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Purpose For patients with localized pancreatic cancer (PC) with vascular involvement, prediction of resectability is critical to define optimal treatment. However, the current definitions of borderline resectable (BR) and locally advanced (LA) disease leave considerable heterogeneity in outcomes within these classifications. Moreover, factors beyond vascular involvement likely affect the ability to undergo resection. Herein, we share our experience developing a model that incorporates detailed radiologic, patient, and treatment factors to predict surgical resectability in patients with BR and LA PC who undergo stereotactic body radiation therapy (SBRT). Methods and materials Patients with BR or LA PC who were treated with SBRT between 2010 and 2016 were included. The primary endpoint was margin negative resection, and predictors included age, sex, race, treatment year, performance status, initial staging, tumor volume and location, baseline and pre-SBRT carbohydrate antigen 19-9 levels, chemotherapy regimen and duration, and radiation dose. In addition, we characterized the relationship between tumors and key arteries (superior mesenteric, celiac, and common hepatic arteries), using overlap volume histograms derived from computed tomography data. A classification and regression tree was built, and leave-one-out cross-validation was performed. Prediction of surgical resection was compared between our model and staging in accordance with the National Comprehensive Care Network guidelines using McNemar’s test. Results A total of 191 patients were identified (128 patients with LA and 63 with BR), of which 87 patients (46%) underwent margin negative resection. The median total dose was 33 Gy. Predictors included the chemotherapy regimen, amount of arterial involvement, and age. Importantly, radiation dose that covers 95% of gross tumor volume (GTV D95), was a key predictor of resectability in certain subpopulations, and the model showed improved accuracy in the prediction of margin negative resection compared with National Comprehensive Care Network guideline staging (75% vs 63%; P Conclusions We demonstrate the ability to improve prediction of surgical resectabiliy beyond the current staging guidelines, which highlights the value of assessing vascular involvement in a continuous manner. In addition, we show an association between radiation dose and resectability, which suggests the potential importance of radiation to allow for resection in certain populations. External data are needed for validation and to increase the robustness of the model.

Purpose We assessed the feasibility and theoretical dosimetric advantages of an injectable hydrogel to increase the space between the head of the pancreas (HOP) and duodenum in a human cadaveric model. Methods and Materials Using 3 human cadaveric specimens, an absorbable radiopaque hydrogel was injected between the HOP and duodenum by way of open laparotomy in 1 case and endoscopic ultrasound (EUS) guidance in 2 cases. The cadavers were subsequently imaged using computed tomography and dissected for histologic confirmation of hydrogel placement. The duodenal dose reduction and planning target volume (PTV) coverage were characterized using pre- and postspacer injection stereotactic body radiation therapy (SBRT) plans for the 2 cadavers with EUS-guided placement, the delivery method that appeared the most clinically desirable. Modeling studies were performed using 60 SBRT plans consisting of 10 previously treated patients with unresectable pancreatic cancer, each with 6 different HOP–duodenum separation distances. The duodenal volume receiving 15 Gy (V15), 20 Gy (V20), and 33 Gy (V33) was assessed for each iteration. Results In the 3 cadaveric studies, an average of 0.9 cm, 1.1 cm, and 0.9 cm HOP–duodenum separation was achieved. In the 2 EUS cases, the V20 decreased from 3.86 cm3 to 0.36 cm3 and 3.75 cm3 to 1.08 cm3 (treatment constraint Conclusions Currently, dose escalation has been limited owing to radiosensitive structures adjacent to the pancreas. We demonstrated the feasibility of hydrogel separation of the HOP and duodenum. Future studies will evaluate the safety and efficacy of this technique with the potential for more effective dose escalation using SBRT or intensity-modulated radiation therapy to improve the outcomes in patients with unresectable pancreatic cancer.

