Stereotactic Body Radiation Therapy Treatment Research Articles

Temporary Organ Displacement to Escalate Radiation Dose to Retroperitoneal Tumors and Decrease Toxicity to Organs at Risk

PurposeTo demonstrate that temporary organ displacement (TOD) by drainage catheter placement and hydrodissection is feasible and reproducible for simulation (SIM) and stereotactic body radiation treatment (SBRT). Materials and MethodsBetween February 2010 and December 2018, 31 consecutive patients (20 men and 11 women; median age, 59 years; range 20–80 years) received both SIM and SBRT with TOD. The minimum required displacement was 10 mm between the gross tumor volume (GTV) and the organ at risk (OAR). Complete displacement was defined as the ability to displace the OAR from the GTV a minimum of 10 mm across the entire boundary. SIM was performed with hydrodissection on the same day. On the day of SBRT, displacement was reproduced by hydrodissection. Displacement was measured on computed tomography images of TOD, SIM, and SBRT. The drain was removed after SBRT. ResultsTOD (hydrodissection) was significantly associated with successful displacement of the OAR from a GTV greater than 10 mm (median, 20 mm vs 4.1 mm, P < .001) and maintained displacement at SIM and SBRT (SIM: 29.4 mm vs 4.1 mm, P < .001; SBRT: 32.4 mm vs 4.1 mm, P < .001). The OAR-GTV boundary showed a median reduction of 35 mm (95% confidence interval, 27.5–37.5 mm) after TOD. TOD achieved complete displacement in 22 of 31 (71%) patients, and 25 of 31 (81%) patients were able to undergo single-fraction ablative SBRT. No patients developed procedure-related complications within 30 days. SIM and SBRT were successful without OAR toxicities within a median of 33 months (range, 3–92 months). ConclusionsTOD with placement of drain and hydrodissection is technically feasible and safe and maintains displacement for SIM and SBRT.

Timing of fluorodeoxyglucose positron emission tomography maximum standardized uptake value for diagnosis of local recurrence of non-small cell lung cancer after stereotactic body radiation therapy.

IntroductionAfter treatment with stereotactic body radiation therapy (SBRT), local recurrence of non‐small cell cancer (NSCLC) can be difficult to differentiate from radiation‐induced changes. Maximum standardized uptake value (SUVmax), measured with 18‐F‐Fluorodeoxyglucose positron emission tomography (FDG‐PET), can have false positives due to acute radiation inflammation. The primary study objective was to determine the utility of SUVmax > 5 to identify local recurrence later than 9 months after SBRT.MethodA retrospective review was performed of FDG‐PET scans for suspicious CT findings after SBRT treatment of stage 1 NSCLC. SUVmax was measured including surrounding opacification. Outcome measures were local recurrence, progression free survival, and overall survival. Receiver operator curve analysis, sensitivity, specificity, and Kaplan‐Meier analysis were performed.ResultsOf 118 patients treated, 42 patients had eligible FDG‐PET scans. They received SBRT (48‐60Gy in 3‐8 fractions) for 49 NSCLC and had 101 follow‐up PET scans. The median time to first PET scan was 9.3 months, and the median follow‐up period was 22.4 months. Local recurrence was diagnosed in 12 patients, at a median of 16 months. Due to selection bias, the included patients had poorer outcomes than the entire cohort, with progression free survival (PFS) at 1, 2, and 3 years of 82.7%, 57.8%, and 45.8%; and overall survival of 97.9%, 79.9%, and 59.1%, respectively. Thirty FDG‐PET scans were performed within 9 months, of which 17% were false positives. A total of 71 FDG‐PET scans were performed beyond 9 months, and the median SUVmax was significantly higher for patients with local recurrence (7.48 vs. 2.14, P < .0001). SUVmax > 5 has a sensitivity of 91% (95% CI 62%‐99.8%) and 100% (89.1%‐100%).ConclusionFor local recurrence of NSCLC, SUVmax > 5 on FDG‐PET scan has good sensitivity and specificity after 6 months, but is highest beyond 9 months after SBRT.

Safety and Efficacy of Stereotactic Body Radiation Therapy for Locoregional Recurrences After Prior Chemoradiation for Advanced Esophageal Carcinoma.

