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Publications (9)35.48 Total impact

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    ABSTRACT: To report quality of life (QOL)/toxicity in men treated with proton beam therapy for localized prostate cancer and to compare outcomes between passively scattered proton therapy (PSPT) and spot-scanning proton therapy (SSPT). Men with localized prostate cancer enrolled on a prospective QOL protocol with a minimum of 2 years' follow-up were reviewed. Comparative groups were defined by technique (PSPT vs SSPT). Patients completed Expanded Prostate Cancer Index Composite questionnaires at baseline and every 3-6 months after proton beam therapy. Clinically meaningful differences in QOL were defined as ≥0.5 × baseline standard deviation. The cumulative incidence of modified Radiation Therapy Oncology Group grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity and argon plasma coagulation were determined by the Kaplan-Meier method. A total of 226 men received PSPT, and 65 received SSPT. Both PSPT and SSPT resulted in statistically significant changes in sexual, urinary, and bowel Expanded Prostate Cancer Index Composite summary scores. Only bowel summary, function, and bother resulted in clinically meaningful decrements beyond treatment completion. The decrement in bowel QOL persisted through 24-month follow-up. Cumulative grade ≥2 GU and GI toxicity at 24 months were 13.4% and 9.6%, respectively. There was 1 grade 3 GI toxicity (PSPT group) and no other grade ≥3 GI or GU toxicity. Argon plasma coagulation application was infrequent (PSPT 4.4% vs SSPT 1.5%; P=.21). No statistically significant differences were appreciated between PSPT and SSPT regarding toxicity or QOL. Both PSPT and SSPT confer low rates of grade ≥2 GI or GU toxicity, with preservation of meaningful sexual and urinary QOL at 24 months. A modest, yet clinically meaningful, decrement in bowel QOL was seen throughout follow-up. No toxicity or QOL differences between PSPT and SSPT were identified. Long-term comparative results in a larger patient cohort are warranted.
    International journal of radiation oncology, biology, physics 10/2013; · 4.59 Impact Factor
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    ABSTRACT: PURPOSE: This study was designed to validate a fully automated adaptive planning (AAP) method which integrates automated recontouring and automated replanning to account for interfractional anatomical changes in prostate cancer patients receiving adaptive intensity modulated radiation therapy (IMRT) based on daily repeated computed tomography (CT)-on-rails images. METHODS AND MATERIALS: Nine prostate cancer patients treated at our institution were randomly selected. For the AAP method, contours on each repeat CT image were automatically generated by mapping the contours from the simulation CT image using deformable image registration. An in-house automated planning tool incorporated into the Pinnacle treatment planning system was used to generate the original and the adapted IMRT plans. The cumulative dose-volume histograms (DVHs) of the target and critical structures were calculated based on the manual contours for all plans and compared with those of plans generated by the conventional method, that is, shifting the isocenters by aligning the images based on the center of the volume (COV) of prostate (prostate COV-aligned). RESULTS: The target coverage from our AAP method for every patient was acceptable, while 1 of the 9 patients showed target underdosing from prostate COV-aligned plans. The normalized volume receiving at least 70 Gy (V70), and the mean dose of the rectum and bladder were reduced by 8.9%, 6.4 Gy and 4.3%, 5.3 Gy, respectively, for the AAP method compared with the values obtained from prostate COV-aligned plans. CONCLUSIONS: The AAP method, which is fully automated, is effective for online replanning to compensate for target dose deficits and critical organ overdosing caused by interfractional anatomical changes in prostate cancer.
    International journal of radiation oncology, biology, physics 05/2013; · 4.59 Impact Factor
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    ABSTRACT: Definitive radiation therapy is the preferred treatment for many men with prostate cancer. Several modalities are used for radiation treatment delivery, including 3-dimensional conformal radiation therapy, intensity-modulated radiation therapy, proton beam therapy, stereotactic body radiation therapy, high-dose-rate prostate brachytherapy, and low-dose-rate prostate brachytherapy. This article reviews technologic advances that have enhanced radiation delivery and describes contemporary radiation treatment techniques for prostate cancer.
