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Sample records for dose-escalated image-guided radiotherapy

  1. Image guided dose escalated prostate radiotherapy: still room to improve

    PubMed Central

    Martin, Jarad M; Bayley, Andrew; Bristow, Robert; Chung, Peter; Gospodarowicz, Mary; Menard, Cynthia; Milosevic, Michael; Rosewall, Tara; Warde, Padraig R; Catton, Charles N

    2009-01-01

    Background Prostate radiotherapy (RT) dose escalation has been reported to result in improved biochemical control at the cost of greater late toxicity. We report on the application of 79.8 Gy in 42 fractions of prostate image guided RT (IGRT). The primary objective was to assess 5-year biochemical control and potential prognostic factors by the Phoenix definition. Secondary endpoints included acute and late toxicity by the Radiotherapy Oncology Group (RTOG) scoring scales. Methods From October/2001 and June/2003, 259 men were treated with at least 2-years follow-up. 59 patients had low, 163 intermediate and 37 high risk disease. 43 had adjuvant hormonal therapy (HT), mostly for high- or multiple risk factor intermediate-risk disease (n = 25). They received either 3-dimensional conformal RT (3DCRT, n = 226) or intensity modulated RT (IMRT) including daily on-line IGRT with intraprostatic fiducial markers. Results Median follow-up was 67.8 months (range 24.4-84.7). There was no severe (grade 3-4) acute toxicity, and grade 2 acute gastrointestinal (GI) toxicity was unusual (10.1%). The 5-year incidence of grade 2-3 late GI and genitourinary (GU) toxicity was 13.7% and 12.1%, with corresponding grade 3 figures of 3.5% and 2.0% respectively. HT had an association with an increased risk of grade 2-3 late GI toxicity (11% v 21%, p = 0.018). Using the Phoenix definition for biochemical failure, the 5 year-bNED is 88.4%, 76.5% and 77.9% for low, intermediate and high risk patients respectively. On univariate analysis, T-category and Gleason grade correlated with Phoenix bNED (p = 0.006 and 0.039 respectively). Hormonal therapy was not a significant prognostic factor on uni- or multi-variate analysis. Men with positive prostate biopsies following RT had a lower chance of bNED at 5 years (34.4% v 64.3%; p = 0.147). Conclusion IGRT to 79.8 Gy results in favourable rates of late toxicity compared with published non-IGRT treated cohorts. Future avenues of investigation for

  2. Potential Applications of Image-Guided Radiotherapy for Radiation Dose Escalation in Patients with Early Stage High-Risk Prostate Cancer

    PubMed Central

    Nguyen, Nam P.; Davis, Rick; Bose, Satya R.; Dutta, Suresh; Vinh-Hung, Vincent; Chi, Alexander; Godinez, Juan; Desai, Anand; Woods, William; Altdorfer, Gabor; D’Andrea, Mark; Karlsson, Ulf; Vo, Richard A.; Sroka, Thomas

    2015-01-01

    Patients with early stage high-risk prostate cancer (prostate specific antigen > 20, Gleason score > 7) are at high risk of recurrence following prostate cancer irradiation. Radiation dose escalation to the prostate may improve biochemical-free survival for these patients. However, high rectal and bladder dose with conventional three-dimensional conformal radiotherapy may lead to excessive gastrointestinal and genitourinary toxicity. Image-guided radiotherapy (IGRT), by virtue of combining the steep dose gradient of intensity-modulated radiotherapy and daily pretreatment imaging, may allow for radiation dose escalation and decreased treatment morbidity. Reduced treatment time is feasible with hypo-fractionated IGRT and it may improve patient quality of life. PMID:25699239

  3. Target localization and toxicity in dose-escalated prostate radiotherapy with image-guided approach using daily planar kilovoltage imaging.

    PubMed

    Nath, S K; Sandhu, A P; Sethi, R A; Jensen, L G; Rosario, M D; Kane, C J; Parsons, J K; Millard, F E; Jiang, S B; Rice, R K; Pawlicki, T; Mundt, A J

    2011-02-01

    Dose escalation with intensity-modulated radiation therapy (IMRT) for carcinoma of the prostate has augmented the need for accurate prostate localization prior to dose delivery. Daily planar kilovoltage (kV) imaging is a low-dose image-guidance technique that is prevalent among radiation oncologists. However, clinical outcomes evaluating the benefit of daily kV imaging are lacking. The purpose of this study was to report our clinical experience, including prostate motion and gastrointestinal (GI) and genitourinary (GU) toxicities, using this modality. A retrospective analysis of 100 patients treated consecutively between December 2005 and March 2008 with definitive external beam IMRT for T1c-T4 disease were included in this analysis. Prescription doses ranged from 74-78 Gy (median, 76) in 2 Gy fractions and were delivered following daily prostate localization using on-board kV imaging (OBI) to localize gold seed fiducial markers within the prostate. Acute and late toxicities were graded as per the NCI CTCAEv3.0. The median follow-up was 22 months. The magnitude and direction of prostate displacement and daily shifts in three axes are reported. Of note, 9.1% and 12.9% of prostate displacements were ≥ 5 mm in the anterior-posterior and superior-inferior directions, respectively. Acute grade 2 GI and GU events occurred in 11% and 39% of patients, respectively, however no grade 3 or higher acute GI or GU events were observed. Regarding late toxicity, 2% and 17% of patients developed grade 2 toxicities, and similarly no grade 3 or higher events had occurred by last follow-up. Thus, kV imaging detected a substantial amount of inter-fractional displacement and may help reduce toxicity profiles, especially high grade events, by improving the accuracy of dose delivery.

  4. Long-term outcomes from dose-escalated image-guided intensity-modulated radiotherapy with androgen deprivation: encouraging results for intermediate- and high-risk prostate cancer

    PubMed Central

    Wilcox, Shea W; Aherne, Noel J; Benjamin, Linus C; Wu, Bosco; de Campos Silva, Thomaz; McLachlan, Craig S; McKay, Michael J; Last, Andrew J; Shakespeare, Thomas P

    2014-01-01

    Purpose Dose-escalated (DE) radiotherapy in the setting of localized prostate cancer has been shown to improve biochemical disease-free survival (bDFS) in several studies. In the same group of patients, androgen deprivation therapy (ADT) has been shown to confer a survival benefit when combined with radiotherapy doses of up to 70 Gy; however, there is currently little long-term data on patients who have received high-dose intensity-modulated radiotherapy (IMRT) with ADT. We report the long-term outcomes in a large cohort of patients treated with the combination of DE image-guided IMRT (IG-IMRT) and ADT. Methods and materials Patients with localized prostate cancer were identified from a centralized database across an integrated cancer center. All patients received DE IG-IMRT, combined with ADT, and had a minimum follow up of 12 months post-radiotherapy. All relapse and toxicity data were collected prospectively. Actuarial bDFS, metastasis-free survival, prostate cancer-specific survival, and multivariate analyses were calculated using the SPSS v20.0 statistical package. Results Seven hundred and eighty-two eligible patients were identified with a median follow up of 46 months. Overall, 4.3% of patients relapsed, 2.0% developed distant metastases, and 0.6% died from metastatic prostate cancer. At 5-years, bDFS was 88%, metastasis-free survival was 95%, and prostate cancer-specific survival was 98%. Five-year grade 2 genitourinary and gastrointestinal toxicity was 2.1% and 3.4%, respectively. No grade 3 or 4 late toxicities were reported. Pretreatment prostate specific antigen (P=0.001) and Gleason score (P=0.03) were significant in predicting biochemical failure on multivariate analysis. Conclusion There is a high probability of tumor control with DE IG-IMRT combined with androgen deprivation, and this is a technique with a low probability of significant late toxicity. Our long term results corroborate the safety and efficacy of treating with IG-IMRT to high doses

  5. Long-term outcomes from dose-escalated image-guided intensity-modulated radiotherapy with androgen deprivation: encouraging results for intermediate- and high-risk prostate cancer.

    PubMed

    Wilcox, Shea W; Aherne, Noel J; Benjamin, Linus C; Wu, Bosco; de Campos Silva, Thomaz; McLachlan, Craig S; McKay, Michael J; Last, Andrew J; Shakespeare, Thomas P

    2014-01-01

    Dose-escalated (DE) radiotherapy in the setting of localized prostate cancer has been shown to improve biochemical disease-free survival (bDFS) in several studies. In the same group of patients, androgen deprivation therapy (ADT) has been shown to confer a survival benefit when combined with radiotherapy doses of up to 70 Gy; however, there is currently little long-term data on patients who have received high-dose intensity-modulated radiotherapy (IMRT) with ADT. We report the long-term outcomes in a large cohort of patients treated with the combination of DE image-guided IMRT (IG-IMRT) and ADT. Patients with localized prostate cancer were identified from a centralized database across an integrated cancer center. All patients received DE IG-IMRT, combined with ADT, and had a minimum follow up of 12 months post-radiotherapy. All relapse and toxicity data were collected prospectively. Actuarial bDFS, metastasis-free survival, prostate cancer-specific survival, and multivariate analyses were calculated using the SPSS v20.0 statistical package. Seven hundred and eighty-two eligible patients were identified with a median follow up of 46 months. Overall, 4.3% of patients relapsed, 2.0% developed distant metastases, and 0.6% died from metastatic prostate cancer. At 5-years, bDFS was 88%, metastasis-free survival was 95%, and prostate cancer-specific survival was 98%. Five-year grade 2 genitourinary and gastrointestinal toxicity was 2.1% and 3.4%, respectively. No grade 3 or 4 late toxicities were reported. Pretreatment prostate specific antigen (P=0.001) and Gleason score (P=0.03) were significant in predicting biochemical failure on multivariate analysis. There is a high probability of tumor control with DE IG-IMRT combined with androgen deprivation, and this is a technique with a low probability of significant late toxicity. Our long term results corroborate the safety and efficacy of treating with IG-IMRT to high doses and compares favorably with published series for

  6. Phase II dose escalation study of image-guided adaptive radiotherapy for prostate cancer: Use of dose-volume constraints to achieve rectal isotoxicity

    SciTech Connect

    Vargas, Carlos; Yan Di; Kestin, Larry L.; Krauss, Daniel; Lockman, David M.; Brabbins, Donald S.; Martinez, Alvaro A. . E-mail: amartinez@beaumont.edu

    2005-09-01

    significant difference by dose level was seen in the 2-year rate of Grade 2 or higher chronic rectal toxicity. These rates were 27%, 15%, 14%, 17%, and 24% for dose levels equal to or less than 72, 73.8, 75.6, 77.4, and 79.2 Gy, respectively (p = 0.3). Grade 2 or higher chronic rectal bleeding was significantly greater for Group 2 than for Group 1, 17% vs. 8% (p = 0.035). Conclusions: High doses (79.2 Gy) were safely delivered in selected patients by our adaptive radiotherapy process. Under the rectal dose-volume histogram constraints for the dose level selection, the risk of chronic rectal toxicity is similar among patients treated to different dose levels. Therefore, rectal chronic toxicity rates reflect the dose-volume cutoff used and are independent of the actual dose levels. On the other hand, a larger PTV will increase the rectal wall dose and chronic rectal toxicity rates. PTV volume and dose constraints should be defined, considering their potential benefit.

  7. Multi-modality functional image guided dose escalation in the presence of uncertainties.

    PubMed

    Alber, Markus; Thorwarth, Daniela

    2014-06-01

    In order to increase local tumour control by radiotherapy without increasing toxicity, it appears promising to harness functional imaging (FI) to guide dose to sub-volumes of the target with a high tumour load and perhaps de-escalate dose to low risk volumes, in order to maximise the efficiency of the deposited radiation dose. A number of problems have to be solved to make focal dose escalation (FDE) efficient and safe: (1) how to combine ambiguous information from multiple imaging modalities; (2) how to take into account uncertainties of FI based tissue classification; (3) how to account for geometric uncertainties in treatment delivery; (4) how to add complementary FI modalities to an existing scheme. A generic optimisation concept addresses these points and is explicitly designed for clinical efficacy and for lowering the implementation threshold to FI-guided FDE. It combines classic tumour control probability modelling with a multi-variate logistic regression model of FI accuracy and an uncomplicated robust optimisation method. Its key elements are (1) that dose is deposited optimally when it achieves equivalent expected effect everywhere in the target volume and (2) that one needs to cap the certainty about the absence of tumour anywhere in the target region. For illustration, an example of a PET/MR-guided FDE in prostate cancer is given. FDE can be safeguarded against FI uncertainties, at the price of a limit on the sensible dose escalation. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  8. Image-guided adaptive brachytherapy dose escalation for cervix cancer via fractionation compensation.

    PubMed

    Shaw, William; Rae, William I D; Alber, Markus L

    In image-guided adaptive brachytherapy (IGABT), dose distributions are optimized for each fraction. Optimum fractional dose can be constant or adapted to previous fractions and a conjecture about the future ones. We evaluate the efficacy of different fraction size schemes, derived from total IGABT dose constraints, against constant per-fraction constraints. This retrospective planning study included 20 IGABT patients where four different fractionation schedules were compared based on modern planning recommendations. A total high-risk-clinical target volume D90 (minimum dose in 90% of the volume) dose aim of 90.0 Gy with constant per-fraction organs at risk (OARs) dose constraint planning (CONST) was compared with conservative and aggressive fractionation compensation (COMP) techniques. COMP allows variations in the per-fraction dose constraints. Dose accumulation was performed through dose summation at a given volume and equivalent uniform dose (EUD) worst-case dose estimates. No significant differences were identifiable between dose metrics of CONST and COMP in the total patient population. However, a subgroup of patients with alternating dose-limiting OARs had significant benefit from COMP. Median high-risk-clinical target volume dose escalation ranged from 5% to 12%, whereas OAR dose increases were lower and ranged from 3% to 8%. EUD-based planning delivered similar tumor doses, although slightly lower OAR doses. By distributing the treatment aim over an increased number of treatment fractions, median tumor dose could be increased by a further 8% per additional treatment fraction at the same OAR dose levels for both CONST and COMP. COMP is effective in patients with alternating dose-limiting OARs and is enhanced using more treatment fractions and EUD constraints. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  9. Image-guided adaptive radiation therapy (IGART): Radiobiological and dose escalation considerations for localized carcinoma of the prostate

    SciTech Connect

    Song, William; Schaly, Bryan; Bauman, Glenn; Battista, Jerry; Van Dyk, Jake

    2005-07-15

    The goal of this work was to evaluate the efficacy of various image-guided adaptive radiation therapy (IGART) techniques to deliver and escalate dose to the prostate in the presence of geometric uncertainties. Five prostate patients with 15-16 treatment CT studies each were retrospectively analyzed. All patients were planned with an 18 MV, six-field conformal technique with a 10 mm margin size and an initial prescription of 70 Gy in 35 fractions. The adaptive strategy employed in this work for patient-specific dose escalation was to increase the prescription dose in 2 Gy-per-fraction increments until the rectum normal tissue complication probability (NTCP) reached a level equal to that of the nominal plan NTCP (i.e., iso-NTCP dose escalation). The various target localization techniques simulated were: (1) daily laser-guided alignment to skin tattoo marks that represents treatment without image-guidance, (2) alignment to bony landmarks with daily portal images, and (3) alignment to the clinical target volume (CTV) with daily CT images. Techniques (1) and (3) were resimulated with a reduced margin size of 5 mm to investigate further dose escalation. When delivering the original clinical prescription dose of 70 Gy in 35 fractions, the 'CTV registration' technique yielded the highest tumor control probability (TCP) most frequently, followed by the 'bone registration' and 'tattoo registration' techniques. However, the differences in TCP among the three techniques were minor when the margin size was 10 mm ({<=}1.1%). Reducing the margin size to 5 mm significantly degraded the TCP values of the 'tattoo registration' technique in two of the five patients, where a large difference was found compared to the other techniques ({<=}11.8%). The 'CTV registration' technique, however, did maintain similar TCP values compared to their 10 mm margin counterpart. In terms of normal tissue sparing, the technique producing the lowest NTCP varied from patient to patient. Reducing the

  10. Impact of obesity on outcomes after definitive dose-escalated intensity-modulated radiotherapy for localized prostate cancer.

    PubMed

    Wang, Lora S; Murphy, Colin T; Ruth, Karen; Zaorsky, Nicholas G; Smaldone, Marc C; Sobczak, Mark L; Kutikov, Alexander; Viterbo, Rosalia; Horwitz, Eric M

    2015-09-01

    Previous publications have demonstrated conflicting results regarding body mass index (BMI) and prostate cancer (CaP) outcomes after definitive radiotherapy (RT) before the dose escalation era. The goal of the current study was to determine whether increasing BMI was associated with outcomes in men with localized CaP who were treated with dose-escalated RT. The authors identified patients with localized (T1b-T4N0M0) CaP who were treated with definitive intensity-modulated RT and image-guided RT from 2001 through 2010. BMI was analyzed as a continuous variable. Adjusting for confounders, multivariable competing risk and Cox proportional hazards regression models were used to assess the association between BMI and the risk of biochemical failure (BF), distant metastases (DM), cause-specific mortality (CSM), and overall mortality. Of the 1442 patients identified, approximately 20% had a BMI <25 kg/m(2) , 48% had a BMI of 25 to 29.9 kg/m(2) , 23% had a BMI of 30 to 34.9 kg/m(2) , 6% had a BMI of 35 to 39.9 kg/m(2) , and 4% had a BMI of ≥40 kg/m(2) . The median follow-up was 47.6 months (range, 1-145 months), with a median age of 68 years (range, 36-89 years). The median dose was 78 grays (range, 76-80 grays) and 30% of patients received androgen deprivation therapy. Increasing BMI was found to be inversely associated with age (P<.001) and pretreatment prostate-specific antigen level (P = .018). On multivariable analysis, increasing BMI was associated with an increased risk of BF (hazard ratio [HR], 1.03; 95% confidence interval [95% CI], 1.00-1.07 [P = .042]), DM (HR, 1.07; 95% CI, 1.02-1.11 [P = .004]), CSM (HR, 1.15; 95% CI, 1.07-1.23 [P<.001]), and overall mortality (HR, 1.05; 95% CI, 1.02-1.08 [P = .004]). For patients with CaP receiving dose-escalated intensity-modulated RT with daily image-guidance, increasing BMI appears to be associated with an increased risk of BF, DM, CSM, and overall mortality. © 2015 American Cancer Society.

  11. The Impact of Dose Escalation on Secondary Cancer Risk After Radiotherapy of Prostate Cancer

    SciTech Connect

    Schneider, Uwe . E-mail: uwe.schneider@psi.ch; Lomax, Antony; Besserer, Juergen; Pemler, Peter; Lombriser, Norbert; Kaser-Hotz, Barbara D.V.M.

    2007-07-01

    Purpose: To estimate secondary cancer risk due to dose escalation in patients treated for prostatic carcinoma with three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated RT (IMRT), and spot-scanned proton RT. Methods and Materials: The organ equivalent dose (OED) concept with a linear-exponential, a plateau, and a linear dose-response curve was applied to dose distributions of 23 patients who received RT of prostate cancer. Conformal RT was used in 7 patients, 8 patients received IMRT with 6- and 15-MV photons, and 8 patients were treated with spot-scanned protons. We applied target doses ranging from 70 Gy to 100 Gy. Cancer risk was estimated as a function of target dose and tumor control probability. Results: At a 100-Gy target dose the secondary cancer risk relative to the 3D treatment plan at 70 Gy was +18.4% (15.0% for a plateau model, 22.3% for a linear model) for the 6-MV IMRT plan, +25.3% (17.0%, 14.1%) for the 15-MV IMRT plan, and -40.7% (-41.3%, -40.0%) for the spot-scanned protons. The increasing risk of developing a radiation-associated malignancy after RT with increasing dose was balanced by the enhanced cure rates at a larger dose. Conclusions: Cancer risk after dose escalation for prostate RT is expected to be equal to or lower than for conventional 3D treatment at 70 Gy, independent of treatment modality or dose-response model. Spot-scanned protons are the treatment of choice for dose escalation because this therapy can halve the risk of secondary cancers.

  12. Impact of dose escalation and adaptive radiotherapy for cervical cancers on tumour shrinkage—a modelling study

    NASA Astrophysics Data System (ADS)

    Røthe Arnesen, Marius; Paulsen Hellebust, Taran; Malinen, Eirik

    2017-03-01

    Tumour shrinkage occurs during fractionated radiotherapy and is regulated by radiation induced cellular damage, repopulation of viable cells and clearance of dead cells. In some cases additional tumour shrinkage during external beam therapy may be beneficial, particularly for locally advanced cervical cancer where a small tumour volume may simplify and improve brachytherapy. In the current work, a mathematical tumour model is utilized to investigate how local dose escalation affects tumour shrinkage, focusing on implications for brachytherapy. The iterative two-compartment model is based upon linear-quadratic radiation response, a doubling time for viable cells and a half-time for clearance of dead cells. The model was individually fitted to clinical tumour volume data from fractionated radiotherapy of 25 cervical cancer patients. Three different fractionation patterns for dose escalation, all with an additional dose of 12.2 Gy, were simulated and compared to standard fractionation in terms of tumour shrinkage. An adaptive strategy where dose escalation was initiated after one week of treatment was also considered. For 22 out of 25 patients, a good model fit was achieved to the observed tumour shrinkage. A large degree of inter-patient variation was seen in predicted volume reduction following dose escalation. For the 10 best responding patients, a mean tumour volume reduction of 34  ±  3% (relative to standard treatment) was estimated at the time of brachytherapy. Timing of initiating dose escalation had a larger impact than the number of fractions applied. In conclusion, the model was found useful in evaluating the impact from dose escalation on tumour shrinkage. The results indicate that dose escalation could be conducted from the start of external beam radiotherapy in order to obtain additional tumour shrinkage before brachytherapy.

  13. Post-Prostatectomy Image-Guided Radiotherapy: The Invisible Target Concept.

    PubMed

    Vilotte, Florent; Antoine, Mickael; Bobin, Maxime; Latorzeff, Igor; Supiot, Stéphane; Richaud, Pierre; Thomas, Laurence; Leduc, Nicolas; Guérif, Stephane; Iriondo-Alberdi, Jone; de Crevoisier, Renaud; Sargos, Paul

    2017-01-01

    In the era of intensity-modulated radiation therapy, image-guided radiotherapy (IGRT) appears crucial to control dose delivery and to promote dose escalation while allowing healthy tissue sparing. The place of IGRT following radical prostatectomy is poorly described in the literature. This review aims to highlight some key points on the different IGRT techniques applicable to prostatic bed radiotherapy. Furthermore, methods used to evaluate target motion and to reduce planning target volume margins will also be explored.

