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ABSTRACT: Patients undergoing radiation for left-sided breast cancer have increased rates of coronary artery disease. Free-breathing intensity-modulated radiation therapy (FB-IMRT) and 3-dimensional conformal deep inspiratory-breath hold (3D-DIBH) reduce cardiac irradiation. The purpose of this study is to compare the dose to organs at risk in FB-IMRT vs 3D-DIBH for patients with left-sided breast cancer. Ten patients with left-sided breast cancer had 2 computed tomography scans: free breathing and voluntary DIBH. Optimization of the IMRT plan was performed on the free-breathing scan using 6 noncoplanar tangential beams. The 3D-DIBH plan was optimized on the DIBH scan and used standard tangents. Mean volumes of the heart, the left anterior descending coronary artery (LAD), the total lung, and the right breast receiving 5% to 95% (5% increments) of the prescription dose were calculated. Mean volumes of the heart and the LAD were lower (p<0.05) in 3D-DIBH for volumes receiving 5% to 80% of the prescription dose for the heart and 5% for the LAD. Mean dose to the LAD and heart were lower in 3D-DIBH (p≤0.01). Mean volumes of the total lung were lower in FB-IMRT for dose levels 20% to 75% (p<0.05), but mean dose was not different. Mean volumes of the right breast were not different for any dose; however, mean dose was lower for 3D-DIBH (p = 0.04). 3D-DIBH is an alternative approach to FB-IMRT that provides a clinically equivalent treatment for patients with left-sided breast cancer while sparing organs at risk with increased ease of implementation.
Medical dosimetry: official journal of the American Association of Medical Dosimetrists 02/2013; · 1.26 Impact Factor
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ABSTRACT: PURPOSE: To investigate pulmonary radiologic changes after lung stereotactic body radiotherapy (SBRT), to distinguish between mass-like fibrosis and tumor recurrence. METHODS AND MATERIALS: Eighty consecutive patients treated with 3- to 5-fraction SBRT for early-stage peripheral non-small cell lung cancer with a minimum follow-up of 12 months were reviewed. The mean biologic equivalent dose received was 150 Gy (range, 78-180 Gy). Patients were followed with serial CT imaging every 3 months. The CT appearance of consolidation was defined as diffuse or mass-like. Progressive disease on CT was defined according to Response Evaluation Criteria in Solid Tumors 1.1. Positron emission tomography (PET) CT was used as an adjunct test. Tumor recurrence was defined as a standardized uptake value equal to or greater than the pretreatment value. Biopsy was used to further assess consolidation in select patients. RESULTS: Median follow-up was 24 months (range, 12.0-36.0 months). Abnormal mass-like consolidation was identified in 44 patients (55%), whereas diffuse consolidation was identified in 12 patients (15%), at a median time from end of treatment of 10.3 months and 11.5 months, respectively. Tumor recurrence was found in 35 of 44 patients with mass-like consolidation using CT alone. Combined with PET, 10 of the 44 patients had tumor recurrence. Tumor size (hazard ratio 1.12, P=.05) and time to consolidation (hazard ratio 0.622, P=.03) were predictors for tumor recurrence. Three consecutive increases in volume and increasing volume at 12 months after treatment in mass-like consolidation were highly specific for tumor recurrence (100% and 80%, respectively). Patients with diffuse consolidation were more likely to develop grade ≥2 pneumonitis (odds ratio 26.5, P=.02) than those with mass-like consolidation (odds ratio 0.42, P=.07). CONCLUSION: Incorporating the kinetics of mass-like consolidation and PET to the current criteria for evaluating posttreatment response will increase the likelihood of correctly identifying patients with progressive disease after lung SBRT.
International journal of radiation oncology, biology, physics 08/2012; · 4.59 Impact Factor
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ABSTRACT: To investigate the prognostic significance of p16 in patients with hypopharyngeal squamous cell carcinoma (HPSCC) and to evaluate the relationship between p16 and human papillomavirus (HPV). Unlike in oropharyngeal SCC (OPSCC), the prognostic significance of p16 in HPSCC and its association with HPV is unclear.
Retrospective medical chart review.
University tertiary referral center.
A total of 27 patients with HPSCC treated with definitive radiation therapy between 2002 and 2011 whose tissue was available for immunohistochemical analysis.
