Jian-Kuen Wu

Volumetric modulated arc therapy for nasopharyngeal carcinoma: A dosimetric comparison with TomoTherapy and step-and-shoot IMRT

PURPOSE Volumetric modulated arc therapy (VMAT), a novel technique, employs a linear accelerator to conduct dynamic modulation rotation radiotherapy. The goal of this study was to compare VMAT with helical tomotherapy (HT) and step-and-shoot intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC) patients with regard to the sparing effect on organs at risk (OARs), dosimetric quality, and efficiency of delivery. MATERIALS AND METHODS Twenty patients with NPC treated by HT were re-planned by VMAT (two arcs) and IMRT (7-9 fields) for dosimetric comparison. The target area received three dose levels (70, 60, and 54 Gy) in 33 fractions using simultaneous integrated boosts technique. The Philips Pinnacle Planning System 9.0 was adopted to design VMAT, using SmartArc as the planning algorithm. For a fair comparison, the planning target volume (PTV) coverage of the 3 plans was normalized to the same level. Dosimetric comparisons between VMAT, HT, and IMRT plans were analyzed to evaluate (1) coverage, homogeneity, and conformity of PTV, (2) sparing of OARs, (3) delivery time, and (4) monitor units (MUs). RESULTS The VMAT, HT, and IMRT plans had similar PTV coverage with an average of 96%. There was no significant difference between VMAT and HT in homogeneity, while the homogeneity indices of VMAT (1.06) and HT (1.06) were better than IMRT plans (1.07, p<0.05). HT plans provided a better conformity index (1.17) than VMAT (1.28, p=0.01) and IMRT (1.36, p=0.02). When compared with IMRT, VMAT and HT had a better sparing effect on brain stem and spinal cord (p<0.05). The effect of parotid sparing was similar between VMAT (mean=26.3 Gy) and HT (mean=27.5 Gy), but better than IMRT (mean=31.3 Gy, p<0.01). The delivery time per fraction for VMAT (5.7 min) were much lower than for HT (9.5 min, p<0.01) and IMRT (9.2 min, p<0.01). CONCLUSIONS Our results indicate that VMAT provides better sparing of normal tissue, homogeneity, and conformity than IMRT, and shorter delivery time than HT.

Treatment and Dosimetric Advantages Between VMAT, IMRT, and Helical TomoTherapy in Prostate Cancer

We investigated the possible treatment and dosimetric advantage of volumetric modulated arc therapy (VMAT) over step-and-shoot intensity-modulated radiation therapy (step-and-hhoot IMRT) and helical tomotherapy (HT). Twelve prostate cancer patients undergoing VMAT to the prostate were included. Three treatment plans (VMAT, step-and-shoot IMRT, HT) were generated for each patient. The doses to clinical target volume and 95% of planning target volume were both ≥ 78 Gy. Target coverage, conformity index, dose to rectum/bladder, monitor units (MU), treatment time, equivalent uniform dose (EUD), normal tissue complication probability (NTCP) of targets, and rectum/bladder were compared between techniques. HT provided superior conformity and significantly less rectal volume exposed to 65 Gy and 40 Gy, as well as EUD/NTCP of rectum than step-and-shoot IMRT, whereas VMAT had a slight dosimetric advantage over step-and-shoot IMRT. Notably, significantly lower MUs were needed for VMAT (309.7 ± 35.4) and step-and-shoot IMRT (336.1 ± 16.8) than for HT (3368 ± 638.7) (p < 0.001). The treatment time (minutes) was significantly shorter for VMAT (2.6 ± 0.5) than step-and-shoot IMRT (3.8 ± 0.3) and HT (3.8 ± 0.6) (p < 0.001). Dose verification of VMAT using point dose and film dosimetry met the accepted criteria. VMAT and step-and-shoot IMRT have comparable dosimetry, but treatment efficiency is significantly higher for VMAT than for step-and-shoot IMRT and HT.

