We introduce a novel dynamic water range shifter (DWRS) that enables range shifting of a mono-energetic proton beam for the purpose of obtaining a water equivalent path length (WEPL). A scintillation screen and a charge-coupled device (CCD) camera were assembled with a mirror for a detecting system. We acquired two sets of proton radiographs with and without the scanned object, and calculated 2D distribution of the WEPL. We first optimized measurement conditions, i.e., the sampling interval and the nearest sampling point from the surface. Then we evaluated the performance of the proton radiography system by use of the step phantoms and a patient-specific range compensator. The step phantom measurement was designed to evaluate WEPL accuracy and standard deviation, and the patient-specific compensator was utilized to evaluate image quality dependency on the shifting motions of the DWRS. Based on the optimization and evaluation in the radiographic setting, a cylindrical phantom having multiple insert holes was used to obtain proton CT and the image contrasts of the holes were evaluated. This study successfully demonstrates the feasibility of using the DWRS for proton radiography and CT.
7024 Background: Gemtuzumab ozogamicin (GO) is effective in favorable-risk acute myelogenous leukemia (AML), while its activity is limited in higher-risk AML in part due to multi-drug resistance (MDR) mechanisms, particularly P-glycoprotein efflux pumps. CPX-351 provides a survival benefit in secondary AML, a disease characterized by high MDR activity. The objective of this trial is to utilize CPX-351 as a bulk cytoreduction agent, to first reduce the high MDR leukemia clones, followed by sequential treatment with GO in a more favorable leukemia environment. Methods: This was a multicenter phase Ib trial of CPX-351 plus GO in relapsed/refractory (R/R) AML patients with standard 3+3 dose escalation design (NCT03904251). Cohort A was treated with CPX-351 100 u/m 2 on days 1, 3, and 5 plus GO 3 mg/m 2 (max 4.5 mg) on day 7. Cohort B was treated with the same regimen plus an additional dose of GO 3 mg/m2 on day 4. The primary endpoint was the maximum tolerated dose (MTD), defined as < 2 dose limiting toxicities (DLTs) in the highest dose cohort. Secondary endpoints were IWG complete remission (CR) rate at day 28-42, liver veno-occlusive disease (VOD) rate diagnosed by the Baltimore criteria, and time of hematologic recovery (defined as ANC > 1000/uL and platelet count > 100,000/uL). Patients were enrolled at 4 University of California Hematologic Malignancies Consortium (UCHMC) centers: UC Los Angeles, UC San Francisco, UC Davis, and UC Irvine. Results: Thirteen participants were enrolled. The median age was 63 years (range 29-75). Eleven had relapsed disease, and two had refractory disease. Most received one prior line of therapy (n = 9). Seven had ELN 2022 adverse-risk disease at initial diagnosis, and two had intermediate-risk disease. The MTD was not reached. DLTs were observed in 1/6 participants in cohort A (grade 3 rash), and 1/6 participants in cohort B (grade 5 intracranial hemorrhage in the setting of severe thrombocytopenia). There were no cases of liver VOD. Of 12 evaluable participants, 4 achieved CR (33%), of whom 3 were negative for measurable residual disease by multiparametric flow cytometry, and 1 one achieved partial remission. The median age of responders was 30 years (range 28-65). The median time to return of normal hematopoiesis in those who achieved remission was 37 days (range 36-43). Three participants received allogeneic hematopoietic cell transplant (alloHCT) following investigational therapy: one remains in remission 34 months post-transplant, one died of infectious complications shortly after alloHCT, and one relapsed at day +60. Conclusions: CPX-351 plus two doses of GO 3 mg/m2 is a feasible treatment with acceptable toxicity and reasonable marrow recovery kinetics. However, only three participants went on to curative alloHCT. Further evaluation for efficacy in a larger patient population is needed to determine the utility of this regimen in R/R AML. Clinical trial information: NCT03904251 .