  14. Post-Prostatectomy Image-Guided Radiotherapy: The Invisible Target Concept

    PubMed Central

    Vilotte, Florent; Antoine, Mickael; Bobin, Maxime; Latorzeff, Igor; Supiot, Stéphane; Richaud, Pierre; Thomas, Laurence; Leduc, Nicolas; Guérif, Stephane; Iriondo-Alberdi, Jone; de Crevoisier, Renaud; Sargos, Paul

    2017-01-01

    In the era of intensity-modulated radiation therapy, image-guided radiotherapy (IGRT) appears crucial to control dose delivery and to promote dose escalation while allowing healthy tissue sparing. The place of IGRT following radical prostatectomy is poorly described in the literature. This review aims to highlight some key points on the different IGRT techniques applicable to prostatic bed radiotherapy. Furthermore, methods used to evaluate target motion and to reduce planning target volume margins will also be explored. PMID:28337425

  15. Hypofractionated Dose Escalated 3D Conformal Radiotherapy for Prostate Cancer: Outcomes from a Mono-Institutional Phase II Study.

    PubMed

    Tramacere, Francesco; Arcangeli, Stefano; Pignatelli, Antonietta; Castagna, Roberta; Portaluri, Maurizio

    2015-05-01

    Based on a radiobiological assumption of a low alpha/beta (α/β) ratio for prostate cancer, hypofractionated radiotherapy has increasingly gained traction in the clinical practice and recent guidelines have confirmed the non-inferiority of this approach. Nevertheless, the largest studies that have used hypofractionation so far, employed image-guided radiation therapy/intensity modulated radiation therapy (IGRT/IMRT) facilities that might have overcome the radiobiological advantages, which remain to be fully confirmed. The aim of this trial was to evaluate the feasibility of a hypofractionated schedule delivered with 3D-Conformal Radiotherapy to prostate and seminal vesicles in combination with hormonal therapy. The study included 97 consecutive patients with localized prostate cancer (PCa), irrespective of risk class, treated with a schedule of 62 Gy in 20 fractions over 5 weeks (4 fractions of 3.1 Gy each per week). According to National Comprehensive Cancer Network (NCCN) prognostic classification, patients were divided into a favourable group (19%), intermediate group (41%) and unfavourable group (40%). Early and late toxicities were scored using the radiation toxicity grading/European Organisation for Research and Treatment of Cancer (RTOG/EORTC) criteria. Additionally, the international prostate symptom index (IPSS) for benign prostate hypertrophy was used to evaluate obstructive urinary symptoms. Biochemical outcome was reported according to the Phoenix definition for biochemical failure. Hormonal therapy (HT) was administrated in 92% of patients. After a median follow-up of 39 months (range=25-52), maximum ≥G2 late genitourinary (GU) and gastrointestinal (GI) toxicities occurred in 8% and 11% patients, respectively. The corresponding figures for acute toxicities were 24% and 15%. Patients with higher IPSS score before enrolment had significantly worse urinary function after treatment. Only 2% of patients died from PCa. Biochemical non-evidence of disease

  16. Dose Escalation of Whole-Brain Radiotherapy for Brain Metastases From Melanoma

    SciTech Connect

    Rades, Dirk; Heisterkamp, Christine; Huttenlocher, Stefan; Bohlen, Guenther; Dunst, Juergen; Haatanen, Tiina; Schild, Steven E.

    2010-06-01

    Purpose: The majority of patients with brain metastases from melanoma receive whole-brain radiotherapy (WBRT). However, the results are poor. Hypofractionation regimens failed to improve the outcome of these patients. This study investigates a potential benefit from escalation of the WBRT dose beyond the 'standard' regimen 30 Gy in 10 fractions (10x3 Gy). Methods and Materials: Data from 51 melanoma patients receiving WBRT alone were retrospectively analyzed. A dosage of 10x3 Gy (n = 33) was compared with higher doses including 40 Gy/20 fractions (n = 11) and 45 Gy/15 fractions (n = 7) for survival (OS) and local (intracerebral) control (LC). Additional potential prognostic factors were evaluated: age, gender, performance status, number of metastases, extracerebral metastases, and recursive partitioning analysis (RPA) class. Results: At 6 months, OS rates were 27% after 10x3 Gy and 50% after higher doses (p = 0.009). The OS rates at 12 months were 4% and 20%. On multivariate analysis, higher WBRT doses (p = 0.010), fewer than four brain metastases (p = 0.012), no extracerebral metastases (p = 0.006), and RPA class 1 (p = 0.005) were associated with improved OS. The LC rates at 6 months were 23% after 10x3 Gy and 50% after higher doses (p = 0.021). The LC rates at 12 months were 0% and 13%. On multivariate analysis, higher WBRT doses (p = 0.020) and fewer than brain metastases (p = 0.002) were associated with better LC. Conclusions: Given the limitations of a retrospective study, the findings suggest that patients with brain metastases from melanoma receiving WBRT alone may benefit from dose escalation beyond 10x3 Gy. The hypothesis generated by this study must be confirmed in a randomized trial stratifying for significant prognostic factors.

  17. Update of Dutch Multicenter Dose-Escalation Trial of Radiotherapy for Localized Prostate Cancer

    SciTech Connect

    Al-Mamgani, Abrahim Putten, Wim L.J. van; Heemsbergen, Wilma D.; Leenders, Geert J.L.H. van; Slot, Annerie; Dielwart, Michel F.H.; Incrocci, Luca; Lebesque, Joos V.

    2008-11-15

    Purpose: To update the analysis of the Dutch dose-escalation trial of radiotherapy for prostate cancer. Patients and Methods: A total of 669 patients with localized prostate cancer were randomly assigned to receive 68 or 78 Gy. The patients were stratified by age, institution, use of neoadjuvant or adjuvant hormonal therapy, and treatment group. The primary endpoint was freedom from failure (FFF), with failure defined as clinical or biochemical failure. Two definitions of biochemical failure were used: the American Society for Therapeutic Radiology and Oncology definition (three consecutive increases in prostate-specific antigen level) and the Phoenix definition (nadir plus 2 {mu}g/L). The secondary endpoints were freedom from clinical failure, overall survival, and genitourinary and gastrointestinal toxicity. Results: After a median follow-up of 70 months, the FFF using the American Society for Therapeutic Radiology and Oncology definition was significantly better in the 78-Gy arm than in the 68-Gy arm (7-year FFF rate, 54% vs. 47%, respectively; p = 0.04). The FFF using the Phoenix definition was also significantly better in the 78-Gy arm than in the 68-Gy arm (7-year FFF rate, 56% vs. 45%, respectively; p = 0.03). However, no differences in freedom from clinical failure or overall survival were observed. The incidence of late Grade 2 or greater genitourinary toxicity was similar in both arms (40% and 41% at 7 years; p = 0.6). However, the cumulative incidence of late Grade 2 or greater gastrointestinal toxicity was increased in the 78-Gy arm compared with the 68-Gy arm (35% vs. 25% at 7 years; p = 0.04). Conclusion: The results of our study have shown a statistically significant improvement in FFF in prostate cancer patients treated with 78 Gy but with a greater rate of late gastrointestinal toxicity.

  18. Dose-Escalation Study of Single-Fraction Stereotactic Body Radiotherapy for Liver Malignancies

    SciTech Connect

    Goodman, Karyn A.; Wiegner, Ellen A.; Maturen, Katherine E.; Zhang Zhigang; Mo Qianxing; Yang, George; Gibbs, Iris C.; Fisher, George A.; Koong, Albert C.

    2010-10-01

    Purpose: We performed a Phase I dose-escalation study to explore the feasibility and safety of treating primary and metastatic liver tumors with single-fraction stereotactic body radiotherapy (SBRT). Methods and Materials: Between February 2004 and February 2008, 26 patients were treated for 40 identifiable lesions. Nineteen patients had hepatic metastases, 5 had intrahepatic cholangiocarcinomas, and 2 had recurrent hepatocellular carcinomas. The prescribed radiation dose was escalated from 18 to 30 Gy at 4-Gy increments with a planned maximum dose of 30 Gy. Cumulative incidence functions accounted for competing risks to estimate local failure (LF) incidence over time under the competing risk of death. Results: All patients tolerated the single-fraction SBRT well without developing a dose-limiting toxicity. Nine acute Grade 1 toxicities, one acute Grade 2 toxicity, and two late Grade 2 gastrointestinal toxicities were observed. After a median of 17 months follow-up (range, 2-55 months), the cumulative risk of LF at 12 months was 23%. Fifteen patients have died: 11 treated for liver metastases and 4 with primary liver tumors died. The median survival was 28.6 months, and the 2-year actuarial overall survival was 50.4%. Conclusions: It is feasible and safe to deliver single-fraction, high-dose SBRT to primary or metastatic liver malignancies measuring {<=}5 cm. Moreover, single-fraction SBRT for liver lesions demonstrated promising local tumor control with minimal acute and long-term toxicity. Single-fraction SBRT appears to be a viable nonsurgical option, but further studies are warranted to evaluate both control rates and impact on quality of life.

  19. Image-guided radiotherapy: from current concept to future perspectives.

    PubMed

    Jaffray, David A

    2012-12-01

    Radiotherapy is a highly effective, targeted therapy for the management of cancer. Technological innovations have enabled the direct integration of imaging technology into the radiation treatment device to increase the precision and accuracy of radiation delivery. As well as addressing a clinical need to better control the placement of the dose within the body, image-guided radiotherapy has enabled innovators in the field to accelerate their exploration of a number of different paradigms of radiation delivery, including toxicity reduction, dose escalation, hypofractionation, voxelization, and adaptation. Although these approaches are already innovative trends in radiation oncology, it is anticipated that they will work synergistically with other innovations in cancer management (including biomarker strategies, novel systemic and local therapies) as part of the broader goal of personalized cancer medicine. This Review discusses the rationale for adopting image-guidance approaches in radiotherapy, and the technology for achieving precision and accuracy in the context of different paradigms within the evolving radiation oncology practice. It also examines exciting advances in radiotherapy technology that suggest a convergence of radiotherapy practice in which patient-specific radiotherapy treatment courses are one of the most personalized forms of intervention in cancer medicine.

  20. Prospective evaluation of a hydrogel spacer for rectal separation in dose-escalated intensity-modulated radiotherapy for clinically localized prostate cancer

    PubMed Central

    2013-01-01

    Background As dose-escalation in prostate cancer radiotherapy improves cure rates, a major concern is rectal toxicity. We prospectively assessed an innovative approach of hydrogel injection between prostate and rectum to reduce the radiation dose to the rectum and thus side effects in dose-escalated prostate radiotherapy. Methods Acute toxicity and planning parameters were prospectively evaluated in patients with T1-2 N0 M0 prostate cancer receiving dose-escalated radiotherapy after injection of a hydrogel spacer. Before and after hydrogel injection, we performed MRI scans for anatomical assessment of rectal separation. Radiotherapy was planned and administered to 78 Gy in 39 fractions. Results From eleven patients scheduled for spacer injection the procedure could be performed in ten. In one patient hydrodissection of the Denonvillier space was not possible. Radiation treatment planning showed low rectal doses despite dose-escalation to the target. In accordance with this, acute rectal toxicity was mild without grade 2 events and there was complete resolution within four to twelve weeks. Conclusions This prospective study suggests that hydrogel injection is feasible and may prevent rectal toxicity in dose-escalated radiotherapy of prostate cancer. Further evaluation is necessary including the definition of patients who might benefit from this approach. Trial registration: German Clinical Trials Register DRKS00003273. PMID:23336502

  1. Positron Emission Tomography-Guided, Focal-Dose Escalation Using Intensity-Modulated Radiotherapy for Head and Neck Cancer

    SciTech Connect

    Madani, Indira . E-mail: indira@krtkg1.ugent.be; Duthoy, Wim; Derie, Cristina R.N.; De Gersem, Werner Ir.; Boterberg, Tom; Saerens, Micky; Jacobs, Filip Ir.; Gregoire, Vincent; Lonneux, Max; Vakaet, Luc; Vanderstraeten, Barbara; Bauters, Wouter; Bonte, Katrien; Thierens, Hubert; Neve, Wilfried de

    2007-05-01

    Purpose: To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided dose escalation, and to determine the maximum tolerated dose in head and neck cancer. Methods and Materials: A Phase I clinical trial was designed to escalate the dose limited to the [{sup 18}-F]fluoro-2-deoxy-D-glucose positron emission tomography ({sup 18}F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10 fractions. Standard IMRT was applied for the remaining 22 fractions of 2.16 Gy. Results: Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level I, and 18 at dose level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of dose-limiting toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at dose level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted {sup 18}F-FDG-PET-delineated region. Conclusions: For head and neck cancer, PET-guided dose escalation appears to be well-tolerated. The maximum tolerated dose was not reached at the investigated dose levels.

  2. Correction: Image guided dose escalated prostate radiotherapy: still room to improve

    PubMed Central

    2009-01-01

    We regret to report that a proofreading error caused an incorrect legend and description of the contents of table 6 to appear in our original publication of this work. The correct description of table 6 is: Univariate analysis of prognostic factors for 5-year nadir + 2 biochemical outcome for men presenting with intermediate risk factors.

  3. Dose-escalated liver stereotactic body radiotherapy (SBRT) at the mean respiratory position

    PubMed Central

    Velec, Michael; Moseley, Joanne L.; Dawson, Laura A.; Brock, Kristy K.

    2014-01-01

    Purpose The dosimetric impact of dose-probability based PTV margins for liver cancer patients receiving SBRT was compared to standard PTV based on the internal target volume (ITV). Plan robustness was evaluated by accumulating the treatment dose to ensure delivery of the intended plan. Methods and Materials Twenty patients planned on exhale CT for 27–50 Gy in 6 fractions using an ITV-based PTV and treated free-breathing were retrospectively evaluated. Iso-toxic, dose-escalated plans were created on mid-position CT, representing the mean breathing position, using a dose-probability PTV. The delivered doses were accumulated using biomechanical deformable registration of the daily cone-beam CT based on liver targeting at the exhale or mean breathing position, for the exhale and mid-position CT plans respectively. Results The dose-probability PTVs were on average 38% smaller than the ITV-based PTV enabling an average±standard deviation increase in the planned dose to 95% of the PTV of 4.0±2.8 Gy (9±5%) on the mid-position CT (p<0.01). For both plans, the delivered minimum GTV doses were greater than the planned nominal prescribed dose in all 20 patients and greater than the planned dose to 95% of the PTV in 18 (90%) patients. Nine patients (45%) had one or more GTVs with a delivered minimum dose more than 5 Gy higher with the mid-position CT plan using dose-probability PTV, compared to the delivered dose with the exhale CT plan using ITV-based PTV. Conclusions For iso-toxic liver SBRT planned and delivered at the mean respiratory, reduced dose-probability PTV enables a mean escalation of 4 Gy (9%) in 6 fractions over ITV-based PTV. This may potentially improve local control without increasing the risk of tumor under-dosing. PMID:25035217

  4. An age-corrected matched-pair study of erectile function in patients treated with dose-escalated adaptive image-guided intensity-modulated radiation therapy vs. high-dose-rate brachytherapy for prostate cancer.

    PubMed

    Marina, Ovidiu; Warner, Jillian; Ye, Hong; Grills, Inga S; Shah, Chirag; Wallace, Michelle; Gustafson, Gary S; Brabbins, Donald S; Martinez, Alvaro A; Krauss, Daniel J

    2014-01-01

    To compare erectile dysfunction (ED) after adaptive dose-escalated image-guided intensity-modulated radiotherapy (IG-IMRT) and high-dose-rate interstitial brachytherapy (HDR) monotherapy. Low- and intermediate-risk prostate cancer patients treated with IG-IMRT or HDR were matched on pretreatment ED, age, Gleason score, T-stage, and prostate specific antigen. Patients who received androgen deprivation therapy were excluded. ED was graded by Common Terminology Criteria for Adverse Events v4. Actuarial rates of ED were computed by the Kaplan-Meier method. There were 384 patients with median followup of 2.0 years (0.5-6.1) for IG-IMRT and 2.0 years (0.5-8.7) for HDR. The median IG-IMRT dose was 75.6 Gy and HDR dose 38 Gy in four fractions. For patients with no pretreatment ED, actuarial rates of requiring intervention (Grade ≥2 ED) at 3 years were 31% for IG-IMRT and 19% for HDR (p=0.23), and impotence despite medical intervention (Grade 3) were 0% for IG-IMRT and 6% for HDR (p=0.06). For patients with Grade 1 pretreatment ED, Grade ≥2 ED at 3 years were 47% for IG-IMRT and 34% for HDR (p=0.79), and Grade 3 ED were 15% in both groups (p=0.59). For patients with Grade 2 pretreatment ED, Grade 3 ED at 3 years were 22% for IG-IMRT and 37% for HDR (p=0.70). No variables were predictive of Grade ≥2 ED following treatment. Rates of ED requiring medical intervention for both IG-IMRT and HDR are low and equivalent. Even patients with ED before treatment are likely to maintain potency with medication use at 3 years following treatment. Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  5. [Good practice of image-guided radiotherapy].

    PubMed

    de Crevoisier, R; Créhange, G; Castelli, J; Lafond, C; Delpon, G

    2015-10-01

    Image-guided radiotherapy (IGRT) aims to take into account the anatomical variations occurring during the course of radiotherapy, by direct or indirect visualization of the target volume followed by a corrective action. The movements of the target, or at least the set-up errors are corrected by moving the treatment table, corresponding to the simplest and most validated IGRT modality in a standard practice. The deformations of the target volume and organs at risk are however much more common, and unfortunately much more complicated to consider, requiring multiple planning before or during the treatment, corresponding to the adaptive radiotherapy strategies. The planning target volume must be carefully chosen according to these anatomic variations. This article reviews the modalities of IGRT, standard or under evaluation, according to the different tumour sites. Copyright © 2015. Published by Elsevier SAS.

  6. Image-Guided Intensity-Modulated Radiotherapy for Pancreatic Carcinoma

    PubMed Central

    Fuss, Martin; Wong, Adrian; Fuller, Clifton D.; Salter, Bill J.; Fuss, Cristina; Thomas, Charles R.

    2007-01-01

    Purpose To present the techniques and preliminary outcomes of ultrasound-based image-guided intensity-modulated radiotherapy (IG-IMRT) for pancreatic cancer. Materials and Methods Retrospective analysis of 41 patients treated between November 2000 and March 2005 with IG-IMRT to mean total doses of 55 Gy (range, 45–64 Gy). We analyzed the clinical feasibility of IG-IMRT, dosimetric parameters, and outcomes, including acute gastrointestinal toxicity (RTOG grading). Survival was assessed for adenocarcinoma (n = 35) and other histologies. Results Mean daily image-guidance corrective shifts were 4.8 ± 4.3 mm, 7.5 ± 7.2 mm, and 4.6 ± 5.9 mm along the x-, y-, and z-axes, respectively (mean 3D correction vector, 11.7 ± 8.4 mm). Acute upper gastrointestinal toxicity was grade 0–1 in 22 patients (53.7%), grade 2 in 16 patients (39%), and grade 3 in 3 patients (7.3%). Lower gastrointestinal toxicity was grade 0–1 in 32 patients (78%), grade 2 in 7 patients (17.1%), and grade 4 in 2 patients (4.9%). Treatment was stopped early in 4 patients following administration of 30 to 54 Gy. Median survival for adenocarcinoma histology was 10.3 months (18.6 months in patients alive at analysis; n = 8) with actuarial 1- and 2-year survivals of 38% and 25%, respectively. Conclusion Daily image-guidance during delivery of IMRT for pancreatic carcinoma is clinically feasible. The data presented support the conclusion that safety margin reduction and moderate dose escalation afforded by implementation of these new radiotherapy technologies yields preliminary outcomes at least comparable with published survival data. PMID:19262697

  7. Sexual Function After Three-Dimensional Conformal Radiotherapy for Prostate Cancer: Results From a Dose-Escalation Trial

    SciTech Connect

    Wielen, Gerard J. van der . E-mail: g.vanderwielen@erasmusmc.nl; Putten, Wim van; Incrocci, Luca

    2007-06-01

    Purpose: The purpose of this study is to provide information about sexual function (SF) after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer while taking important factors into account that influence SF. Methods and Materials: Between June 1997 and February 2003, a total of 268 patients from a randomized dose-escalation trial comparing 68 Gy and 78 Gy agreed to participate in an additional part of the trial that evaluated SF. Results: At baseline 28% of patients had erectile dysfunction (ED). After 1 year, 27% of the pretreatment potent patients had developed ED. After 2 years this percentage had increased to 36%. After 3 years it almost stabilized at 38%. Satisfaction with sexual life was significantly correlated with ED. After 2 years one third of the pre-treatment potent patients still had considerable to very much sexual desire and found sex (very) important. No significant differences were found between the two dose-arms. Potency aids were used on a regular base by 14% of the patients. Conclusion: By taking adjuvant hormonal therapy (HT), HT during follow-up and potency aids into account, we found a lower percentage of ED after 3D-CRT than reported in previous prospective studies. A large group of patients still had sexual desire, considered sex important and 14% used potency aids after 3D-CRT.