Twenty-two patients were treated with chemoradiation, and 5 with radiation alone. All tumor biopsy specimens were analyzed for p16 and, when sufficient tissue was available, for HPV DNA.
Overall survival (OS), locoregional control (LRC), disease-free survival (DFS), and laryngoesophageal dysfunction-free survival (LEDFS) were analyzed according to p16 status.
Findings for p16 were positive in 9 tumors and negative in 18 tumors. Median follow-up was 29.3 months. There was no significant difference in OS, LRC, DFS, or LEDFS for patients with p16-positive vs p16-negative tumors. Only 1 of the 19 tumors tested for HPV was found to be HPV positive. When used as a test for HPV, p16 had a positive predictive value of 17%.
In contrast to OPSCC, p16 expression in patients with HPSCC had a low positive predictive value for HPV and did not predict improved OS, LRC, DFS, or LEDFS. Thus, for HPSCC, p16 is not a prognostic biomarker. Caution must be taken when extrapolating the prognostic significance of p16 in patients with OPSCC to patients with head and neck SCC of other subsites.
Archives of otolaryngology--head & neck surgery 06/2012; 138(6):556-61. · 1.92 Impact Factor
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ABSTRACT: We evaluated a panel of 8 immunohistochemical biomarkers as predictors of clinical response to definitive intensity-modulated radiotherapy in patients with oropharyngeal squamous cell carcinoma (OPSCC). 106 patients with OPSCC were treated to a total dose of 66-70 Gy and retrospectively analyzed for locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). All tumors had p16 immunohistochemical staining, and 101 tumors also had epidermal growth factor receptor (EGFR) staining. 53% of the patients had sufficient archived pathologic specimens for incorporation into a tissue microarray for immunohistochemical analysis for cyclophilin B, cyclin D1, p21, hypoxia-inducible factor-1α (HIF-1α), carbonic anhydrase, and major vault protein. Median followup was 27.2 months. 66% of the tumors were p16 positive, and 34% were p16 negative. On univariate analysis, the following correlations were statistically significant: p16 positive staining with higher LRC (P = 0.005) and longer DFS (P < 0.001); cyclin D1 positive staining with lower LRC (P = 0.033) and shorter DFS (P = 0.002); HIF-1α positive staining with shorter DFS (P = 0.039). On multivariate analysis, p16 was the only significant independent predictor of DFS (P = 0.023). After immunohistochemical examination of a panel of 8 biomarkers, our study could only verify p16 as an independent prognostic factor in OPSCC.
International Journal of Otolaryngology 01/2012; 2012:685951.
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ABSTRACT: The research quantitatively evaluates the dosimetric advantage of a helical tomotherapy (HT) intensity-modulated radiation therapy simultaneous integrated boost (SIB) compared to a conventional HT sequential (SEQ) boost for primary intracranial tumors.
Hypothetical lesions (planning target volumes or PTVs) were contoured within computed tomography scans from normal controls. A dose of 50 Gy was prescribed to the larger PTV1, while the boost PTV2 received a total of 60 Gy. HT SEQ and HT SIB plans were generated and compared. We evaluated the mean brain dose, the volume of normal brain receiving 45 Gy (V45), the volume of normal brain receiving 5 Gy (V5), and the integral dose. In addition, patients who were treated with the HT SEQ technique were replanned with the HT SIB technique and compared.
The average reduction in mean brain dose with the HT SIB plan compared to the composite HT SEQ plan was 11·0% [standard error (SE): 0·5]. The reductions in brains V45 and V5 were 43·7% (SE: 2·3) and 3·9% (SE: 0·6), respectively. The reduction in the integral dose was 11·0% (SE: 0·5). When comparing the SIB plan to the first 50 Gy only of the SEQ plan, there was only a 2·5% increase in the mean brain dose and a 2·9% increase in brain V45. This increase was dependent on the relative volumes of PTV2 and PTV1. These results were confirmed for the patient plans compared.
Treating primary brain tumors with the HT SIB technique provides significant sparing of normal brain parenchyma compared to a conventional HT SEQ boost.
Neurological Research 10/2011; 33(8):820-4. · 1.52 Impact Factor
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ABSTRACT: Voluntary deep inhalation breath hold (VDIBH) reduces heart dose during left breast irradiation. We present results of the first study performed to quantify reproducibility of breath hold using bony anatomy, heart position, and heart dose for VDIBH patients at treatment table.
