Fiducial Placement Research Articles

Technical Note: Angiographic Trans-Arterial Guided Gold Fiducial Placement for Tumor Tracking in Cyber Knife-Based Stereotactic Radiotherapy for Lung Lesions.

Technical Note: Angiographic Trans-Arterial Guided Gold Fiducial Placement for Tumor Tracking in Cyber Knife-Based Stereotactic Radiotherapy for Lung Lesions.

Safety And Efficacy Of Short-Course Preoperative Stereotactic Body Radiation Therapy For Resectable Pancreatic Cancer: A Prospective Clinical Trial

Resected adenocarcinoma of the pancreatic head has a high risk of locoregional relapse. Adjuvant chemotherapy has become standard of care while the benefit of radiotherapy is still debated. In a prospective clinical trial, we investigated the safety and efficacy of preoperative SBRT in patients with resectable adenocarcinoma of the pancreatic head. A single institution IRB approved pilot study was conducted. Eligible patients had a histologic diagnosis of pancreatic head adenocarcinoma. Patients were determined to be resectable following consultation with hepatobiliary surgery and based on NCCN guidelines. Patients underwent CT simulation with stereotactic s-ray body markers and gold fiducial placement as clinically warranted. A dose of 25 Gy in 5 fractions was prescribed to the PTV which included the gross tumor plus margin of 3-5mm. Patients underwent pancreaticoduodenectomy 1-3 weeks following completion of SBRT. Adjuvant treatment was delivered per medical oncology. Our primary objective was to evaluate the feasibility of preop SBRT and assess the rate of acute radiation toxicity and impact on surgical complication rate. Data from trial patients were compared with institutional historical controls who underwent pancreaticoduodenectomy alone during the same time frame. Wilcoxon Rank Sum test was used for continuous data and Fisher exact test for categorical data. Eighteen patients were enrolled between March 2015 and May 2018. Thirteen patients completed SBRT and underwent surgery. Three patients underwent SBRT but did not undergo pancreaticoduodenectomy due to locally extensive or metastatic disease found at surgery. One patient underwent SBRT then was found on imaging to have suspicious lung lesions and did not undergo surgery. One patient was enrolled but did not receive SBRT due to lung lesions found on screening imaging. SBRT was well tolerated with only 1 case of grade 2 toxicity. For resected patients, a median of 7 days elapsed between end of SBRT and surgery (range 3-20). Surgery was not delayed in any patient due to SBRT. See table 1 for surgical details. Five of ten patients analyzed had significant treatment response (TRG Grade 2) noted on pathology. Preoperative SBRT for resectable pancreatic cancer appears to be feasible and safe. While there was an increased rate of fibrosis noted during surgery, this did not appear to lengthen operating time, hospital stay or result in more complications. Additional follow up is needed for evaluating oncologic outcomes.Abstract 1191; Table 1Preop SBRT N=13Surgery Only N=21p valueMedian Operating Time330 min356 min0.86Median Blood Loss200 cc200 cc0.40Median Hospital Stay6100.08Increased Fibrosis8 of 13 patients2 of 21 patients0.002Major Complications1 of 13 patients2 of 21 patients1.00R0 Resection8 of 13 patients16 of 21 patients0.45 Open table in a new tab

Stereotactic body radiotherapy with periprostatic hydrogel spacer for localized prostate cancer: toxicity profile and early oncologic outcomes