Purpose: This study aimed to investigate the feasibility of stereotactic body radiation therapy (SBRT) as salvage therapy for locally recurrent esophageal cancer. We hypothesized that SBRT would provide durable treated tumor control with minimal associated toxicity in patients with progressive disease after definitive radiation, chemotherapy, and surgical resection.Methods: This single-institution retrospective study assessed outcomes in patients who received SBRT for locoregional failure of esophageal cancer after initial curative-intent treatment. Only patients who had received neoadjuvant chemoradiation (≥41.4 Gy) for esophageal cancer were selected. Subsequent surgical resection was optional but institutional follow-up by an oncologist was required. The primary endpoints of this study were gastrointestinal and constitutional toxicity, scored with the Common Terminology Criteria for Adverse Events v5.0. A secondary outcome, treated-tumor control, was assessed with RECIST v1.1.Results: Nine patients (11 locoregional recurrences) treated with SBRT were reviewed, with a median follow-up time of 10.5 months. Most patients initially presented with T3 (88.9%), N1 (55.6%), moderately differentiated (66.7%) adenocarcinoma (88.9%), and had received a median 50.4 Gy delivered over 28 fractions with concurrent carboplatin/paclitaxel chemotherapy followed by surgical resection. Median time to recurrence was 16.3 months. Median total dose delivered by SBRT was 27.5 Gy (delivered in five fractions). Two patients experienced acute grade 1 fatigue and vomiting. No patient experienced grade 3 or higher toxicity. One patient experienced failure in the SBRT treatment field at 5.8 months after treatment and six patients developed distant failure. The median progression-free survival time for SBRT-treated tumors was 5.0 months, and median overall survival time was 12.9 months.Conclusions: This single-institution study demonstrated the feasibility of SBRT for locoregional recurrence of esophageal cancer with minimal treatment-related toxicity and high rates of treated tumor control. Prospective studies identifying ideal salvage SBRT candidates for locoregional failure as well as validating its safety are needed.

Using FFF Beams to Improve the Therapeutic Ratio of Lung SBRT.

To investigate the extent to which lung stereotactic body radiotherapy (SBRT) treatment plans can be improved by replacing conventional flattening filter (FF) beams with flattening filter-free (FFF) beams. We selected 15 patients who had received SBRT with conventional 6-MV photon beams for early-stage lung cancer. We imported the patients' treatment plans into the Eclipse 13.6 treatment planning system, in which we configured the AAA dose calculation model using representative beam data for a TrueBeam accelerator operated in 6-MV FFF mode. We then created new treatment plans by replacing the conventional FF beams in the original plans with FFF beams. The FFF plans had better target coverage than the original FF plans did. For the planning target volume, FFF plans significantly improved the D98, D95, D90, homogeneity index, and uncomplicated tumor control probability. In most cases, the doses to organs at risk were lower in FFF plans. FFF plans significantly reduced the mean lung dose, V10, V20, V30, and normal tissue complication probability for the total lung and improved the dosimetric indices for the ipsilateral lung. For most patients, FFF beams achieved lower maximum doses to the esophagus, heart, and the spinal cord; and a lower chest wall V30. Compared with FF beams, FFF beams achieved lower doses to organs at risk, especially the lung, without compromising tumor coverage; in fact, FFF beams improved coverage in most cases. Thus, replacing FF beams with FFF beams can achieve a better therapeutic ratio.

Scatter imaging during lung stereotactic body radiation therapy characterized with phantom studies

By collecting photons scattered out of the therapy beam, scatter imaging creates images of the treated volume. Two phantoms were used to assess the possible application of scatter imaging for markerless tracking of lung tumors during stereotactic body radiation therapy (SBRT) treatment. A scatter-imaging camera was assembled with a CsI flat-panel detector and a 5 mm diameter pinhole collimator. Scatter images were collected during the irradiation of phantoms with megavoltage photons. To assess scatter image quality, spherical phantom lung tumors of 2.1–2.8 cm diameters were placed inside a static, anthropomorphic phantom. To show the efficacy of the technique with a moving target (3 cm diameter), the position of a simulated tumor was tracked in scatter images during sinusoidal motion (15 mm amplitude, 0.25 Hz frequency) in a dynamic lung phantom in open-field, dynamic conformal arc (DCA), and volumetric modulated arc therapy (VMAT) deliveries. Anatomical features are identifiable on static phantom scatter images collected with 10 MU of delivered dose (2.1 cm diameter lung tumor contrast-to-noise ratio of 4.4). The contrast-to-noise ratio increases with tumor size and delivered dose. During dynamic motion, the position of the 3.0 cm diameter lung tumor was identified with a root-mean-square error of 0.8, 1.2, and 2.9 mm for open field (0.3 s frame integration), DCA (0.5 s), and VMAT (0.5 s), respectively. Based on phantom studies, scatter imaging is a potential technique for markerless lung tumor tracking during SBRT without additional imaging dose. Quality scatter images may be collected at low, clinically relevant doses (10 MU). Scatter images are capable of sub-millimeter tracking precision, but modulation decreases accuracy.