Data from 10 left breast cancer patients undergoing VDIBH whole-breast irradiation were analyzed. Two computed tomography (CT) scans, free breathing (FB) and VDIBH, were acquired to compare dose to critical structures. Pretreatment weekly kV orthogonal images and tangential ports were acquired. The displacement difference from spinal cord to sternum across the isocenter between coregistered planning Digitally Reconstructed Radiographs (DRRs) and kV imaging of bony thorax is a measure of breath hold reproducibility. The difference between bony coregistration and heart coregistration was the measured heart shift if the patient is aligned to bony anatomy.
Percentage of dose reductions from FB to VDIBH: mean heart dose (48%, SD 19%, p = 0.002), mean LAD dose (43%, SD 19%, p = 0.008), and maximum left anterior descending (LAD) dose (60%, SD 22%, p = 0.008). Average breath hold reproducibility using bony anatomy across the isocenter along the anteroposterior (AP) plane from planning to treatment is 1 (range, 0-3; SD, 1) mm. Average heart shifts with respect to bony anatomy between different breath holds are 2 ± 3 mm inferior, 1 ± 2 mm right, and 1 ± 3 mm posterior. Percentage dose changes from planning to delivery: mean heart dose (7%, SD 6%); mean LAD dose, ((9%, SD 7%)S, and maximum LAD dose, (11%, SD 11%) SD 11%, p = 0.008).
We observed excellent three-dimensional bony registration between planning and pretreatment imaging. Reduced delivered dose to heart and LAD is maintained throughout VDIBH treatment.
International journal of radiation oncology, biology, physics 04/2011; 81(4):e569-76. · 4.59 Impact Factor
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ABSTRACT: To investigate the feasibility of lung ventilation-based treatment planning, computed tomography and hyperpolarized (HP) helium-3 (He-3) magnetic resonance imaging (MRI) ventilation images of 6 subjects were coregistered for intensity-modulated radiation therapy planning in Tomotherapy. Highly-functional lungs (HFL) and less-functional lungs (LFL) were contoured based on their ventilation image intensities, and a cylindrical planning-target-volume was simulated at locations adjacent to both HFL and LFL. Annals of an anatomy-based plan (Plan 1) and a ventilation-based plan (Plan 2) were generated. The following dosimetric parameters were determined and compared between the 2 plans: percentage of total/HFL volume receiving ≥20 Gy, 15 Gy, 10 Gy, and 5 Gy (TLV(20), HFLV(20), TLV(15), HFLV(15), TLV(10), HFLV(10), TLV(5), HFLV(5)), mean total/HFL dose (MTLD/HFLD), maximum doses to all organs at risk (OARs), and target dose conformality. Compared with Plan 1, Plan 2 reduced mean HFLD (mean reduction, 0.8 Gy), MTLD (mean reduction, 0.6 Gy), HFLV(20) (mean reduction, 1.9%), TLV(20) (mean reduction, 1.5%), TLV(15) (mean reduction, 1.7%), and TLV(10) (mean reduction, 2.1%). P-values of the above comparisons are less than 0.05 using the Wilcoxon signed rank test. For HFLV(15), HFLV(10), TLV(5), and HTLV(5), Plan 2 resulted in lower values than plan 1 but the differences are not significant (P-value range, 0.063-0.219). Plan 2 did not significantly change maximum doses to OARs (P-value range, 0.063-0.563) and target conformality (P = 1.000). HP He-3 MRI of patients with lung disease shows a highly heterogeneous ventilation capacity that can be utilized for functional treatment planning. Moderate but statistically significant improvements in sparing functional lungs were achieved using helical tomotherapy plans.
Medical dosimetry: official journal of the American Association of Medical Dosimetrists 03/2011; 36(4):389-96. · 1.26 Impact Factor
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ABSTRACT: The purpose of this study was to compare the outcomes and local control rates of patients with peripheral T1 and T2 non-small-cell lung cancer treated with stereotactic body radiation therapy.
The records of 40 consecutive patients treated with 3- or 5-fraction lung stereotactic body radiation therapy for peripheral, clinical stage I non-small-cell lung cancer were reviewed. Stereotactic body radiation therapy was delivered at a median dose of 60 Gy. Doses to organs at risk were limited based on the Radiation Therapy Oncology Group 0236 treatment protocol. Patients were staged clinically. Median follow was 12.5 months.