BackgroundMultiple phase I-II clinical trials have reported on the efficacy and safety of prostate stereotactic body radiotherapy (SBRT) for the treatment of prostate cancer. However, few have reported outcomes for prostate SBRT using periprostatic hydrogel spacer (SpaceOAR; Augmenix). Herein, we report safety and efficacy outcomes from our institutional prostate SBRT experience with SpaceOAR placement.MethodsFifty men with low- or intermediate-risk prostate cancer treated at a single institution with linear accelerator-based SBRT to 3625 cGy in 5 fractions, with or without androgen deprivation therapy (ADT) were included. All patients underwent SpaceOAR and fiducial marker placement followed by pre-treatment MRI. Toxicity assessments were conducted at least weekly while on treatment, 1 month after treatment, and every follow-up visit thereafter. Post-treatment PSA measurements were obtained 4 months after SBRT, followed by every 3–6 months thereafter. Acute toxicity was documented per RTOG criteria.ResultsMedian follow up time was 20 (range 4–44) months. Median PSA at time of diagnosis was 7.4 (2.7–19.5) ng/ml. Eighteen men received 6 months of ADT for unfavorable intermediate risk disease. No PSA failures were recorded. Median PSA was 0.9 ng/mL at 20 months; 0.08 and 1.32 ng/mL in men who did and did not receive ADT, respectively. Mean prostate-rectum separation achieved with SpaceOAR was 9.6 ± 4 mm at the prostate midgland.No grade ≥ 3 GU or GI toxicity was recorded. During treatment, 30% of men developed new grade 2 GU toxicity (urgency or dysuria). These symptoms were present in 30% of men at 1 month and in 12% of men at 1 year post-treatment. During treatment, GI toxicity was limited to grade 1 symptoms (16%), although 4% of men developed grade 2 symptoms during the first 4 weeks after SBRT. All GI symptoms were resolving by the 1 month post-treatment assessment and no acute or late rectal toxicity was reported > 1 month after treatment.ConclusionsPeriprostatic hydrogel placement followed by prostate SBRT resulted in minimal GI toxicity, and favorable early oncologic outcomes. These results indicate that SBRT with periprostatic spacer is a well-tolerated, safe, and convenient treatment option for localized prostate cancer.

Evaluation of the feasibility of intrapancreatic delivery of drug-loaded microparticles via EUS-guided fine needle injection using a swine model.

Background and study aims Patients with pancreatic cancer often have locally advanced or metastatic disease and are not candidates for curative surgery. Polymer-based microparticles (MPs) represent a drug delivery system that offers sustained release of a chemotherapeutic drug after intralesional injection for local tumor management. The aim of this study was to determine the feasibility of endoscopic ultrasound-guided fine-needle injection (EUS-FNI) of drug-loaded MPs tagged with a fluorophore and fiducial markers for locating the injection site. Secondary aims were to determine the tissue-specific effects of MPs. Methods Five pigs underwent EUS with selection of an injection site within the pancreas that was marked by placing fiducial markers prior to the MPs injection. EUS-FNI of either blank microparticles (BMPs), containing no drug, or gemcitabine-loaded microparticles (GMPs) was performed. A saline flush containing Spot Endoscopic Marker was used to expel any residual MPs in the needle shaft and tattoo the injection site. Results A green fluorescent protein flashlight was used to successfully identify the site of MP injection sites in the dissected pancreas. Frozen sections of pig pancreas demonstrated a defined deposit, confirming the delivery of the MPs. Finally, fluorescence microscopy showed activation of caspase-mediated cell death in pancreases of animals that received injections of GMPs. Conclusions This pilot study demonstrated that fiducial marker placement and pancreatic EUS-FNI of MPs was successful in all pigs with no animals demonstrating pancreatitis. Further studies are needed to determine the role for intralesional injection of drug-loaded MPs in borderline resectable or unresectable pancreatic cancer.

A Phase I/II Trial of Fairly Brief Androgen Suppression and Stereotactic Radiation Therapy for High-Risk Prostate Cancer (FASTR-2): Preliminary Results and Toxicity Analysis

PurposeFASTR was designed to provide a compact treatment course for high-risk prostate cancer patients but was discontinued because of excess toxicity. We present the results of FASTR-2, which used a lower dose to the prostate (35 Gy vs 40 Gy), smaller posterior PTV margin (4 mm vs 5 mm) and omitted nodal radiation to lower the volumes of rectum receiving high and intermediate doses compared with FASTR. Gastrointestinal (GI) and genitourinary (GU) toxicities at baseline, 6 weeks, 6 months, and 1 year and biochemical control rates are presented. Methods and MaterialsEligibility included high-risk prostate cancer (cT3/4, prostate-specific antigen >20 or Gleason Score ≥8), age ≥70 or refused standard treatment, and no evidence of metastatic disease. Patients received 18 months of androgen deprivation therapy starting 2 months before radiation. Clinical target volume was defined as prostate plus proximal 1-cm seminal vesicles. PTV was a nonuniform expansion around clinical target volume (4 mm posteriorly, 5 mm in all other directions). Volumetric arc therapy was used for treatment delivery (35 Gy delivered in 5 weekly fractions of 7 Gy each), and cone beam computed tomography with soft tissue matching (no fiducial placement) was used for daily image guidance. Toxicity was assessed at 6 weeks, 6 months, and 1 year according to Common Toxicity Criteria. ResultsIn the study, 30 patients were enrolled in FASTR-2 between 2015 and 2017. Two patients were withdrawn owing to ineligibility after enrollment. One patient (3.7%) reported grade 2 GI toxicity at 6 weeks. There was no reported grade ≥2 GI toxicity at 6 months or 1 year. There were no reported episodes of rectal bleeding. Four patients (14.8%), 5 patients (17.9%), and 5 patients (21.7%) reported grade 2 GU toxicity at 6 weeks, 6 months, and 1 year, respectively. There were no reported cases of grade ≥3 GU toxicity. The most common toxicities were nocturia and urinary frequency or urgency. ConclusionsFASTR-2 was more tolerable than FASTR, with no grade ≥3 toxicities reported, in keeping with expectations based on our previous FASTR analysis. Long-term follow-up is necessary to ensure disease control and toxicity outcomes are comparable to conventional high-risk treatment paradigms.