Unique role of proximal rectal dose in late rectal complications for patients with cervical cancer undergoing high-dose-rate intracavitary brachytherapy

PURPOSE To investigate the correlation of the radiation dose to the upper rectum, proximal to the International Commission of Radiation Units and Measurements (ICRU) rectal point, with late rectal complications in patients treated with external beam radiotherapy (EBRT) and high-dose-rate (HDR) intracavitary brachytherapy (ICRT) for carcinoma of the uterine cervix. METHODS AND MATERIALS Between June 1997 and February 2001, 75 patients with cervical carcinoma completed definitive or preoperative RT and were retrospectively reviewed. Of the 75 patients, 62 with complete dosimetric data and a minimal follow-up of at least 1 year were included in this analysis. Of the 62 patients, 36 (58%) also received concurrent chemotherapy, mainly with cisplatin during EBRT. EBRT consisted of a mean of 50.1 +/- 1.3 Gy of 18-MV photons to the pelvis. A parametrial boost was given to 55 patients. Central shielding was used after 40-45 Gy of pelvic RT. HDR ICRT followed EBRT, with a median dose of 5 Gy/fraction given twice weekly for a median of four fractions. The mean dose to point A from HDR ICRT was 23.9 +/- 3.0 Gy. In addition to the placement of a rectal tube with a lead wire during ICRT, 30-40 mL of contrast medium was instilled into the rectum to demonstrate the anterior rectal wall up to the rectosigmoid junction. Late rectal complications were recorded according to the Radiation Therapy Oncology Group grading system. The maximal rectal dose taken along the rectum from the anal verge to the rectosigmoid junction and the ICRU rectal dose were calculated. Statistical tests were used for the correlation of Grade 2 or greater rectal complications with patient-related variables and dosimetric factors. Correlations among the point A dose, ICRU rectal dose, and maximal proximal rectal dose were analyzed. RESULTS Fourteen patients (23%) developed Grade 2 or greater rectal complications. Patient-related factors, definitive or preoperative RT, and the use of concurrent chemotherapy were not associated with the occurrence of rectal complications. The maximal rectal dose during ICRT was at the proximal rectum rather than at the ICRU rectal point in 55 (89%) of 62 patients. Patients with Grade 2 or greater rectal complications had received a significantly greater total maximal proximal rectal dose from ICRT (25.6 Gy vs. 19.2 Gy, p = 0.019) and had a greater maximal proximal rectal dose/point A dose ratio (1.025 vs. 0.813, p = 0.024). In contrast, patients with and without rectal complications had a similar dose at point A (25.0 Gy vs.23.6 Gy, p = 0.107). The differences in the ICRU rectal dose (17.8 Gy vs.15.4 Gy, p = 0.065) and the ICRU rectal dose/point A dose ratio (0.71 vs. 0.66, p = 0.210) did not reach statistical significance. Patients with >62 Gy of a direct dose sum from EBRT and ICRT to the proximal rectum (12 of 29 vs. 2 of 33, p = 0.001) and >110 Gy of a total maximal proximal rectal biologic effective dose (13 of 40 vs. 1 of 22, p = 0.012) presented with a significantly increased frequency of Grade 2 or greater rectal complications. The correlations between the maximal proximal rectal dose and the ICRU rectal dose were less satisfactory (Pearson coefficient 0.375). Moreover, 11 of the 14 patients with rectal complications had colonoscopic findings of radiation colitis at the proximal rectum, the area with the maximal rectal dose. CONCLUSION Eighty-nine percent of our patients had a maximal rectal dose from ICRT at the proximal rectum instead of the ICRU rectal point. The difference between patients with and without late rectal complications was more prominent for the proximal rectal dose than for the ICRU rectal dose. It is important and useful to contrast the whole rectal wall up to the rectosigmoid junction and to calculate the dose at the proximal rectum for patients undergoing HDR ICRT.