Twenty-seven (67%) patients and 13 (33%) patients had T1 and T2 tumors, respectively. Thirty-seven (94%) patients were medically inoperable. Nine (23%) patients had chest wall pain after stereotactic body radiation therapy. Symptomatic pneumonitis developed in 4 (10%) patients. Increasing tumor size correlated with worse local control and overall survival. The median recurrence-free survival for T1 and T2 tumors was 30.6 months (95% confidence interval [CI], 26.9-34.2) and 20.5 months (95% CI, 14.3-26.5), respectively (P = .038). Local control at 2 years was 90% and 70% in T1 and T2 tumors, respectively (P = .03). The median survival for T1 and T2 tumors was 20 months (95% CI, 20.1-31.6) and 16.7 months (95% CI, 10.8-21.2), respectively (P = .073).
Stereotactic body radiation therapy for T2 non-small-cell lung cancer has a higher local recurrence rate and trended toward a worse survival than did T1 lesions. Tumor size is an important predictor of response to stereotactic body radiation therapy and should be considered in treatment planning.
The Journal of thoracic and cardiovascular surgery 09/2010; 140(3):583-9. · 3.41 Impact Factor
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ABSTRACT: To investigate the effects of breathing variation on gating window internal target volume (ITVGW) in respiratory gated radiation therapy.
Two-dimensional dynamic MRI (dMRI) of lung motion was acquired in ten volunteers and eight lung cancer patients. Resorted dMRI using 4DCT acquisition method (RedCAM) was generated for selected subjects by simulating the image rebinning process. A dynamic software generated phantom (dSGP) was created by moving a solid circle (to mimic the "tumor") with dMRI-determined motion trajectories. The gating window internal target area (ITAGw, 2D counterpart of ITVGW) was determined from both RedCAM and dSGP/dMRI. Its area (A), major axis (L1), minor axis (L2), and similarity (S) were calculated and compared.
In the phantom study of 3 cm tumor, measurements of the ITAGW from dSGP (A =10.0 +/- 1.3 cm2, L1=3.8 +/- 0.4 cm, and L2=3.3 +/- 0.1 cm) are significantly (p <0.001) greater than those from RedCAM (A=8.5 +/- 0.7 cm(2), L1 =3.5 +/- 0.2 cm, and L2=3.1 +/- 0.1 cm). Similarly, the differences are significantly greater (p <0.001) for the 1 cm tumor (A=1.9 +/- 0.5 cm(2), L1 =1.9 +/- 0.4 cm, and L2=1.3 +/- 0.1 cm in dSGP; A=l1.3 +/- 0.1 cm(2), L1=1.5 +/- 0.2 cm, and L2 = 1.1 +/- 0.1 cm in RedCAM). In patient studies, measurements of the ITAGW from dMRI (A =15.5 +/- 8.2 cm(2), Ll=5.0 +/- 1.1 cm, and L2=3.8 +/- 1.2 cm) are also significantly greater (p <0.05) than those from RedCAM (A=13.2 +/- 8.5 cm(2), L1=4.3 +/- 1.4 cm, and L2=3.7 +/- 1.2 cm). Similarities were 0.9 +/- 0.1, 0.8 +/- 0.1, and 0.8 +/- 0.1 in the 3 cm tumor phantom, 1 cm tumor phantom, and patient studies, respectively.
ITVGW can be underestimated by 4DCT due to breathing variations. An additional margin may be needed to account for this potential error in generating a PTVGW. Cautions need to be taken when generating ITVGW from 4DCT in respiratory gated radiation therapy, especially for small tumors (<3 cm) with a large motion range (>1 cm).
Medical Physics 08/2010; 37(8):3927-34. · 2.83 Impact Factor
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ABSTRACT: Patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with intensity-modulated radiotherapy (IMRT) were stratified by p16 status, neck dissection, and chemotherapy to correlate these factors with outcomes.
A total of 112 patients with OPSCC treated with IMRT from 2002 to 2008 were retrospectively analyzed. All patients received RT to 66-70 Gray. Forty-five of the tumors were p16 positive (p16+), 27 were p16 negative (p16-), and 41 had unknown p16 status. Sixty-two patients had postradiation neck dissections. Nine patients with p16- tumors and 28 patients with p16+ tumors received chemotherapy. The distribution of T, N, and stage grouping among the p16+ and p16- patients was not significantly different, and 87.5% patients had stage III/IV disease.