A standardized treatment regimen for unresectable isolated local recurrence (ILR) of pancreatic ductal adenocarcinoma has not been established. This study evaluated the outcomes for patients with ILR who underwent stereotactic body radiation therapy (SBRT). The records of patients with ILR who underwent SBRT between 2010 and 2016 were retrospectively reviewed. Symptom palliation and treatment-related toxicity were recorded. Associations between patient or treatment characteristics and overall survival (OS), progression-free survival (PFS), and local progression-free survival (LPFS) were assessed. The study identified 51 patients who received SBRT for ILR. Of the 51 patients, 26 (51%) had not received radiation therapy before SBRT. The median OS was 36 months after diagnosis. From the first day of SBRT, the median OS, PFS, and LPFS were respectively 16, 7, and 10 months. Patients with a recurrence-free interval of 9 months or longer after surgery had superior OS (P = 0.019). Maintenance chemotherapy after SBRT was associated with superior OS (P

Purpose Stereotactic body radiation therapy (SBRT) allows for high radiation doses to be delivered to the pancreatic tumors with limited toxicity. Nevertheless, the respiratory motion of the pancreas introduces major uncertainty during SBRT. Ultrasound imaging is a non-ionizing, non-invasive, and real-time technique for intrafraction monitoring. A configuration is not available to place the ultrasound probe during pancreas SBRT for monitoring. Methods and Materials An arm-bridge system was designed and built. A CT scan of the bridge-held ultrasound probe was acquired and fused to ten previously treated pancreatic SBRT patient CTs as virtual simulation CTs. Both step-and-shoot intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) planning were performed on virtual simulation CT. The accuracy of our tracking algorithm was evaluated by programmed motion phantom with simulated breath-hold 3D movement. An IRB-approved volunteer study was also performed to evaluate feasibility of system setup. Three healthy subjects underwent the same patient setup required for pancreas SBRT with active breath control (ABC). 4D ultrasound images were acquired for monitoring. Ten breath-hold cycles were monitored for both phantom and volunteers. For the phantom study, the target motion tracked by ultrasound was compared with motion tracked by the infrared camera. For the volunteer study, the reproducibility of ABC breath-hold was assessed. Results The volunteer study results showed that the arm-bridge system allows placement of an ultrasound probe. The ultrasound monitoring showed less than 2 mm reproducibility of ABC breath-hold in healthy volunteers. The phantom monitoring accuracy is 0.14 ± 0.08 mm, 0.04 ± 0.1 mm, and 0.25 ± 0.09 mm in three directions. On dosimetry part, 100% of virtual simulation plans passed protocol criteria. Conclusions Our ultrasound system can be potentially used for real-time monitoring during pancreas SBRT without compromising planning quality. The phantom study showed high monitoring accuracy of the system, and the volunteer study showed feasibility of the clinical workflow.

// John F. Ryan 1 , Lauren M. Rosati 1 , Vincent P. Groot 2 , Dung T. Le 3 , Lei Zheng 3 , Daniel A. Laheru 3 , Eun J. Shin 3 , Juan Jackson 1 , Joseph Moore 1 , Amol K. Narang 1 and Joseph M. Herman 1, 4 1 Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 2 Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 3 Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 4 Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Correspondence to: Joseph M. Herman, email: JMHerman@mdanderson.org Keywords: stereotactic body radiation therapy (SBRT); palliative care; pancreatic cancer; radiation; elderly Received: November 07, 2017 Accepted: March 02, 2018 Published: March 27, 2018 ABSTRACT Stereotactic body radiation therapy (SBRT) represents a promising treatment option for patients with localized pancreatic ductal adenocarcinoma (PDAC) who cannot tolerate surgical therapy. We retrospectively reviewed the records of patients with localized PDAC treated with SBRT at our institution between 2010 and 2016 to identify patients deemed medically inoperable due to poor performance status, advanced age, and/or comorbid conditions. Overall survival (OS), progression-free survival (PFS), and local progression-free survival (LPFS) were estimated using Kaplan-Meier curves. Twenty-nine patients were included. Median age was 74 (IQR 68-79). Thirteen patients (45%) had an Eastern Cooperative Oncology Group performance status of 2. Six patients (19%) had chronic obstructive pulmonary disease, 9 (31%) had cardiovascular disease, and 17 (58%) had diabetes mellitus. SBRT was delivered over 5 fractions to a median dose of 28 Gy (IQR, 25-33). Twenty-two patients (76%) received induction chemotherapy prior to SBRT, and 9 (31%) received maintenance chemotherapy after SBRT. Median OS was 13 months from diagnosis. Median OS and PFS were 8 and 6 months from SBRT, respectively. Six and 12-month LPFS rates were 91% and 78%, respectively. Patients receiving induction chemotherapy had superior survival from diagnosis than those who did not (14 vs. 7 months, p = 0.01). Three patients (10%) experienced acute grade ≥3 toxicity, and 1 patient (4%) experienced grade ≥3 late toxicity. Symptom relief was achieved at three-month follow-up in 8 of 11 patients (73%) experiencing abdominal pain. These results suggest SBRT may be safe and effective for patients who cannot tolerate surgery.