Using Cone-Beam Computed Tomography to Evaluate the Impact of Bladder Filling Status on Target Position in Prostate Radiotherapy

Purpose:To assess bladder filling status and its impact on target position during daily intensity-modulated radiation therapy (IMRT) using cone-beam computed tomography (CBCT) in prostate cancer patients.Patients and Methods:23 patients with prostate cancer undergoing image-guided IMRT (78 Gy in 39 fractions) were included. On-board CBCT images were acquired daily and an endorectal balloon was placed daily. All patients were instructed to have a full bladder. The interfraction changes in bladder dimensions in left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions were measured from CBCT images. Distances from the uppermost part of prostate to pubic bone (PP) and from the uppermost part of prostate to treatment isocenter (PI) were measured to determine changes in target position. Standard deviation (SD) in all fractions of each patient was used to compare the variations between patients. Bladder dimension change ratio and Z-score were used to normalize data between patients.Results:A total of 867 CBCT images were evaluated. The average LR, AP, and SI bladder dimensions were 7.8 ± 1.5 cm, 6.7 ± 1.4 cm, and 5.6 ± 1.7 cm, respectively. The average LR, AP, and SI bladder dimension change ratios were 0.88 ± 0.17, 0.90 ± 0.15, and 0.86 ± 0.32, respectively. The SD was significantly greater in SI dimension than in LR (p < 0.001) and AP (p < 0.001) dimensions. The interfraction changes in the three bladder dimensions were significantly larger than those of target position, and did not correlate with target position changes.Conclusion:Though they were not negligible, changes in bladder filling status did not have a significant impact on target position.Ziel:Beurteilung des Blasenfüllungszustands und seines Einflusses auf die Zielposition bei der täglichen intensitätsmodulierten Radiotherapie (IMRT) unter Einsatz der Cone-Beam-Computertomographie (CBCT) bei Patienten mit Prostatakarzinom.Patienten und Methodik:Es wurden 23 Patienten mit Prostatakarzinom erfasst, die mit bildgesteuerter IMRT (78 Gy verteilt auf 39 Fraktionen) behandelt wurden. Täglich wurden On-Board-CBCT-Bilder aufgenommen und ein endorektaler Ballonkatheter eingesetzt. Alle Patienten wurden angewiesen, mit voller Blase zu erscheinen. Anhand der CBCT-Bilder wurden Änderungen der Blasenausdehnung von Fraktion zu Fraktion in Links-rechts-(LR-), Anterior-posterior-(AP-) und Superior-inferior-(SI-)Richtung gemessen. Um Änderungen der Zielposition zu ermitteln, wurde jeweils der Abstand vom obersten Punkt der Prostata zum Schambein (PP) und vom obersten Punkt der Prostata zum Bestrahlungsisozentrum (PI) gemessen. Die Standardabweichung (SD) bei allen Fraktionen der Patienten wurde verwendet, um die Variationen zwischen Patienten zu vergleichen. Der Änderungsquotient der Blasenausdehnung und der Z-Wert wurden verwendet, um Daten zwischen den Patienten zu normalisieren.Ergebnisse:Insgesamt wurden 867 CBCT-Bilder ausgewertet. Die durchschnittliche LR-, AP- bzw. SI-Blasenausdehnung betrug 7,8 ± 1,5 cm, 6,7 ± 1,4 cm bzw. 5,6 ± 1,7 cm. Der durchschnittliche Änderungsquotient der LR-, AP- bzw. SI-Blasenausdehnung lag bei 0,88 ± 0,17, 0,90 ± 0,15 bzw. 0,86 ± 0.32. Die SD war bei der SI-Ausdehnung signifikant größer als bei der LR- (p < 0,001) und der AP-Ausdehnung (p < 0,001). Die Änderungen der drei Parameter für die Blasenausdehnung von Fraktion zu Fraktion waren signifikant größer als jene der Zielposition und korrelierten nicht mit Änderungen der Zielposition.Schlussfolgerung:Änderungen im Blasenfüllungszustand hatten, obwohl sie nicht zu vernachlässigen waren, keine signifikanten Auswirkungen auf die Zielposition.