The median follow-up was 26.3 months. For patients with p16+ tumors, p16- tumors, and the overall cohort, the actuarial 3-year locoregional progression-free survival rate was 97.8%,73.5%, and 90.5% respectively (P = .006) and the disease-free survival rate was 88.2%, 61.4%, and 81.7%, respectively (P = .004). Patients with p16+ tumors had an 89.5% and 87.5% pathologic complete response (CR) on neck dissection with and without chemotherapy, respectively. In contrast, patients with p16- tumors had a 66.7% and 25.0% pathologic CR on neck dissection with and without chemotherapy, respectively.
In this series, p16 status was found to be a significant predictive biomarker and patients with p16+ tumors had much better outcomes than patients with p16- tumors. Further investigation is warranted to determine whether less intense therapy is appropriate for selected patients with p16+ OPSCC, whereas more aggressive strategies are needed to improve outcomes in patients with p16- disease.
Cancer 03/2010; 116(11):2645-54. · 4.77 Impact Factor
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Neal Dunlap,
Alyson McIntosh,
Ke Sheng,
Wensha Yang,
Benton Turner,
Asal Shoushtari,
Jason Sheehan,
David R Jones,
Weigo Lu,
Keneth Ruchala,
Gustavo Olivera,
Donald Parnell,
James L Larner,
Stanley H Benedict, Paul W Read
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ABSTRACT: Stereotactic body radiation therapy (SBRT) treatments have high-dose gradients and even slight patient misalignment from the simulation to treatment could lead to target underdosing or organ at risk (OAR) overdosing. Daily real-time SBRT treatment planning could minimize the risk of geographic miss. As an initial step toward determining the clinical feasibility of developing real-time SBRT treatment planning, we determined the calculation time of helical TomoTherapy-based STAT radiation therapy (RT) treatment plans for simple liver, lung, and spine SBRT treatments to assess whether the planning process was fast enough for practical clinical implementation. Representative SBRT planning target volumes for hypothetical liver, peripheral lung, and thoracic spine lesions and adjacent OARs were contoured onto a planning computed tomography scan (CT) of an anthropomorphic phantom. Treatment plans were generated using both STAT RT "full scatter" and conventional helical TomoTherapy "beamlet" algorithms. Optimized plans were compared with respect to conformality index (CI), heterogeneity index (HI), and maximum dose to regional OARs to determine clinical equivalence and the number of required STAT RT optimization iterations and calculation times were determined. The liver and lung dosimetry for the STAT RT and standard planning algorithms were clinically and statistically equivalent. For the liver lesions, "full scatter" and "beamlet" algorithms showed a CI of 1.04 and 1.04 and HI of 1.03 and 1.03, respectively. For the lung lesions, "full scatter" and "beamlet" algorithms showed a CI of 1.05 and 1.03 and HI of 1.05and 1.05, respectively. For spine lesions, "full scatter" and "beamlet" algorithms showed a CI of 1.15 and 1.14 and HI of 1.22 and 1.14, respectively. There was no difference between treatment algorithms with respect to maximum doses to the OARs. The STAT RT iteration time with current treatment planning systems is 45 sec, and the treatment planning required 3 iterations or 135 sec for STAT RT liver and lung SBRT plans and 7 iterations or 315 sec for STAT RT spine SBRT plans. Helical TomoTherapy-based STAT RT treatment planning with the "full scatter" algorithm provides levels of dosimetric conformality, heterogeneity, and OAR avoidance for SBRT treatments that are clinically equivalent to those generated with the Helical TomoTherapy "beamlet" algorithm. STAT RT calculation times for simple SBRT treatments are fast enough to warrant further investigation into their potential incorporation into an SBRT program with daily real-time planning. Development of methods for accurate target and OAR determination on megavoltage computed tomography scans incorporating high-resolution diagnostic image co-registration software and CT detector-based exit dose measurement for quality assurance are necessary to build a real-time SBRT planning and delivery program.