  8. SU-E-T-183: Feasibility of Extreme Dose Escalation for Glioblastoma Multiforme Using 4π Radiotherapy

    SciTech Connect

    Nguyen, D; Rwigema, J; Yu, V; Kaprealian, T; Kupelian, P; Selch, M; Low, D; Sheng, K

    2014-06-01

    Purpose: GBM recurrence primarily occurs inside or near the high-dose radiation field of original tumor site requiring greater than 100 Gy to significantly improve local control. We utilize 4π non-coplanar radiotherapy to test the feasibility of planning target volume (PTV) margin expansions or extreme dose escalations without incurring additional radiation toxicities. Methods: 11 GBM patients treated with VMAT to a prescription dose of 59.4 Gy or 60 Gy were replanned with 4π. Original VMAT plans were created with 2 to 4 coplanar or non-coplanar arcs using 3 mm hi-res MLC. The 4π optimization, using 5 mm MLC, selected and inverse optimized 30 beams from a candidate pool of 1162 beams evenly distributed through 4π steradians. 4π plans were first compared to clinical plans using the same prescription dose. Two more studies were then performed to respectively escalate the GTV and PTV doses to 100 Gy, followed by a fourth plan expanding the PTV by 5 mm and maintaining the prescription dose. Results: The standard 4π plan significantly reduced (p<0.01) max and mean doses to critical structures by a range of 47.0–98.4% and 61.0–99.2%, respectively. The high dose PTV/high dose GTV/expanded PTV studies showed a reduction (p<0.05) or unchanged* (p>0.05) maximum dose of 72.1%/86.7%/77.1% (chiasm), 7.2%*/27.7%*/30.7% (brainstem), 39.8%*/84.2%/51.9%* (spinal cord), 69.0%/87.0%/66.9% (L eye), 76.2%/88.1%/84.1% (R eye), 95.0%/98.6%/97.5% (L lens), 93.9%/98.8%/97.6% (R lens), 74.3%/88.5%/72.4% (L optical nerve), 80.4%/91.3%/75.7% (R optical nerve), 64.8%/84.2%/44.9%* (L cochlea), and 85.2%/93.0%/78.0% (R cochlea), respectively. V30 and V36 for both brain and (brain - PTV) were reduced for all cases except the high dose PTV plan. PTV dose coverage increased for all 4π plans. Conclusion: Extreme dose escalation or further margin expansion is achievable using 4π, maintaining or reducing OAR doses. This study indicates that clinical trials employing 4π delivery using

  9. Dose Escalation and Quality of Life in Patients With Localized Prostate Cancer Treated With Radiotherapy: Long-Term Results of the Dutch Randomized Dose-Escalation Trial (CKTO 96-10 Trial)

    SciTech Connect

    Al-Mamgani, Abrahim; Putten, Wim L.J. van; Wielen, Gerard J. van der; Levendag, Peter C.; Incrocci, Luca

    2011-03-15

    Purpose: To assess the impact of dose escalation of radiotherapy on quality of life (QoL) in prostate cancer patients. Patients and Methods: Three hundred prostate cancer patients participating in the Dutch randomized trial (CKTO 69-10) comparing 68 Gy with 78 Gy were the subject of this analysis. These patients filled out the SF-36 QoL questionnaire before radiotherapy (baseline) and 6, 12, 24, and 36 months thereafter. Changes in QoL over time of {>=}10 points were considered clinically relevant. Repeated-measures regression analyses were applied to estimate and test the QoL changes over time, the differences between the two arms, and for association with a number of covariates. Results: At 3-year follow-up, the summary score physical health was 73.2 for the 68-Gy arm vs. 71.6 for the 78-Gy arm (p = 0.81), and the summary score mental health was 76.7 for the 68-Gy arm vs. 76.1 for the 78-Gy arm (p = 0.97). Statistically significant (p < 0.01) deterioration in QoL scores over time was registered in both arms in six scales. The deterioration over time was more pronounced in the high-dose arm for most scales. However, clinically relevant deterioration (>10 points) was seen for only two scales. None of the tested covariates were significantly correlated with QoL scores. Conclusion: Dose escalation did not result in significant deterioration of QoL in prostate cancer patients. In both randomization arms, statistically significant decreases in QoL scores over time were seen in six scales. The deterioration of QoL was more pronounced in the physical than in the mental health domain and in some scales more in the high- than in the low-dose arm, but the differences between arms were not statistically significant.

  10. Role of Intensity-Modulated Radiotherapy in Reducing Toxicity in Dose Escalation for Localized Prostate Cancer

    SciTech Connect

    Al-Mamgani, Abrahim Heemsbergen, Wilma D.; Peeters, Stephanie T.H.; Lebesque, Joos V.

    2009-03-01

    Purpose: To compare the acute and late gastrointestinal (GI) and genitourinary (GU) toxicity in prostate cancer patients treated to a total dose of 78 Gy with either a three-conformal radiotherapy technique with a sequential boost (SEQ) or a simultaneous integrated boost using intensity-modulated radiotherapy (SIB-IMRT). Patients and Methods: A total of 78 prostate cancer patients participating in the randomized Dutch trial comparing 68 Gy and 78 Gy were the subject of this analysis. They were all treated at the same institution to a total dose of 78 Gy. The median follow-up was 76 and 56 months for the SEQ and SIB-IMRT groups, respectively. The primary endpoints were acute and late GI and GU toxicity. Results: A significantly lower incidence of acute Grade 2 or greater GI toxicity occurred in patients treated with SIB-IMRT compared with SEQ (20% vs. 61%, p = 0.001). For acute GU toxicity and late GI and GU toxicity, the incidence was lower after SIB-IMRT, but these differences were not statistically significant. No statistically significant difference were found in the 5-year freedom from biochemical failure rate (Phoenix definition) between the two groups (70% for the SIB-IMRT group vs. 61% for the SEQ group, p = 0.3). The same was true for the 5-year freedom from clinical failure rate (90% vs. 72%, p = 0.07). Conclusion: The results of our study have shown that SIB-IMRT reduced the toxicity without compromising the outcome in patients with localized prostate cancer treated to 78 Gy radiation.

  11. Dose escalation study of carbon ion radiotherapy for locally advanced carcinoma of the uterine cervix

    SciTech Connect

    Kato, Shingo . E-mail: s.kato@nirs.go.jp; Ohno, Tatsuya; Tsujii, Hirohiko; Nakano, Takashi; Mizoe, Jun-etsu; Kamada, Tadashi; Miyamoto, Tadaaki; Tsuji, Hiroshi; Kato, Hirotoshi; Yamada, Shigeru; Kandatsu, Susumu; Yoshikawa, Kyosan; Ezawa, Hidefumi; Suzuki, Michiya

    2006-06-01

    Purpose: To evaluate the toxicity and efficacy of carbon ion radiotherapy (CIRT) for locally advanced cervical cancer by two phase I/II clinical trials. Methods and Materials: Between June 1995 and January 2000, 44 patients were treated with CIRT. Thirty patients had Stage IIIB disease, and 14 patients had Stage IVA disease. Median tumor size was 6.5 cm (range, 4.2-11.0 cm). The treatment consisted of 16 fractions of whole pelvic irradiation and 8 fractions of local boost. In the first study, the total dose ranged from 52.8 to 72.0 gray equivalents (GyE) (2.2-3.0 GyE per fraction). In the second study, the whole pelvic dose was fixed at 44.8 GyE, and an additional 24.0 or 28.0 GyE was given to the cervical tumor (total dose, 68.8 or 72.8 GyE). Results: No patient developed severe acute toxicity. In contrast, 8 patients developed major late gastrointestinal complications. The doses resulting in major complications were {>=}60 GyE. All patients with major complications were surgically salvaged. The 5-year local control rate for patients in the first and second studies was 45% and 79%, respectively. When treated with {>=}62.4 GyE, the local control was favorable even for the patients with stage IVA disease (69%) or for those with tumors {>=}6.0 cm (64%). Conclusions: In CIRT for advanced cervical cancer, the dose to the intestines should be limited to <60 GyE to avoid major complications. Although the number of patients in this study was small, the results support continued investigation to confirm therapeutic efficacy.

  12. Incorporating Androgen Deprivation With Dose-Escalated External-Beam Radiotherapy for Prostate Cancer.

    PubMed

    Dosoretz, Arie P; Yu, James B

    2016-05-20

    was concerned about the potential for greater urinary incontinence and/or urinary irritation associated with these treatments compared with external-beam radiotherapy (RT).(1,2).

  13. Feasibility of dose escalation using intensity-modulated radiotherapy in posthysterectomy cervical carcinoma

    SciTech Connect

    D'Souza, Warren D. . E-mail: wdsou001@umaryland.edu; Ahamad, Anesa A.; Iyer, Revathy B.; Salehpour, Mohammad R.; Jhingran, Anuja; Eifel, Patricia J.

    2005-03-15

    Purpose: To evaluate retrospectively the utility of intensity-modulated radiotherapy (IMRT) in reducing the volume of normal tissues receiving radiation at varying dose levels when the female pelvis after hysterectomy is treated to doses of 50.4 Gy and 54 Gy. Methods and materials: Computed tomography scans from 10 patients who had previously undergone conventional postoperative RT were selected. The clinical tumor volume (vaginal apex and iliac nodes) and organs at risk were contoured. Margins were added to generate the planning tumor volume. The Pinnacle and Corvus planning systems were used to develop conventional and IMRT plans, respectively. Conventional four-field plans were prescribed to deliver 45 Gy (4F{sub 45Gy}) or 50.4 Gy; eight-field IMRT plans were prescribed to deliver 50.4 Gy (IMRT{sub 50.4Gy}) or 54 Gy (IMRT{sub 54Gy}) to the planning tumor volume. All plans were normalized so that {>=}97% of the planning tumor volume received the prescribed dose. Student's t test was used to compare the volumes of organs at risk receiving the same doses with different plans. Results: The mean volume of bowel receiving {>=}45 Gy was lower with the IMRT{sub 50.4Gy} (33% lower) and IMRT{sub 54Gy} (18% lower) plans than with the 4F{sub 45Gy} plan. The mean volume of rectum receiving {>=}45 Gy or {>=}50 Gy was also significantly reduced with the IMRT plans despite an escalation of the prescribed dose from 45 Gy with the conventional plans to 54 Gy with IMRT. The mean volume of bladder treated to 45 Gy was the same or slightly lower with the IMRT{sub 50.4Gy} and IMRT{sub 54Gy} plans compared with the 4F{sub 45Gy} plan. Compared with the 4F{sub 45Gy} plan, the IMRT{sub 50.4Gy} plan resulted in a smaller volume of bowel receiving 35-45 Gy and a larger volume of bowel receiving 50-55 Gy. Compared with the 4F{sub 45Gy} plan, the IMRT{sub 54Gy} plan resulted in smaller volumes of bowel receiving 45-50 Gy; however, small volumes of bowel received 55-60 Gy with the IMRT plan

  14. Dynamic targeting image-guided radiotherapy

    SciTech Connect

    Huntzinger, Calvin; Munro, Peter; Johnson, Scott; Miettinen, Mika; Zankowski, Corey; Ahlstrom, Greg; Glettig, Reto; Filliberti, Reto; Kaissl, Wolfgang; Kamber, Martin; Amstutz, Martin; Bouchet, Lionel; Klebanov, Dan; Mostafavi, Hassan; Stark, Richard

    2006-07-01

    Volumetric imaging and planning for 3-dimensional (3D) conformal radiotherapy and intensity-modulated radiotherapy (IMRT) have highlighted the need to the oncology community to better understand the geometric uncertainties inherent in the radiotherapy delivery process, including setup error (interfraction) as well as organ motion during treatment (intrafraction). This has ushered in the development of emerging technologies and clinical processes, collectively referred to as image-guided radiotherapy (IGRT). The goal of IGRT is to provide the tools needed to manage both inter- and intrafraction motion to improve the accuracy of treatment delivery. Like IMRT, IGRT is a process involving all steps in the radiotherapy treatment process, including patient immobilization, computed tomogaphy (CT) simulation, treatment planning, plan verification, patient setup verification and correction, delivery, and quality assurance. The technology and capability of the Dynamic Targeting{sup TM} IGRT system developed by Varian Medical Systems is presented. The core of this system is a Clinac (registered) or Trilogy{sup TM} accelerator equipped with a gantry-mounted imaging system known as the On-Board Imager{sup TM} (OBI). This includes a kilovoltage (kV) x-ray source, an amorphous silicon kV digital image detector, and 2 robotic arms that independently position the kV source and imager orthogonal to the treatment beam. A similar robotic arm positions the PortalVision{sup TM} megavoltage (MV) portal digital image detector, allowing both to be used in concert. The system is designed to support a variety of imaging modalities. The following applications and how they fit in the overall clinical process are described: kV and MV planar radiographic imaging for patient repositioning, kV volumetric cone beam CT imaging for patient repositioning, and kV planar fluoroscopic imaging for gating verification. Achieving image-guided motion management throughout the radiation oncology process

  15. Preoperative Single-Fraction Partial Breast Radiotherapy – A Novel Phase I Dose-Escalation Protocol with Radiation Response Biomarkers

    PubMed Central

    Horton, Janet K.; Blitzblau, Rachel C.; Yoo, Sua; Geradts, Joseph; Chang, Zheng; Baker, Jay A.; Georgiade, Gregory S.; Chen, Wei; Siamakpour-Reihani, Sharareh; Wang, Chunhao; Broadwater, Gloria; Groth, Jeff; Palta, Manisha; Dewhirst, Mark; Barry, William T.; Duffy, Eileen A.; Chi, Jen-Tsan A.; Hwang, E. Shelley

    2015-01-01

    Summary This phase I dose-escalation trial evaluates the feasibility of single-dose preoperative partial breast irradiation delivered with external beam techniques in early stage breast cancer patients. No acute dose-limiting toxicity was observed at 15, 18, or 21Gy. Paired pre- and post-radiation imaging and tumor biopsies offer unique insight into the biology of breast cancer radiation response. Purpose Women with biologically favorable early stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large post-operative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase I trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. Methods Women 55 or older with clinically node negative, ER+ and/or PR+, HER2-, T1 invasive carcinomas or low-intermediate grade in situ disease ≤2cm were enrolled (n=32). Intensity-modulated radiotherapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21Gy (n=16) to the tumor with a 1.5cm margin. Lumpectomy was performed within 10 days. Paired pre- and post-radiation MRI images and patient tumor samples were analyzed. Results No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent and chronic toxicities were grade 1-2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation. Conclusions Preoperative single

  16. [Task sharing with radiotherapy technicians in image-guided radiotherapy].

    PubMed

    Diaz, O; Lorchel, F; Revault, C; Mornex, F

    2013-10-01

    The development of accelerators with on-board imaging systems now allows better target volumes reset at the time of irradiation (image-guided radiotherapy [IGRT]). However, these technological advances in the control of repositioning led to a multiplication of tasks for each actor in radiotherapy and increase the time available for the treatment, whether for radiotherapy technicians or radiation oncologists. As there is currently no explicit regulatory framework governing the use of IGRT, some institutional experiments show that a transfer is possible between radiation oncologists and radiotherapy technicians for on-line verification of image positioning. Initial training for every technical and drafting procedures within institutions will improve audit quality by reducing interindividual variability.

  17. Late Gastrointestinal Toxicity After Dose-Escalated Conformal Radiotherapy for Early Prostate Cancer: Results From the UK Medical Research Council RT01 Trial (ISRCTN47772397)

    SciTech Connect

    Syndikus, Isabel; Morgan, Rachel C.; Sydes, Matthew R.; Graham, John D.; Dearnaley, David P.

    2010-07-01

    Purpose: In men with localized prostate cancer, dose-escalated conformal radiotherapy (CFRT) improves efficacy outcomes at the cost of increased toxicity. We present a detailed analysis to provide further information about the incidence and prevalence of late gastrointestinal side effects. Methods and Materials: The UK Medical Research Council RT01 trial included 843 men with localized prostate cancer, who were treated for 6 months with neoadjuvant radiotherapy and were randomly assigned to either 64-Gy or 74-Gy CFRT. Toxicity was evaluated before CFRT and during long-term follow-up using Radiation Therapy Oncology Group (RTOG) grading, the Late Effects on Normal Tissue: Subjective, Objective, Management (LENT/SOM) scale, and Royal Marsden Hospital assessment scores. Patients regularly completed Functional Assessment of Cancer Therapy--Prostate (FACT-P) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) questionnaires. Results: In the dose-escalated group, the hazard ratio (HR) for rectal bleeding (LENT/SOM grade {>=}2) was 1.55 (95% CI, 1.17-2.04); for diarrhea (LENT/SOM grade {>=}2), the HR was 1.79 (95% CI, 1.10-2.94); and for proctitis (RTOG grade {>=}2), the HR was 1.64 (95% CI, 1.20-2.25). Compared to baseline scores, the prevalence of moderate and severe toxicities generally increased up to 3 years and than lessened. At 5 years, the cumulative incidence of patient-reported severe bowel problems was 6% vs. 8% (standard vs. escalated, respectively) and severe distress was 4% vs. 5%, respectively. Conclusions: There is a statistically significant increased risk of various adverse gastrointestinal events with dose-escalated CFRT. This remains at clinically acceptable levels, and overall prevalence ultimately decreases with duration of follow-up.

  18. Phase I dose-escalation study of helical intensity-modulated radiotherapy-based stereotactic body radiotherapy for hepatocellular carcinoma

    PubMed Central

    Kim, Jun Won; Seong, Jinsil; Lee, Ik Jae; Woo, Joong Yeol; Han, Kwang-Hyub

    2016-01-01

    Background Phase I trial was conducted to determine feasibility and toxicity of helical intensity-modulated radiotherapy (IMRT)-based stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC). Results Eighteen patients (22 lesions) were enrolled. With no DLT at 52 Gy (13 Gy/fraction), protocol was amended for further escalation to 60 Gy (15 Gy/fraction). Radiologic complete response rate was 88.9%. Two outfield intrahepatic, 2 distant, 4 concurrent local and outfield, and 1 concurrent local, outfield and distant failures (no local failure at dose levels 3–4) occurred. The worst toxicity was grade 3 hematologic in five patients, with no gastrointestinal toxicity > grade 1. At median follow-up of 28 months for living patients, 2-year local control, progression-free (PFS), and overall survival rates were 71.3%, 49.4% and 69.3%, respectively. Multi-segmental recurrences prior to SBRT was independent prognostic factor for PFS (p = 0.033). Materials and Methods Eligible patients had Child-Pugh's class A or B, unresectable HCC, ≤ 3 lesions, and cumulative tumor diameter ≤ 6 cm. Starting at 36 Gy in four fractions, dose was escalated with 2 Gy/fraction per dose-level. CTCAE v 3.0 ≥ grade 3 gastrointestinal toxicity and radiation induced liver disease defined dose-limiting toxicity (DLT). Conclusions Helical IMRT-based SBRT was tolerable and showed encouraging results. Confirmatory phase II trial is underway. PMID:27213593

  19. Superiority of helical tomotherapy on liver sparing and dose escalation in hepatocellular carcinoma: a comparison study of three-dimensional conformal radiotherapy and intensity-modulated radiotherapy

    PubMed Central

    Zhao, Qianqian; Wang, Renben; Zhu, Jian; Jin, Linzhi; Zhu, Kunli; Xu, Xiaoqing; Feng, Rui; Jiang, Shumei; Qi, Zhonghua; Yin, Yong

    2016-01-01

    Background and purpose To compare the difference of liver sparing and dose escalation between three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and helical tomotherapy (HT) for hepatocellular carcinoma. Patients and methods Sixteen unresectable HCC patients were enrolled in this study. First, some evaluation factors of 3DCRT, IMRT, and HT plans were calculated with prescription dose at 50 Gy/25 fractions. Then, the doses were increased using HT or IMRT independently until either the plans reached 70 Gy or any normal tissue reached the dose limit according to quantitative analysis of normal tissue effects in the clinic criteria. Results The conformal index of 3DCRT was lower than that of IMRT (P<0.001) or HT (P<0.001), and the homogeneity index of 3DCRT was higher than that of IMRT (P<0.001) or HT (P<0.001). HT took the longest treatment time (P<0.001). For V50% (fraction of normal liver treated to at least 50% of the isocenter dose) of the normal liver, there was a significant difference: 3DCRT > IMRT > HT (P<0.001). HT had a lower Dmean (mean dose) and V20 (Vn, the percentage of organ volume receiving ≥n Gy) of liver compared with 3DCRT (P=0.005 and P=0.005, respectively) or IMRT (P=0.508 and P=0.007, respectively). Dmean of nontarget normal liver and V30 of liver were higher for 3DCRT than IMRT (P=0.005 and P=0.005, respectively) or HT (P=0.005 and P=0.005, respectively). Seven patients in IMRT (43.75%) and nine patients in HT (56.25%) reached the isodose 70 Gy, meeting the dose limit of the organs at risk. Conclusion HT may provide significantly better liver sparing and allow more patients to achieve higher prescription dose in HCC radiotherapy. PMID:27445485

  20. Hypofractionated Boost to the Dominant Tumor Region With Intensity Modulated Stereotactic Radiotherapy for Prostate Cancer: A Sequential Dose Escalation Pilot Study

    SciTech Connect

    Miralbell, Raymond; Molla, Meritxell; Rouzaud, Michel; Hidalgo, Alberto; Toscas, Jose Ignacio; Lozano, Joan; Sanz, Sergi B.Sc.; Ares, Carmen; Jorcano, Sandra; Linero, Dolors; Escude, Lluis

    2010-09-01

    Purpose: To evaluate the feasibility, tolerability, and preliminary outcomes in patients with prostate cancer treated according to a hypofractionated dose escalation protocol to boost the dominant tumor-bearing region of the prostate. Methods and Materials: After conventional fractionated external radiotherapy to 64 to 64.4Gy, 50 patients with nonmetastatic prostate cancer were treated with an intensity-modulated radiotherapy hypofractionated boost under stereotactic conditions to a reduced prostate volume to the dominant tumor region. A rectal balloon inflated with 60cc of air was used for internal organ immobilization. Five, 8, and 8 patients were sequentially treated with two fractions of 5, 6, or 7Gy, respectively (normalized total dose in 2Gy/fraction [NTD{sub 2Gy}] < 100Gy, low-dose group), whereas 29 patients received two fractions of 8Gy each (NTD{sub 2Gy} > 100Gy, high-dose group). Androgen deprivation was given to 33 patients. Acute and late toxicities were assessed according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (RTOG/EORTC) scoring system. Results: Two patients presented with Grade 3 acute urinary toxicity. The 5-year probabilities of {>=}Grade 2 late urinary and late low gastrointestinal (GI) toxicity-free survival were 82.2% {+-} 7.4% and 72.2% {+-} 7.6%, respectively. The incidence and severity of acute or late toxicities were not correlated with low- vs. high-dose groups, pelvic irradiation, age, or treatment with or without androgen deprivation. The 5-year biochemical disease-free survival (b-DFS) and disease-specific survival were 98% {+-} 1.9% and 100%, respectively. Conclusion: Intensity-modulated radiotherapy hypofractionated boost dose escalation under stereotactic conditions was feasible, and showed excellent outcomes with acceptable long-term toxicity. This approach may well be considered an alternative to high-dose-rate brachytherapy.