Calcium Bioavailability of Nanonized Pearl Powder for Adults

The present study was aimed to evaluate the calcium bioavailability of pearl powder for humans. Both the nanonized pearl powder (NPP) and the micronized pearl powder (MPP) prepared by a dry grinder were tested. A group of healthy adults free from hyperthyroidism, hypercalcemia, and hypocalcemia were recruited as the subjects for oral administration with the pearl powder. The bioavailability was evaluated by the serum total calcium increment, the serum intact parathyroid hormone (iPTH) reduction, and the urine calcium/creatinine ratio increment in 6 h after administration. The results show better absorption and retention of calcium from NPP, as reflected with the shorter time elapsed before the maximum concentration of calcium appeared in the serum, higher iPTH reduction, more calcium absorption, and higher maximum calcium concentration (C(max)) in serum after ingestion, than that from MPP. We conclude that pearl powder is a beneficial source of calcium for adults and that nanonization improves its calcium bioavailability.

Lumbosacral spine and marrow cavity modeling of acute hematologic toxicity in patients treated with intensity modulated radiation therapy for squamous cell carcinoma of the anal canal

PURPOSE To identify various dosimetric parameters of bone marrow cavity that correlate with acute hematologic toxicity (HT) in patients with anal squamous cell carcinoma treated with definitive chemoradiation therapy (CRT). METHODS AND MATERIALS We analyzed 32 patients receiving CRT. The whole pelvic bone marrow (PBM) and the lumbosacral spine (LSS) subregion were contoured for each patient. Marrow cavities were contoured using the Hounsfield units (HUs) of 100, 150, 200, and 250 as maximum density threshold levels. The volume of each region receiving at least 5, 10, 15, 20, 30, and 40 Gy was calculated. The endpoint was grade ≥3 HT (HT3+). Normal-tissue complication probability (NTCP) was evaluated with the Lyman-Kutcher-Burman (LKB) model. Maximal likelihood estimate was used to compare the parameter set. Logistic regression was used to test associations between HT and both dosimetric and clinical parameters. RESULTS Ten patients (31%) experienced HT3+. While dose to both LSS and PBM significantly predicted for HT3+, LSS was superior to PBM by logistic regression and LKB modeling. Constrained optimization of the LKB model for HT3+ yielded the parameters m = 0.21, n = 1, and TD50 = 32 Gy for LSS. The NTCP fits were better with the whole bone than with marrow cavity using any HU threshold. Mean LSS doses of 21 Gy and 23.5 Gy result in a 5% and 10% risk of HT3+, respectively. Mean dose and low-dose radiation parameters (V5, V10, V15, V20) of whole bone or bone cavities of LSS were correlated most significantly with HT3+. CONCLUSIONS For predicting the risk of HT3+, whole-bone contours were superior to marrow cavity and LSS was superior to PBM by LKB modeling. The results confirm PBM and LSS as parallel organs when predicting hematologic toxicity. Recommended dose constraints to the LSS are V10 ≤80%. An LSS mean dose of 23.5 Gy is associated with a 10% risk of HT.