Medical dosimetry: official journal of the American Association of Medical Dosimetrists 01/2010; 35(4):312-9. · 1.26 Impact Factor
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ABSTRACT: We report the case of a primary nasopharyngeal interdigitating dendritic cell tumor (IDDCT). A 25-year old male presented with bilateral decreased hearing, double vision, and ataxia. Flexible nasopharyngoscopy reviewed a large mass obstructing and filling the entire nasopharynx. MRI and PET-CT confirmed the presence of the primary tumor and demonstrated bilateral cervical lymphadenopathy. Biopsy of the nasopharynx revealed a hematolymphoid neoplasm with dendritic cell differentiation, most consistent with an IDDCT. The lesion was unresectable. The patient was treated with definitive radiotherapy to 66 Gy to the primary tumor and 50 Gy to the bilateral cervical lymphatics using an IMRT technique. A complete response was achieved and the patient remains disease free at the primary site 23 months after completion of radiotherapy.
Rare tumors 01/2010; 2(1):e9.
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ABSTRACT: We report a case of a primary pericardial malignant mesothelioma. A 59-year-old male presented with episodic chest pain and dyspnea on exertion. Cardiac magnetic resonance imaging revealed a large mass in the pericardium attached to the right ventricle. Partial resection of the mass was undertaken revealing malignant mesothelioma, byphasic type. The patient was treated with chemotherapy intermittently over a period of 3 years, but his disease continued to progress. The patient was then treated with definitive radiation therapy to 64 Gy to the primary tumor using a six field 3D conformal technique. The patient remains free of progressive disease 86 months from the time of diagnosis and 50 months from the completion of his radiotherapy.
Rare tumors 01/2010; 2(3):e51.
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ABSTRACT: Patients with human papillomavirus (HPV)-positive oropharyngeal carcinoma (OC) have better prognosis than patients with HPV-negative OC. The objective of the current study was to assess how different practices across the United States treat patients with OC with respect to screening for HPV DNA or p16.
Five hundred forty-two randomly selected radiation oncologists were sent an 11-question survey by email regarding the use of HPV/p16 screening in OC. The questionnaire addressed demographics of the practice, intensity-modulated radiotherapy (IMRT) use, screening practices for HPV DNA or p16, which year this began, the use of HPV or p16 data to direct patient care, and future plans for its use if it had not already been instituted.
One hundred ninety-two responses (39.6%) were received. Thirty-five percent of respondents (67 of 188) reported screening for HPV DNA routinely, whereas 4.8% of respondents (9 of 188) reported screening for p16. Of the physicians who did not use screening techniques, 37.2% (44 of 118 respondents) reported future plans to institute these screening techniques, 20% (9 of 45 respondents) stated plans to institute these techniques in the next 6 months, 55.5% (25 of 45 respondents) stated plans to institute these techniques within 6 months to 1 year, and 22.2% (10 of 45 respondents) stated plans to institute these techniques within 1 to 2 years. Academic physicians were more likely to use screening techniques (62.7%; P < .001) compared with private practitioners (31.4%). Only 12.4% of respondents reported using HPV or p16 data to direct care.
Approximately 40.4% of radiation oncology practices that responded to a survey in the United States screened for HPV DNA or p16 in OC, whereas only 12.4% used it to further direct care. This number appears to be growing rapidly. Clinical trials to further elucidate how HPV or p16 status should direct care in OC are warranted.
Cancer 11/2009; 116(2):514-9. · 4.77 Impact Factor
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ABSTRACT: To identify factors that predict complete response of cervical nodal disease to radiation therapy (RT) in patients with oropharyngeal squamous cell carcinoma (OP-SCCA).
Histologic analysis of prospectively collected specimens and retrospective medical chart review.
Tertiary referral center.
Sixty-nine patients with OP-SCCA treated from January 1, 2002, through June 1, 2008.
Definitive RT, with or without chemotherapy and with or without neck dissection (ND).
Presence of a viable tumor in post-RT ND specimen.
Tissue specimens from 69 patients with OP-SCCA treated primarily with RT, with or without chemotherapy, were evaluated. Of these, 47 (68.1%) were strongly and diffusely positive for p16 expression by immunohistochemical analysis, signifying human papillomavirus positivity. Patients with p16-positive and p16-negative tumors (hereinafter, p16+ and p16-, respectively) had similarly sized primary tumors on presentation, but p16+ primary tumors were associated with more advanced neck disease (nodal stages N2c-N3; 31.9% vs 4.5% for p16- tumors) and more contralateral nodes (27.7% vs 4.5% for p16- tumors). Forty-seven patients (59.0%) underwent planned posttreatment ND (a total of 55 NDs). The NDs performed for p16- tumors were significantly more likely to have viable tumor in the specimen (50.0% vs 18.0% for p16+ tumors; P = .02). In addition, p16+ necks with residual viable cancer were characterized by incomplete response on post-RT imaging, tobacco and alcohol use, and extracapsular spread on pretreatment imaging.