Pancreatic cancer (PCA) remains a disease with a poor prognosis. The majority of PCA patients are unable to undergo surgical resection, which is the only potentially curative option at this time. A combination of chemotherapy and chemoradiation (CRT) are standard options for patients with locally advanced, unresectable disease, however, local control and patient outcomes remains poor. Stereotactic body radiation therapy (SBRT) is an emerging treatment option for PCA. SBRT delivers potentially ablative doses to the pancreatic tumor plus a small margin over a short period of time. Early studies with single-fraction SBRT demonstrated excellent tumor control with high rates of toxicity. The implementation of SBRT (3-5 doses) has demonstrated promising outcomes with favorable tumor control and toxicity rates. Herein we discuss the evolving role of SBRT in PCA treatment.

Rationale: Glioblastoma (GBM) is the most common and deadly primary CNS malignancy in adults. The addition of tumor treating fields (TTFields), a non-invasive anti-mitotic therapy approved for use in newly-diagnosed or recurrent GBM, following standard resection and chemoradiation has been shown to significantly improve both overall and progression-free survival in a randomized phase III clinical trial. Preclinical evidence suggests that TTFields may disrupt mitotic spindles and exhibit a similar synergism with radiotherapy (RT) to other microtubule inhibitors. The ability to treat patients concurrently with RT and TTFields is thus of considerable clinical interest. The TTFields device array applicator worn on the scalp may affect radiation dose distribution, an effect that may be mitigated but also be made more difficult to account for by the routine repositioning of the applicator during therapy to avoid skin toxicity. In preparation for a clinical trial, we have therefore undertaken a phantom investigation to evaluate the effect of varying TTFields array position on RT dosimetry and planning target volume (PTV) coverage. Methods: Radiation beams and contours were copied to an anthropomorphic phantom from the treatment plan of a newly-diagnosed GBM patient receiving standard adjuvant RT. Four CT scans of the phantom were employed: one lacking the TTFields array and three with the array placed in varying positions over the cranium of the phantom to simulate routine replacement and repositioning of the array as would occur in clinical use. Dosimetric recalculations were then performed for each scan using the Philips Pinnacle treatment planning system and the dosimetric average of the three array positions was calculated using Varian Velocity software. Results: Recalculation of the treatment plan of our test patient onto the phantom wearing the TTFields array resulted in reduction of the isodose covering 95% of the PTV by 5.5 cGy/day over the course of treatment as compared to the phantom with no array (to 51.6 Gy from 53.4 Gy). This small difference in PTV coverage is unlikely to be of clinical significance, obviating the need for time-intensive replanning each time the skin position of the array has changed. Conclusion: We plan to confirm this novel finding by further investigating the impact of repositioning TTFields arrays on the radiation treatment plans of a larger, sequential cohort of newly-diagnosed GBM patients. These preliminary studies will ultimately be the foundation of a clinical trial evaluating the concurrent use of TTFields during standard radiotherapy. Citation Format: Gregory C. Stachelek, Jimm Grimm, Joseph Moore, Juan F. Jackson, Kristin Redmond, Chetan Bettegowda, Lawrence Kleinberg. Preliminary investigation into the dosimetric impact of tumor treating field arrays on concurrent radiotherapy for newly-diagnosed glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 676.