Mathematical estimation and in vivo dose measurement for cone-beam computed tomography on prostate cancer patients

BACKGROUND AND PURPOSE Cone-beam computed tomography (CBCT) increases the doses on normal tissues. Our study sought to develop a mathematical model that would provide an estimate of and verify in vivo rectal dose from CBCT in prostate cancer patients. MATERIALS AND METHODS Thermoluminescent dosimeters (TLDs) and Rando phantoms were used to measure doses to the pelvic region. We used an endorectal balloon to measure rectal doses for 10 prostate cancer patients who underwent radiotherapy and for whom we were able to acquire CBCT images. A solid water phantom and TLDs were used to correlate the rectal doses with body thickness/widths. A mathematical method was established to simulate the dose to which the patient is exposed during CBCT for the determined body parameters. The estimated doses were compared with the measured doses to determine the effectiveness of the model. RESULTS The average measured rectal dose from CBCT was 2.8+/-0.3 cGy. The mathematical method was able to predict the rectal dose, with the limits of agreement of -0.03+/-0.18 cGy. The average difference between predictions and measurements was -1.1+/-3.6%. CONCLUSION Our mathematical model was effective in estimating the exposed dose from CBCT.

Practically acquired and modified cone-beam computed tomography images for accurate dose calculation in head and neck cancer

BackgroundOn-line cone-beam computed tomography (CBCT) may be used to reconstruct the dose for geometric changes of patients and tumors during radiotherapy course. This study is to establish a practical method to modify the CBCT for accurate dose calculation in head and neck cancer.Patients and MethodsFan-beam CT (FBCT) and Elekta’s CBCT were used to acquire images. The CT numbers for different materials on CBCT were mathematically modified to match them with FBCT. Three phantoms were scanned by FBCT and CBCT for image uniformity, spatial resolution, and CT numbers, and to compare the dose distribution from orthogonal beams. A Rando phantom was scanned and planned with intensity-modulated radiation therapy (IMRT). Finally, two nasopharyngeal cancer patients treated with IMRT had their CBCT image sets calculated for dose comparison.ResultsWith 360° acquisition of CBCT and high-resolution reconstruction, the uniformity of CT number distribution was improved and the otherwise large variations for background and high-density materials were reduced significantly. The dose difference between FBCT and CBCT was < 2% in phantoms. In the Rando phantom and the patients, the dose–volume histograms were similar. The corresponding isodose curves covering ≥ 90% of prescribed dose on FBCT and CBCT were close to each other (within 2 mm). Most dosimetric differences were from the setup errors related to the interval changes in body shape and tumor response.ConclusionThe specific CBCT acquisition, reconstruction, and CT number modification can generate accurate dose calculation for the potential use in adaptive radiotherapy.ZielDie On-line-Cone-Beam-Computertomographie (CBCT) kann zur Anpassung der Dosis bei geometrischen Änderungen der Patientenlagerung und des Tumorvolumens während der Strahlentherapie verwendet werden. Diese Studie zeigt eine praktischen Methode zur Änderung der Cone-Beam-CTs zur exakten Berechnung der Dosierung bei der Radiotherapie von Kopf- und Hals-Tumoren.Patienten und MethodenFan-Beam-CTs (FBCT) und CBCTs (Elekta) wurden zur Bildakquisition verwendet. Die CT-Dichtewerte für die verschiedenen Materialien des CBCT wurden mathematisch zur Anpassung an das FBCT verändert. Drei Phantome wurden mit FBCT und CBCT zur Bildergleichheit, räumlichen Auflösung und der Bestimmung der CT-Dichtewerte sowie zum Vergleich der Dosierungsverteilung in orthogonaler Richtung gescannt. Ein Rando-Phantom wurde gescannt und mit intensitätsmodulierter Strahlentherapie (IMRT) geplant. Schließlich wurden für zwei Nasopharynxkarzinom-Patienten, die mit IMRT behandelt wurden, die CBCT-Bilder zum Dosierungsvergleich berechnet.ErgebnisseMit der 360°-Erfassung des CBCT und einer hochaufgelösten Rekonstruktion wurden sowohl die Übereinstimmung der CT-Dichtewerte verbessert als auch die sonst großen Abweichungen des Hintergrundes und bei dichteren Materialien erheblich reduziert. Die Dosisdifferenz zwischen FBCT und CBCT lag bei den Phantomen bei < 2%. Bei den Rando-Phantomen und den Patienten waren die Dosis-Volumen-Histogramme ähnlich. Die entsprechenden Isodose-Kurven, welche ≥ 90% der Volumina der FBCT und CBCT abdeckten, lagen nahe beieinander (innerhalb von 2 mm). Die meisten Dosisunterschiede entstanden durch Positionierungsungenauigkeiten, die durch veränderte Körperkonturen und die Tumorrückbildung entstanden.SchlussfolgerungDie spezifische CBCT-Erfassung, Rekonstruktion und die Änderung der CT-Dichtewerte können eine exakte Dosisberechnung für die potentielle Verwendung in der adaptiven Strahlentherapie generieren.