    Journal of the National Comprehensive Cancer Network: JNCCN 04/2013; 11(4):414-21. · 5.11 Impact Factor
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    ABSTRACT: We performed a comprehensive comparative study of the plan quality between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) for the treatment of prostate cancer. Eleven patients with prostate cancer treated at our institution were randomly selected for this study. For each patient, a VMAT plan and a series of IMRT plans using an increasing number of beams (8, 12, 16, 20, and 24 beams) were examined. All plans were generated using our in-house-developed automatic inverse planning (AIP) algorithm. An existing eight-beam clinical IMRT plan, which was used to treat the patient, was used as the reference plan. For each patient, all AIP-generated plans were optimized to achieve the same level of planning target volume (PTV) coverage as the reference plan. Plan quality was evaluated by measuring mean dose to and dose-volume statistics of the organs at risk, especially the rectum, from each type of plan. For the same PTV coverage, the AIP-generated VMAT plans had significantly better plan quality in terms of rectum sparing than the eight-beam clinical and AIP-generated IMRT plans (p < 0.0001). However, the differences between the IMRT and VMAT plans in all the dosimetric indices decreased as the number of beams used in IMRT increased. IMRT plan quality was similar or superior to that of VMAT when the number of beams in IMRT was increased to a certain number, which ranged from 12 to 24 for the set of patients studied. The superior VMAT plan quality resulted in approximately 30% more monitor units than the eight-beam IMRT plans, but the delivery time was still less than 3 min. Considering the superior plan quality as well as the delivery efficiency of VMAT compared with that of IMRT, VMAT may be the preferred modality for treating prostate cancer.
    International journal of radiation oncology, biology, physics 07/2012; 83(4):1169-78. · 4.59 Impact Factor
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    ABSTRACT: NK cells have therapeutic potential for a wide variety of human malignancies. However, because NK cells expand poorly in vitro, have limited life spans in vivo, and represent a small fraction of peripheral white blood cells, obtaining sufficient cell numbers is the major obstacle for NK-cell immunotherapy. Genetically-engineered artificial antigen-presenting cells (aAPCs) expressing membrane-bound IL-15 (mbIL15) have been used to propagate clinical-grade NK cells for human trials of adoptive immunotherapy, but ex vivo proliferation has been limited by telomere shortening. We developed K562-based aAPCs with membrane-bound IL-21 (mbIL21) and assessed their ability to support human NK-cell proliferation. In contrast to mbIL15, mbIL21-expressing aAPCs promoted log-phase NK cell expansion without evidence of senescence for up to 6 weeks of culture. By day 21, parallel expansion of NK cells from 22 donors demonstrated a mean 47,967-fold expansion (median 31,747) when co-cultured with aAPCs expressing mbIL21 compared to 825-fold expansion (median 325) with mbIL15. Despite the significant increase in proliferation, mbIL21-expanded NK cells also showed a significant increase in telomere length compared to freshly obtained NK cells, suggesting a possible mechanism for their sustained proliferation. NK cells expanded with mbIL21 were similar in phenotype and cytotoxicity to those expanded with mbIL15, with retained donor KIR repertoires and high expression of NCRs, CD16, and NKG2D, but had superior cytokine secretion. The mbIL21-expanded NK cells showed increased transcription of the activating receptor CD160, but otherwise had remarkably similar mRNA expression profiles of the 96 genes assessed. mbIL21-expanded NK cells had significant cytotoxicity against all tumor cell lines tested, retained responsiveness to inhibitory KIR ligands, and demonstrated enhanced killing via antibody-dependent cell cytotoxicity. Thus, aAPCs expressing mbIL21 promote improved proliferation of human NK cells with longer telomeres and less senescence, supporting their clinical use in propagating NK cells for adoptive immunotherapy.
    PLoS ONE 01/2012; 7(1):e30264. · 3.53 Impact Factor
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    ABSTRACT: To describe our experiences with patient-specific quality assurance (QA) for patients with prostate cancer receiving spot scanning proton therapy (SSPT) using single-field uniform dose (SFUD). The first group of 249 patients with prostate cancer treated with SSPT using SFUD was included in this work. The scanning-beam planning target volume and number of monitor units were recorded and checked for consistency. Patient-specific dosimetric measurements were performed, including the point dose for each plan, depth doses, and two-dimensional (2D) dose distribution in the planes perpendicular to the incident beam direction for each field at multiple depths. The γ-index with 3% dose or 3-mm distance agreement criteria was used to evaluate the 2D dose distributions. We observed a linear relationship between the number of monitor units and scanning-beam planning target volume. The difference between the measured and calculated point doses (mean ± SD) was 0.0% ± 0.7% (range, -2.9% to 1.8%). In general, the depth doses exhibited good agreement except at the distal end of the spread-out Bragg peak. The pass rate of γ-index (mean ± SD) for 2D dose comparison was 96.2% ± 2.6% (range, 90-100%). Discrepancies between the measured and calculated dose distributions primarily resulted from the limitation of the model used by the treatment planning system. We have established a patient-specific QA program for prostate cancer patients receiving SSPT using SFUD.