Interim Results of a Prospective Prostate-Specific Membrane Antigen-Directed Focal Stereotactic Reirradiation Trial for Locally Recurrent Prostate Cancer

To report the feasibility, toxicity, and preliminary outcomes (metabolic and biochemical) of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-directed focal prostate reirradiation using linear accelerator (LINAC)-based stereotactic body radiation treatment (SBRT). From March 2016 to March 2019, 25 patients were enrolled in a prospective single institution trial (ACTRN12617000035325). Eligibility criteria included patients with biopsy proven isolated prostate recurrence after definitive irradiation, with concordant multiparametric MRI and 68Ga-PSMA PET/CT findings, and a prostate-specific antigen of less than 15 ng/mL at the time of recurrence. The study included a sequential dose escalation component with the first 18 patients receiving 36 Gy in 6 fractions on alternate days with subsequent patients receiving 38 Gy in 6 fractions assuming acceptable toxicity. Median age was 72 years (range, 62-83) with a median time between first radiation treatment and salvage SBRT of 8.3 years (range, 4.5- 13.6). Median prostate-specific antigen at reirradiation was 4.1 (range, 1.1-16.6). The median follow-up was 25 months (range, 13-46). Acute grade 1 and 2 genitourinary (GU) toxicity occurred in 6 (24%) and 1 (4%) men, respectively. Acute grade 1 gastrointestinal (GI) toxicity occurred in 8% with one acute grade 3 GI toxicity (4%) due to a rectal ulcer overlying the hydrogel. Late grade 1 and 2 GU toxicity occurred in 28% and 4%. Late grade 1 GI toxicity occurred in 8% with no grade 2 or greater toxicity. Twenty-four patients have undergone per-protocol 12-month 68Ga-PSMA PET/CT, of which 23 (92%) demonstrated a complete metabolic response. Biochemical freedom from failure was 80% at 2 years with 3 out of 4 of the biochemical failures exhibiting recurrent local disease. PSMA-directed salvage focal reirradiation to the prostate using linear accelerator-based SBRT is feasible and safe. Toxicity was low, with very favorable short term local and biochemical control in a carefully selected cohort of patients.

Assessing the role of Stereotactic Body Radiation Therapy in a large cohort of patients with lymph node oligometastases: Does it affect systemic treatment’s intensification?

Background and purposeLymph nodes (LN) are common site of oligometastases and stereotactic body radiation therapy (SBRT) represents an effective ablative treatment. Aim of this study was to analyze a large cohort of nodal oligometastases treated with SBRT to identify impact on systemic therapy intensification, pattern of recurrence, and predictive factors. Materials and methodsWe included patients with a maximum of 5 oligometastases. Concomitant treatments were allowed. Patients were treated with Volumetric Modulated Arc Therapy (VMAT) and end points were local control of treated metastases (LC), locoregional nodal control (LRNC), distant nodal control (DNC), distant metastases free survival (DMFS), overall survival (OS) and freedom from treatment intensification (FFTI). Results418 LN were treated in 278 patients with 327 SBRT treatments. Patients were more commonly affected by colorectal (20.9%) and prostate cancer (17.99%). Most represented schedule was 45 Gy in 6 fractions, with a median BED10 of 78.75 Gy. After median follow-up of 15.1 months, LC at 1 and 2 years were 87.2% and 76.8%, respectively. Prostate primary tumor, small volume, oligorecurrence, and BED10 ≥75 Gy were associated with higher LC. One and 2 years FFTI were 82.8% and 74.5%; in patients reporting intensification of systemic therapy, median time was 8.43 months, while for patients who repeated SBRT, median FFTI was 14.6 months. Rates of LRNC at 1 and 2 years were 70.9% and 57.6%, and DNC were 82.0% and 77.9%. ConclusionWith the present analysis, we confirmed on a large cohort the benefit from SBRT on lymph node oligometastases in multidisciplinary management. Combination of SBRT with new systemic therapies, including immunotherapy and targeted therapy, should be investigated to reduce the risk of progression out of the field of irradiation.

Preliminary clinical experience with Calypso anchored beacons for tumor tracking in lung SBRT.