Skin Dose Impact from Vacuum Immobilization Device and Carbon Fiber Couch in Intensity Modulated Radiation Therapy for Prostate Cancer

To investigate the unexpected skin dose increase from intensity-modulated radiation therapy (IMRT) on vacuum cushions and carbon-fiber couches and then to modify the dosimetric plan accordingly. Eleven prostate cancer patients undergoing IMRT were treated in prone position with a vacuum cushion. Two under-couch beams scattered the radiation from the vacuum cushion and carbon-fiber couch. The IMRT plans with both devices contoured were compared with the plans not contouring them. The skin doses were measured using thermoluminescent dosimeters (TLDs) placed on the inguinal regions in a single IMRT fraction. Tissue equivalent thickness was transformed for both devices with the relative densities. The TLD-measured skin doses (59.5 +/- 9.5 cGy and 55.6 +/- 5.9 cGy at left and right inguinal regions, respectively) were significantly higher than the calculated doses (28.7 +/- 4.7 cGy; p = 2.2 x 10(-5) and 26.2 +/- 4.3 cGy; p = 1.5 x 10(-5)) not contouring the vacuum cushion and carbon-fiber couch. The calculated skin doses with both devices contoured (59.1 +/- 8.8 cGy and 55.5 +/- 5.7 cGy) were similar to the TLD-measured doses. In addition, the calculated skin doses using the vacuum cushion and a converted thickness of the simulator couch were no different from the TLD-measured doses. The recalculated doses of rectum and bladder did not change significantly. The dose that covered 95% of target volume was less than the prescribed dose in 4 of 11 patients, and this problem was solved after re-optimization applying the corrected contours. The vacuum cushion and carbon-fiber couch contributed to increased skin doses. The tissue-equivalent-thickness method served as an effective way to correct the dose variations.

Reduced incidence of interstitial pneumonitis after allogeneic hematopoietic stem cell transplantation using a modified technique of total body irradiation

Allogeneic hematopoietic stem cell transplantation is a curative-intent treatment for patients with high-risk hematologic diseases. However, interstitial pneumonitis (IP) and other toxicities remain major concerns after total body irradiation (TBI). We have proposed using linear accelerators with rice-bag compensators for intensity modulation (IM-TBI), as an alternative to the traditional cobalt-60 teletherapy with lung-shielding technique (Co-TBI). Patients who received a TBI-based myeloablative conditioning regimen between 1995 and 2014 were recruited consecutively. Before March 2007, TBI was delivered using Co-TBI (n = 181); afterward, TBI was administered using IM-TBI (n = 126). Forty-four patients developed IP; of these cases, 19 were idiopathic. The IP-related mortality rate was 50% in the total IP cohort and 63% in the idiopathic subgroup. The 1-year cumulative incidences of IP and idiopathic IP were 16.5% and 7.4%, respectively; both rates were significantly higher in the Co-TBI group than in the IM-TBI group. Multivariate analysis revealed that Co-TBI was an independent prognostic factor for both total and idiopathic IP. In the acute myeloid leukemia subgroup, patients with different TBI techniques had similar outcomes for both overall and relapse-free survival. In conclusion, IM-TBI is an easy and effective TBI technique that could substantially reduce the complication rate of IP without compromising treatment efficacy.