In conjunction with other clinical parameters, p16 status can help predict the need for post-RT ND in patients with OP-SCCA. Although close observation may be warranted in selected patients with p16+ tumors, patients with p16- tumors are at much higher risk for residual neck disease, even when initial nodal disease is less advanced.
Archives of otolaryngology--head & neck surgery 11/2009; 135(11):1126-32. · 1.92 Impact Factor
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ABSTRACT: Helical tomotherapy-based STAT radiation therapy (RT) uses an efficient software algorithm for rapid intensity-modulated treatment planning, enabling conformal radiation treatment plans to be generated on megavoltage computed tomography (MVCT) scans for CT simulation, treatment planning, and treatment delivery in one session. We compared helical tomotherapy-based STAT RT dosimetry with standard linac-based 3D conformal plans and standard helical tomotherapy-based intensity-modulated radiation therapy (IMRT) dosimetry for palliative treatments of whole brain, a central obstructive lung mass, multilevel spine disease, and a hip metastasis. Specifically, we compared the conformality, homogeneity, and dose with regional organs at risk (OARs) for each plan as an initial step in the clinical implementation of a STAT RT rapid radiation palliation program. Hypothetical planning target volumes (PTVs) were contoured on an anthropomorphic phantom in the lung, spine, brain, and hip. Treatment plans were created using three planning techniques: 3D conformal on Pinnacle³, helical tomotherapy, and helical tomotherapy-based STAT RT. Plan homogeneity, conformality, and dose to OARs were analyzed and compared. STAT RT and tomotherapy improved conformality indices for spine and lung plans (CI spine = 1.21, 1.17; CI lung = 1.20, 1.07, respectively) in comparison with standard palliative anteroposterior/posteroanterior (AP/PA) treatment plans (CI spine = 7.01, CI lung = 7.30), with better sparing of heart, esophagus, and spinal cord. For palliative whole-brain radiotherapy, STAT RT and tomotherapy reduced maximum and mean doses to the orbits and lens (maximum/mean lens dose: STAT RT = 2.94/2.65 Gy, tomotherapy = 3.13/2.80 Gy, Lateral opposed fields = 7.02/3.65 Gy), with an increased dose to the scalp (mean scalp dose: STAT RT = 16.19 Gy, tomotherapy = 15.61 Gy, lateral opposed fields = 14.01 Gy). For bony metastatic hip lesions, conformality with both tomotherapy techniques (CI = 1.01 each) is superior to AP/PA treatments (CI = 1.21), as expected. Helical tomotherapy-based STAT RT treatment planning provides clinically acceptable dosimetry, with conformality and homogeneity that is superior to standard linac-based 3D conformal planning and is only slightly inferior to standard helical tomotherapy IMRT dosimetry. STAT RT facilitates rapid treatment planning and delivery for palliative radiation of patients with metastatic disease, with relative sparing of adjacent OARs compared with standard 3D conformal plans.
Medical dosimetry: official journal of the American Association of Medical Dosimetrists 10/2009; 35(4):280-6. · 1.26 Impact Factor
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ABSTRACT: Cardiac-synchronized brain motion is well documented, but the accurate measurement of such motion on the pixel-by-pixel basis has been hampered by the lack of proper imaging technique. In this article, the authors present the implementation of an autotracking spiral cine displacement-encoded stimulation echo (DENSE) magnetic resonance imaging (MRI) technique for the measurement of pulsatile brain motion during the cardiac cycle. Displacement-encoded dynamic MR images of three healthy volunteers were acquired throughout the cardiac cycle using the spiral cine-DENSE pulse sequence gated to the R wave of an electrocardiogram. Pixelwise Lagrangian displacement maps were computed, and 2D displacement as a function of time was determined for selected regions of interests. Different intracranial structures exhibited characteristic motion amplitude, direction, and pattern throughout the cardiac cycle. Time-resolved displacement curves revealed the pathway of pulsatile motion from brain stem to peripheral brain lobes. These preliminary results demonstrated that the spiral cine-DENSE MRI technique can be used to measure cardiac-synchronized pulsatile brain motion on the pixel-by-pixel basis with high temporal/spatial resolution and sensitivity.