To present our preliminary experience with the recently released Calypso lung beacons to track lung tumor location during stereotactic body radiation therapy (SBRT). Five recent lung SBRT patients had Calypso lung beacons implanted for tumor tracking during treatment. Beacons were placed by a pulmonologist using fluoroscopic navigation within 1 week prior to planning four-dimensional computed tomography (4DCT) acquisition. Patients were immobilized in a full-body double-vacuum bag. For the first three patients, a verification 4DCT was obtained prior to the first fraction with the patient in the treatment position to assess both beacon migration and motion of tumor and beacons relative to planning day. For each treatment fraction, Calypso was used to position the patient. A verification cone-beam CT (CBCT) confirmed the Calypso-defined target position was appropriate. Real-time Calypso tracking information was also acquired and compared to an action level that was used to determine if the tumor migrated outside of the planning target volume. For four patients, the implant procedure was well tolerated, with average CBCT-based shifts being within 0.2mm of the shifts reported by Calypso at the time of imaging. The other patient had a small pneumothorax due to very peripheral tumor location and experienced beacon migration. However, the patient quickly recovered from the pneumothorax, and after deactivating that beacon, motion tracking was possible throughout his treatment. All patients were successfully treated with SBRT using the newly released Calypso lung beacons, with initial positioning confirmed by this clinic's current clinical standard of CBCT. The system allowed us to validate, with real-time confirmation, that the planned internal target volumes were appropriate to each day's extent of actual tumor motion. An efficient and effective workflow for utilizing the new lung beacons for SBRT treatments was developed.

On the use of single‐isocenter VMAT plans for SBRT treatment of synchronous multiple lung lesions: Plan quality, treatment efficiency, and early clinical outcomes

Cone‐beam computed tomography (CT)‐guided volumetric‐modulated arc therapy (VMAT) plans for stereotactic body radiotherapy (SBRT) treatment of synchronous multiple lung lesions with a flattening filter‐free (FFF) beam is a safe and highly effective treatment option for oligometastases lung cancer patients. Fourteen patients with metastatic non–small‐cell lung cancer (NSCLC) lesions (two to five) received a single‐isocenter VMAT SBRT treatment in our clinic. Four‐dimensional (4D) CT‐based treatment plans were generated using advanced AcurosXB‐based dose calculation algorithm using heterogeneity corrections with a single isocenter placed between/among the lesions. Compared to 10X‐FFF and traditional flattened 6X (6X‐FF) beams, 6X‐FFF beam produced highly conformal radiosurgical dose distribution to each target volume, reduced dose to adjacent organs at risk (OAR), and significantly reduced the lung SBRT fraction duration to < 3.5 min/fraction for 54/50 Gy treatments in 3/5 fractions — significantly improving patient convenience and clinic workflow. Early follow‐up CT imaging (mean, 9 months) results show high local control rates (100%) with no acute lung or rib toxicity. Longer clinical follow up in a larger patient cohort is ongoing to further validate the outcomes of this treatment approach.

Deep learning for identification of critical regions associated with toxicities after liver stereotactic body radiation therapy.

Radiation therapy (RT) is prescribed for curative and palliative treatment for around 50% of patients with solid tumors. Radiation-induced toxicities of healthy organs accompany many RTs and represent one of the main limiting factors during dose delivery. The existing RT planning solutions generally discard spatial dose distribution information and lose the ability to recognize radiosensitive regions of healthy organs potentially linked to toxicity manifestation. This study proposes a universal deep learning-based algorithm for recognitions of consistent dose patterns and generation of toxicity risk maps for the abdominal area. We investigated whether convolutional neural networks (CNNs) can automatically associate abdominal computed tomography (CT) images and RT dose plans with post-RT toxicities without being provided segmentation of abdominal organs. The CNNs were also applied to study RT plans, where doses at specific anatomical regions were reduced/increased, with the aim to pinpoint critical regions sparing of which significantly reduces toxicity risks. The obtained risk maps were computed for individual anatomical regions inside the liver and statistically compared to the existing clinical studies. A database of 122 liver stereotactic body RT (SBRT) executed at Stanford Hospital from July 2004 and November 2015 was assembled. All patients treated for primary liver cancer, mainly hepatocellular carcinoma and cholangiocarcinoma, with complete follow-ups were extracted from the database. The SBRT treatment doses ranged from 26 to 50Gy delivered in 1-5 fractions for primary liver cancer. The patients were followed up for 1-68months depending on the survival time. The CNNs were trained to recognize acute and late grade 3+ biliary stricture/obstruction, hepatic failure or decompensation, hepatobiliary infection, liver function test (LFT) elevation or/and portal vein thrombosis, named for convenience hepatobiliary (HB) toxicities. The toxicity prediction accuracy was of 0.73 measured in terms of the area under the receiving operator characteristic curve. Significantly higher risk scores (P<0.05) of HB toxicity manifestation were associated with irradiation for the hepatobiliary tract in comparison to the risk scores for liver segments I-VIII and portal vein. This observation is in strong agreement with anatomical and clinical expectations. In this work, we proposed and validated a universal deep learning-based solution for the identification of radiosensitive anatomical regions. Without any prior anatomical knowledge, CNNs automatically recognized the importance of hepatobiliary tract sparing during liver SBRT.