  1. Image-Guided Radiotherapy and -Brachytherapy for Cervical Cancer

    PubMed Central

    Dutta, Suresh; Nguyen, Nam Phong; Vock, Jacqueline; Kerr, Christine; Godinez, Juan; Bose, Satya; Jang, Siyoung; Chi, Alexander; Almeida, Fabio; Woods, William; Desai, Anand; David, Rick; Karlsson, Ulf Lennart; Altdorfer, Gabor

    2015-01-01

    Conventional radiotherapy for cervical cancer relies on clinical examination, 3-dimensional conformal radiotherapy (3D-CRT), and 2-dimensional intracavitary brachytherapy. Excellent local control and survival have been obtained for small early stage cervical cancer with definitive radiotherapy. For bulky and locally advanced disease, the addition of chemotherapy has improved the prognosis but toxicity remains significant. New imaging technology such as positron-emission tomography and magnetic resonance imaging has improved tumor delineation for radiotherapy planning. Image-guided radiotherapy (IGRT) may decrease treatment toxicity of whole pelvic radiation because of its potential for bone marrow, bowel, and bladder sparring. Tumor shrinkage during whole pelvic IGRT may optimize image-guided brachytherapy (IGBT), allowing for better local control and reduced toxicity for patients with cervical cancer. IGRT and IGBT should be integrated in future prospective studies for cervical cancer. PMID:25853092

  2. Image-guided radiotherapy and -brachytherapy for cervical cancer.

    PubMed

    Dutta, Suresh; Nguyen, Nam Phong; Vock, Jacqueline; Kerr, Christine; Godinez, Juan; Bose, Satya; Jang, Siyoung; Chi, Alexander; Almeida, Fabio; Woods, William; Desai, Anand; David, Rick; Karlsson, Ulf Lennart; Altdorfer, Gabor

    2015-01-01

    Conventional radiotherapy for cervical cancer relies on clinical examination, 3-dimensional conformal radiotherapy (3D-CRT), and 2-dimensional intracavitary brachytherapy. Excellent local control and survival have been obtained for small early stage cervical cancer with definitive radiotherapy. For bulky and locally advanced disease, the addition of chemotherapy has improved the prognosis but toxicity remains significant. New imaging technology such as positron-emission tomography and magnetic resonance imaging has improved tumor delineation for radiotherapy planning. Image-guided radiotherapy (IGRT) may decrease treatment toxicity of whole pelvic radiation because of its potential for bone marrow, bowel, and bladder sparring. Tumor shrinkage during whole pelvic IGRT may optimize image-guided brachytherapy (IGBT), allowing for better local control and reduced toxicity for patients with cervical cancer. IGRT and IGBT should be integrated in future prospective studies for cervical cancer.

  3. Phase I study of hypofractionated dose-escalated thoracic radiotherapy for limited-stage small-cell lung cancer

    SciTech Connect

    Yee, Don . E-mail: donyee@cancerboard.ab.ca; Halperin, Ross; Hanson, John; Nijjar, Tirath; Butts, Charles; Smylie, Michael; Reiman, Tony; Roa, Wilson

    2006-06-01

    Purpose: To determine the maximal tolerated dose of hypofractionated thoracic radiotherapy with concurrent chemotherapy for limited-stage small-cell lung cancer patients. Methods and Materials: Three radiotherapy regimens were used. Radiotherapy was given in two phases: patients initially received 20 Gy in 10 fractions to gross tumor plus uninvolved mediastinal nodes, followed by a boost to gross disease of 30, 38, or 42 Gy in 15 fractions. Radiotherapy was planned with conformal techniques. All patients received four cycles of cisplatin (25 mg/m{sup 2}) and etoposide (100 mg/m{sup 2}) chemotherapy. Radiotherapy commenced with Day 1 of Cycle 2 of chemotherapy. All complete/near-complete responders were offered prophylactic cranial irradiation. The maximal tolerated dose of radiotherapy was based on the dose that caused unacceptably high rates of radiotherapy-related toxicity. Results: Thirteen patients were accrued. All patients who commenced radiotherapy received all prescribed chemo- and radiotherapy. There were no treatment-related deaths. There was one Grade 3 acute nonhematologic toxicity in the 50-Gy group. Of the 6 patients given 58 Gy, 3 experienced acute Grade 3 esophagitis. With a median follow-up of 7 months, median overall survival was 9.5 months. Conclusions: The maximal tolerated dose of thoracic radiotherapy with concurrent chemotherapy on this trial was 50 Gy in 25 daily fractions.

  4. Dose-Escalated Intensity-Modulated Radiotherapy Is Feasible and May Improve Locoregional Control and Laryngeal Preservation in Laryngo-Hypopharyngeal Cancers

    SciTech Connect

    Miah, Aisha B.; Bhide, Shreerang A.; Guerrero-Urbano, M. Teresa; Clark, Catharine; Bidmead, A. Margaret; St Rose, Suzanne; Barbachano, Yolanda; A'Hern, Roger; Tanay, Mary; Hickey, Jennifer; Nicol, Robyn; Newbold, Kate L.; Harrington, Kevin J.; Nutting, Christopher M.

    2012-02-01

    Purpose: To determine the safety and outcomes of induction chemotherapy followed by dose-escalated intensity-modulated radiotherapy (IMRT) with concomitant chemotherapy in locally advanced squamous cell cancer of the larynx and hypopharynx (LA-SCCL/H). Methods and Materials: A sequential cohort Phase I/II trial design was used to evaluate moderate acceleration and dose escalation. Patients with LA-SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions (Fx) to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Acute and late toxicities and tumor control rates were recorded. Results: Between September 2002 and January 2008, 60 patients (29 DL1, 31 DL2) with Stage III (41% DL1, 52% DL2) and Stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 51.2 (12.1-77.3) months and for DL2 was 36.2 (4.2-63.3) months. Acute Grade 3 (G3) dysphagia was higher in DL2 (87% DL2 vs. 59% DL1), but other toxicities were equivalent. One patient in DL1 required dilatation of a pharyngeal stricture (G3 dysphagia). In DL2, 2 patients developed benign pharyngeal strictures at 1 year. One underwent a laryngo-pharyngectomy and the other a dilatation. No other G3/G4 toxicities were reported. Overall complete response was 79% (DL1) and 84% (DL2). Two-year locoregional progression-free survival rates were 64.2% (95% confidence interval, 43.5-78.9%) in DL1 and 78.4% (58.1-89.7%) in DL2. Two-year laryngeal preservation rates were 88.7% (68.5-96.3%) in DL1 and 96.4% (77.7-99.5%) in DL2. Conclusions: At a mean follow-up of 36 months, dose-escalated chemotherapy-IMRT at DL2 has so far been safe to deliver. In this study, DL2 delivered high rates of locoregional control, progression-free survival, and organ preservation and has been selected as the experimental arm in a Cancer Research UK Phase III

  5. Evaluating changes in tumor volume using magnetic resonance imaging during the course of radiotherapy treatment of high-grade gliomas: Implications for conformal dose-escalation studies

    SciTech Connect

    Tsien, Christina . E-mail: ctsien@umich.edu; Gomez-Hassan, Diana; Haken, Randall K. ten; Tatro, Daniel C.; Junck, L.; Chenevert, T.L.; Lawrence, T.

    2005-06-01

    tumors had tumor progression, based on MRI obtained during Week 3 of radiotherapy. Median increase in GTV (Week 3) was 11.7 cc (range, 9.8-21.3). Retrospective DVH analysis of PTV (Pre-Rx) and PTV (Week 3) demonstrated a decrease in V{sub 95%}(PTV volume receiving 95% of the prescribed dose) in those 3 cases. Conclusions: Routine MR imaging during radiotherapy may be essential in ensuring tumor coverage if highly conformal radiotherapy techniques such as stereotactic boost and intensity-modulated radiotherapy are used in dose-escalation trials that utilize smaller treatment margins.

  6. A phase 1 dose-escalation study of the oral histone deacetylase inhibitor abexinostat in combination with standard hypofractionated radiotherapy in advanced solid tumors

    PubMed Central

    Deutsch, Eric; Moyal, Elizabeth Cohen-Jonathan; Gregorc, Vanesa; Zucali, Paolo Andrea; Menard, Jean; Soria, Jean-Charles; Kloos, Ioana; Hsu, Jeff; Luan, Ying; Liu, Emily; Vezan, Remus; Graef, Thorsten; Rivera, Sofia

    2017-01-01

    Current treatments for advanced solid tumors tend to be only palliative. Although radiotherapy is administered with a curative intent, radioresistance and dose-limiting toxicities pose limitations to treatment. Abexinostat, an oral pan-histone deacetylase inhibitor, demonstrated enhanced sensitivity to radiation in various solid tumor cell lines. We conducted an exploratory, phase 1, dose-escalation study of abexinostat in combination with standard hypofractionated radiotherapy in patients with advanced solid tumors treated in a palliative setting. Among 58 treated patients, the median age was 61.5 years (range, 20-82); 47% of the patients had M1 stage disease, and 95% had received previous chemotherapy alone or chemotherapy in combination with surgery and/or radiotherapy. The recommended phase 2 dose was determined to be 90 mg/m2 (140 mg). Of the 51 patients evaluable for response, best overall response was 8% (1 complete response [CR], 3 partial responses [PRs]), and best loco-regional response was 12% (1 CR and 5 PRs) at a median follow-up of 16 weeks. Of note, patients with target or non-target brain lesions showed encouraging responses, with 1 patient achieving a best loco-regional response of CR. Treatment-emergent grade ≥3 adverse events (AEs) were few, with most common being thrombocytopenia (17%), lymphopenia (12%), and hypokalemia (7%). Six patients (10%) discontinued treatment due to AEs. No grade ≥3 prolongation of the QTc interval was observed, with no treatment discontinuations due to this AE. Oral abexinostat combined with radiotherapy was well tolerated in patients with advanced solid tumors. The combination may have potential for treatment of patients with brain lesions. PMID:28915584

  7. A phase 1 dose-escalation study of the oral histone deacetylase inhibitor abexinostat in combination with standard hypofractionated radiotherapy in advanced solid tumors.

    PubMed

    Deutsch, Eric; Cohen-Jonathan Moyal, Elizabeth; Gregorc, Vanesa; Zucali, Paolo Andrea; Menard, Jean; Soria, Jean-Charles; Kloos, Ioana; Hsu, Jeff; Luan, Ying; Liu, Emily; Vezan, Remus; Graef, Thorsten; Rivera, Sofia

    2016-12-24

    Current treatments for advanced solid tumors tend to be only palliative. Although radiotherapy is administered with a curative intent, radioresistance and dose-limiting toxicities pose limitations to treatment. Abexinostat, an oral pan-histone deacetylase inhibitor, demonstrated enhanced sensitivity to radiation in various solid tumor cell lines. We conducted an exploratory, phase 1, dose-escalation study of abexinostat in combination with standard hypofractionated radiotherapy in patients with advanced solid tumors treated in a palliative setting. Among 58 treated patients, the median age was 61.5 years (range, 20-82); 47% of the patients had M1 stage disease, and 95% had received previous chemotherapy alone or chemotherapy in combination with surgery and/or radiotherapy. The recommended phase 2 dose was determined to be 90 mg/m2 (140 mg). Of the 51 patients evaluable for response, best overall response was 8% (1 complete response [CR], 3 partial responses [PRs]), and best loco-regional response was 12% (1 CR and 5 PRs) at a median follow-up of 16 weeks. Of note, patients with target or non-target brain lesions showed encouraging responses, with 1 patient achieving a best loco-regional response of CR. Treatment-emergent grade ≥3 adverse events (AEs) were few, with most common being thrombocytopenia (17%), lymphopenia (12%), and hypokalemia (7%). Six patients (10%) discontinued treatment due to AEs. No grade ≥3 prolongation of the QTc interval was observed, with no treatment discontinuations due to this AE. Oral abexinostat combined with radiotherapy was well tolerated in patients with advanced solid tumors. The combination may have potential for treatment of patients with brain lesions.

  8. Lung sparing and dose escalation in a robust-inspired IMRT planning method for lung radiotherapy that accounts for intrafraction motion.

    PubMed

    McCann, Claire; Purdie, Thomas; Hope, Andrew; Bezjak, Andrea; Bissonnette, Jean-Pierre

    2013-06-01

    To test the efficacy of a simple, robust-inspired intensity modulated radiotherapy (IMRT) planning strategy for lung radiotherapy designed to reduce lung dose and escalate tumor dose using realistic dose accumulation tools. A deformable image registration tool was used to plan and accumulate dose over all phases of the breathing cycle for conventional and robust-inspired IMRT strategies of eight nonsmall cell lung cancer patients exhibiting peak-to-peak respiratory motion with amplitudes ranging from 1 to 2 cm in the craniocaudal direction. The authors' robust-inspired plans were designed to have smaller beam apertures based on target location during exhale, combined with edge-enhanced intensity maps to ensure target coverage during inspiration. For these, a new planning target volume defined as the rPTV was generated from a 5-mm isotropic expansion of the clinical target volume (CTV) on end-exhale combined with a boost volume, set to 110% of the prescription dose. Plans were evaluated in terms of (i) lung sparing and (ii) dose escalation for mean lung dose (MLD) isotoxicity. CTV and planning target volumes (PTV) coverage and lung dose were compared to the conventional IMRT approach. Robust-inspired plans showed potential lung dose reductions in seven out of eight patients. For non-GTV lung, percent reductions of 3%-14% in MLD and 6%-15% in V20 were observed. For seven of eight cases, the robust-like approach yielded increased accumulated doses to CTV. Isotoxicity studies for MLD showed increased dose to the CTV and the rPTV, in the range of 104%-118% and 95%-114% of prescription dose, respectively. A 4D dose calculation based on deformable image registration was used to evaluate a robust-inspired planning strategy for lung radiotherapy. This method offers notable reductions to lung dose while improving tumor coverage through the use of reduced geometric margins combined with edge enhancements.

  9. Results of the Phase I Dose-Escalating Study of Motexafin Gadolinium With Standard Radiotherapy in Patients With Glioblastoma Multiforme

    SciTech Connect

    Ford, Judith M. Seiferheld, Wendy; Alger, Jeffrey R.; Wu, Genevieve; Endicott, Thyra J.; Mehta, Minesh; Curran, Walter; Phan, See-Chun

    2007-11-01

    Purpose: Motexafin gadolinium (MGd) is a putative radiation enhancer initially evaluated in patients with brain metastases. This Phase I trial studied the safety and tolerability of a 2-6-week course (10-22 doses) of MGd with radiotherapy for glioblastoma multiforme. Methods and Materials: A total of 33 glioblastoma multiforme patients received one of seven MGd regimens starting at 10 doses of 4 mg/kg/d MGd and escalating to 22 doses of 5.3 mg/kg/d MGd (5 or 10 daily doses then three times per week). The National Cancer Institute Cancer Therapy Evaluation Program toxicity and stopping rules were applied. Results: The maximal tolerated dose was 5.0 mg/kg/d MGd (5 d/wk for 2 weeks, then three times per week) for 22 doses. The dose-limiting toxicity was reversible transaminase elevation. Adverse reactions included rash/pruritus (45%), chills/fever (30%), and self-limiting vesiculobullous rash of the thumb and fingers (42%). The median survival of 17.6 months prompted a case-matched analysis. In the case-matched analysis, the MGd patients had a median survival of 16.1 months (n = 31) compared with the matched Radiation Therapy Oncology Group database patients with a median survival of 11.8 months (hazard ratio, 0.43; 95% confidence interval, 0.20-0.94). Conclusion: The maximal tolerated dose of MGd with radiotherapy for glioblastoma multiforme in this study was 5 mg/kg/d for 22 doses (daily for 2 weeks, then three times weekly). The baseline survival calculations suggest progression to Phase II trials is appropriate, with the addition of MGd to radiotherapy with concurrent and adjuvant temozolomide.

  10. Stereotactic Body Radiotherapy for Recurrent Squamous Cell Carcinoma of the Head and Neck: Results of a Phase I Dose-Escalation Trial

    SciTech Connect

    Heron, Dwight E.; Ferris, Robert L.; Karamouzis, Michalis; Andrade, Regiane S.; Deeb, Erin L.; Burton, Steven; Gooding, William E.; Branstetter, Barton F.; Mountz, James M.; Johnson, Jonas T.; Argiris, Athanassios; Grandis, Jennifer R.; Lai, Stephen Y.

    2009-12-01

    Purpose: To evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) in previously irradiated patients with squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods: In this Phase I dose-escalation clinical trial, 25 patients were treated in five dose tiers up to 44 Gy, administered in 5 fractions over a 2-week course. Response was assessed according to the Response Evaluation Criteria in Solid Tumors and [{sup 18}F]-fluorodeoxyglucose standardized uptake value change on positron emission tomography-computed tomography (PET-CT). Results: No Grade 3/4 or dose-limiting toxicities occurred. Four patients had Grade 1/2 acute toxicities. Four objective responses were observed, for a response rate of 17% (95% confidence interval 2%-33%). The maximum duration of response was 4 months. Twelve patients had stable disease. Median time to disease progression was 4 months, and median overall survival was 6 months. Self-reported quality of life was not significantly affected by treatment. Fluorodeoxyglucose PET was a more sensitive early-measure response to treatment than CT volume changes. Conclusion: Reirradiation up to 44 Gy using SBRT is well tolerated in the acute setting and warrants further evaluation in combination with conventional and targeted therapies.

  11. Impact of Fraction Size on Lung Radiation Toxicity: Hypofractionation may be Beneficial in Dose Escalation of Radiotherapy for Lung Cancers

    SciTech Connect

    Jin Jinyue; Kong Fengming; Chetty, Indrin J.; Ajlouni, Munther; Ryu, Samuel; Ten Haken, Randall; Movsas, Benjamin

    2010-03-01

    Purpose: To assess how fraction size impacts lung radiation toxicity and therapeutic ratio in treatment of lung cancers. Methods and Materials: The relative damaged volume (RDV) of lung was used as the endpoint in the comparison of various fractionation schemes with the same normalized total dose (NTD) to the tumor. The RDV was computed from the biologically corrected lung dose-volume histogram (DVH), with an alpha/beta ratio of 3 and 10 for lung and tumor, respectively. Two different (linear and S-shaped) local dose-effect models that incorporated the concept of a threshold dose effect with a single parameter D{sub L50} (dose at 50% local dose effect) were used to convert the DVH into the RDV. The comparison was conducted using four representative DVHs at different NTD and D{sub L50} values. Results: The RDV decreased with increasing dose/fraction when the NTD was larger than a critical dose (D{sub CR}) and increased when the NTD was less than D{sub CR}. The D{sub CR} was 32-50 Gy and 58-87 Gy for a small tumor (11 cm{sup 3}) for the linear and S-shaped local dose-effect models, respectively, when D{sub L50} was 20-30 Gy. The D{sub CR} was 66-97 Gy and 66-99 Gy, respectively, for a large tumor (266 cm{sup 3}). Hypofractionation was preferred for small tumors and higher NTDs, and conventional fractionation was better for large tumors and lower NTDs. Hypofractionation might be beneficial for intermediate-sized tumors when NTD = 80-90 Gy, especially if the D{sub L50} is small (20 Gy). Conclusion: This computational study demonstrated that hypofractionated stereotactic body radiotherapy is a better regimen than conventional fractionation in lung cancer patients with small tumors and high doses, because it generates lower RDV when the tumor NTD is kept unchanged.

  12. Dose-Volume Parameters of the Corpora Cavernosa Do Not Correlate With Erectile Dysfunction After External Beam Radiotherapy for Prostate Cancer: Results From a Dose-Escalation Trial

    SciTech Connect

    Wielen, Gerard J. van der Hoogeman, Mischa S.; Dohle, Gert R.; Putten, Wim L.J. van; Incrocci, Luca

    2008-07-01

    Purpose: To analyze the correlation between dose-volume parameters of the corpora cavernosa and erectile dysfunction (ED) after external beam radiotherapy (EBRT) for prostate cancer. Methods and Materials: Between June 1997 and February 2003, a randomized dose-escalation trial comparing 68 Gy and 78 Gy was conducted. Patients at our institute were asked to participate in an additional part of the trial evaluating sexual function. After exclusion of patients with less than 2 years of follow-up, ED at baseline, or treatment with hormonal therapy, 96 patients were eligible. The proximal corpora cavernosa (crura), the superiormost 1-cm segment of the crura, and the penile bulb were contoured on the planning computed tomography scan and dose-volume parameters were calculated. Results: Two years after EBRT, 35 of the 96 patients had developed ED. No statistically significant correlations between ED 2 years after EBRT and dose-volume parameters of the crura, the superiormost 1-cm segment of the crura, or the penile bulb were found. The few patients using potency aids typically indicated to have ED. Conclusion: No correlation was found between ED after EBRT for prostate cancer and radiation dose to the crura or penile bulb. The present study is the largest study evaluating the correlation between ED and radiation dose to the corpora cavernosa after EBRT for prostate cancer. Until there is clear evidence that sparing the penile bulb or crura will reduce ED after EBRT, we advise to be careful in sparing these structures, especially when this involves reducing treatment margins.

  13. Characterizing geometric accuracy and precision in image guided gated radiotherapy

    NASA Astrophysics Data System (ADS)

    Tenn, Stephen Edward

    Gated radiotherapy combined with intensity modulated or three-dimensional conformal radiotherapy for tumors in the thorax and abdomen can deliver dose distributions which conform closely to tumor shapes allowing increased tumor dose while sparing healthy tissues. These conformal fields require more accurate and precise placement than traditional fields or tumors may receive suboptimal dose thereby reducing tumor control probability. Image guidance based on four-dimensional computed tomography (4DCT) provides a means to improve accuracy and precision in radiotherapy. The ability of 4DCT to accurately reproduce patient geometry and the ability of image guided gating equipment to position tumors and place fields around them must be characterized in order to determine treatment parameters such as tumor margins. Fiducial based methods of characterizing accuracy and precision of equipment for 4DCT planning and image guided gated radiotherapy (IGGRT) are presented with results for specific equipment. Fiducial markers of known geometric orientation are used to characterize 4DCT image reconstruction accuracy. Accuracy is determined under different acquisition protocols, reconstruction phases, and phantom trajectories. Targeting accuracy of fiducial based image guided gating is assessed by measuring in-phantom field positions for different motions, gating levels and target rotations. Synchronization parameters for gating equipment are also determined. Finally, end-to-end testing is performed to assess overall accuracy and precision of the equipment under controlled conditions. 4DCT limits fiducial geometric distance errors to 2 mm for repeatable target trajectories and to 5 mm for a pseudo-random trajectory. Largest offsets were in the longitudinal direction. If correctly calibrated and synchronized, the IGGRT system tested here can target reproducibly moving tumors with accuracy better than 1.2 mm. Gating level can affect accuracy if target motion is asymmetric about the

  14. Comparison of image-guided radiotherapy technologies for prostate cancer.

    PubMed

    Das, Satya; Liu, Tian; Jani, Ashesh B; Rossi, Peter; Shelton, Joseph; Shi, Zheng; Khan, Mohammad K

    2014-12-01

    Radiation oncology has seen a rapid increase in the use of image-guided radiotherapy technology (IGRT) for prostate cancer patients over the past decade. The increase in the use of IGRT is largely driven by the fact that these technologies have been approved by the Food and Drug Administration and are now readily reimbursed by many insurance companies. Prostate cancer patients undergoing intensity modulated radiotherapy (IMRT) now have access to a wide variety of IGRTs that can cost anywhere from $500,000 or more in upfront costs, and can add anywhere from 10 to 15 thousand dollars to a course of IMRT. Some of the IGRT options include daily cone beam computed tomography, ultrasound, orthogonal x-ray units using implanted fiducial markers, implanted radiofrequency markers with the ability to localize and track prostate motion during radiotherapy (Calypso 4D), and cine magnetic resonance imaging. Although these technologies add to the cost of IMRT, there is little direct comparative effectiveness data to help patients, physicians, and policy makers decide if one technology is better than another. In our critical review, the first of its kind, we summarize the advantages, disadvantages, and the limitations of each technology. We also provide an overview of existing literature as it pertains to the comparison of existing IGRTs. Lastly, we provide insights about the need for future outcomes research that may have a significant impact on health policies as it comes to reimbursement in the modern era.