Medical Physics 08/2009; 36(8):3413-9. · 2.83 Impact Factor
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ABSTRACT: To develop a dynamic magnetic resonance imaging (MRI) tagging technique using hyperpolarized helium-3 (HP He-3) to track lung motion.
An accelerated non-Cartesian k-space trajectory was used to gain acquisition speed, at the cost of introducing image artifacts, providing a viable strategy for obtaining whole-lung coverage with adequate temporal resolution. Multiple-slice two-dimensional dynamic images of the lung were obtained in three healthy subjects after inhaling He-3 gas polarized to 35%-40%. Displacement, strain, and ventilation maps were computed from the observed motion of the grid peaks.
Both temporal and spatial variations of pulmonary mechanics were observed in normal subjects, including shear motion between different lobes of the same lung.
These initial results suggest that dynamic imaging of grid-tagged hyperpolarized magnetization may potentially be a powerful tool for observing and quantifying pulmonary biomechanics on a regional basis and for assessing, validating, and improving lung deformable image registration algorithms.
International journal of radiation oncology, biology, physics 07/2009; 75(1):276-84. · 4.59 Impact Factor
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ABSTRACT: To evaluate a helical tomotherapy-based rodent radiosurgery platform that reproduces human image-guided radiosurgery treatment to study radiobiologic effects of stereotactic radiosurgery on lung tissues using functional magnetic resonance imaging (MRI).
Hypofractionated radisourgery (20 Gy x 3) was delivered to the right lung of three New Zealand rabbits using Helical TomoTherapy with MVCT image guidance. Contrast-enhanced MR perfusion, hyperpolarized helium-3 MR ventilation, and CT were obtained before radiation and monthly for 4 months after radiation. All MRI was performed on a 1.5-T whole-body scanner with broad-band capabilities.
Precise dose delivery to 1.6 cc of the lower right lung was achieved without additional immobilization. No deficits were detected at baseline with respect to perfusion and ventilation. Lung perfusion deficits in the irradiated lung regions began at 2 months after radiation and worsened with time. No ventilation deficits were observed after radiation. Decrease in lung CT density in irradiated regions was observed after radiation, but the changes were less significant than those in perfusion MRI.
We demonstrated that highly conformal radiation can be reproducibly delivered to a small volume of rodent lung on a widely available clinical unit. The radiation-induced lung injury can be detected as early as 2 months after radiation with perfusion MRI. The primary pattern of injury agrees with previously reported endothelial damage to radiosurgical radiation doses. This experimental design provides a cost-effective methodology for producing radiosurgical injuries in rodents that reproduces current human treatments for studying radiation injury and agents that might affect it.
International journal of radiation oncology, biology, physics 05/2009; 73(5):1588-95. · 4.59 Impact Factor
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ABSTRACT: It has been proposed that quantum dots (QDs) can be used to excite conjugated photosensitizers and produce cytotoxic singlet oxygen. To study the potential of using such a conjugate synergistically with radiotherapy to enhance cell killing, we investigated the energy transfer from megavoltage (MV) X-rays to a photosensitizer using QDs as the mediator and quantitated the enhancement in cell killing.
The photon emission efficiency of QDs on excitation by 6-MV X-rays was measured using dose rates of 100-600 cGy/min. A QD-Photofrin conjugate was synthesized by formation of an amide bond. The role of Förster resonance energy transfer in the energy transferred to the Photofrin was determined by measuring the degree of quenching at different QD/Photofrin molar ratios. The enhancement of H460 human lung carcinoma cell killing by radiation in the presence of the conjugates was studied using a clonogenic survival assay.
The number of visible photons generated from QDs excited by 6-MV X-rays was linearly proportional to the radiation dose rate. The Förster resonance energy transfer efficiency approached 100% as the number of Photofrin molecules conjugated to the QDs increased. The combination of the conjugate with radiation resulted in significantly lower H460 cell survival in clonogenic assays compared with radiation alone.
The novel QD-Photofrin conjugate shows promise as a mediator for enhanced cell killing through a linear and highly efficient energy transfer from X-rays to Photofrin.
International journal of radiation oncology, biology, physics 12/2008; 72(3):633-5. · 4.59 Impact Factor