Abstract PR05: Radiation-assisted Amplification Sequencing (RAMP-Seq): Evaluating the use of stereotactic body radiation therapy (SBRT) for enriching circulating tumor DNA in liquid biopsies

Abstract Purpose: To determine if the administration of stereotactic body radiation therapy (SBRT) to known tumor masses temporarily elevates levels of circulating tumor DNA (ctDNA) derived from target or distal masses and to identify an optimal period of peak ctDNA enrichment for liquid biopsy. Experimental Design and Procedures: We used deep, whole-exome sequencing (WES) or 100-gene capture with UMI-based error corrected sequencing of cell-free DNA (cfDNA) of individuals undergoing SBRT as standard-of-care (SOC) to determine (a) whether SBRT treatment induces elevated levels of ctDNA in blood plasma as confirmed by biopsy-proven cases, and (b) the optimal window of ctDNA enrichment for sample collection. We collected blood draws every 24-72 hours from each patient prior to and during SBRT treatment (n=20), as well as for two weeks following the final dose (n=3). CfDNA and genomic DNA were isolated from blood plasma and solid tissue biopsies, respectively, and subjected to whole-exome capture and next-generation sequencing with the Illumina HiSeq 2500 platform. Sequencing data were aligned and mutations were called using BWA MEM and Mutect pipelines as previously described (Butler et al., 2019). Genomic DNA extracted from buffy coat was prepared and used as a matched normal in mutation calling. Variant allele frequencies (VAF) of Mutect calls were compared between baseline and post-treatment samples to determine enrichment levels. WES of bulk tumor DNA from pathology-proven cancer patients was used to confirm that the variants identified in the cfDNA sequencing originated in the target tissue. Data Summary: Preliminary data suggest that SBRT induces enrichment of ctDNA in blood plasma by at least 10-fold within 24-96 hours following treatment. When variants identified in separate biopsies of multiple tumors in a single individual were analyzed after SBRT, we found that increases were not uniform among variant clusters, suggesting an abscopal response from nonradiated tumor tissues found elsewhere in the patient. Conclusions: The ability to detect tumor-derived genomic variants in cfDNA has been a major challenge to liquid biopsy applications, particularly in early-stage cancers and recurrence settings. This novel detection strategy, RAMP-Seq, utilizes highly conformational radiation to induce ctDNA enrichment from tumor-cell death, making previously undetectable levels of ctDNA well within the range of standard sequencing and analysis methods. Such an approach has valuable applications from diagnosis of early-stage cancer to genotyping lesions normally inaccessible by a traditional biopsy. Abscopal effects have also been observed, suggesting that induction of ctDNA enrichment by radiating the target lesion can also result in the increase of ctDNA derived from distal lesions. Taken together, these findings offer promising new approaches to both early- and advanced-stage cancer characterization and intervention. This abstract is also being presented as Poster A44. Citation Format: Christopher Boniface, Kathryn Baker, Chris Dieg, Carol Halsey, Ramtin Rahmani, Mark Deffenbach, Charles Thomas, Garth Tormoen, Nima Nabavizadeh, Paul Spellman. Radiation-assisted Amplification Sequencing (RAMP-Seq): Evaluating the use of stereotactic body radiation therapy (SBRT) for enriching circulating tumor DNA in liquid biopsies [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr PR05.

Implementation of advanced radiotherapy technology to improve clinical outcomes in rural NSW.

Availability of advanced radiotherapy technology to treat cancer is limited in regional Australia. At Central West Cancer Care Centre, the utilisation rate of intensity-modulated radiotherapy and volumetric modulated arc therapy was significantly lower compared to other NSW public health services. Stereotactic ablative body radiotherapy treatment was not available at Central West Cancer Care Centre. To increase the intensity-modulated radiotherapy/volumetric modulated arc therapy utilisation rate and to make stereotactic ablative body radiotherapy treatment available through quality improvement projects with multi-disciplinary collaboration. Central West Cancer Care Centre is part of Western NSW Local health District. Central West Cancer Care Centre has two linear accelerators for delivering intensity-modulated radiotherapy, volumetric modulated arc therapy and stereotactic ablative body radiotherapy treatments, and a computed tomography simulator with 4D computed tomography capability. Intensity-modulated radiotherapy/volumetric modulated arc therapy utilisation rate increases to>65% Stereotactic ablative body radiotherapy available to Central West Cancer Care Centre patients STRATEGY FOR CHANGE: A multi-disciplinary active of team radiation oncologists, medical physics specialists and radiation therapists developed an implementation plan for each treatment technique. There was a significant increase in use of advanced techniques. The impact on patients included the following: Fewer side effects and improved control of disease as the advanced techniques directed the dose to the tumour and reduced the radiation dose to organ at risk. Treatment completed sooner than conventional radiotherapy, as the required dose required fewer trips to the hospital. Rural and remote patients were not required to travel to a metropolitan centre to have stereotactic ablative body radiotherapy treatment. Strong commitment from a trained team and a collaborative approach is important for the implementation of advanced technology in regional centres.