Improved respiratory motion tracking through a novel fiducial marker placement guidance system during electromagnetic navigational bronchoscopy (ENB)

BackgroundStereotactic ablative radiotherapy (SABR) is a treatment option for patients with early stage non-small cell lung cancer (NSCLC) and recurrent or oligometastatic disease who are not surgical candidates. Due to the continuous motion of tumors within the lungs, implementing a strategy to track the target lesion is crucial. One method is to place fiducial markers which the robotic SABR system is able to track during treatment. However, placing these markers in a manner that maximizes tracking efficacy can be challenging. Using a novel fiducial placement guidance system (FPGS) during fiducial deployment may offer a way to improve the quantity of fiducials tracked by the robotic SABR system.MethodThis was an institutional, retrospective review identifying all patients who received robotic SABR for lung tumors from May 2015 until January 2017. The FPGS was instituted in May 2016. The median number of fiducials tracked and the rate of complication was compared between patients whose fiducials were placed using FPGS versus those that were not.ResultsA total of 128 patients with 147 treated lung lesions were identified. Of the lesions that utilized FPGS (n = 44), 28 had 2 tracked fiducials (63.6%), 14 had 3 (31.8%) and 2 had 4 (4.6%). Of the lesions treated without FPGS (n = 103), 5 had 1 tracked fiducial (4.9%), 91 had 2 (88.4%), 6 had 3 (5.8%), and 2 had 4 (1.9%). A significant improvement in the median number of fiducials tracked per fraction was observed for the lesions with fiducials placed using FPGS on Wilcoxon rank sum test (p < 0.001). The rate of complication was low and not statistically different between cohorts (p = 0.44).ConclusionsThe FPGS can be used during the deployment of fiducial markers and may increase the number of fiducials tracked.Trial registrationAn exemption for this retrospective review was granted by the East Carolina University IRB under UMCIRB 15-001726.

Electromagnetic Transponder Based Tracking and Gating in the Radiotherapeutic Treatment of Thoracic Malignancies

PurposeThis report details our institutional workflow and technique for use of the Calypso electromagnetic transponder system with respiratory gating for localization and tracking of lung tumors during stereotactic radiation therapy for early stage thoracic malignancies. Methods and MaterialsSixteen patients underwent bronchoscopic fiducial placement of 3 transponders in small airways in proximity to the primary tumor. Transponders were placed <19 cm from the most anterior skin location of the patient for appropriate tracking functionality. Patients underwent simulation with 4-dimensional assessment and were treated with transponder based positional gating if tumors moved >5 mm in any direction. Tumor motion <5 mm was not gated and treated using an internal target volume approach. A 5 mm uniform planning target volume was used. Before treatment, fiducial placement and tumor location were verified by daily kilovoltage (kV) and cone beam computed tomography image guidance. Tracking limits were placed based on the movement of the transponders from the centroid of the structures on the maximum intensity projection image. The Calypso treatment system paused treatment automatically if beacons shifted beyond the predefined tracking limits. ResultsAll 16 patients underwent successful implantation of the electromagnetic transponders. Eight patients exhibited tumor motion sufficient to require respiratory gating, and the other 8 patients were treated using a free breathing internal target volume technique. Difficulty with transponder sensing was experienced in 3 patients as a result of anatomic interference with the placement of the sensing arrays; each of these cases was successfully treated after making setup modifications. Triggered imaging of fiducials during treatment was consistent with real-time positioning determined by the Calypso tracking system. ConclusionsRespiratory gated electromagnetic based transponder guided stereotactic body radiation therapy using the workflow described is feasible and well tolerated in selected patients with early stage lung malignancies.