Tumor treating fields (TTFields) is a noninvasive, regional antimitotic treatment approved for the treatment of newly-diagnosed and recurrent glioblastoma (GBM) including use concurrent with temozolomide. As anti-mitotic therapies may have synergy with radiotherapy, we have developed a plan to implement use of this therapy during radiotherapy and to test safety and tolerability. In preparation for the clinical trial, we plan tests evaluating impact of placement of the applicator (transducer array) on RT targeting and dosimetry using an anthropomorphic phantom, aquaplast immobilization, and intensity-modulated radiotherapy. In this first test, several strategies were employed to ensure minimal degradation of targeting accuracy: 1) the CT scan artifacts due to the array were reduced by use of the Metal Artifact Reduction for Orthopedic Implants (O-MAR) algorithm, 2) radiation was delivered to a tumor location that did not require the radiation beam to pass through the array, by using an arrangement of six noncoplanar intensity modulated radiation therapy (IMRT) beams entering inferiorly, 3) the cone beam CT (CBCT) alignment was performed with a region of interest box that excluded any of the arrays. The end result was an X,Y,Z targeting error of 0.58 mm, -0.59 mm, 0.40 mm, for a 3D Euclidean error of 0.92 mm, well within the acceptable range for GBM irradiation. An extensive series of systematic tests of comprehensive geometries is planned to determine the accuracy in various tumor locations and geometries including dosimetric effects. The data obtained from these preclinical investigations, when completed, will support optimal testing of concurrent TTFields and radiation for safety/tolerability and ultimately efficacy.

Stereotactic radiotherapy (SRT) for secretory pituitary adenoma offers precise localization of dose with potential sparing of optic and hypothalamic functions. We collated the indications, treatment parameters, and both the clinical and biochemical results of Stereotactic radiotherapy for ACTH- 1 and prolactin-secreting pituitary adenoma. Between May 1990 and February 1996, nine patients (4 males and 5 females) with a mean age of 31.9 years had fractionated SRT for ACTH- or prolactin-secreting pituitary adenomas (Cushing's disease: n = 5; prolactinoma: n = 3; Nelson's syndrome: n = 1). These 9 patients had subtotal transphenoidal resections before SRT. An additional patient with Cushing's disease had aborted transphenoidal surgery and single-fraction Stereotactic radiosurgery (SRS). Prior to SRT, 4 patients received planned conventional fractionated external beam radiotherapy (XRT) (median dose 33.3 Gy). The median SRT dose was 34.5 Gy (range 14.4–50.4 Gy). The median total radiation dose (XRT plus SRT) for patients receiving fractionated treatment was 47.7 Gy. The median follow-up was 62 months (range 22–91 months). One patient with Nelson's syndrome was lost to follow-up. Of the 9 evaluable patients, none required reoperation for growth of pituitary tumor and all had radiographic control as shown by serial MRI scans. In 4 of the 6 patients with Cushing's disease, treatment resulted in normalization of hormone levels and resolution of symptoms. All 4 patients were able to discontinue medications. In 2 patients, normalization occurred within 4 months of treatment. Two patients with Cushing's disease failed, requiring adrenalectomy. For patients with prolactinoma, treatments resulted in a significant decrease of plasma prolactin levels. All patients treated for prolactinoma became asymptomatic; 2 were able to discontinue bromocriptine and 1 patient had a successful pregnancy. After radiation therapy, 1 patient developed new hypopituitarism. None of the patients developed worsened visual acuity, visual fields, or new neurological deficits. SRT with or without XRT may yield meaningful reductions in hormone levels with concomitant clinical improvement in selected patients with prolactinomas or Cushing's disease. In certain situations, combining conventional XRT with SRT is appropriate. Modifications of the Stereotactic radiation delivery may maximally reduce the hypothalamic dose, thereby possibly reducing the risk of clinical hypopituitarism. This treatment is safe and is without visual or other neurological toxicity.