Purpose External beam radiotherapy (EBRT) has been commonly applied as salvage or a combination locoregional modality after transarterial chemoembolization (TACE) for hepatocellular carcinomas (HCCs). This study reports oncologic outcomes and feasibility after application of the two modalities in our center.Methods Forty consecutive patients who underwent EBRT due to incomplete responses of TACE were evaluated. Fourteen patients (35.0%) received stereotactic body radiotherapy (SBRT) and the remaining patients received conventionally fractionated radiotherapy (RT). A majority of patients who underwent SBRT received doses of 27 to 48 Gy in 3–4 fractions [median EQD2 (Equivalent dose in 2 Gy per fraction radiotherapy): 57.0 Gy]. Conventionally fractionated RT was performed with a median EQD2 of 47.8 Gy.Results The median follow-up duration was 14.4 months (range: 2.6–83.0 months). A majority (77.5%) of patients were regarded as having Child-Pugh grade A. The median tumor size was 3.4 cm (range: 0.8–20.1 cm). Ten patients (25.0%) had thrombosis at a main portal branch. The 1- and 2-year overall survival (OS) and progression-free survival (PFS) rates were 82.2% and 42.1% and 55.8% and 32.1%, respectively. The local control rates were 89.1% and 89.1% at 1 and 2 years, respectively. The albumin level was a significant factor affecting OS (p = .002), and the BCLC stage significantly affected PFS (p = .001). Intrahepatic, out-of-field recurrence was the main cause of disease progression (60.0%), and distant metastasis developed in 12 patients (30.0%) during follow-up. Non-classic radiation-induced liver disease was seen in five (12.5%) patients, and two (5%) patients experienced grade ≥3 hepatic toxicities.Conclusions EBRT after incomplete TACE was feasible and yielded favorable oncologic outcomes. However, disease progression related to intrahepatic failure remained a hindrance.
Summary External beam radiotherapy (EBRT) for hepatocellular carcinoma (HCC) has not been widely used due to lack of high‐level evidence, despite its potent local therapeutic effect. While clinical evidence has accumulated and meta‐analyses of observational studies have provided integrated information to help in clinical decision‐making, a recent randomized trial demonstrated the benefit of EBRT in cases of HCC with major vessel invasion. Based on these trends, the efficacy of EBRT has been better recognized, and EBRT has been more frequently recommended in several international treatment guidelines newly updated in 2018. This review examined the key issues of EBRT in the guidelines updated in 2018 as well as recently published noteworthy randomized trials and meta‐analyses. Ongoing trials to identify the trends and direction of future research on EBRT for HCC were also reviewed.
Purpose: To evaluate the modeling of couch with a commercial proton treatment planning system (TPS, Eclipse, v8.12). Method and Materials: To keep the shape and dimensions of an actual proton treatment couch, it was scanned using CT scanner and inserted into the TPS system by replacing CT couch of all transverse CT slices. Results: The experimental data shows that the range of proton beam is shorten by 0.99 ± 0.01cm and spread‐out Bragg peak (SOBP) varies 0.10 ±0.09cm with insertion of proton couch when the beam direction is perpendicular to proton couch (0° in our configuration). While the average range shift in proton beam increases from 0.99cm to 1.70cm as the angle of the beam increases from 0° to 55°, there were no distinct SOBP changes with beam angle revealing less than 0.1cm variation. Our results suggest that the dosimetic factors such as range, profile, output factor remained almost same with the insertion of proton couch, whereas the beam range is largely dependent on both the insertion of couch and beam angle to couch. Using inserted CT scanned proton couch in TPS, the calculated and measured beam range was cross‐compared and the results show that the range of proton beam is shorten by ∼0.7cm in TPS, which shows ∼0.3cm difference with actual measurement. The difference between computed and measured range was compensated by assigning appropriate densities to the inserted proton couch, which is called digital couch. Measured and computed PDD with the digital couch show that the beam range and SOBP are well matched for various beam angles revealing the difference of 0.01±0.02cm and 0.12±0.03cm, respetively. Conclusion: These results suggest that the digital couch with relevant density assignment may be a good solution for proton couch modeling, which can be used for commercial proton TPS.
Abstract Purpose External beam radiotherapy (EBRT) has been commonly applied as salvage or a combination locoregional modality after transarterial chemoembolization (TACE) for hepatocellular carcinomas (HCCs). This study reports oncologic outcomes and feasibility after application of the two modalities in our center. Methods Forty consecutive patients who underwent EBRT due to incomplete responses of TACE were evaluated. Fourteen patients (35.0%) received stereotactic body radiotherapy (SBRT) and the remaining patients received conventionally fractionated radiotherapy (RT). A majority of patients who underwent SBRT received doses of 27 to 48 Gy in 3–4 fractions (median *EQD 2 : 57.0 Gy). Conventionally fractionated RT was performed with a median EQD 2 of 47.8 Gy. Results The median follow-up duration was 14.4 months (range: 2.6–83.0 months). A majority (77.5%) of patients were regarded as having Child-Pugh grade A. The median tumor size was 3.4 cm (range: 0.8–20.1 cm). Ten patients (25.0%) had thrombosis at a main portal branch. The 1- and 2-year overall survival (OS) and progression-free survival (PFS) rates were 82.2% and 42.1% and 55.8% and 32.1%, respectively. The local control rates were 89.1% and 89.1% at 1 and 2 years, respectively. The albumin level was a significant factor affecting OS ( p = 0.002), and the BCLC stage significantly affected PFS ( p = 0.001). Intrahepatic, out-of-field recurrence was the main cause of disease progression (60.0%), and distant metastasis developed in 12 patients (30.0%) during follow-up. Non-classic radiation-induced liver disease was seen in five (12.5%) patients, and two (5%) patients experienced grade ≥ 3 hepatic toxicities. Conclusions EBRT after incomplete TACE was feasible and yielded favorable oncologic outcomes. However, disease progression related to intrahepatic failure remained a hindrance. *EQD2: Equivalent dose in 2 Gy per fraction radiotherapy