  15. An image guided small animal stereotactic radiotherapy system

    PubMed Central

    Sha, Hao; Udayakumar, Thirupandiyur S.; Johnson, Perry B.; Dogan, Nesrin; Pollack, Alan; Yang, Yidong

    2016-01-01

    Small animal radiotherapy studies should be performed preferably on irradiators capable of focal tumor irradiation and healthy tissue sparing. In this study, an image guided small animal arc radiation treatment system (iSMAART) was developed which can achieve highly precise radiation targeting through the utilization of onboard cone beam computed tomography (CBCT) guidance. The iSMAART employs a unique imaging and radiation geometry where animals are positioned upright. It consists of a stationary x-ray tube, a stationary flat panel detector, and a rotatable and translational animal stage. System performance was evaluated in regards to imaging, image guidance, animal positioning, and radiation targeting using phantoms and tumor bearing animals. The onboard CBCT achieved good signal, contrast, and sub-millimeter spatial resolution. The iodine contrast CBCT accurately delineated orthotopic prostate tumors. Animal positioning was evaluated with ∼0.3 mm vertical displacement along superior-inferior direction. The overall targeting precision was within 0.4 mm. Stereotactic radiation beams conformal to tumor targets can be precisely delivered from multiple angles surrounding the animal. The iSMAART allows radiobiology labs to utilize an image guided precision radiation technique that can focally irradiate tumors while sparing healthy tissues at an affordable cost. PMID:26958942

  16. Interfractional dose variations in the stomach and the bowels during breathhold intensity-modulated radiotherapy for pancreatic cancer: Implications for a dose-escalation strategy.

    PubMed

    Nakamura, Akira; Shibuya, Keiko; Nakamura, Mitsuhiro; Matsuo, Yukinori; Shiinoki, Takehiro; Nakata, Manabu; Mizowaki, Takashi; Hiraoka, Masahiro

    2013-02-01

    the safety thresholds (1.4 and 3.8 ml, respectively). From the multiple regression analyses, only the margin size (P < 0.001) and the POV V39Gy (P < 0.001) were significantly associated with the distribution of recalculated V39Gy for the stomach. Multiple factors, including the margin size (P = 0.020) and the POV V39Gy (P < 0.001) were associated with the recalculated V39Gy for the duodenum. However, none of the POV parameters for the small intestine were associated with the recalculated V39Gy. Considerable interfractional dose variation was observed in three critical OARs. At the escalated prescription dose of breathhold IMRT, the dose variations could exceed the dose variations using 3D-CRT at the safe prescription dose level, indicating that a dose-escalation strategy based solely on the initial advantageous dose distribution in a breathhold IMRT can be problematic. Given the current limitations for predicting or coping with variation throughout the treatment course, the use of POV should be considered for safely delivering escalated doses to patients with pancreatic cancer.

  17. Concept for quantifying the dose from image guided radiotherapy.

    PubMed

    Schneider, Uwe; Hälg, Roger; Besserer, Jürgen

    2015-09-17

    Radiographic image guidance is routinely used for patient positioning in radiotherapy. All radiographic guidance techniques can give a significant radiation dose to the patient. The dose from diagnostic imaging is usually managed by using effective dose minimization. In contrast, image-guided radiotherapy adds the imaging dose to an already high level of therapeutic radiation which cannot be easily managed using effective dose. The purpose of this work is the development of a concept of IGRT dose quantification which allows a comparison of imaging dose with commonly accepted variations of therapeutic dose. It is assumed that dose variations of the treatment beam which are accepted in the spirit of the ALARA convention can also be applied to the additional imaging dose. Therefore we propose three dose categories: Category I: The imaging dose is lower than a 2% variation of the therapy dose. Category II: The imaging dose is larger than in category I, but lower than the therapy dose variations between different treatment techniques. Category III: The imaging dose is larger than in Category II. For various treatment techniques dose measurements are used to define the dose categories. The imaging devices were categorized according to the measured dose. Planar kV-kV imaging is a category I imaging procedure. kV-MV imaging is located at the edge between category I and II and is for increasing fraction size safely a category I imaging technique. MV-MV imaging is for all imaging technologies a category II procedure. MV fan beam CT for localization is a category I technology. Low dose protocols for kV CBCT are located between category I and II and are for increasing fraction size a category I imaging technique. All other investigated Pelvis-CBCT protocols are category II procedures. Fan beam CT scout views are category I technology. Live imaging modalities are category III for conventional fractionation, but category II for stereotactic treatments. Dose from radiotherapy

  18. [Image-guided radiotherapy: rational, modalities and results].

    PubMed

    de Crevoisier, R; Louvel, G; Cazoulat, G; Leseur, J; Lafond, C; Lahbabi, K; Chira, C; Lagrange, J-L

    2009-01-01

    The objective of Image-Guided Radiotherapy (IGRT) is to take in account the inter- or/and intrafraction anatomic variations (organ motion and deformations) in order to improve treatment accuracy. The IGRT should therefore translate in a clinical benefit the recent advances in both tumor definition thanks to functional imaging, and dose distribution thanks to intensity modulated radiotherapy. The IGRT enables direct or indirect tumor visualization during radiation delivery. If the tumor position does not correspond with the theoretical location of target derived from planning system, the table is moved. In case of important uncertainties related to target deformation, a new planning can be discussed. IGRT is realized by different types of devices which can vary in principle and as well as in their implementation: from LINAC-integrated-kV (or MV)-Cone Beam CTs to helicoidal tomotherapy, Cyberknife and Novalis low-energy stereoscopic imaging system. These techniques led to a more rational choice of Planning Target Volume. Being recently introduced in practice, the clinical results of this technique are still limited. Nevertheless, until so far, IGRT has showed promising results with reports of minimal acute toxicity. This review describes IGRT for various tumor localizations. The dose delivered by on board imaging should be taken in account. A strong quality control is required for safety and proper prospective evaluation of the clinical benefit of IGRT.

  19. Temporary organ displacement coupled with image-guided, intensity-modulated radiotherapy for paraspinal tumors

    PubMed Central

    2013-01-01

    Background To investigate the feasibility and dosimetric improvements of a novel technique to temporarily displace critical structures in the pelvis and abdomen from tumor during high-dose radiotherapy. Methods Between 2010 and 2012, 11 patients received high-dose image-guided intensity-modulated radiotherapy with temporary organ displacement (TOD) at our institution. In all cases, imaging revealed tumor abutting critical structures. An all-purpose drainage catheter was introduced between the gross tumor volume (GTV) and critical organs at risk (OAR) and infused with normal saline (NS) containing 5-10% iohexol. Radiation planning was performed with the displaced OARs and positional reproducibility was confirmed with cone-beam CT (CBCT). Patients were treated within 36 hours of catheter placement. Radiation plans were re-optimized using pre-TOD OARs to the same prescription and dosimetrically compared with post-TOD plans. A two-tailed permutation test was performed on each dosimetric measure. Results The bowel/rectum was displaced in six patients and kidney in four patients. One patient was excluded due to poor visualization of the OAR; thus 10 patients were analyzed. A mean of 229 ml (range, 80–1000) of NS 5-10% iohexol infusion resulted in OAR mean displacement of 17.5 mm (range, 7–32). The median dose prescribed was 2400 cGy in one fraction (range, 2100–3000 in 3 fractions). The mean GTV Dmin and PTV Dmin pre- and post-bowel TOD IG-IMRT dosimetry significantly increased from 1473 cGy to 2086 cGy (p=0.015) and 714 cGy to 1214 cGy (p=0.021), respectively. TOD increased mean PTV D95 by 27.14% of prescription (p=0.014) while the PTV D05 decreased by 9.2% (p=0.011). TOD of the bowel resulted in a 39% decrease in mean bowel Dmax (p=0.008) confirmed by CBCT. TOD of the kidney significantly decreased mean kidney dose and Dmax by 25% (0.022). Conclusions TOD was well tolerated, reproducible, and facilitated dose escalation to previously radioresistant tumors

  20. Fluoroscopic tumor tracking for image-guided lung cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Lin, Tong; Cerviño, Laura I.; Tang, Xiaoli; Vasconcelos, Nuno; Jiang, Steve B.

    2009-02-01

    Accurate lung tumor tracking in real time is a keystone to image-guided radiotherapy of lung cancers. Existing lung tumor tracking approaches can be roughly grouped into three categories: (1) deriving tumor position from external surrogates; (2) tracking implanted fiducial markers fluoroscopically or electromagnetically; (3) fluoroscopically tracking lung tumor without implanted fiducial markers. The first approach suffers from insufficient accuracy, while the second may not be widely accepted due to the risk of pneumothorax. Previous studies in fluoroscopic markerless tracking are mainly based on template matching methods, which may fail when the tumor boundary is unclear in fluoroscopic images. In this paper we propose a novel markerless tumor tracking algorithm, which employs the correlation between the tumor position and surrogate anatomic features in the image. The positions of the surrogate features are not directly tracked; instead, we use principal component analysis of regions of interest containing them to obtain parametric representations of their motion patterns. Then, the tumor position can be predicted from the parametric representations of surrogates through regression. Four regression methods were tested in this study: linear and two-degree polynomial regression, artificial neural network (ANN) and support vector machine (SVM). The experimental results based on fluoroscopic sequences of ten lung cancer patients demonstrate a mean tracking error of 2.1 pixels and a maximum error at a 95% confidence level of 4.6 pixels (pixel size is about 0.5 mm) for the proposed tracking algorithm.

  1. The Percent of Positive Biopsy Cores Improves Prediction of Prostate Cancer-Specific Death in Patients Treated With Dose-Escalated Radiotherapy

    SciTech Connect

    Qian Yushen; Feng, Felix Y.; Halverson, Schuyler; Blas, Kevin; Sandler, Howard M.; Hamstra, Daniel A.

    2011-11-01

    Purpose: To examine the prognostic utility of the percentage of positive cores (PPC) at the time of prostate biopsy for patients treated with dose-escalated external beam radiation therapy. Methods and Materials: We performed a retrospective analysis of patients treated at University of Michigan Medical Center to at least 75 Gy. Patients were stratified according to PPC by quartile, and freedom from biochemical failure (nadir + 2 ng/mL), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival (OS) were assessed by log-rank test. Receiver operator characteristic (ROC) curve analysis was used to determine the optimal cut point for PPC stratification. Finally, Cox proportional hazards multivariate regression was used to assess the impact of PPC on clinical outcome when adjusting for National Comprehensive Cancer Network (NCCN) risk group and androgen deprivation therapy. Results: PPC information was available for 651 patients. Increasing-risk features including T stage, prostate-specific antigen, Gleason score, and NCCN risk group were all directly correlated with increasing PPC. On log-rank evaluation, all clinical endpoints, except for OS, were associated with PPC by quartile, with worse clinical outcomes as PPC increased, with the greatest impact seen in the highest quartile (>66.7% of cores positive). ROC curve analysis confirmed that a cut point using two-thirds positive cores was most closely associated with CSS (p = 0.002; area under ROC curve, 0.71). On univariate analysis, stratifying patients according to PPC less than or equal to 66.7% vs. PPC greater than 66.7% was prognostic for freedom from biochemical failure (p = 0.0001), FFM (p = 0.0002), and CSS (p = 0.0003) and marginally prognostic for OS (p = 0.055). On multivariate analysis, after adjustment for NCCN risk group and androgen deprivation therapy use, PPC greater than 66.7% increased the risk for biochemical failure (p = 0.0001; hazard ratio [HR], 2.1 [95% confidence

  2. Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study.

    PubMed

    Marincek, Nicolas; Jörg, Ann-Catherine; Brunner, Philippe; Schindler, Christian; Koller, Michael T; Rochlitz, Christoph; Müller-Brand, Jan; Maecke, Helmut R; Briel, Matthias; Walter, Martin A

    2013-01-15

    We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1-4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1-158) months, 34 (range: 1-118) months and 29 (range: 1-113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211).

  3. Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study

    PubMed Central

    2013-01-01

    Background We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. Methods In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Results Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1–4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1–158) months, 34 (range: 1–118) months and 29 (range: 1–113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Conclusions Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. Trial registration ClinicalTrials.gov number:NCT00978211 PMID:23320604

  4. Dose escalation of Stereotactic Body Radiotherapy (SBRT) for locally advanced unresectable pancreatic cancer patients with CyberKnife: protocol of a phase I study.

    PubMed

    Qing, Shui-Wang; Ju, Xiao-Ping; Cao, Yang-Sen; Zhang, Huo-Jun

    2017-01-09

    Dose escalation of SBRT for locally advanced pancreatic cancer patients had been reported in several studies in one or three fractions, and phase I protocol was developed to investigate the maximum tolerated dose with CyberKnife for locally advanced unresectable pancreatic cancer patients in five fractions. The study is designed as a mono-center phase I study. The primary endpoint is to determine the maximum tolerated dose by frequency of III/IV GI (gastrointestinal) toxicity. Adverse events (AE) according to Common Toxicity Criteria (CTC) version 4. Doses of 7 Gy, 7.5 Gy, 8 Gy, 8.5 Gy, 9 Gy, 9.5Gy x 5 respectively would be delivered while meeting with normal tissue constraints. A minimum of three patients will be included for each dosage level. And an interval is 4 weeks from the first patient treatment to the next patient treatment at each dose level. The maximal tolerated dose will be defined as the dose for which at least two patients in three, or at least three patients in nine, will present with a limiting toxicity. Since the dose and fractions of SBRT treatment for locally advanced pancreatic cancer patients are still unknown, we propose to conduct a Phase I study determining the maximum tolerated dose of CyberKnife SBRT for the treatment of locally advanced pancreatic tumor based on a 5 fractions treatment regimen. This trial protocol has been approved by the Ethics committee of Changhai hospital. The ethics number is 2016-030-01. Clinical trials number: NCT02716207 . Date of registration: 20 March 2016.

  5. Radiation Dose Escalation in Stage III Non-Small-Cell Lung Cancer

    PubMed Central

    Terakedis, Breanne; Sause, William

    2011-01-01

    For patients with stage III non-small-cell lung cancer with unresectable or inoperable tumors, definitive chemoradiotherapy is often utilized. Historically, local control and overall survival rates have been poor. In an effort to improve local control, new chemotherapeutic agents in combination with higher doses of radiotherapy have been investigated. Early dose escalation trials date back to the 1980s, and the feasibility and efficacy of dose escalation for patients with inoperable stage III lung cancer continue to be topics of investigation. Herein, we review the evolution of chemotherapy as it relates to treatment of unresectable stage III lung cancer, and we outline the early and the more recent dose escalation studies. While dose escalation appears to provide a modest benefit in terms of preventing local failure and improving overall survival, advances in diagnostic imaging and radiotherapy treatment have possibly resulted in selection of a more favorable patient population. These variables make statements regarding the benefit of dose escalation challenging. PMID:22645713

  6. SU-C-BRA-01: 18F-NaF PET/CT-Directed Dose Escalation in Stereotactic Body Radiotherapy for Spine Oligometastases From Prostate Cancer

    SciTech Connect

    Wu, L; Zhang, W; Li, M; Peng, X; Xie, L; Lin, Z; Kwee, S; Wang, H; Kuang, Y

    2015-06-15

    Purpose: To investigate the technical feasibility of SBRT dose painting using {sup 18}F-NaF positron emission tomography (PET) scans guidance in patients with spine oligometastases from prostate cancer. Methods: As a proof of concept, six patients with 14 spine oligometastatic lesions from prostate cancer who had {sup 18}F-NaF PET/CT scan prior to treatment were retrospectively included. GTV{sub reg} was delineated according to the regular tumor boundary shown on PET and/or CT images; and GTV{sub MATV} was contoured based on a net metabolically active tumor volume (MATV) defined by 60% of the SUV{sub max} values on {sup 18}F-NaF PET images. The PTVs (PTV{sub reg} and PTV{sub MATV}) were defined as respective GTVs (plus involved entire vertebral body for PTV{sub reg}) with a 3-mm isotropic expansion margin. Three 1-fraction SBRT plans using VMAT technique along with 10 MV FFF beams (Plan{sub 24Gy}, Plan{sub 24–27Gy}, and Plan{sub 24–30Gy}) were generated for each patient. All plans included a dose of 24 Gy prescribed to PTV{sub reg}. The Plan{sub 24–27Gy} and Plan{sub 24–30Gy} also included a simultaneous boost dose of 27 Gy or 30 Gy prescribed to the PTV{sub MATV}, respectively. The feasibility of 18F-NaF PET-guided SBRT dose escalation was evaluated by its ability to achieve the prescription dose objectives while adhering to organ-at-risk (OAR) dose constraints. The normal tissue complication probabilities (NTCP) calculated by radiological models were also compared between the plans. Results: In all 33 SBRT plans generated, the planning objectives and dose constraints were met without exception. Plan{sub 24–27Gy} and Plan{sub 24–30Gy} had a significantly higher dose in PTV{sub MATV} than Plan{sub 24Gy} (p < 0.05), respectively, while maintaining a similar OAR sparing profile and NTCP values. Conclusion: Using VMAT with FFF beams to incorporate a simultaneous {sup 18}F-NaF PET-guided radiation boost dose up to 30 Gy into a SBRT plan is technically

  7. Internal target volume for post-hysterectomy vaginal recurrences of cervical cancers during image-guided radiotherapy.

    PubMed

    Upasani, Maheshkumar N; Chopra, Supriya; Engineer, Reena; Mahantshetty, Umesh; Medhi, Seema; Mehta, Zubin; Shrivastava, Shyam K

    2015-10-01

    The outcome of post-surgical recurrences of cervical cancer may be improved through radiation dose escalation, which hinges on accurate identification and treatment of the target. The present study quantifies target motion during course of image-guided radiotherapy (IGRT) for vault cancers. All patients underwent planning CT simulation after bladder-filling protocol. A daily pre-treatment megavoltage CT was performed. All translations and rotations were recorded. Post-registration displacement of gross tumour volume (GTV) and centre of mass (COM) of GTV was independently recorded by two observers for fractions one to seven. Day 1 image sets served as reference images against which the displacements of COM were measured. We calculated the displacements of common volume (CV) and encompassing volume (EV) of GTV for both the observers. A total of 90 image data sets of 15 patients were available for evaluation. Individual patient GTV and average GTV by both the observers were comparable. The average shifts for EV were 2.4 mm [standard deviation (SD) ±1.2] in the mediolateral, 4.2 mm (SD ±2.8) in the anteroposterior and 4.0 mm (SD ±2.1) in superoinferior directions. Similarly, the average shifts for CV were 1.9 mm (SD ±0.6) in the mediolateral, 3.7 mm (SD ±2.7) in the anteroposterior and 4.4 mm (SD ±2.7) in superoinferior directions. Using Stroom's/van Herk's formula, the minimum recommended margins would be 4.5/5.2, 8.2/9.4 and 7.3/8.3 mm, respectively, for lateral, anteroposterior and superoinferior directions. Differential directional internal margin is recommended in patients undergoing IGRT for post-surgical recurrence of cervical cancers. Internal organ motion of vault cancers can be accounted for by a directional margin to the gross tumour.

  8. Phase II Trial of Radiation Dose Escalation With Conformal External Beam Radiotherapy and High-Dose-Rate Brachytherapy Combined With Long-Term Androgen Suppression in Unfavorable Prostate Cancer: Feasibility Report

    SciTech Connect

    Valero, Jeanette; Cambeiro, Mauricio; Galan, Carlos; Teijeira, Mercedes; Romero, Pilar; Zudaire, Javier; Moreno, Marta; Ciervide, Raquel; Aristu, Jose Javier; Martinez-Monge, Rafael

    2010-02-01

    Purpose: To determine the feasibility of combined long-term luteinizing hormone-releasing hormone agonist-based androgen suppressive therapy (AST) and dose escalation with high-dose-rate (HDR) brachytherapy for high-risk (HRPC) or very-high-risk prostate cancer (VHRPC). Methods and Materials: Between January 2001 and October 2006, 134 patients (median age, 70 years) with either National Comprehensive Cancer Network criteria-defined HRPC (n = 47, 35.1%) or VHRPC (n = 87, 64.9%) were prospectively enrolled in this Phase II trial. Tumor characteristics included a median pretreatment prostate-specific antigen level of 14.6 ng/mL, a median clinical stage of T2c, and a median Gleason score of 7. Three-dimensional conformal radiotherapy (54 Gy in 30 fractions) was followed by HDR brachytherapy (19 Gy in 4 b.i.d. treatments). Androgen suppressive therapy started 0-3 months before three-dimensional conformal radiotherapy and continued for 2 years. Results: One implant was repositioned with a new procedure (0.7%). Five patients (3.7%) discontinued AST at a median of 13 months (range, 6-18 months) because of disease progression (n = 1), hot flashes (n = 2), fatigue (n = 1), and impotence (n = 1). After a median follow-up of 37.4 months (range, 24-90 months), the highest Radiation Therapy Oncology Group-defined late urinary toxicities were Grade 0 in 47.8%, Grade 1 in 38.1%, Grade 2 in 7.5%, and Grade 3 in 6.7% of patients. Maximal late gastrointestinal toxicities were Grade 0 in 73.1%, Grade 1 in 16.4%, Grade 2 in 7.5%, and Grade 3 in 2.9% of patients. There were no Grade 4 or 5 events. Conclusions: Intermediate-term results show that dose escalation with HDR brachytherapy combined with long-term AST is feasible and has a toxicity profile similar to that reported by previous HDR brachytherapy studies.