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.

ACR–ASTRO Practice Parameter for the Performance of Stereotactic Body Radiation Therapy

To standardize the practice of stereotactic body radiation therapy (SBRT), the American College of Radiology (ACR) and the American Society for Radiation Oncology (ASTRO) cooperatively developed the practice parameter for SBRT. SBRT is a treatment technique that delivers radiation dose to a well-defined extracranial target in 5 fractions or less and usually employs a higher dose per fraction than used in conventional radiation. The ACR-ASTRO Practice Parameter for the Performance of Stereotactic Body Radiation Therapy was revised according to the process described on the ACR website ("The Process for Developing ACR Practice Parameters and Technical Standards," www.acr.org/ClinicalResources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters of the ACR Commission on Radiation Oncology in collaboration with the ASTRO. Both societies then reviewed and approved the document. Given the complexities of SBRT, a separate document was created to develop a technical standard for the medical physics of SBRT (ACR-AAPM Technical Standard for Medical Physics Performance Monitoring of Stereotactic Body Radiation Therapy). Workflow, qualifications and responsibilities of personnel, specifications, documentation, quality control/safety/improvement, simulation/treatment, and follow-up were addressed in this practice parameter. This practice parameter assists practitioners in providing safe and appropriate SBRT treatment and care for patients when clinically indicated. As technologies and techniques continue to evolve, this document will be reviewed, revised and renewed accordingly to a 5 year or sooner timeline specified by the ACR.

Clinical efficacy of Stereotactic Body Radiation Therapy (SBRT) for adrenal gland metastases: A multi-center retrospective study from China

To evaluate the efficacy and safety of CyberKnife Stereotactic Body Radiation Therapy (SBRT) in the treatment of adrenal gland metastases (AGM), we designed a large-scale multicenter retrospective study to report the safety and efficacy of SBRT for inoperable AGM. In this study, 75 (61 males, 14 females) patients with 84 AGM and Karnofsky performance score ≥70 were treated by SBRT from October 2006 to January 2017. Of these, the purpose of treatment were controlling all known metastatic sites for 21 patients while 54 for palliation of bulky adrenal metastases. The efficacy and safety of SBRT were evaluated during follow-up. Potential factors predictive of local control (LC) and overall survival (OS) were identified by univariate and multivariate analysis. Median follow-up time was 12.7 months (range 1.8–96.4). The complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) rates were 23.8%, 23.8%, 31.0% and 21.4%, respectively. The 0.5, 1, and 2-year LC rates were 93.6%, 83.8%, and 62.1%, respectively; OS rates on the same follow-up intervals were 93.7%, 62.5%, and 49.6%, respectively, and the corresponding PFS rates were 48.5%, 33.9%, and 16.0%, respectively. The treatment was well tolerated with 2 patients reporting grade-3 diarrhea and fatigue, respectively. Multivariate analysis showed that simultaneous treatment of SBRT for other metastatic lesions, the number of AGM, initiation of systemic therapy, and the maximum diameter of AGM were predictive of LC rates. Moreover, patients with AGM < 5 cm had a superior OS compared with those with AGM ≥ 5 cm (28.0 months vs. 17.6 months, P = 0.032). SBRT is an effective therapeutic option for treatment of AGM with high LC rates with minimal toxicity.

Radiation-Induced Immunity in Kidney Cancer Patients: Seq-ing Commonality Between Peripheral and Intratumoral T cell Repertoires

Abstract Radiation has long been part of the standard of care for cancer treatment. Clinical studies combining immunotherapy with radiation have shown promising response rates implicating radiotherapy as an inducer of tumor immunity. Due to the scarcity of human samples treated in situ with radiation, exploration of this phenomenon has been largely limited to murine models. While these data draw connections between intratumoral immune responses and wider effects in peripheral blood, advances in patient care are restricted by inherent differences between murine models and human disease. Therefore, to identify commonality between local intratumoral and systemic responses to radiation, we analyzed clinical trial samples from renal cell carcinoma (RCC) patients treated with stereotactic body radiation therapy (SBRT) at the primary tumor. With access to patient tumors and peripheral blood, we hypothesized that SBRT initiates local and systemic anti-tumor immunity. Pathway analysis from tumor RNAseq data showed SBRT-specific immune processes: TCR activation, increased costimulation, and chemokine signaling. Deeper examination through single cell RNA sequencing identified the sources of these signals. In parallel, analysis by T cell receptor sequencing (TCRseq) showed increased tumor T cell clonality with SBRT treatment. TCRseq of serial blood samples revealed tumor-enriched T cell clonotypes reaching peak abundance 2 weeks post-SBRT. This expansion was not sustained and contracted towards baseline levels 4 weeks after SBRT. Collectively, these results indicate a critical interval following radiation, wherein tumor-enriched T cell clones are expanded in circulation, that could be utilized to bolster responses to immunotherapy.