Purpose: To clinically evaluate the accuracy of an automatic patient positioning system based on the image correlation of two edge images in radiotherapy. Method and Materials: Ninety‐six head & neck images from eight patients undergoing proton therapy were compared with a digitally reconstructed radiograph (DRR) of planning CT. Two edge images, a reference image and a test image, were extracted by applying a Canny edge detector algorithm to a DRR and a 2D x‐ray image, respectively, of each patient before positioning. The value for patient positioning was determined using an optimization algorithm based on an image correlation factor, which recognizes shifts between two edge images by translating and rotating the test image with respect to the reference image. Results: In a simulation using a humanoid phantom, performed to verify the effectiveness of the proposed method, no registration errors were observed for given ranges of rotation, pitch and translation in the x, y and z directions. For real patients, however, there were discrepancies between the automatic positioning method and manual positioning by physicians or technicians. Using edged head coronal‐ and sagittal‐view images, the average differences in registration between these two methods for the x, y and z directions were 0.10 cm, 0.09 cm and 0.11 cm, respectively, whereas the maximum discrepancies were 0.34 cm, 0.38 cm, and 0.50 cm, respectively. For rotation and pitch, the average registration errors were 0.96° and 1.25°, respectively, and the maximum errors were 3.6° and 2.3°, respectively. Conclusion: The proposed automatic patient positioning system based on edge image comparison was relatively accurate for head & neck patients. However, image deformation during treatment may render the automatic method less accurate, since the test image many differ significantly from the reference image.
Abstract Purpose The features of past and contemporary phase III clinical trials for radiotherapy were reviewed to activate future clinical trials and to advise on actual clinical practice. Methods and materials The phase III clinical trials for radiotherapy were searched in the database of ‘ ClinicalTrials.gov ’ by the U.S. National Institute of Health. Using the staring date, the studies during each period of 4 years were collected for the past (from Jan 2000 to Dec 2003) and contemporary (July 2014 to June 2018) years. For the investigated subjects, the patterns of studies were classified as: Category A, the comparisons of rival radiotherapy protocols; Category B, the comparisons of multidisciplinary approaches; Category C, the investigation of supplementary agents; and Category D, the investigation of optimal partners for concurrent radiotherapy. Results The number of studies increased, from 96 past to 158 contemporary studies. The patterns of studies were similar with the mild increase of Category A in the contemporary years (22.9% vs. 29.1%). For the study locations and the funding sources, the Chinese studies (2.1% vs. 34.2%, P < 0.001) and the affiliated institutions of researchers (37.5% vs. 72.2%, P < 0.001) markedly increased in the contemporary years from the past Western studies and non-profit organization, respectively. The robust radiation techniques were more usual in the contemporary years (11.5% vs. 44.9%, P < 0.001). The fractionation schedule and delivery technique were the common issues in both past and contemporary years of Category A. In Category B, the indications of stereotactic radiotherapy was the rising concern, with eight ongoing studies. Except for the studies of palliative or prophylactic goals and stereotactic radiotherapy, the escape from conventional fraction size was 37.9% (36/95) in the contemporary years with the median fraction size of 2.5 Gy (range 2.05–6.6 Gy) in the comparison with 19.0% (15/79) in the past years ( P = 0.006). Conclusions To activate the clinical trials for radiotherapy, the funding sources would be diversified, including industrial support. Hypofractionated schedules using robust techniques could be preemptively considered in actual clinical practice.
Aim: To analyze the outcomes in pancreatic cancer (PC) cases with a microscopically-positive resection margin (R1 resection) treated with postoperative radiotherapy (PORT). Patients and Methods: We retrospectively analyzed the outcomes in 62 patients who received PORT for PC with R1 resection between 2001 and 2012. All patients received three-dimensional conformal radiotherapy. Concurrent chemotherapy was administered to 58 patients. Results: The median follow-up was 20.1 months. The median survival was 22.0 months and the 3-year overall survival rate was 25%. The 3-year disease-free survival and local recurrence-free survival rates were 12% and 54%, respectively. Local recurrence occurred in 23 patients (44%), distant failure in 45 (87%), and both in 16 (31%). By multivariate analysis, the postoperative cancer antigen 19-9 (CA19-9) level and adjuvant chemotherapy were independent prognostic factors for survival. Conclusion: PORT is associated with a relatively favorable survival outcome in PC with R1 resection. Chemotherapy and postoperative CA19-9 level were significant prognostic factors for survival.
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