  9. 3D-image-guided HDR-brachytherapy versus 2D HDR - brachytherapy after external beam radiotherapy for early T-stage nasopharyngeal carcinoma.

    PubMed

    Ren, YuFeng; Zhao, QuanCheng; Liu, Hui; Huang, YingJuan; Wang, ZhenYu; Cao, XinPing; Teh, Bin S; Wen, BiXiu

    2014-11-29

    Two-dimensional high-dose-rate brachytherapy (2D-HDR-BT) is an effective method of dose escalation for local tumor control in early T-stage nasopharyngeal carcinoma (NPC). Treatment outcomes for 3D-image-guided high-dose-rate brachytherapy (3D-image-guided-HDR-BT) after external beam radiotherapy (ERT) have not been examined in early T-stage NPC patients. The current study was designed to evaluate whether addition of 3D-HDR-BT to ERT showed further improvement in treatment outcomes in patients with early T-stage NPC when compared to 2D-HDR-BT after ERT. The current study retrospectively analyzed and compared treatment outcomes for patients with nonmetastatic stage T1-2b NPC treated with 2D-HDR-BT (n =101) or 3D-HDR-BT (n =118) after ERT. Patients in both groups were treated with ERT at a mean dose of 60 Gy and a brachytherapy dose of 12Gy (8 ~ 20Gy), 2.5 ~ 5Gy per fraction under local anesthesia. Compared to patients treated with 2D-HDR-BT after ERT, patients treated with 3D-HDR-BT after ERT showed improvement in five-year actuarial local control survival rates (p = 0.024), local/regional relapse-free survival rates (p = 0.038), and disease-free survival rates (p = 0.021). Multivariate analysis showed that NPC patients treated with 3D-HDR-BT had improved local control survival (p = 0.042). The incidence rates of acute or chronic complications were similar between two groups. The current study showed that 3D-image-guided HDR-BT after ERT was an effective treatment modality for patients with stage T1-2 NPC with acceptable complications. The improvement in local tumor control and disease free survival is likely due to improved conformal dose distributions.

  10. Carbon-ion radiotherapy for locally advanced or unfavorably located choroidal melanoma: A Phase I/II dose-escalation study

    SciTech Connect

    Tsuji, Hiroshi . E-mail: h_tsuji@nirs.go.jp; Ishikawa, Hitoshi; Yanagi, Takeshi; Hirasawa, Naoki; Kamada, Tadashi; Mizoe, Jun-Etsu; Kanai, Tatsuaki; Tsujii, Hirohiko; Ohnishi, Yoshitaka

    2007-03-01

    Purpose: To evaluate the applicability of carbon ion beams for the treatment of choroidal melanoma with regard to normal tissue morbidity and local tumor control. Methods and Materials: Between January 2001 and February 2006, 59 patients with locally advanced or unfavorably located choroidal melanoma were enrolled in a Phase I/II clinical trial of carbon-ion radiotherapy at the National Institute of Radiologic Sciences. The primary endpoint of this study was normal tissue morbidity, and secondary endpoints were local tumor control and patient survival. Of the 59 subjects enrolled, 57 were followed >6 months and analyzed. Results: Twenty-three patients (40%) developed neovascular glaucoma, and three underwent enucleation for eye pain due to elevated intraocular pressure. Incidence of neovascular glaucoma was dependent on tumor size and site. Five patients had died at analysis, three of distant metastasis and two of concurrent disease. All but one patient, who developed marginal recurrence, were controlled locally. Six patients developed distant metastasis, five in the liver and one in the lung. Three-year overall survival, disease-free survival, and local control rates were 88.2%, 84.8%, and 97.4%, respectively. No apparent dose-response relationship was observed in either tumor control or normal tissue morbidity at the dose range applied. Conclusion: Carbon-ion radiotherapy can be applied to choroidal melanoma with an acceptable morbidity and sufficient antitumor effect, even with tumors of unfavorable size or site.

  11. 70 Gy Versus 80 Gy in Localized Prostate Cancer: 5-Year Results of GETUG 06 Randomized Trial;Prostate cancer; Dose escalation; Conformal radiotherapy; Randomized trial

    SciTech Connect

    Beckendorf, Veronique; Guerif, Stephane; Le Prise, Elisabeth; Cosset, Jean-Marc; Bougnoux, Agnes; Chauvet, Bruno; Salem, Naji; Chapet, Olivier; Bourdain, Sylvain; Bachaud, Jean-Marc; Maingon, Philippe; Hannoun-Levi, Jean-Michel; Malissard, Luc; Simon, Jean-Marc; Pommier, Pascal; Hay, Men; Dubray, Bernard; Lagrange, Jean-Leon; Luporsi, Elisabeth; Bey, Pierre

    2011-07-15

    Purpose: To perform a randomized trial comparing 70 and 80 Gy radiotherapy for prostate cancer. Patients and Methods: A total of 306 patients with localized prostate cancer were randomized. No androgen deprivation was allowed. The primary endpoint was biochemical relapse according to the modified 1997-American Society for Therapeutic Radiology and Oncology and Phoenix definitions. Toxicity was graded using the Radiation Therapy Oncology Group 1991 criteria and the late effects on normal tissues-subjective, objective, management, analytic scales (LENT-SOMA) scales. The patients' quality of life was scored using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item cancer-specific and 25-item prostate-specific modules. Results: The median follow-up was 61 months. According to the 1997-American Society for Therapeutic Radiology and Oncology definition, the 5-year biochemical relapse rate was 39% and 28% in the 70- and 80-Gy arms, respectively (p = .036). Using the Phoenix definition, the 5-year biochemical relapse rate was 32% and 23.5%, respectively (p = .09). The subgroup analysis showed a better biochemical outcome for the higher dose group with an initial prostate-specific antigen level >15 ng/mL. At the last follow-up date, 26 patients had died, 10 of their disease and none of toxicity, with no differences between the two arms. According to the Radiation Therapy Oncology Group scale, the Grade 2 or greater rectal toxicity rate was 14% and 19.5% for the 70- and 80-Gy arms (p = .22), respectively. The Grade 2 or greater urinary toxicity was 10% at 70 Gy and 17.5% at 80 Gy (p = .046). Similar results were observed using the LENT-SOMA scale. Bladder toxicity was more frequent at 80 Gy than at 70 Gy (p = .039). The quality-of-life questionnaire results before and 5 years after treatment were available for 103 patients with no differences found between the 70- and 80-Gy arms. Conclusion: High-dose radiotherapy provided a

  12. Image-guided radiotherapy and motion management in lung cancer

    PubMed Central

    2015-01-01

    In this review, image guidance and motion management in radiotherapy for lung cancer is discussed. Motion characteristics of lung tumours and image guidance techniques to obtain motion information are elaborated. Possibilities for management of image guidance and motion in the various steps of the treatment chain are explained, including imaging techniques and beam delivery techniques. Clinical studies using different motion management techniques are reviewed, and finally future directions for image guidance and motion management are outlined. PMID:25955231

  13. Clinical Application of High-Dose, Image-Guided Intensity-Modulated Radiotherapy in High-Risk Prostate Cancer

    SciTech Connect

    Bayley, Andrew; Rosewall, Tara; Craig, Tim; Bristow, Rob; Chung, Peter; Gospodarowicz, Mary; Menard, Cynthia; Milosevic, Michael; Warde, Padraig; Catton, Charles

    2010-06-01

    Purpose: To report the feasibility and early toxicity of dose-escalated image-guided IMRT to the pelvic lymph nodes (LN), prostate (P), and seminal vesicles (SV). Methods and Materials: A total of 103 high-risk prostate cancer patients received two-phase, dose-escalated, image-guided IMRT with 3 years of androgen deprivation therapy. Clinical target volumes (CTVs) were delineated using computed tomography/magnetic resonance co-registration and included the prostate, portions of the SV, and the LN. Planning target volume margins (PTV) used were as follows: P (10 mm, 7 mm posteriorly), SV (10 mm), and LN (5 mm). Organs at risk (OaR) were the rectal and bladder walls, femoral heads, and large and small bowel. The IMRT was planned with an intended dose of 55.1 Gy in 29 fractions to all CTVs (Phase 1), with P+SV consecutive boost of 24.7 Gy in 13 fractions. Daily online image guidance was performed using bony landmarks and intraprostatic markers. Feasibility criteria included delivery of intended doses in 80% of patients, 95% of CTV displacements incorporated within PTV during Phase 1, and acute toxicity rate comparable to that of lower-dose pelvic techniques. Results: A total of 91 patients (88%) received the total prescription dose. All patients received at least 72 Gy. In Phase 1, 63 patients (61%) received the intended 55.1 Gy, whereas 87% of patients received at least 50 Gy. Dose reductions were caused by small bowel and rectal wall constraints. All CTVs received the planned dose in >95% of treatment fractions. There were no Radiation Therapy Oncology Group acute toxicities greater than Grade 3, although there were five incidences equivalent to Grade 3 within a median follow-up of 23 months. Conclusion: These results suggest that dose escalation to the PLN+P+SV using IMRT is feasible, with acceptable rates of acute toxicity.

  14. Reduced rectal toxicity with ultrasound-based image guided radiotherapy using BAT (B-mode acquisition and targeting system) for prostate cancer.

    PubMed

    Bohrer, Markus; Schröder, Peter; Welzel, Grit; Wertz, Hansjörg; Lohr, Frank; Wenz, Frederik; Mai, Sabine Kathrin

    2008-12-01

    To evaluate the effect of image guided radiotherapy with stereotactic ultrasound BAT (B-mode acquisition and targeting system) on rectal toxicity in conformal radiotherapy of prostate cancer. 42 sequential patients with prostate cancer undergoing radiotherapy before and after the introduction of BAT were included. Planning computed tomography (CT) was performed with empty rectum and moderately filled bladder. The planning target volume (PTV) included the prostate and seminal vesicles with a safety margin of 1.5 cm in anterior and lateral direction. In posterior direction the anterior 1/3 of the rectum circumference were included. Total dose was 66 Gy and a boost of 4 Gy excluding the seminal vesicles. 22 patients (BAT group) were treated with daily stereotactic ultrasound positioning, for the other 20 patients (NoBAT group) an EPID (electronic portal imaging device) was performed once a week. Acute and late genito-urinary (GU) and rectal toxicity and PSA values were evaluated after 1.5, 3, 6, 9 and 12 months. The total median follow up of toxicity was 3 years in the BAT group and 4 years in the NoBAT group. In the NoBAT group significant more rectal toxicity occurred, while in GU toxicity no difference was seen. Two patients in the NoBAT group showed late rectal toxicity grade 3, no toxicity>grade 2 occurred in the BAT group. There was no significant difference in PSA reduction between the groups. Without BAT significant more acute and a trend to more late rectal toxicity was found. With regard to dose escalation this aspect is currently evaluated with a larger number of patients using intensity-modulated radiotherapy (IMRT).

  15. Dose-Escalated Radiotherapy for High-Risk Prostate Cancer: Outcomes in Modern Era With Short-Term Androgen Deprivation Therapy

    SciTech Connect

    Liauw, Stanley L.; Stadler, Walter M.; Correa, David B.S.; Weichselbaum, Ralph R.; Jani, Ashesh B.

    2010-05-01

    Purpose: Randomized data have supported the use of long-term androgen deprivation therapy (ADT) combined with radiotherapy (RT) for men with high-risk prostate cancer. The present study reviewed the outcomes of intermediate- and high-risk men treated with RT and short-term ADT. Materials and Methods: A total of 184 men with any single risk factor of prostate-specific antigen >=10 ng/mL, clinical Stage T2b or greater, or Gleason score >=7 were treated with primary external beam RT for nonmetastatic adenocarcinoma of the prostate. The median radiation dose was 74 Gy; 55% were treated with intensity-modulated RT. All patients received ADT for 1 to 6 months (median, 4), consisting of a gonadotropin-releasing hormone analog. Univariate and multivariable analyses were performed for risk factors, including T stage, Gleason score, radiation dose, and prostate-specific antigen level. Results: With a median follow-up of 51 months, the 4-year freedom from biochemical failure (FFBF) using the nadir plus 2 ng/mL definition was 83% for all patients. Clinical Stage T3 disease was the only variable tested associated with FFBF on univariate (4-year FFBF rate, 46% vs. 87% for Stage T1-T2c disease; p = .0303) and multivariable analysis (hazard ratio, 3.9; p = .0016). On a subset analysis of high-risk patients (National Comprehensive Cancer Network criteria), those with clinical Stage T3 disease (4-year FFBF rate, 46% vs. 80%; p = .0303) and a radiation dose <74 Gy (4-year FFBF rate, 64% vs. 80%) had a poorer outcome on univariate analysis. However, clinical Stage T3 disease and radiation dose were not significant on multivariable analysis, although a statistical multivariable trend was seen for both (p = .0650 and p = .0597, respectively). Conclusion: Short-term ADT and RT might be acceptable for men with intermediate- and high-risk prostate cancer, especially for clinically localized disease treated with doses of >=74 Gy.

  16. Dose escalation for prostate cancer radiotherapy: predictors of long-term biochemical tumor control and distant metastases-free survival outcomes.

    PubMed

    Zelefsky, Michael J; Pei, Xin; Chou, Joanne F; Schechter, Michael; Kollmeier, Marisa; Cox, Brett; Yamada, Yoshiya; Fidaleo, Anthony; Sperling, Dahlia; Happersett, Laura; Zhang, Zhigang

    2011-12-01

    Higher radiation dose levels have been shown to be associated with improved tumor-control outcomes in localized prostate cancer (PCa) patients. Identify predictors of biochemical tumor control and distant metastases-free survival (DMFS) outcomes for patients with clinically localized PCa treated with conformal external-beam radiotherapy (RT) as well as present an updated nomogram predicting long-term biochemical tumor control after RT. This retrospective analysis comprised 2551 patients with clinical stages T1-T3 PCa. Median follow-up was 8 yr, extending >20 yr. Prescription doses ranged from 64.8 to 86.4 Gy. A total of 1249 patients (49%) were treated with neoadjuvant and concurrent androgen-deprivation therapy (ADT); median duration of ADT was 6 mo. A proportional hazards regression model predicting the probability of biochemical relapse and distant metastases after RT included pretreatment prostate-specific antigen (PSA) level, clinical stage, biopsy Gleason sum, ADT use, and radiation dose. A nomogram predicting the probability of biochemical relapse after RT was developed. Radiation dose was one of the important predictors of long-term biochemical tumor control. Dose levels < 70.2 Gy and 70.2-79.2 Gy were associated with 2.3- and 1.3-fold increased risks of PSA relapse compared with higher doses. Improved PSA relapse-free survival (PSA-RFS) outcomes with higher doses were observed for all risk groups. Use of ADT, especially for intermediate- and high-risk patients, was associated with significantly improved biochemical tumor-control outcomes. A nomogram predicting PSA-RFS was generated and was associated with a concordance index of 0.67. T stage, Gleason score, pretreatment PSA, ADT use, and higher radiation doses were also noted to be significant predictors of improved DMFS outcomes. Higher radiation dose levels were consistently associated with improved biochemical control outcomes and reduction in distant metastases. The use of short-course ADT in

  17. Effect of image-guided hypofractionated stereotactic radiotherapy on peripheral non-small-cell lung cancer

    PubMed Central

    Wang, Shu-wen; Ren, Juan; Yan, Yan-li; Xue, Chao-fan; Tan, Li; Ma, Xiao-wei

    2016-01-01

    The objective of this study was to compare the effects of image-guided hypofractionated radiotherapy and conventional fractionated radiotherapy on non-small-cell lung cancer (NSCLC). Fifty stage- and age-matched cases with NSCLC were randomly divided into two groups (A and B). There were 23 cases in group A and 27 cases in group B. Image-guided radiotherapy (IGRT) and stereotactic radiotherapy were conjugately applied to the patients in group A. Group A patients underwent hypofractionated radiotherapy (6–8 Gy/time) three times per week, with a total dose of 64–66 Gy; group B received conventional fractionated radiotherapy, with a total dose of 68–70 Gy five times per week. In group A, 1-year and 2-year local failure survival rate and 1-year local failure-free survival rate were significantly higher than in group B (P<0.05). The local failure rate (P<0.05) and distant metastasis rate (P>0.05) were lower in group A than in group B. The overall survival rate of group A was significantly higher than that of group B (P=0.03), and the survival rate at 1 year was 87% vs 63%, (P<0.05). The median survival time of group A was longer than that of group B. There was no significant difference in the incidence of complications between the two groups (P>0.05). Compared with conventional fractionated radiation therapy, image-guided hypofractionated stereotactic radiotherapy in NSCLC received better treatment efficacy and showed good tolerability. PMID:27574441

  18. Automatic localization of the prostate for on-line or off-line image-guided radiotherapy

    SciTech Connect

    Smitsmans, Monique H.P.; Wolthaus, Jochem W.H.; Artignan, Xavier; Bois, Josien de; Jaffray, David A.; Lebesque, Joos V.; Herk, Marcel van . E-mail: portal@nki.nl

    2004-10-01

    Purpose: With higher radiation dose, higher cure rates have been reported in prostate cancer patients. The extra margin needed to account for prostate motion, however, limits the level of dose escalation, because of the presence of surrounding organs at risk. Knowledge of the precise position of the prostate would allow significant reduction of the treatment field. Better localization of the prostate at the time of treatment is therefore needed, e.g. using a cone-beam computed tomography (CT) system integrated with the linear accelerator. Localization of the prostate relies upon manual delineation of contours in successive axial CT slices or interactive alignment and is fairly time-consuming. A faster method is required for on-line or off-line image-guided radiotherapy, because of prostate motion, for patient throughput and efficiency. Therefore, we developed an automatic method to localize the prostate, based on 3D gray value registration. Methods and materials: A study was performed on conventional repeat CT scans of 19 prostate cancer patients to develop the methodology to localize the prostate. For each patient, 8-13 repeat CT scans were made during the course of treatment. First, the planning CT scan and the repeat CT scan were registered onto the rigid bony structures. Then, the delineated prostate in the planning CT scan was enlarged by an optimum margin of 5 mm to define a region of interest in the planning CT scan that contained enough gray value information for registration. Subsequently, this region was automatically registered to a repeat CT scan using 3D gray value registration to localize the prostate. The performance of automatic prostate localization was compared to prostate localization using contours. Therefore, a reference set was generated by registering the delineated contours of the prostates in all scans of all patients. Gray value registrations that showed large differences with respect to contour registrations were detected with a {chi

  19. Internal target volume for post-hysterectomy vaginal recurrences of cervical cancers during image-guided radiotherapy

    PubMed Central

    Upasani, Maheshkumar N; Engineer, Reena; Mahantshetty, Umesh; Medhi, Seema; Mehta, Zubin; Shrivastava, Shyam K

    2015-01-01

    Objective: The outcome of post-surgical recurrences of cervical cancer may be improved through radiation dose escalation, which hinges on accurate identification and treatment of the target. The present study quantifies target motion during course of image-guided radiotherapy (IGRT) for vault cancers. Methods: All patients underwent planning CT simulation after bladder-filling protocol. A daily pre-treatment megavoltage CT was performed. All translations and rotations were recorded. Post-registration displacement of gross tumour volume (GTV) and centre of mass (COM) of GTV was independently recorded by two observers for fractions one to seven. Day 1 image sets served as reference images against which the displacements of COM were measured. We calculated the displacements of common volume (CV) and encompassing volume (EV) of GTV for both the observers. Results: A total of 90 image data sets of 15 patients were available for evaluation. Individual patient GTV and average GTV by both the observers were comparable. The average shifts for EV were 2.4 mm [standard deviation (SD) ±1.2] in the mediolateral, 4.2 mm (SD ±2.8) in the anteroposterior and 4.0 mm (SD ±2.1) in superoinferior directions. Similarly, the average shifts for CV were 1.9 mm (SD ±0.6) in the mediolateral, 3.7 mm (SD ±2.7) in the anteroposterior and 4.4 mm (SD ±2.7) in superoinferior directions. Using Stroom's/van Herk's formula, the minimum recommended margins would be 4.5/5.2, 8.2/9.4 and 7.3/8.3 mm, respectively, for lateral, anteroposterior and superoinferior directions. Conclusion: Differential directional internal margin is recommended in patients undergoing IGRT for post-surgical recurrence of cervical cancers. Advances in knowledge: Internal organ motion of vault cancers can be accounted for by a directional margin to the gross tumour. PMID:26248870

  20. Monte Carlo modeling of ultrasound probes for image guided radiotherapy

    SciTech Connect

    Bazalova-Carter, Magdalena; Schlosser, Jeffrey; Chen, Josephine; Hristov, Dimitre

    2015-10-15

    X6-1 probe in vertical orientation caused the highest attenuation of the 6 and 15 MV beams, which at 10 cm depth accounted for 33% and 43% decrease compared to the respective (15 × 15) cm{sup 2} open fields. The C5-2 probe in horizontal orientation, on the other hand, caused a dose increase of 10% and 53% for the 6 and 15 MV beams, respectively, in the buildup region at 0.5 cm depth. For the X6-1 probe in vertical orientation, the dose at 5 cm depth for the 3-cm diameter 6 MV and 5-cm diameter 15 MV beams was attenuated compared to the corresponding open fields to a greater degree by 65% and 43%, respectively. Conclusions: MC models of two US probes used for real-time image guidance during radiotherapy have been built. Due to the high beam attenuation of the US probes, the authors generally recommend avoiding delivery of treatment beams that intersect the probe. However, the presented MC models can be effectively integrated into US-guided radiotherapy treatment planning in cases for which beam avoidance is not practical due to anatomy geometry.