Purpose: SBRT shows excellent tumor control and toxicity rates for patients with locally advanced pancreatic cancer (PCA). Herein, we evaluate the feasibility of using VMAT with ABC for PCA SBRT. Methods: Nine PCA patients previously treated via SBRT utilizing 11-beam step-and-shoot IMRT technique in our center were retrospectively identified, among whom eight patients received 3300cGy in 5 fractions while one received 3000cGy in 5 fractions. A VMAT plan was generated on each patient’s planning CT in Pinnacle v9.8 on Elekta Synergy following the same PCA SBRT clinical protocol. Three partial arcs (182°–300°, 300°-60°, and 60°-180°) with 2°/4° control-point spacing were used. The dosimetric difference between the VMAT and the original IMRT plans was analyzed. IMRT QA was performed for the VMAT plans using MapCheck2 in MapPHAN and the total delivery time was recorded. To mimic the treatment situation with ABC, where patients hold their breath for 20–30 seconds, the delivery was intentionally interrupted every 20–30 seconds. For each plan, the QA was performed with and without beam interruption. Gamma analysis (2%/2mm) was used to compare the planned and measured doses. Results: All VMAT plans with 2mm dose grid passed the clinic protocol with similar PTV coverage and OARs sparing, where PTV V_RxDose was 92.7±2.1% (VMAT) vs. 92.1±2.6% (IMRT), and proximal stomach V15Gy was 3.60±2.69 cc (VMAT) vs. 4.80±3.13 cc (IMRT). The mean total MU and delivery time of the VMAT plans were 2453.8±531.1 MU and 282.1±56.0 seconds. The gamma passing rates of absolute dose were 94.9±3.4% and 94.5±4.0% for delivery without and with interruption respectively, suggesting the dosimetry of VMAT delivery with ABC for SBRT won’t be compromised. Conclusion: This study suggests that PCA SBRT using VMAT with ABC is a feasible technique without compromising plan dosimetry. The combination of VMAT with ABC will potentially reduce the SBRT treatment time.

PURPOSE: To report clinical experience with an implantable capsule for treating endobronchial carcinoma by means of bronchoscopic insertion and retrieval. MATERIALS AND METHODS: The capsule consists of a plastic cylinder containing high-activity iodine-125 seeds and four restraining legs. Twelve patients with recurrent (n = 11) or inoperable carcinoma (n = 1) received a median dose of 4,500 (range, 2,633-6,299) cGy at a 1-cm radius from the center of the implant. RESULTS: No acute toxicities were observed. Five patients had complete regression of the endobronchial tumor, evidenced at bronchoscopy 2 months after therapy, and four patients had partial regression. Three patients failed to return for bronchoscopy. Symptomatic relief was achieved in eight of 10 patients with dyspnea, four of nine with cough, and two of three with hemoptysis. The median survival of the 12 patients was 6 months. The actuarial 1-year survival rate was 25%. CONCLUSION: This capsule is safe and efficacious in treating recurrent or ...