Abstract CT164: A Phase II clinical trial of GVAX pancreas vaccine (with Cyclophosphamide) in combination with Nivolumab and Stereotactic Body Radiation Therapy (SBRT) followed by definitive resection for patients with borderline resectable pancreatic adenocarcinoma (BR-PDAC)

Abstract Background: A strong rationale exists for the use of preoperative therapy in BR-PDAC, because upfront surgery in these patients results in a high probability of incomplete resection. Recently, the Alliance A021101 trial, which utilized neoadjuvant FOLFIRINOX and chemoradiation, demonstrated the safety and clinical activity of neoadjuvant therapy in BR-PDAC. The present clinical trial will evaluate the safety and clinical activity of neoadjuvant Stereotactic Body Radiation Therapy (SBRT) in combination with neoadjuvant cyclophosphamide (Cy)/GVAX pancreas vaccine/nivolumab immunotherapy after completion of standard chemotherapy in patients with BR- PDAC. GVAX is an allogeneic, whole-cell, GM-CSF-secreting vaccine that induces T-cell immunity against tumor-associated antigens. GVAX has previously been studied in combination with low-dose Cy to inhibit regulatory T cells. In prior studies, neoadjuvant Cy/GVAX induced high levels of PD-L1 expression and the formation of novel vaccine-induced, immunologically active, tertiary lymphoid aggregates. Methods: In this multi-center, open label, phase II clinical trial, patients with BR-PDAC will receive a total of four 28-day cycles of FOLFIRINOX. Subsequently they will undergo EUS-guided fiducial placement along with SBRT simulation and core biopsy. Within 2-6 weeks after chemotherapy, patients will receive their first dose of combination immunotherapy, consisting of Cy 200 mg/m2 IV and nivolumab 240mg IV on day 1 followed by 5 x 108 GVAX vaccine cells, administered as six intradermal injections, on day 2. Approximately three weeks later, patients will receive their second dose of combined immunotherapy on the same day as initiation of SBRT (6.6 Gy x 5 days). Following completion of immunotherapy and SBRT, patients will undergo repeat imaging, surgical re-evaluation and if resectable, proceed to definitive surgical resection. This study will recruit 50 patients to achieve 45 evaluable patients receiving immunotherapy. The primary endpoint is pCR rate. Secondary endpoints include: rate of R0 resections, ORR, OS, distant metastasis free survival, adverse events (graded by NCI CTCAE). Additionally, exploratory objectives include evaluating: 1. intratumoral immune infiltrates in pre- and post-treatment biopsy specimens utilizing immunohistochemistry and transcriptional analysis, 2. circulating biomarkers including plasma tumor DNA and circulating tumor cells. Key inclusion criteria for this study include: having BR- PDAC, no more than 1 month or 1 cycle (28 days) of systemic therapy for PDAC, and ECOG performance status of ≤ 1. This clinical trial is open, actively recruiting and is supported by BMS and the Skip Viragh Foundation. Clinical trial information: NCT03161379. Citation Format: Arsen Osipov, Elizabeth Sugar, Anna Ferguson, Jennifer Durham, Christina Rodriguez, Rose Parkinson, Laura Sena, Lei Zheng, Christopher Wolfgang, Richard Burkhart, Jin He, Matthew Weiss, Amol Narang, Daniel Laheru, Nilofer Azad, Elizabeth Jaffee, Colin Weekes, Mark Yarchoan. A Phase II clinical trial of GVAX pancreas vaccine (with Cyclophosphamide) in combination with Nivolumab and Stereotactic Body Radiation Therapy (SBRT) followed by definitive resection for patients with borderline resectable pancreatic adenocarcinoma (BR-PDAC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT164.

Role of Convex Probe Endobronchial Ultrasound in the Diagnosis and Treatment of Nonmalignant Diseases.

Here we present a comprehensive review of the literature concerning the utility of convex probe endobronchial ultrasound (CP-EBUS) in the diagnosis and treatment of nonmalignant conditions and discuss the associated complications. CP-EBUS has been conventionally used for the staging of lung cancer and sampling of mediastinal and hilar nodes. However, its application is not limited to malignant conditions, and it is gaining acceptance as a diagnostic modality of choice for nonmalignant conditions such as tuberculosis, sarcoidosis, pulmonary embolism, thyroid lesions, and cysts. Moreover, its therapeutic value allows for extended applications such as mediastinal and thyroid cyst drainage, fiducial marker placement for radiation therapy, and transbronchial needle injection. The noninvasiveness, low complication rate, high diagnostic yield, and satisfactory sensitivity and specificity values are the main attributes that lend credence to the use of CP-EBUS as a standalone primary diagnostic and therapeutic tool in pulmonary medicine in the foreseeable future.