  1. Monte Carlo modeling of ultrasound probes for image guided radiotherapy

    PubMed Central

    Bazalova-Carter, Magdalena; Schlosser, Jeffrey; Chen, Josephine; Hristov, Dimitre

    2015-01-01

    orientation caused the highest attenuation of the 6 and 15 MV beams, which at 10 cm depth accounted for 33% and 43% decrease compared to the respective (15 × 15) cm2 open fields. The C5-2 probe in horizontal orientation, on the other hand, caused a dose increase of 10% and 53% for the 6 and 15 MV beams, respectively, in the buildup region at 0.5 cm depth. For the X6-1 probe in vertical orientation, the dose at 5 cm depth for the 3-cm diameter 6 MV and 5-cm diameter 15 MV beams was attenuated compared to the corresponding open fields to a greater degree by 65% and 43%, respectively. Conclusions: MC models of two US probes used for real-time image guidance during radiotherapy have been built. Due to the high beam attenuation of the US probes, the authors generally recommend avoiding delivery of treatment beams that intersect the probe. However, the presented MC models can be effectively integrated into US-guided radiotherapy treatment planning in cases for which beam avoidance is not practical due to anatomy geometry. PMID:26429248

  2. Quantitative Assessment of Image-Guided Radiotherapy for Paraspinal Tumors

    SciTech Connect

    Stoiber, Eva M.; Lechsel, Gerhard; Giske, Kristina; Muenter, Marc W.; Hoess, Angelika; Bendl, Rolf; Debus, Juergen; Huber, Peter E.; Thieke, Christian

    2009-11-01

    Purpose: To evaluate stereotactic positioning uncertainties of patients with paraspinal tumors treated with fractionated intensity-modulated radiotherapy; and to determine whether target-point correction via rigid registration is sufficient for daily patient positioning. Patients and Methods: Forty-five patients with tumors at the cervical, thoracic, and lumbar spine received regular control computed-tomography (CT) scans using an in-room CT scanner. All patients were immobilized with the combination of Scotch cast torso and head masks. The positioning was evaluated regarding translational and rotational errors by applying a rigid registration algorithm based on mutual information. The registration box was fitted to the target volume for optimal registration in the high-dose area. To evaluate the suitability of the rigid registration result for correcting the target volume position we subsequently registered three small subsections of the upper, middle, and lower target volume. The resulting residual deviations reflect the extent of the elastic deformations, which cannot be covered by the rigid-body registration procedure. Results: A total of 321 control CT scans were evaluated. The rotational errors were negligible. Translational errors were smallest for cervical tumors (-0.1 +- 1.1, 0.3 +- 0.8, and 0.1 +- 0.9 mm along left-right, anterior-posterior, and superior-inferior axes), followed by thoracic (0.8 +- 1.1, 0.3 +- 0.8, and 1.1 +- 1.3 mm) and lumbar tumors (-0.7 +- 1.3, 0.0 +- 0.9, and 0.5 +- 1.6 mm). The residual deviations of the three subsections were <1 mm. Conclusions: The applied stereotactic patient setup resulted in small rotational errors. However, considerable translational positioning errors may occur; thus, on the basis of these data daily control CT scans are recommended. Rigid transformation is adequate for correcting the target volume position.

  3. Development of a MicroCT-Based Image-Guided Conformal Radiotherapy System for Small Animals

    PubMed Central

    Zhou, Hu; Rodriguez, Manuel; van den Haak, Fred; Nelson, Geoffrey; Jogani, Rahil; Xu, Jiali; Zhu, Xinzhi; Xian, Yongjiang; Tran, Phuoc T.; Felsher, Dean W.; Keall, Paul J.; Graves, Edward E.

    2009-01-01

    Purpose The need for clinically-relevant radiation therapy technology for the treatment of preclinical models of disease has spurred the development of a variety of dedicated platforms for small animal irradiation. Our group has taken the approach of adding the ability to deliver conformal radiotherapy to an existing 120 kVp micro-computed tomography (microCT) scanner. Methods A GE eXplore RS120 microCT scanner was modified by the addition of a two-dimensional subject translation stage and a variable aperture collimator. Quality assurance protocols for these devices, including measurement of translation stage positioning accuracy, collimator aperture accuracy, and collimator alignment with the x-ray beam, were devised. Use of this system for image-guided radiotherapy was assessed by irradiation of a solid water phantom as well as of two mice bearing spontaneous MYC-induced lung tumors. Radiation damage was assessed ex vivo by immunohistochemical detection of γH2AX foci. Results The positioning error of the translation stage was found to be less than 0.05 mm, while after alignment of the collimator with the x-ray axis through adjustment of its displacement and rotation, the collimator aperture error was less than 0.1 mm measured at isocenter. CT image-guided treatment of a solid water phantom demonstrated target localization accuracy to within 0.1 mm. γH2AX foci were detected within irradiated lung tumors in mice, with contralateral lung tissue displaying background staining. Conclusions Addition of radiotherapy functionality to a microCT scanner is an effective means of introducing image-guided radiation treatments into the preclinical setting. This approach has been shown to facilitate small animal conformal radiotherapy while leveraging existing technology. PMID:20395069

  4. High pathological response rate in locally advanced esophageal cancer after neoadjuvant combined modality therapy: dose finding of a weekly chemotherapy schedule with protracted venous infusion of 5-fluorouracil and dose escalation of cisplatin, docetaxel and concurrent radiotherapy.

    PubMed

    Pasini, F; de Manzoni, G; Pedrazzani, C; Grandinetti, A; Durante, E; Gabbani, M; Tomezzoli, A; Griso, C; Guglielmi, A; Pelosi, G; Maluta, S; Cetto, G L; Cordiano, C

    2005-07-01

    This phase I study was aimed at defining the toxicity profile and pathological response rate of a neoadjuvant schedule including weekly docetaxel and cisplatin, protracted venous infusion (PVI) of 5-FU and concomitant radiotherapy (RT) in locally advanced esophageal cancer. The schedule consisted of a first phase of chemotherapy alone and a second phase of concurrent chemoradiation. Initial doses were: docetaxel and cisplatin 20 mg/m2 on days 1, 8, 15, 29, 36 and 43 plus 5-FU 150 mg/m2 PVI on days 1-21 and 29-49; RT (40 Gy) started on day 29. In the following steps the doses were escalated up to docetaxel 35 mg/m2 and cisplatin 25 mg/m2 on days 1, 8, 15, 29, 36, 43, 50 and 57 plus 5-FU 180 mg/m2 PVI on days 1-21 and 150 mg/m2 PVI on days 29-63 concurrently with RT 50 Gy. Forty-seven patients were enrolled and 46 completed the planned treatment. During the concomitant phase, grade 3-4 hematological toxicities occurred in three patients (6.5%) (or 3/174 cycles) and non-hematological toxicities in six patients (13%) (or 7/179 cycles). A pathological downstaging was obtained in 59.6% of the cases (28/47): complete remission (pCR) in 14 patients, near pCR (residual microfoci on the primary pN0) in eight patients, pT2 pN0 in three patients and partial response on the primary with positive lymph nodes in three patients. Six (13%) and 13 (28%) patients were considered stable and non-responders, respectively. In the last dose level, eight pCR and four near-pCR were obtained out of 15 patients. The maximum tolerable dose was not formally defined because dose escalation was stopped at the last dose level. This schedule represents a feasible treatment and the high pathological response rate is extremely encouraging; the doses found in the last dose-level are the basis for an ongoing phase II study at our institution.

  5. MR Imaging Based Treatment Planning for Radiotherapy of Prostate Cancer

    DTIC Science & Technology

    2007-02-01

    image- guided stereotactic localization in the hypofractionated treatment of lung cancer. Int. J. Rad. Oncol. Bio. Phys. 66: 738-747, 2006. Chapters...L, Ma C. Benefit of 3D image-guided stereotactic localization in the hypofractionated treatment of lung cancer. Proc. Medical Physics, 33(6), 1993...9. Amer AM, Mott J, Mackay RI, et al. Prediction of the benefits from dose-escalated hypofractionated intensity-modulated radiotherapy for

  6. Computed tomography imaging-guided radiotherapy by targeting upconversion nanocubes with significant imaging and radiosensitization enhancements

    PubMed Central

    Xing, Huaiyong; Zheng, Xiangpeng; Ren, Qingguo; Bu, Wenbo; Ge, Weiqiang; Xiao, Qingfeng; Zhang, Shengjian; Wei, Chenyang; Qu, Haiyun; Wang, Zheng; Hua, Yanqing; Zhou, Liangping; Peng, Weijun; Zhao, Kuaile; Shi, Jianlin

    2013-01-01

    The clinical potentials of radiotherapy could not be achieved completely because of the inaccurate positioning and inherent radioresistance of tumours. In this study, a novel active-targeting upconversion theranostic agent (arginine-glycine-aspartic acid-labelled BaYbF5: 2% Er3+ nanocube) was developed for the first time to address these clinical demands. Heavy metal-based nanocubes (~10 nm) are potential theranostic agents with bifunctional features: computed tomography (CT) contrast agents for targeted tumour imaging and irradiation dose enhancers in tumours during radiotherapy. Remarkably, they showed low toxicity and excellent performance in active-targeting CT imaging and CT imaging-guided radiosensitizing therapy, which could greatly concentrate and enlarge the irradiation dose deposition in tumours to enhance therapeutic efficacy and minimize the damage to surrounding tissues. PMID:23624542

  7. Stereotactic Image-Guided Intensity Modulated Radiotherapy Using the HI-ART II Helical Tomotherapy System

    SciTech Connect

    Holmes, Timothy W. Hudes, Richard; Dziuba, Sylwester; Kazi, Abdul; Hall, Mark; Dawson, Dana

    2008-07-01

    The highly integrated adaptive radiation therapy (HI-ART II) helical tomotherapy unit is a new radiotherapy machine designed to achieve highly precise and accurate treatments at all body sites. The precision and accuracy of the HI-ART II is similar to that provided by stereotactic radiosurgery systems, hence the historical distinction between external beam radiotherapy and stereotactic procedures based on differing precision requirements is removed for this device. The objectives of this work are: (1) to describe stereotactic helical tomotherapy processes (SRS, SBRT); (2) to show that the precision and accuracy of the HI-ART meet the requirements defined for SRS and SBRT; and (3) to describe the clinical implementation of a stereotactic image-guided intensity modulated radiation therapy (IG-IMRT) system that incorporates optical motion management.

  8. Constructing a clinical decision-making framework for image-guided radiotherapy using a Bayesian Network

    NASA Astrophysics Data System (ADS)

    Hargrave, C.; Moores, M.; Deegan, T.; Gibbs, A.; Poulsen, M.; Harden, F.; Mengersen, K.

    2014-03-01

    A decision-making framework for image-guided radiotherapy (IGRT) is being developed using a Bayesian Network (BN) to graphically describe, and probabilistically quantify, the many interacting factors that are involved in this complex clinical process. Outputs of the BN will provide decision-support for radiation therapists to assist them to make correct inferences relating to the likelihood of treatment delivery accuracy for a given image-guided set-up correction. The framework is being developed as a dynamic object-oriented BN, allowing for complex modelling with specific subregions, as well as representation of the sequential decision-making and belief updating associated with IGRT. A prototype graphic structure for the BN was developed by analysing IGRT practices at a local radiotherapy department and incorporating results obtained from a literature review. Clinical stakeholders reviewed the BN to validate its structure. The BN consists of a sub-network for evaluating the accuracy of IGRT practices and technology. The directed acyclic graph (DAG) contains nodes and directional arcs representing the causal relationship between the many interacting factors such as tumour site and its associated critical organs, technology and technique, and inter-user variability. The BN was extended to support on-line and off-line decision-making with respect to treatment plan compliance. Following conceptualisation of the framework, the BN will be quantified. It is anticipated that the finalised decision-making framework will provide a foundation to develop better decision-support strategies and automated correction algorithms for IGRT.

  9. Accurate calibration of a stereo-vision system in image-guided radiotherapy

    SciTech Connect

    Liu Dezhi; Li Shidong

    2006-11-15

    Image-guided radiotherapy using a three-dimensional (3D) camera as the on-board surface imaging system requires precise and accurate registration of the 3D surface images in the treatment machine coordinate system. Two simple calibration methods, an analytical solution as three-point matching and a least-squares estimation method as multipoint registration, were introduced to correlate the stereo-vision surface imaging frame with the machine coordinate system. Both types of calibrations utilized 3D surface images of a calibration template placed on the top of the treatment couch. Image transformational parameters were derived from corresponding 3D marked points on the surface images to their given coordinates in the treatment room coordinate system. Our experimental results demonstrated that both methods had provided the desired calibration accuracy of 0.5 mm. The multipoint registration method is more robust particularly for noisy 3D surface images. Both calibration methods have been used as our weekly QA tools for a 3D image-guided radiotherapy system.

  10. Comparison of daily versus nondaily image-guided radiotherapy protocols for patients treated with intensity-modulated radiotherapy for head and neck cancer.

    PubMed

    Yu, Yao; Michaud, Anthony L; Sreeraman, Radhika; Liu, Tianxiao; Purdy, James A; Chen, Allen M

    2014-07-01

    The purpose of this study was to determine the feasibility of nondaily image-guided radiotherapy (RT) strategies with intensity-modulated radiotherapy (IMRT) for head and neck cancer. Alignment data was analyzed from 103 consecutive patients treated by IMRT for head and neck cancer who had undergone daily imaging with onboard mega-voltage CT (MVCT), resulting in 3275 images. Geometric setup errors that would have occurred using less-than-daily imaging were hypothetically estimated for 4 temporal less-than-daily image-guided RT protocols. For image-guided RT on the first fraction, weekly image-guided RT, first 5 + weekly image-guided RT, and alternating day image-guided RT, the respective incidences of geometric miss were 50.5%, 33.8%, 30.1%, and 15.7% assuming 3-mm uncertainty margins; and 18.7%, 11.7%, 10.3%, and 4.1% with 5-mm margins. Less-than-daily image-guided RT strategies result in a high incidence of potential miss when 3-mm uncertainty margins are utilized. Less-than-daily image-guided RT strategies should incorporate margins of at least 5 mm. Copyright © 2013 Wiley Periodicals, Inc.

  11. Dosimetric Advantages of Four-Dimensional Adaptive Image-Guided Radiotherapy for Lung Tumors Using Online Cone-Beam Computed Tomography

    SciTech Connect

    Harsolia, Asif; Hugo, Geoffrey D.; Kestin, Larry L. Grills, Inga S.; Yan Di

    2008-02-01

    Purpose: This study compares multiple planning techniques designed to improve accuracy while allowing reduced planning target volume (PTV) margins though image-guided radiotherapy (IGRT) with four-dimensional (4D) cone-beam computed tomography (CBCT). Methods and Materials: Free-breathing planning and 4D-CBCT scans were obtained in 8 patients with lung tumors. Four plans were generated for each patient: 3D-conformal, 4D-union, 4D-offline adaptive with a single correction (offline ART), and 4D-online adaptive with daily correction (online ART). For the 4D-union plan, the union of gross tumor volumes from all phases of the 4D-CBCT was created with a 5-mm expansion applied for setup uncertainty. For offline and online ART, the gross tumor volume was delineated at the mean position of tumor motion from the 4D-CBCT. The PTV margins were calculated from the random components of tumor motion and setup uncertainty. Results: Adaptive IGRT techniques provided better PTV coverage with less irradiated normal tissues. Compared with 3D plans, mean relative decreases in PTV volumes were 15%, 39%, and 44% using 4D-union, offline ART, and online ART planning techniques, respectively. This resulted in mean lung volume receiving {>=} 20Gy (V20) relative decreases of 21%, 23%, and 31% and mean lung dose relative decreases of 16%, 26%, and 31% for the 4D-union, 4D-offline ART, and 4D-online ART, respectively. Conclusions: Adaptive IGRT using CBCT is feasible for the treatment of patients with lung tumors and significantly decreases PTV volume and dose to normal tissues, allowing for the possibility of dose escalation. All analyzed 4D planning strategies resulted in improvements over 3D plans, with 4D-online ART appearing optimal.

  12. Development of an integral system test for image-guided radiotherapy

    SciTech Connect

    Rowbottom, Carl G.; Jaffray, David A.

    2004-12-01

    An integral system test was developed to determine the precision and accuracy of an image-guided radiotherapy system involving an x-ray volumetric imaging device mounted onto the gantry of a medical linear accelerator. The test was designed to interrogate the system components as a whole without deconstructing the individual sources of error. The integral system test was based on the imaging of an unambiguous stationary object in the treatment position and so took no account of patient related errors. An array of micromosfets interspersed within slices of a tissue equivalent phantom was developed as an imaging test object. It has previously been demonstrated that micromosfets have a very small active volume, are clearly visible on CT images, and produce no significant artifacts. In addition, the active volume of the micromosfets can be accurately inferred radiographically via the use of x-ray volumetric imaging. X-ray volumetric imaging was performed with the object in the treatment position, then reconstructed and transferred to a treatment planning system. With the phantom remaining undisturbed in the treatment position a series of treatment fields were designed to produce a series of fields with the leaf edge sweeping across active volume of the micromosfets. The fields were delivered with a micro-MLC to dosimetrically verify the position of the mosfets and compare with dose values produced by the treatment planning system. It was demonstrated that the systematic gantry flex could be accounted for by the imaging and delivery systems. For the delivery system small changes in leaf positions of the micro-MLC were required to account for gantry flex. The position of the micromosfets determined by the 50% dose position was on average (0.15{+-}0.13) mm away from the position determined radiographically for the x and y axes, and (1.0{+-}0.14) mm for the z axis. This implies that a margin of approximately 0.2 mm in the axial plane and 1.0 mm in the superior

  13. Clinical Experience With Image-Guided Radiotherapy in an Accelerated Partial Breast Intensity-Modulated Radiotherapy Protocol

    SciTech Connect

    Leonard, Charles E.; Tallhamer, Michael M.S.; Johnson, Tim; Hunter, Kari C.M.D.; Howell, Kathryn; Kercher, Jane; Widener, Jodi; Kaske, Terese; Paul, Devchand; Sedlacek, Scot; Carter, Dennis L.

    2010-02-01

    Purpose: To explore the feasibility of fiducial markers for the use of image-guided radiotherapy (IGRT) in an accelerated partial breast intensity modulated radiotherapy protocol. Methods and Materials: Nineteen patients consented to an institutional review board approved protocol of accelerated partial breast intensity-modulated radiotherapy with fiducial marker placement and treatment with IGRT. Patients (1 patient with bilateral breast cancer; 20 total breasts) underwent ultrasound guided implantation of three 1.2- x 3-mm gold markers placed around the surgical cavity. For each patient, table shifts (inferior/superior, right/left lateral, and anterior/posterior) and minimum, maximum, mean error with standard deviation were recorded for each of the 10 BID treatments. The dose contribution of daily orthogonal films was also examined. Results: All IGRT patients underwent successful marker placement. In all, 200 IGRT treatment sessions were performed. The average vector displacement was 4 mm (range, 2-7 mm). The average superior/inferior shift was 2 mm (range, 0-5 mm), the average lateral shift was 2 mm (range, 1-4 mm), and the average anterior/posterior shift was 3 mm (range, 1 5 mm). Conclusions: This study shows that the use of IGRT can be successfully used in an accelerated partial breast intensity-modulated radiotherapy protocol. The authors believe that this technique has increased daily treatment accuracy and permitted reduction in the margin added to the clinical target volume to form the planning target volume.

  14. Quality of life in patients with prostate cancer treated with radical image-guided radiotherapy

    PubMed Central

    Tabor, Kamil; Prokop, Elżbieta; Kulik, Roland

    2014-01-01

    Aim of the study The evaluation of quality of life during image-guided radiotherapy (IGRT) in patients with prostate cancer. Materials and methods The study consisted of 180 prostate cancer patients treated with radical radiotherapy (IGRT). The patients were irradiated using conformal or dynamic techniques with 2 Gy fractionation doses to a total dose of 76 Gy. Patients in the high-risk group (41%) were also irradiated to the pelvic lymph nodes. Quality of life was assessed with EORTC questionnaires: general QLQ-C30 and prostate-specific module QLQ-PR25, which were filled in by patients before and upon completion of radiotherapy. A change of ≥ 10 points in a linearised scale (0–100) was considered clinically significant. Results Global quality of life decreased slightly during radiotherapy (from 61 to 57 points), but from the clinical point of view, likewise most of the other quality of life parameters remained stable. In the general module (QLQ-C30) only diarrhoea changed in a clinically relevant way, i.e. by 10 points (from 10 to 20 points), which was mainly observed in patients with elective pelvic irradiation (increase of 18 points, from 10 to 28 points). In the prostate-specific module (QLQ-PR25) only urinary symptoms changed significantly, i.e. by 13 points (from 24 to 37 points). Conclusions The quality of life in patients with prostate cancer does not change in a clinically significant way during radiotherapy, which corroborates good treatment tolerance. Increased urinary symptoms and, in the case of pelvic irradiation, also increased diarrhoea have a negative impact on symptom-related quality of life. PMID:25258588

  15. Reliability of the Bony Anatomy in Image-Guided Stereotactic Radiotherapy of Brain Metastases

    SciTech Connect

    Guckenberger, Matthias Baier, Kurt; Guenther, Iris; Richter, Anne; Wilbert, Juergen; Sauer, Otto; Vordermark, Dirk; Flentje, Michael

    2007-09-01

    Purpose: To evaluate whether the position of brain metastases remains stable between planning and treatment in cranial stereotactic radiotherapy (SRT). Methods and Materials: Eighteen patients with 20 brain metastases were treated with single-fraction (17 lesions) or hypofractionated (3 lesions) image-guided SRT. Median time interval between planning and treatment was 8 days. Before treatment a cone-beam CT (CBCT) and a conventional CT after application of i.v. contrast were acquired. Setup errors using automatic bone registration (CBCT) and manual soft-tissue registration of the brain metastases (conventional CT) were compared. Results: Tumor size was not significantly different between planning and treatment. The three-dimensional setup error (mean {+-} SD) was 4.0 {+-} 2.1 mm and 3.5 {+-} 2.2 mm according to the bony anatomy and the lesion itself, respectively. A highly significant correlation between automatic bone match and soft-tissue registration was seen in all three directions (r {>=} 0.88). The three-dimensional distance between the isocenter according to bone match and soft-tissue registration was 1.7 {+-} 0.7 mm, maximum 2.8 mm. Treatment of intracranial pressure with steroids did not influence the position of the lesion relative to the bony anatomy. Conclusion: With a time interval of approximately 1 week between planning and treatment, the bony anatomy of the skull proved to be an excellent surrogate for the target position in image-guided SRT.

