and Bladder V34 >12cc’s (HR 3.21, CI 1.05-9.80, p = .04) predicted for acute obstruction. Prostate size ≥70cc’s (HR 4.46, CI 1.21-16.43, p = .025) was the lone predictor for grade 3+ genitourinary outcome. Acute obstructive uropathy is measurable, though rare, in a large series of men undergoing prostate SBRT. Prostate size ≥70cc’s and Bladder V34 >12cc’s portend for an increased risk of acute obstruction. Those experiencing acute obstruction do not appear more likely to experience long-term genitourinary toxicity after definitive prostate SBRT.

The CT appearance pattern of radiation-induced lung injury and tumor recurrence after stereotactic body radiation therapy in early stage non-small cell lung cancer.

BackgroundRadiographic changes after stereotactic body radiation therapy (SBRT) have not been well studied. The purpose of this study was to investigate the computed tomography (CT) appearance pattern of radiation-induced lung injury (RILI) and recurrence after SBRT in patients with early stage non-small cell lung cancer (NSCLC).MethodsWe retrospectively analyzed clinical data of inoperable early stage NSCLC patients undergoing SBRT treatment from February 2012 to June 2018. All patients had undergone serial CT scanning before SBRT and after completion of SBRT. An experienced radiation oncologist and radiologist reviewed all CT images, and identified the RILI and CT high-risk features (HRFs).ResultsA total of 60 patients were enrolled in this study; 55 patients had RILI (91.67%) and 7 patients had local failure. In the early CT findings of observers 1 and 2, there were diffuse ground glass opacities (GGOs) in 3 and 4 patients, diffuse consolidation in 10 and 12 patients, patchy consolidation in 22 and 15 patients, patchy GGOs in 19 and 24 patients, and no changes in 5 and 4 patients, respectively (kappa =0.706). In the late CT findings of observer 1 and 2, there were modified conventional patterns in 37 and 37 patients, mass-like patterns in 10 and 9 patients, scar-like patterns in 7 and 8 patients, and no changes in 5 and 5 patients, respectively (kappa =0.726). In the results of the CT-based HRFs of disease local failure, there were ≥1 HRFs in 7 patients, ≥2 HRFs in 7 patients, ≥3 HRFs in 6 patients, ≥4 HRFs in 5 patients, and ≥5 HRFs in 3 patients, respectively. Patients with only 1 HRF showed high sensitivity (100%) and low specificity (52.80%), with the specificity increasing and the sensitivity decreasing as the number of HRFs increased.ConclusionsThe agreement of the CT appearance on RILI between 2 observers was good. Regular follow-up and attention to HRFs are vital for better identifying RILI and local disease failure.

A Phase 2 Study of Post-Operative Stereotactic Body Radiation Therapy (SBRT) for Solid Tumor Spine Metastases

In patients with spinal instability, cord compression, or neurologic deficits, the standard of care is surgery followed by radiation therapy (RT). Recurrence rates after conventional RT remain high. The purpose of this study is to prospectively examine the efficacy of postoperative stereotactic body RT (SBRT) in patients who have undergone surgical intervention for spine metastases. We hypothesize that postoperative SBRT to the spine would be associated with higher local control than historical rates after conventional RT. Thirty-five adult patients with a Karnofsky Performance Status score ≥40 and spine metastases from solid tumors with no prior overlapping RT and target volumes ≤3 consecutive vertebral levels were enrolled. Thirty-three patients were treated. Two patients underwent treatment to 2 target volumes for a total of 35 target volumes. All patients received SBRT 30 Gy in 5 fractions. Patients were followed with neurological examinations and computed tomography and/or magnetic resonance imaging every 3 months. Neurologic function was assessed at the same time points using the American Spinal Injury Association (ASIA) impairment score. Pain was rated according to the 10-point visual analogue scale and MD Anderson Cancer Center brief pain index. Toxicity was recorded according to National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4. The primary objective was the rate of radiographic local recurrence at 12 months after completion of SBRT. Patient characteristics were as follows: 34.3% had radioresistant primaries; 71.4% were ASIA E and the remainder ASIA D; and the median baseline Karnofsky Performance Status score was 70 (range, 50-100). Radiographic and symptomatic local control at 1 year were 90% (95% confidence interval, 76%-98%). The median time to recurrence in these 3 patients was 3.5 months (range, 3.4-5.8 months), all had radiosensitive tumors, and all recurrences were epidural. No patients experienced wound dehiscence, hardware failure, or spinal cord myelopathy. The median time to return to systemic therapy was 0.5 months (range, 0-9.4 months). This prospective study of postoperative spine SBRT demonstrates excellent local control with low toxicity. These data suggest superior rates of local control compared with conventional RT; however, a formal comparative study is warranted.

Change in Apparent Diffusion Coefficient Is Associated With Local Failure After Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer: A Prospective Clinical Trial

Response assessment with computed tomography after stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC) is challenging because myriad anatomic changes can occur after treatment. Diffusion-weighted magnetic resonance imaging (MRI) may provide additional data to guide therapy response. The primary objective was to evaluate the effect of SBRT on the mean apparent diffusion coefficient (ADC). This is a prospective clinical study of patients with NSCLC who received SBRT to the primary lung lesion. Patients underwent MRI scans before and at 1 month after completion of SBRT. MRI consisted of T1- and T2-weighted sequences, along with postcontrast, dynamic-contrast, and diffusion-weighted sequences with construction of ADC maps. Two blinded radiologists generated the ADC. SBRT was given over 5 fractions. A total of 13 patients were enrolled. Twelve patients were eligible for analysis. An average increase of 50% and 46% in mean single-plane ADC was observed after treatment by readers 1 and 2, respectively (P < .01, both reviewers). There was good interobserver agreement of single-plane ADC values between the 2 radiologists (Pearson correlation of 0.85 [baseline] and 0.89 [1-month post-SBRT], P < .001 for both). There was also a significant 18% increase in mean volumetric ADC on the 1-month scan (Wilcoxon P = .02). Two patients developed a local failure after SBRT, 1 at 6 months and the other at 34 months. Using a threshold of volumetric ADC increase of greater than 40%, 2 of 2 patients demonstrated local failure compared with 0 of 10 patients below this limit. A statistically significant increase in ADC was observed 1 month after treatment. An ADC increase of 40% at 1 month was associated with a higher rate of local failure. This pilot study provides impetus for studying ADC as a radiomic biomarker in patients receiving lung SBRT for NSCLC.