Stereotactic body radiation therapy (SBRT) in a developing country: Patterns of failure and response rates.

e21010 Background: Surgery remains the treatment of choice for early stage lung cancer. For patients without clinical conditions or those who refuse to this procedure, Stereotactic Body Radiation Therapy (SBRT) is the treatment of choice. It is important to understand the patterns of treatment response and toxicities within this practice. Therefore, we aim to analyze and review our data on lung SBRT for Non-Small Cell Lung Cancer (NSCLC) treated in our institution. Purpose: To describe response and toxicity patterns for NSCLC treatment with SBRT in a single third world country private institution. Methods: We retrospectively collected and analyzed data from patients treated at a single private institution in Rio de Janeiro between January 2017 and May 2019. Inclusion criteria were histopathological diagnosis of NSCLC, 18 years old or older, SBRT treatment, who were closely followed-up according to international guidelines. All data was analyzed and reviewed by the radiation oncologist and medical oncologist responsible, as well as kept in a reliable way for future comparisons. Results: 121 patients were analyzed. 77 were excluded. Only patients diagnosed with NSCLC from 2017 to 2019 who received SBRT as primary treatment. The average age was 74 (56-94). The highest prevalence among patients were females 68% (n = 30). 26 patients were smokers (59%), 4 non-smokers (9%) and 14 patients were not recorded in the medical records. Molecular assessment for non-smokers will not be described in this study. Adenocarcinoma was the most common subtype (77%, n = 35), 15% were squamous cell carcinoma subtype (n = 7), 4.4% poorly differentiated (n = 2). The patients were distributed between early stage lung cancer and metastatic disease - foreseeing oligometastatic disease being continuously treated as potentially curable. 11 patients are not classified in the medical record. Twelve patients had metastasis: central nervous system (33%), lung (41%), bone (8.3%) and patients with more than two metastases 16.6% (bone and CNS, bone and lung). Eleven patients had adjuvant chemotherapy (QT) 25%. Ten of the patients (22%) had toxicities, all with different doses and SBRT fractions. Among them, cough was the most prevalent (40%); nausea / vomiting and rash accounted for 30%; pneumonitis accounted for 17%; and mucositis in 10% of patients. Of the 44 patients, 7 died. Conclusions: The study data corroborates the worldwide published literature. SBRT in treating early stage lung cancer is a safe and effective treatment modality, with acceptable low-grade toxicities and high response rates.

The effect of stereotactic body radiotherapy (SBRT) using flattening filter-free beams on cardiac implantable electronic devices (CIEDs) in clinical situations.

PurposeThis study focused on determining risks from stereotactic radiotherapy using flattening filter‐free (FFF) beams for patients with cardiac implantable electronic device (CIEDs). Two strategies were employed: a) a retrospective analysis of patients with CIEDs who underwent stereotactic radiosurgery (SRS)/SBRT at the Peter MacCallum Cancer Centre between 2014 and 2018 and b) an experimental study on the impact of FFF beams on CIEDs.MethodsA retrospective review was performed. Subsequently, a phantom study was performed using 30 fully functional explanted CIEDs from two different manufacturers. Irradiation was carried out in a slab phantom with 6‐MV and 10‐MV FFF beams. First, a repetition‐rate test (RRT) with a range of beam pulse frequencies was conducted. Then, multifraction SBRT (48 Gy/4 Fx) and single‐fraction SBRT (28 Gy/1 Fx) treatment plans were used for lung tumors delivered to the phantom.ResultsBetween 2014 and 2018, 13 cases were treated with an FFF beam (6 MV, 1400 MU/min or 10 MV, 2400 MU/min), and 15 cases were treated with a flattening filter (FF) beam (6 MV, 600 MU/min). All the devices were positioned outside the treatment field at a distance of more than 5 cm, except for one case, and no failures were reported due to SBRT/SRS. In the phantom rep‐rate tests, inappropriate sensing occurred, starting at a rep‐rate of 1200 MU/min. Cardiac implantable electronic device anomalies during and after delivering VMAT‐SBRT with a 10‐MV FFF beam were observed.ConclusionsThe study showed that caution should be paid to managing CIED patients when they undergo SBRT using FFF beams, as it is recommended by AAPM TG‐203. Correspondingly, it was found that for FFF beams although there is small risk from dose‐rate effects, delivering high dose of radiation with beam energy greater than 6 MV and high‐dose rate to CIEDs positioned in close vicinity of the PTV may present issues.