Stereotactic prostate focal reirradiation therapy for local recurrence: preliminary results of Hartmann Oncology Radiotherapy Group.

Objective:Our objective was to report our experience and to evaluate the feasibility and toxicity of focal salvage stereotactic body radiation therapy (SBRT) in patients with post-radiation local recurrence of prostate cancer.Methods:We retrospectively reviewed medical records of patients treated with Cyberknife ® between October 2014 and April 2017 at our institution for a focal reirradiation delivered to the prostate/prostatic bed for local recurrence after radical or adjuvant radiotherapy. All patients underwent prostate biopsies at recurrence at the time of fiducial markers placement, had choline PET/CT and pelvic MRI. The treatment consisted in 36 Gy in six fractions delivered every other day. Post reirradiation toxicities were assessed according to the CTCAE v4 (Common Terminology Criteria for Adverse Events).Results:42 patients were treated with followed with a median follow-up of 21 months (range 3 – 31). 34 patients had biopsy proven recurrence. The initial treatment was radical prostatectomy and radiation therapy for 9 patients and radiation therapy alone for 33 patients. 23 patients from the group of prostate reirradiation had placement of rectal spacers. No Grade 4 or 5 toxicity were observed. 27 acute urinary events were recorded: 18 patients experienced Grade 1, 9 patients experienced Grade 2 toxicity and 1 patient experienced Grade 3 urinary toxicity, namely cystitis and/or dysuria. No Grade 2 or more digestive toxicity was observed. Rectal doses were significantly lower with rectal spacers.Conclusion:Salvage focal Cyberknife ® seems feasible and show promising results.Advances in knowledge:SBRT for local prostate cancer recurrence after initial radiotherapy is well tolerated with short follow-up.

Su1173 EUS-GUIDED FIDUCIAL PLACEMENT WITH STEREOTACTIC RADIOTHERAPY COMPARED TO CONVENTIONAL RADIOTHERAPY FOR ESOPHAGEAL CANCER: X MARKS THE SPOT!

In patients with esophageal cancer (EC) receiving radiation therapy (RT), target volumes are established to facilitate effective therapy while minimizing radiation injury to normal tissue. Delineation of target volume at RT planning CT scan can be challenging in EC cases due to inflammation, edema and food/debris in a collapsed lumen. Endoscopic Ultrasound (EUS) guided gold fiducial placement in EC allows precise lesion targeting, with an aim to improve treatment accuracy using Image Guided Radiation Therapy (IGRT); however, data on this are limited.

Image Annotation by Eye Tracking: Accuracy and Precision of Centerlines of Obstructed Small-Bowel Segments Placed Using Eye Trackers.

Small-bowel obstruction (SBO) is a common and important disease, for which machine learning tools have yet to be developed. Image annotation is a critical first step for development of such tools. This study assesses whether image annotation by eye tracking is sufficiently accurate and precise to serve as a first step in the development of machine learning tools for detection of SBO on CT. Seven subjects diagnosed with SBO by CT were included in the study. For each subject, an obstructed segment of bowel was chosen. Three observers annotated the centerline of the segment by manual fiducial placement and by visual fiducial placement using a Tobii 4c eye tracker. Each annotation was repeated three times. The distance between centerlines was calculated after alignment using dynamic time warping (DTW) and statistically compared to clinical thresholds for diagnosis of SBO. Intra-observer DTW distance between manual and visual centerlines was calculated as a measure of accuracy. These distances were 1.1 ± 0.2, 1.3 ± 0.4, and 1.8 ± 0.2 cm for the three observers and were less than 1.5 cm for two of three observers (P < 0.01). Intra- and inter-observer DTW distances between centerlines placed with each method were calculated as measures of precision. These distances were 0.6 ± 0.1 and 0.8 ± 0.2 cm for manual centerlines, 1.1 ± 0.4 and 1.9 ± 0.6 cm for visual centerlines, and were less than 3.0 cm in all cases (P < 0.01). Results suggest that eye tracking-based annotation is sufficiently accurate and precise for small-bowel centerline annotation for use in machine learning-based applications.