    International journal of radiation oncology, biology, physics 02/2011; 81(2):552-9. · 4.59 Impact Factor
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    ABSTRACT: In intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT), the use of posterior oblique beams has become common. Beam attenuation by the treatment couch is not negligible when the couch is in the beam portal. In this study, we established the relationship of relative dose vs. beam angle for two Varian 21EX linacs, one equipped with the Exact couch (standard couch) with sliding side support rails, and the other equipped with the Exact image-guided radiation therapy (IGRT) carbon fiber couch. Measurements were performed using an ion chamber placed at the center of an acrylic cylindrical phantom positioned at the linac isocenter for 6 MV and 18 MV photon beams. Measurements were performed at three different field sizes (3 × 3, 5 × 5, and 10 × 10 cm2), and were repeated with the phantom positioned at different longitudinal locations on the couches. To evaluate beam attenuation by the standard couch in a clinical setting, two test IMRT plans and two test VMAT plans on the standard couch were delivered. The plans were generated with the sliding rails at the "in" position and delivered with the rails at both "in" and "out" positions. The dose difference to the ion chamber was determined. For oblique fields with 6 MV photons, the standard couch attenuated the radiation beam by up to 26.8%, while the carbon fiber IGRT couch attenuated the beam by up to 4.1%. In the clinical evaluation, the highest dose difference between rails set at the "in" and "out" positions was 2.6% in the IMRT case and 2.1% in the VMAT case. The magnitude of potential dose difference has been quantified and could be used for a quick estimation of dose difference due to couch attenuation in IMRT and VMAT.
    Journal of Applied Clinical Medical Physics 01/2011; 12(3):3471. · 0.96 Impact Factor
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    ABSTRACT: After a new in-vault CT-on-rails system repeatedly malfunctioned following use of a high-energy radiotherapy beam, we investigated the presence and impact of neutron radiation on this electronic system, as well as neutron shielding options. We first determined the CT scanner's failure rate as a function of the number of 18 MV monitor units (MUs) delivered. We then re-examined the failure rate with both 2.7-cm-thick and 7.6-cm-thick borated polyethylene (BPE) covering the linac head for neutron shielding. To further examine shielding options, as well as to explore which neutrons were relevant to the scanner failure, Monte Carlo simulations were used to calculate the neutron fluence and spectrum in the bore of the CT scanner. Simulations included BPE covering the CT scanner itself as well as covering the linac head. We found that the CT scanner had a 57% chance of failure after the delivery of 200 MUs. While the addition of neutron shielding to the accelerator head reduced this risk of failure, the benefit was minimal and even 7.6 cm of BPE was still associated with a 29% chance of failure after the delivery of 200 MU. This shielding benefit was achieved regardless of whether the linac head or CT scanner was shielded. Additionally, it was determined that fast neutrons were primarily responsible for the electronic failures. As illustrated by the CT-on-rails system in the current study, physicists should be aware that electronic systems may be highly sensitive to neutron radiation. Medical physicists should therefore monitor electronic systems that have not been evaluated for potential neutron sensitivity. This is particularly relevant as electronics are increasingly common in the therapy vault and newer electronic systems may exhibit increased sensitivity.
    Medical Physics 01/2011; 38(1):34-9. · 2.91 Impact Factor
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    ABSTRACT: To evaluate the impact of the number and location of intraprostatic fiducial markers on the accuracy and reproducibility of daily prostate target alignment and to evaluate the migration of such markers. Three gold fiducial markers were implanted transrectally under ultrasound guidance near the apex, middle, and base of the prostate in 10 prostate cancer patients. The patients had pretreatment in-room computed tomography (CT) scans three times a week, for approximately 25 CT scans per patient during the 8-week treatment course. A total of 1280 alignments were performed using different alignment scenarios: whole-prostate soft tissue alignment (the gold standard), bone alignment, and seven permutations of alignments using one, two, or three fiducial markers. The results of bone alignment and fiducial alignment were compared with the results of whole-prostate alignment. Fiducial migration was also evaluated. Single-fiducial-marker alignment was more accurate and reproducible than bone alignment. However, due to organ deformation, single fiducial markers did not always reliably represent the position of the entire prostate. The use of two-fiducial combinations was more accurate and reproducible than single-fiducial alignment, and use of all three fiducials was the best. Use of an apex fiducial together with a base fiducial rivaled the use of all three fiducials markers together. Fiducial migration was minimal. The number and the location of implanted fiducial markers affect the accuracy and reliability of daily prostate target alignment. The use of two or more fiducial markers is recommended.
    International journal of radiation oncology, biology, physics 06/2009; 74(4):1283-9. · 4.59 Impact Factor