A simple, yet novel hybrid-dynamic conformal arc therapy planning via flattening filter-free beam for lung stereotactic body radiotherapy.

PurposeDue to multiple beamlets in the delivery of highly modulated volumetric arc therapy (VMAT) plans, dose delivery uncertainties associated with small‐field dosimetry and interplay effects can be concerns in the treatment of mobile lung lesions using a single‐dose of stereotactic body radiotherapy (SBRT). Herein, we describe and compare a simple, yet clinically useful, hybrid 3D‐dynamic conformal arc (h‐DCA) planning technique using flattening filter‐free (FFF) beams to minimize these effects.Materials and MethodsFifteen consecutive solitary early‐stage I‐II non‐small‐cell lung cancer (NSCLC) patients who underwent a single‐dose of 30 Gy using 3–6 non‐coplanar VMAT arcs with 6X‐FFF beams in our clinic. These patients’ plans were re‐planned using a non‐coplanar hybrid technique with 2–3 differentially‐weighted partial dynamic conformal arcs (DCA) plus 4–6 static beams. About 60–70% of the total beam weight was given to the DCA and the rest was distributed among the static beams to maximize the tumor coverage and spare the organs‐at‐risk (OAR). The clinical VMAT and h‐DCA plans were compared via RTOG‐0915 protocol for conformity and dose to OAR. Additionally, delivery efficiency, accuracy, and overall h‐DCA planning time were recorded.ResultsAll plans met RTOG‐0915 requirements. Comparison with clinical VMAT plans h‐DAC gave better target coverage with a higher dose to the tumor and exhibited statistically insignificance differences in gradient index, D2cm, gradient distance and OAR doses with the exception of maximal dose to skin (P = 0.015). For h‐DCA plans, higher values of tumor heterogeneity and tumor maximum, minimum and mean doses were observed and were 10%, 2.8, 1.0, and 2.0 Gy, on average, respectively, compared to the clinical VMAT plans. Average beam on time was reduced by a factor of 1.51. Overall treatment planning time for h‐DCA was about an hour.ConclusionDue to no beam modulation through the target, h‐DCA plans avoid small‐field dosimetry and MLC interplay effects and resulting in enhanced target coverage by improving tumor dose (characteristic of FFF‐beam). The h‐DCA simplifies treatment planning and beam on time significantly compared to clinical VMAT plans. Additionally, h‐DCA allows for the real time target verification and eliminates patient‐specific VMAT quality assurance; potentially offering cost‐effective, same or next day SBRT treatments. Moreover, this technique can be easily adopted to other disease sites and small clinics with less extensive physics or machine support.

Use of surface-guided radiation therapy in combination with IGRT for setup and intrafraction motion monitoring during stereotactic body radiation therapy treatments of the lung and abdomen.

Background and purposeMultiple techniques can be used to assist with more accurate patient setup and monitoring during Stereotactic body radiation therapy (SBRT) treatment. This study analyzes the accuracy of 3D surface mapping with Surface‐guided radiation therapy (SGRT) in detecting interfraction setup error and intrafraction motion during SBRT treatments of the lung and abdomen.Materials and MethodsSeventy‐one patients with 85 malignant thoracic or abdominal tumors treated with SBRT were analyzed. For initial patient setup, an alternating scheme of kV/kV imaging or SGRT was followed by cone beam computed tomography (CBCT) for more accurate tumor volumetric localization. The CBCT six degree shifts after initial setup with each method were recorded to assess interfraction setup error. Patients were then monitored continuously with SGRT during treatment. If an intrafractional shift in any direction >2 mm for longer than 2 sec was detected by SGRT, then CBCT was repeated and the recorded deltas were compared to those detected by SGRT.ResultsInterfractional shifts after SGRT setup and CBCT were small in all directions with mean values of <5 mm and < 0.5 degrees in all directions. Additionally, 25 patients had detected intrafraction motion by SGRT during a total of 34 fractions. This resulted in 25 (73.5%) additional shifts of at least 2 mm on subsequent CBCT. When comparing the average vector detected shift by SGRT to the resulting vector shift on subsequent CBCT, no significant difference was found between the two.ConclusionsSurface‐guided radiation therapy provides initial setup within 5 mm for patients treated with SBRT and can be used in place of skin marks or planar kV imaging prior to CBCT. In addition, continuous monitoring with SGRT during treatment was valuable in detecting potentially clinically meaningful intrafraction motion and was comparable in magnitude to shifts from additional CBCT scans. PTV margin reduction may be feasible for SBRT in the lung and abdomen when using SGRT for continuous patient monitoring during treatment.