Development and Implementation of a Simulation-Based Educational Workshop on Gynecological Brachytherapy: Pilot Study at a National Meeting

PurposeDespite the importance of brachytherapy in the curative treatment of locally advanced cervical cancer, reviews of practice patterns in the United States have identified a decline in brachytherapy use in clinically appropriate patient populations. A survey of radiation oncologists identified lack of time and lack of guidance as barriers. To address these barriers, the purpose of this study was to develop a simulation-based educational (SBE) gynecologic brachytherapy workshop. Methods and materialsThe SBE gynecologic brachytherapy workshop was developed with expertise from 2 institutions, combining procedural simulation with a practical discussion of brachytherapy applicator insertion techniques. The primary outcome was feasibility of workshop deployment, defined as completion of all workshop components in the time allotted. Preworkshop and postworkshop surveys were also administered to assess efficacy, a secondary outcome. ResultsThe workshop took place at a national radiation oncology meeting, and all workshop components were completed in the 2 hours allotted. SBE stations focused on (1) fiducial placement, (2-3) applicator selection, (4) suturing, and (5) pelvic examination and applicator placement. Fourteen participants completed surveys. Respondents included residents and attending physicians. More than 50% of respondents were from academic practices and practiced gynecologic brachytherapy weekly or more. Curricular objectives for this workshop were for ≥20% trainees to report increased confidence in practice and ≥20% of trainees to report increased familiarity with applicators. After participation in the workshop, confidence in applicator choice improved in 9 of 13 participants (69%), confidence in complication management improved in 8 of 13 participants (62%), and familiarity with applicators improved in 7 of 13 participants (54%). These differences were statistically significant at α = .05. ConclusionsThis study demonstrated feasibility in using simulation for gynecologic brachytherapy education at a national meeting. Although most respondents were experienced in brachytherapy, more than half reported increased confidence and familiarity with aspects of the procedure after the workshop. Future work should address interstitial needle placement and improved time management of workshop stations.

Phase II multi-institutional study of nivolumab (Nivo), cabiralizumab (Cabira), and stereotactic body radiotherapy (SBRT) for locally advanced unresectable pancreatic cancer (LAUPC).

TPS4163 Background: Treatment of LAUPC most commonly involves chemotherapy +/- RT. Patients(pts) who can be downstaged and undergo R0 resection have significant improvement in overall survival, but conventional chemoRT converts &lt; 10% of patients with LAUPC. If the effects of RT can be augmented then higher R0 resection rates may be achieved and improve survival. In pre-clinical models, RT leads to increased expression of M-CSF from pancreatic tumor cells and marked immune suppression within the tumor microenvironment via expansion of tumor associated macrophages (TAMs). Concurrent blockade of M-CSF with RT reduces TAM infiltration, prevents the generation of tumor promoting T cell populations, and increases the therapeutic effect of RT. RT also induces up-regulation of PD-L1 in TAMs, another mode of immune suppression that can account for RT resistance in LAUPC. (Seifert et al. 2016). These data suggest the efficacy of RT in LAUPC is limited by its promotion of innate and adaptive immune suppression. CSF1R blockade with Cabira combined with PD-1 blockade with Nivo may enhance the efficacy of SBRT by reprogramming the TAM compartment in tumors, thereby preventing an immune suppressive phenotype and augmenting T-cell mediated anti-tumor response. Methods: Single arm phase II study designed to evaluate safety, tolerability, and surgical resection rate in LAUPC pts treated with concurrent Nivo, Cabira, and SBRT. Exploratory endpoints include immune changes within blood and tissue following treatment and correlation with clinical endpoints. Key eligibility: completion of 2- 6 months standard induction chemotherapy, normal organ and marrow function, pre- and on-treatment biopsy, and PS ≤ 1. Following initial biopsy and placement of fiducials, Cabira 4mg/kg and Nivo 240mg are given D1 of every 14 day cycle. SBRT 6.6 Gy x 5 consecutive fractions starts D8. After 2 cycles, repeat biopsy and imaging is performed. Treatment with Cabira and Nivo continues every 2 weeks and imaging is done every 8 weeks, at which time pt is assessed for surgical resection. If pt is downstaged, treatment is discontinued and pt proceeds to surgery. Preliminary 6 pt safety cohort is monitored for unacceptable toxicities. If &lt; 3 unacceptable toxicities in the first 6 subjects enrolled, then plan for expansion phase with 14 more pts. As of abstract submission, 3 pts have been enrolled. Clinical trial information: NCT03599362.