Real-time stereovision-guidance has been introduced for efficient and convenient fractionated stereotactic radiotherapy (FSR) and image-guided intensity-modulated radiation therapy (IMRT). This first pilot study is to clinically evaluate its accuracy and precision as well as impact on treatment doses. Sixty-one FSR patients wearing stereotactic masks (SMs) and nine IMRT patients wearing flexible masks (FMs), were accrued. Daily target reposition was initially based-on biplane-radiographs and then adjusted in six degrees of freedom under real-time stereovision guidance. Mean and standard deviation of the head displacements measured the accuracy and precision. Head positions during beam-on times were measured with real-time stereovisions and used for determination of delivered doses. Accuracy ± precision in direction with the largest errors shows improvement from 0.4 ± 2.3 mm to 0.0 ± 1.0 mm in the inferior-to-superior direction for patients wearing SM or from 0.8 ± 4.3 mm to 0.4 ± 1.7 mm in the posterior-to-anterior direction for patients wearing FM. The image-guidance increases target volume coverage by >30% for small lesions. Over half of head position errors could be removed from the stereovision-guidance. Importantly, the technique allows us to check head position during beam-on time and makes it possible for having frameless head refixation without tight masks.

Purpose To provide the long-term outcomes of patients treated with fractionated conformal radiotherapy (FCRT) for presumed optic nerve sheath meningiomas (ONSMs). Patients and Methods Between 1995 and 2002, 9 patients with a presumed ONSM were treated with FCRT at our institution. The indications for FCRT were significant visual dysfunction at presentation, progression of visual dysfunction during a period of observation, tumor growth documented by sequential imaging, or a combination of these findings. In 2 patients, FCRT was performed as adjuvant therapy, and in 7, it was the initial and primary treatment. Results Of the 9 patients, 6 were women and 3 were men, with a mean age of 47 years. All 9 patients had evidence of optic nerve dysfunction in the affected eye, characterized by reduced visual acuity, a visual field defect, and a relative afferent pupillary defect. In addition, 2 patients had proptosis and 1 had diplopia. The mean follow-up period was 98 ± 31.7 months (median, 90; range, 61–151). After FCRT, the visual function improved in the 7 patients who had undergone FCRT as the primary treatment. However, 2 patients who were blind in their affected eye at FCRT remained blind. In 4 of the 7 patients with improvement, the improvement was documented within 1–3 months after FCRT. The tumor control rate was 100%. Proptosis and diplopia also regressed in 100% of patients. At 2 years after FCRT, 1 patient had developed radiation retinopathy. Conclusion The results of our study have shown that FCRT is a safe and effective treatment of ONSMs, affording satisfactory long-term tumor control, good functional outcome, and low treatment morbidity. FCRT should be considered the treatment of choice for patients with presumed ONSMs for whom the treatment has been deemed appropriate.

Purpose We assessed clinical outcome and long-term tumor control after fractionated stereotactic radiotherapy (FSRT) for unilateral schwannoma. Methods and Materials Between 1995 and 2007, 496 patients were treated with fractionated stereotactic radiotherapy at Johns Hopkins Hospital (Baltimore, MD); 385 patients had radiologic follow-up that met the inclusion criteria. The primary endpoint was treatment failure. Secondary endpoints were radiologic progression and clinical outcome. Logistic regression analysis assessed the association of age, race, tumor side, sex, and pretreatment symptoms. Results In 11 patients (3%) treatment failed, and they required salvage (microsurgical) treatment. Radiologic progression was observed in 116 patients (30.0%), including 35 patients (9%) in whom the treatment volume more than doubled during the follow-up period, although none required surgical resection. Tumors with baseline volumes of less than 1 cm 3 were 18.02 times more likely to progress than those with tumor volumes of 1 cm 3 or greater (odds ratio, 18.02; 95% confidence interval, 4.25–76.32). Treatment-induced neurologic morbidity included 8 patients (1.6%) with new facial weakness, 12 patients (2.8%) with new trigeminal paresthesias, 4 patients (0.9%) with hydrocephalus (1 communicating and 3 obstructive), and 2 patients (0.5%) with possibly radiation-induced neoplasia. Conclusions Although the rate of treatment failure is low (3%), careful follow-up shows that radiologic progression occurs frequently. When reporting outcome, the "no salvage surgery needed" and "no additional treatment needed" criteria for treatment success need to be complemented by the radiologic data.