Accelerated partial breast irradiation (APBI) using intensity modulated radiation therapy (IMRT) in stage 0-II breast cancer: A preliminary report of 57 cases.

e12068 Background: Randomized trials in Stage 0-II breast cancer have proven that APBI given via HDR implant in 5 days is equivalent to whole breast External Radiation Therapy (XRT) given in 5-6 weeks in regard to breast tumor local recurrence (LR). However, complications have been significant. Recently APBI using non-invasive IMRT given in 5 fractions has been shown in another randomized trial to be equivalent to XRT in 6 weeks, with respect to LR. IMRT was superior in regard to acute effects, late effects, and cosmesis. In the randomized clinical trial of APBI IMRT, the Clinical Target Volume (CTV) was defined by the injection of individual fiducial markers bordering the surgical cavity. At our institution, we have used the Biozorb fiducial system to localize the CTV for IMRT. We sought to confirm the APBI IMRT results with this simpler less labor intensive fiducial placement system. Methods: Between 2017 and 2019, 57 patients have undergone IMRT targeted to a Biozorb defined CTV with the walls of the surgical cavity sewn to the Biozorb device. Eligible patients were older than age 40, had tumor sizes ≤ 3 cm, negative surgical margins, and negative sentinel node dissections. IMRT dose was 30 Gy given in 5 fractions. Dose Constraints were as follows : V-30 Gy &lt; 105%, Ipsilateral Breast V-15 Gy &lt; 50%, Ipsilateral Lung V-10 Gy &lt; 20%, Contralateral Lung V-5 Gy &lt; 10%, Heart V-3 Gy &lt; 20%, Contralateral Breast Dmax &lt; 2 Gy and Skin Dmax &lt; 27 Gy. The Planning Target Volume (PTV) ranged from 27 to 355 cc with a median of 80 cc. PTV = CTV + 1-2 cm. Results: Follow-up ranged from 1-14 months with a median of 7 months. LR has been 0% (0/57). There were no skin reactions. One patient developed pain around the Biozorb site. This resolved within 2 days on a short course of steroids. Cosmetic results as rated by the Surgeon, Radiation Oncologist, and Nurse, were rated excellent in 100% (57/57) of cases. Conclusions: Non-invasive APBI with IMRT targeted to Biozorb has resulted in LR, complications, and cosmetic results which compare favorably to invasive APBI given with HDR implant. At last follow-up, there have been no LR, skin reactions, or complications. Cosmesis has been excellent in 100% of patients.

Endoscopic Ultrasound Placement of Preloaded Fiducial Markers Shortens Procedure Time Compared to Back-Loaded Markers

Fiducial markers are inert radiopaque gold or carbon markers implanted in or near pancreatic tumor to demarcate areas for image-guided radiation therapy. Endoscopic ultrasound (EUS) pre-loaded fiducial needles (PLNs) have been developed to circumvent technical issues associated with traditional back-loaded fiducials (BLNs). We performed a randomized controlled trial to compare procedure times in patients with pancreatic adenocarcinoma undergoing EUS-guided placement of BLNs vs PLNs. In a prospective study, 44 patients with pancreatic adenocarcinoma referred for fiducial marker placement at 2 tertiary care centers were assigned to groups that received PLNs (n=22) or BLNs (n= 22); each group had the same proportion of patients with tumors of different locations (head or neck vs body or tail).The procedure was standardized among all endoscopists and placement of a minimum of 3 markers inside the tumor was defined as technical success. The times for procedure and fiducial placement were recorded, total number of fiducial markers used documented, and grade of procedure difficulty ranked by passing the needle or deploying the fiducials. Other recorded variables included tumor characteristics, fluoroscopy use, and the number of fiducials clearly seen by EUS and fluoroscopy. The primary aim was to compare the duration of EUS-guided fiducial insertion of BLNs vs PLNs. The median placement time was significantly shorter in the PLN group (9 min) than the BLN group (16 min) (P < .001). However, the 44% reduction in time did not reach pre-specified levels (≥60%). Similar results were found after stratifying by tumor location. Deployment of BLNs was easier than deployment of PLNs (P= .03). There was no significant difference between groups in technical success, number of fiducials placed, EUS or fluoroscopic visualization, or adverse events. During simulation computed tomography and image-guided radiation therapy, there was no difference between groups in visualization of fiducials, migration rate, or accuracy of placement. In a randomized controlled trial of 44 patients with pancreatic adenocarcinoma, we found EUS-guided placement of PLNs to require less time and produce similar results compared withBLNs. Further refinements in PLN delivery system are needed to increase the ease of deployment. Clinicaltrials.gov no: NCT02332863.

Single community-based institutional series of stereotactic body radiation therapy (SBRT) for treatment of liver metastases.

Stereotactic body radiation therapy (SBRT) is a safe and effective option for treatment of liver metastases. However, existing data are mostly reported by high-volume centers. There have been reports that advanced radiotherapy techniques performed at low-volume centers result in inferior outcomes. Our goal was to assess the implementation of SBRT for the treatment of liver metastases at a low-volume center by studying the efficacy and toxicity of this technology through retrospective database review at a single, community-based institution. We performed an IRB approved patient registry study. Patients had a median age of 65, KPS of at least 70 (median 90) and primary tumor controlled. All patients underwent fiducial marker placement under CT-guidance 1-2 weeks prior to planning scans. Gross tumor volume (GTV) was delineated using contrast enhanced CT scans, as well as fusion with PET and/or MRI scans. GTV was expanded by 5 mm to create the planning target volume (PTV). Treatment was delivered by image guided stereotactic robotic radiosurgery with respiratory motion tracking. Lesions were treated with 3 fractions to a median total dose of 54 Gy. Overall survival, progression-free survival (PFS) and local failure-free survival were estimated using the Kaplan-Meier method. Log-rank statistic was used to compare local control based on GTV volume. Between 2006 and 2016, 42 consecutively treated patients with 81 metastatic liver lesions were treated with SBRT. Median follow-up was 25 months. Major primary tumor sites were colon (n=18) and lung (n=7). Synchronous extrahepatic disease was present in 15% of the treated lesions and 46% had prior local treatment of liver metastases. The number of lesions treated concurrently ranged from 1 to 4. Lesions had a median maximum diameter of 2.5 cm (range, 0.5-9.5 cm), and a mean volume of 53 cc (range, 0.5-363.0 cc). Kaplan-Meier estimated 1- and 2-year overall survival was 72% and 62%. Estimated 1- and 2-year progression free survival was 32% and 23%. Estimated 1- and 2-year local control was 86% and 80%. Two-year local control was worse for lesions >50 cc compared to lesions ≤50 cc (62% vs. 84%, P=0.04). Toxicity occurred in 26% of treatment courses and included grade 1 (n=12) and grade 2 toxicity (n=3). These results are comparable to available published data regarding the safety and efficacy of liver metastasis SBRT on trial at high volume institutions. Our findings, therefore, demonstrate the successful implementation of a liver metastasis SBRT program in the low-volume, community-hospital setting. These findings suggest that low-volume and high-volume centers are both options for liver metastasis SBRT.

P22 - Does Fiducial Marker Placement Prior to SBRT Increase the Risk of Metastatic Disease in Patients with Unresectable Pancreatic Cancer?

P22 - Does Fiducial Marker Placement Prior to SBRT Increase the Risk of Metastatic Disease in Patients with Unresectable Pancreatic Cancer?

Rectal Endoscopic Ultrasound in Clinical Practice.

Endoscopic ultrasound (EUS) is routinely utilized for evaluation of disorders of the lower gastrointestinal tract. In this review, we summarize the current status of rectal EUS in clinical practice and describe recent developments in diagnostic and therapeutic rectal EUS. Recent guidelines recommend rectal EUS for rectal cancer staging as a second line modality in cases where MRI is contraindicated. Forward-viewing echoendoscopes and through the scope EUS miniprobes allow for EUS imaging of lesions through the entire colon and for evaluation beyond stenoses or luminal narrowings. EUS can be used to assess perianal disease and drain pelvic abscess associated with IBD, along with newer applications currently under investigation. For rectal varices, EUS can confirm the diagnosis, assess the optimal site for banding, guide therapy placement with sclerotherapy and/or coils, and assess response to treatment by confirming absence of flow. Therapeutic rectal EUS is emerging as a promising modality for drainage of pelvic fluid collection drainage and fiducial placement for rectal or prostatic cancer. Drug delivery mechanisms and substances that may increase the scope of therapy with rectal EUS are in varying stages of development. Rectal EUS continues to be an important modality for evaluation of benign and malignant disorders of the lower gastrointestinal tract, although its use as a cancer staging modality has declined due to improvements in MRI technology. Various technologies to enhance ultrasound imaging and for therapeutics have been developed that have or may contribute to expanded indications for rectal EUS.

EP-1393 Prospective fiducial placement in liver tumours: Effectiveness, placement 'quality' and toxicities

EP-1393 Prospective fiducial placement in liver tumours: Effectiveness, placement 'quality' and toxicities