  16. The value of image-guided intensity-modulated radiotherapy in challenging clinical settings

    PubMed Central

    Treece, S J; Mukesh, M; Rimmer, Y L; Tudor, S J; Dean, J C; Benson, R J; Gregory, D L; Horan, G; Jefferies, S J; Russell, S G; Williams, M V; Wilson, C B; Burnet, N G

    2013-01-01

    Objective To illustrate the wider potential scope of image-guided intensity-modulated radiotherapy (IG-IMRT), outside of the “standard” indications for IMRT. Methods Nine challenging clinical cases were selected. All were treated with radical intent, although it was accepted that in several of the cases the probability of cure was low. IMRT alone was not adequate owing to the close proximity of the target to organs at risk, the risk of geographical miss, or the need to tighten planning margins, making image-guided radiotherapy an essential integral part of the treatment. Discrepancies between the initial planning scan and the daily on-treatment megavoltage CT were recorded for each case. The three-dimensional displacement was compared with the margin used to create the planning target volume (PTV). Results All but one patient achieved local control. Three patients developed metastatic disease but benefited from good local palliation; two have since died. A further patient died of an unrelated condition. Four patients are alive and well. Toxicity was low in all cases. Without daily image guidance, the PTV margin would have been insufficient to ensure complete coverage in 49% of fractions. It was inadequate by >3 mm in 19% of fractions, and by >5 mm in 9%. Conclusion IG-IMRT ensures accurate dose delivery to treat the target and avoid critical structures, acting as daily quality assurance for the delivery of complex IMRT plans. These patients could not have been adequately treated without image guidance. Advances in knowledge IG-IMRT can offer improved outcomes in less common clinical situations, where conventional techniques would provide suboptimal treatment. PMID:23255544

  17. SU-E-J-191: Motion Prediction Using Extreme Learning Machine in Image Guided Radiotherapy

    SciTech Connect

    Jia, J; Cao, R; Pei, X; Wang, H; Hu, L

    2015-06-15

    Purpose: Real-time motion tracking is a critical issue in image guided radiotherapy due to the time latency caused by image processing and system response. It is of great necessity to fast and accurately predict the future position of the respiratory motion and the tumor location. Methods: The prediction of respiratory position was done based on the positioning and tracking module in ARTS-IGRT system which was developed by FDS Team (www.fds.org.cn). An approach involving with the extreme learning machine (ELM) was adopted to predict the future respiratory position as well as the tumor’s location by training the past trajectories. For the training process, a feed-forward neural network with one single hidden layer was used for the learning. First, the number of hidden nodes was figured out for the single layered feed forward network (SLFN). Then the input weights and hidden layer biases of the SLFN were randomly assigned to calculate the hidden neuron output matrix. Finally, the predicted movement were obtained by applying the output weights and compared with the actual movement. Breathing movement acquired from the external infrared markers was used to test the prediction accuracy. And the implanted marker movement for the prostate cancer was used to test the implementation of the tumor motion prediction. Results: The accuracy of the predicted motion and the actual motion was tested. Five volunteers with different breathing patterns were tested. The average prediction time was 0.281s. And the standard deviation of prediction accuracy was 0.002 for the respiratory motion and 0.001 for the tumor motion. Conclusion: The extreme learning machine method can provide an accurate and fast prediction of the respiratory motion and the tumor location and therefore can meet the requirements of real-time tumor-tracking in image guided radiotherapy.

  18. NBN gain is predictive for adverse outcome following image-guided radiotherapy for localized prostate cancer

    PubMed Central

    Sykes, Jenna; Zafarana, Gaetano; Chu, Kenneth C.; Ramnarine, Varune R.; Ishkanian, Adrian; Sendorek, Dorota H.S.; Pasic, Ivan; Lam, Wan L.; Jurisica, Igor; van der Kwast, Theo; Milosevic, Michael; Boutros, Paul C.; Bristow, Robert G.

    2014-01-01

    Despite the use of clinical prognostic factors (PSA, T-category and Gleason score), 20-60% of localized prostate cancers (PCa) fail primary local treatment. Herein, we determined the prognostic importance of main sensors of the DNA damage response (DDR): MRE11A, RAD50, NBN, ATM, ATR and PRKDC. We studied copy number alterations in DDR genes in localized PCa treated with image-guided radiotherapy (IGRT; n=139) versus radical prostatectomy (RadP; n=154). In both cohorts, NBN gains were the most frequent genomic alteration (14.4 and 11% of cases, respectively), and were associated with overall tumour genomic instability (p<0.0001). NBN gains were the only significant predictor of 5yrs biochemical relapse-free rate (bRFR) following IGRT (46% versus 77%; p=0.00067). On multivariate analysis, NBN gain remained a significant independent predictor of bRFR after adjusting for known clinical prognostic variables (HR=3.28, 95% CI 1.56–6.89, Wald p-value=0.0017). No DDR-sensing gene was prognostic in the RadP cohort. In vitro studies correlated NBN gene overexpression with PCa cells radioresistance. In conclusion, NBN gain predicts for decreased bRFR in IGRT, but not in RadP patients. If validated independently, Nibrin gains may be the first PCa predictive biomarker to facilitate local treatment decisions using precision medicine approaches with surgery or radiotherapy. PMID:25415046

  19. Long-term decision regret after post-prostatectomy image-guided intensity-modulated radiotherapy.

    PubMed

    Shakespeare, Thomas P; Chin, Stephen; Manuel, Lucy; Wen, Shelly; Hoffman, Matthew; Wilcox, Shea W; Aherne, Noel J

    2017-02-01

    Decision regret (DR) may occur when a patient believes their outcome would have been better if they had decided differently about their management. Although some studies investigate DR after treatment for localised prostate cancer, none report DR in patients undergoing surgery and post-prostatectomy radiotherapy. We evaluated DR in this group of patients overall, and for specific components of therapy. We surveyed 83 patients, with minimum 5 years follow-up, treated with radical prostatectomy (RP) and post-prostatectomy image-guided intensity-modulated radiotherapy (IG-IMRT) to 64-66 Gy following www.EviQ.org.au protocols. A validated questionnaire identified DR if men either indicated that they would have been better off had they chosen another treatment, or they wished they could change their mind about treatment. There was an 85.5% response rate, with median follow-up post-IMRT 78 months. Adjuvant IG-IMRT was used in 28% of patients, salvage in 72% and ADT in 48%. A total of 70% of patients remained disease-free. Overall, 16.9% of patients expressed DR for treatment, with fourfold more regret for the RP component of treatment compared to radiotherapy (16.9% vs 4.2%, P = 0.01). DR for androgen deprivation was 14.3%. Patients were regretful of surgery due to toxicity, not being adequately informed about radiotherapy as an alternative, positive margins and surgery costs (83%, 33%, 25% and 8% of regretful patients respectively). Toxicity caused DR in the three radiotherapy-regretful and four ADT-regretful patients. Patients were twice as regretful overall, and of surgery, for salvage vs adjuvant approaches (both 19.6% vs 10.0%). Decision regret after RP and post-prostatectomy IG-IMRT is uncommon, although patients regret RP more than post-operative IG-IMRT. This should reassure urologists referring patients for post-prostatectomy IG-IMRT, particularly in the immediate adjuvant setting. Other implications include appropriate patient selection for RP (and

  20. Image-guided adaptive gating of lung cancer radiotherapy: a computer simulation study.

    PubMed

    Aristophanous, Michalis; Rottmann, Joerg; Park, Sang-June; Nishioka, Seiko; Shirato, Hiroki; Berbeco, Ross I

    2010-08-07

    The purpose of this study is to investigate the effect that image-guided adaptation of the gating window during treatment could have on the residual tumor motion, by simulating different gated radiotherapy techniques. There are three separate components of this simulation: (1) the 'Hokkaido Data', which are previously measured 3D data of lung tumor motion tracks and the corresponding 1D respiratory signals obtained during the entire ungated radiotherapy treatments of eight patients, (2) the respiratory gating protocol at our institution and the imaging performed under that protocol and (3) the actual simulation in which the Hokkaido Data are used to select tumor position information that could have been collected based on the imaging performed under our gating protocol. We simulated treatments with a fixed gating window and a gating window that is updated during treatment. The patient data were divided into different fractions, each with continuous acquisitions longer than 2 min. In accordance to the imaging performed under our gating protocol, we assume that we have tumor position information for the first 15 s of treatment, obtained from kV fluoroscopy, and for the rest of the fractions the tumor position is only available during the beam-on time from MV imaging. The gating window was set according to the information obtained from the first 15 s such that the residual motion was less than 3 mm. For the fixed gating window technique the gate remained the same for the entire treatment, while for the adaptive technique the range of the tumor motion during beam-on time was measured and used to adapt the gating window to keep the residual motion below 3 mm. The algorithm used to adapt the gating window is described. The residual tumor motion inside the gating window was reduced on average by 24% for the patients with regular breathing patterns and the difference was statistically significant (p-value = 0.01). The magnitude of the residual tumor motion depended on the

  1. Image-guided adaptive gating of lung cancer radiotherapy: a computer simulation study

    NASA Astrophysics Data System (ADS)

    Aristophanous, Michalis; Rottmann, Joerg; Park, Sang-June; Nishioka, Seiko; Shirato, Hiroki; Berbeco, Ross I.

    2010-08-01

    The purpose of this study is to investigate the effect that image-guided adaptation of the gating window during treatment could have on the residual tumor motion, by simulating different gated radiotherapy techniques. There are three separate components of this simulation: (1) the 'Hokkaido Data', which are previously measured 3D data of lung tumor motion tracks and the corresponding 1D respiratory signals obtained during the entire ungated radiotherapy treatments of eight patients, (2) the respiratory gating protocol at our institution and the imaging performed under that protocol and (3) the actual simulation in which the Hokkaido Data are used to select tumor position information that could have been collected based on the imaging performed under our gating protocol. We simulated treatments with a fixed gating window and a gating window that is updated during treatment. The patient data were divided into different fractions, each with continuous acquisitions longer than 2 min. In accordance to the imaging performed under our gating protocol, we assume that we have tumor position information for the first 15 s of treatment, obtained from kV fluoroscopy, and for the rest of the fractions the tumor position is only available during the beam-on time from MV imaging. The gating window was set according to the information obtained from the first 15 s such that the residual motion was less than 3 mm. For the fixed gating window technique the gate remained the same for the entire treatment, while for the adaptive technique the range of the tumor motion during beam-on time was measured and used to adapt the gating window to keep the residual motion below 3 mm. The algorithm used to adapt the gating window is described. The residual tumor motion inside the gating window was reduced on average by 24% for the patients with regular breathing patterns and the difference was statistically significant (p-value = 0.01). The magnitude of the residual tumor motion depended on the

  2. Integral test phantom for dosimetric quality assurance of image guided and intensity modulated stereotactic radiotherapy

    SciTech Connect

    Letourneau, Daniel; Keller, Harald; Sharpe, Michael B.; Jaffray, David A.

    2007-05-15

    The objective of this work is to develop a dosimetric phantom quality assurance (QA) of linear accelerators capable of cone-beam CT (CBCT) image guided and intensity-modulated radiotherapy (IG-IMRT). This phantom is to be used in an integral test to quantify in real-time both the performance of the image guidance and the dose delivery systems in terms of dose localization. The prototype IG-IMRT QA phantom consisted of a cylindrical imaging phantom (CatPhan) combined with an array of 11 radiation diodes mounted on a 10 cm diameter disk, oriented perpendicular to the phantom axis. Basic diode response characterization was performed for 6 and 18 MV photons. The diode response was compared to planning system calculations in the open and penumbrae regions of simple and complex beam arrangements. The clinical use of the QA phantom was illustrated in an integral test of an IG-IMRT treatment designed for a clinical spinal radiosurgery case. The sensitivity of the phantom to multileaf collimator (MLC) calibration and setup errors in the clinical setting was assessed by introducing errors in the IMRT plan or by displacing the phantom. The diodes offered good response linearity and long-term reproducibility for both 6 and 18 MV. Axial dosimetry of coplanar beams (in a plane containing the beam axes) was made possible with the nearly isoplanatic response of the diodes over 360 deg. of gantry (usually within {+-}1%). For single beam geometry, errors in phantom placement as small as 0.5 mm could be accurately detected (in gradient {>=}1%/mm). In clinical setting, MLC systematic errors of 1 mm on a single MLC bank introduced in the IMRT plan were easily detectable with the QA phantom. The QA phantom demonstrated also sufficient sensitivity for the detection of setup errors as small as 1 mm for the IMRT delivery. These results demonstrated that the prototype can accurately and efficiently verify the entire IG-IMRT process. This tool, in conjunction with image guidance capabilities

  3. Dose Escalation Improves Cancer-Related Events at 10 Years for Intermediate- and High-Risk Prostate Cancer Patients Treated With Hypofractionated High-Dose-Rate Boost and External Beam Radiotherapy

    SciTech Connect

    Martinez, Alvaro A.; Gonzalez, Jose; Ye Hong; Ghilezan, Mihai; Shetty, Sugandh; Kernen, Kenneth; Gustafson, Gary; Krauss, Daniel; Vicini, Frank; Kestin, Larry

    2011-02-01

    Purpose: To evaluate the 10-year outcomes of intermediate- and high-risk prostate cancer patients treated with a prospective dose escalation hypofractionated trial of pelvic external beam radiation therapy (P-EBRT) with a high-dose-rate (HDR) brachytherapy boost. Methods and Materials: From 1992 to 2007, 472 patients were treated with a HDR boost at William Beaumont Hospital. They had at least one of the following: a prostate-specific antigen (PSA) level of >10 ng/ml, a Gleason score of {>=}7, or clinical stage {>=}T2b. Patients received 46-Gy P-EBRT and an HDR boost. The HDR dose fractionation was divided into two dose levels. The prostate biologically equivalent dose (BED) low-dose-level group received <268 Gy, and the high-dose group received >268 Gy . Phoenix biochemical failure (BF) definition was used. Results: Median follow-up was 8.2 years (range, 0.4-17 years). The 10-year biochemical failure rate of 43.1% vs. 18.9%, (p < 0.001), the clinical failure rate of 23.4% vs. 7.7%, (p < 0.001), and the distant metastasis of 12.4% vs. 5.7%, (p = 0.028) were all significantly better for the high-dose level group. On Cox multivariate analysis, higher BED levels (p = 0.017; hazard ratio [HR]= 0.586), pretreatment PSA assays (p < 0.001, HR = 1.022), and Gleason scores (p = 0.004) were significant variables for reduced biochemical failure. Higher dose levels (p, 0.002; HR, 0.397) and Gleason scores (p < 0.001) were significant for clinical failure. Grade 3 genitourinary complications were 2% and 3%, respectively, and grade 3 gastrointestinal complication was <0.5%. Conclusions: This prospective trial using P-EBRT with HDR boost and hypofractionated dose escalation demonstrates a strong dose-response relationship for intermediate- and high-risk prostate cancer patients. The improvement at 10 years for locoregional control with higher radiation doses (BED, > 268Gy) has significantly decreased biochemical and clinical failures as well as distant metastasis.

  4. Dual source and dual detector arrays tetrahedron beam computed tomography for image guided radiotherapy.

    PubMed

    Kim, Joshua; Lu, Weiguo; Zhang, Tiezhi

    2014-02-07

    Cone-beam computed tomography (CBCT) is an important online imaging modality for image guided radiotherapy. But suboptimal image quality and the lack of a real-time stereoscopic imaging function limit its implementation in advanced treatment techniques, such as online adaptive and 4D radiotherapy. Tetrahedron beam computed tomography (TBCT) is a novel online imaging modality designed to improve on the image quality provided by CBCT. TBCT geometry is flexible, and multiple detector and source arrays can be used for different applications. In this paper, we describe a novel dual source-dual detector TBCT system that is specially designed for LINAC radiation treatment machines. The imaging system is positioned in-line with the MV beam and is composed of two linear array x-ray sources mounted aside the electrical portal imaging device and two linear arrays of x-ray detectors mounted below the machine head. The detector and x-ray source arrays are orthogonal to each other, and each pair of source and detector arrays forms a tetrahedral volume. Four planer images can be obtained from different view angles at each gantry position at a frame rate as high as 20 frames per second. The overlapped regions provide a stereoscopic field of view of approximately 10-15 cm. With a half gantry rotation, a volumetric CT image can be reconstructed having a 45 cm field of view. Due to the scatter rejecting design of the TBCT geometry, the system can potentially produce high quality 2D and 3D images with less radiation exposure. The design of the dual source-dual detector system is described, and preliminary results of studies performed on numerical phantoms and simulated patient data are presented.

  5. Biological Image-Guided Radiotherapy in Rectal Cancer: Challenges and Pitfalls

    SciTech Connect

    Roels, Sarah; Slagmolen, Pieter; Lee, John A.; Loeckx, Dirk; Maes, Frederik; Stroobants, Sigrid; Ectors, Nadine; Penninckx, Freddy; Haustermans, Karin

    2009-11-01

    Purpose: To investigate the feasibility of integrating multiple imaging modalities for image-guided radiotherapy in rectal cancer. Patients and Methods: Magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) were performed before, during, and after preoperative chemoradiotherapy (CRT) in patients with resectable rectal cancer. The FDG-PET signals were segmented with an adaptive threshold-based and a gradient-based method. Magnetic resonance tumor volumes (TVs) were manually delineated. A nonrigid registration algorithm was applied to register the images, and mismatch analyses were carried out between MR and FDG-PET TVs and between TVs over time. Tumor volumes delineated on the images after CRT were compared with the pathologic TV. Results: Forty-five FDG-PET/CT and 45 MR images were analyzed from 15 patients. The mean MRI and FDG-PET TVs showed a tendency to shrink during and after CRT. In general, MRI showed larger TVs than FDG-PET. There was an approximately 50% mismatch between the FDG-PET TV and the MRI TV at baseline and during CRT. Sixty-one percent of the FDG-PET TV and 76% of the MRI TV obtained after 10 fractions of CRT remained inside the corresponding baseline TV. On MRI, residual tumor was still suspected in all 6 patients with a pathologic complete response, whereas FDG-PET showed a metabolic complete response in 3 of them. The FDG-PET TVs delineated with the gradient-based method matched closest with pathologic findings. Conclusions: Integration of MRI and FDG-PET into radiotherapy seems feasible. Gradient-based segmentation is recommended for FDG-PET. Spatial variance between MRI and FDG-PET TVs should be taken into account for target definition.

  6. Incremental learning with selective memory (ILSM): towards fast prostate localization for image guided radiotherapy.

    PubMed

    Gao, Yaozong; Zhan, Yiqiang; Shen, Dinggang

    2014-02-01

    Image-guided radiotherapy (IGRT) requires fast and accurate localization of the prostate in 3-D treatment-guided radiotherapy, which is challenging due to low tissue contrast and large anatomical variation across patients. On the other hand, the IGRT workflow involves collecting a series of computed tomography (CT) images from the same patient under treatment. These images contain valuable patient-specific information yet are often neglected by previous works. In this paper, we propose a novel learning framework, namely incremental learning with selective memory (ILSM), to effectively learn the patient-specific appearance characteristics from these patient-specific images. Specifically, starting with a population-based discriminative appearance model, ILSM aims to "personalize" the model to fit patient-specific appearance characteristics. The model is personalized with two steps: backward pruning that discards obsolete population-based knowledge and forward learning that incorporates patient-specific characteristics. By effectively combining the patient-specific characteristics with the general population statistics, the incrementally learned appearance model can localize the prostate of a specific patient much more accurately. This work has three contributions: 1) the proposed incremental learning framework can capture patient-specific characteristics more effectively, compared to traditional learning schemes, such as pure patient-specific learning, population-based learning, and mixture learning with patient-specific and population data; 2) this learning framework does not have any parametric model assumption, hence, allowing the adoption of any discriminative classifier; and 3) using ILSM, we can localize the prostate in treatment CTs accurately (DSC  ∼ 0.89 ) and fast (  ∼ 4 s), which satisfies the real-world clinical requirements of IGRT.

  7. Incremental Learning With Selective Memory (ILSM): Towards Fast Prostate Localization for Image Guided Radiotherapy

    PubMed Central

    Gao, Yaozong; Zhan, Yiqiang

    2015-01-01

    Image-guided radiotherapy (IGRT) requires fast and accurate localization of the prostate in 3-D treatment-guided radiotherapy, which is challenging due to low tissue contrast and large anatomical variation across patients. On the other hand, the IGRT workflow involves collecting a series of computed tomography (CT) images from the same patient under treatment. These images contain valuable patient-specific information yet are often neglected by previous works. In this paper, we propose a novel learning framework, namely incremental learning with selective memory (ILSM), to effectively learn the patient-specific appearance characteristics from these patient-specific images. Specifically, starting with a population-based discriminative appearance model, ILSM aims to “personalize” the model to fit patient-specific appearance characteristics. The model is personalized with two steps: backward pruning that discards obsolete population-based knowledge and forward learning that incorporates patient-specific characteristics. By effectively combining the patient-specific characteristics with the general population statistics, the incrementally learned appearance model can localize the prostate of a specific patient much more accurately. This work has three contributions: 1) the proposed incremental learning framework can capture patient-specific characteristics more effectively, compared to traditional learning schemes, such as pure patient-specific learning, population-based learning, and mixture learning with patient-specific and population data; 2) this learning framework does not have any parametric model assumption, hence, allowing the adoption of any discriminative classifier; and 3) using ILSM, we can localize the prostate in treatment CTs accurately (DSC ∼0.89) and fast (∼4 s), which satisfies the real-world clinical requirements of IGRT. PMID:24495983

  8. Dual source and dual detector arrays tetrahedron beam computed tomography for image guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Kim, Joshua; Lu, Weiguo; Zhang, Tiezhi

    2014-02-01

    Cone-beam computed tomography (CBCT) is an important online imaging modality for image guided radiotherapy. But suboptimal image quality and the lack of a real-time stereoscopic imaging function limit its implementation in advanced treatment techniques, such as online adaptive and 4D radiotherapy. Tetrahedron beam computed tomography (TBCT) is a novel online imaging modality designed to improve on the image quality provided by CBCT. TBCT geometry is flexible, and multiple detector and source arrays can be used for different applications. In this paper, we describe a novel dual source-dual detector TBCT system that is specially designed for LINAC radiation treatment machines. The imaging system is positioned in-line with the MV beam and is composed of two linear array x-ray sources mounted aside the electrical portal imaging device and two linear arrays of x-ray detectors mounted below the machine head. The detector and x-ray source arrays are orthogonal to each other, and each pair of source and detector arrays forms a tetrahedral volume. Four planer images can be obtained from different view angles at each gantry position at a frame rate as high as 20 frames per second. The overlapped regions provide a stereoscopic field of view of approximately 10-15 cm. With a half gantry rotation, a volumetric CT image can be reconstructed having a 45 cm field of view. Due to the scatter rejecting design of the TBCT geometry, the system can potentially produce high quality 2D and 3D images with less radiation exposure. The design of the dual source-dual detector system is described, and preliminary results of studies performed on numerical phantoms and simulated patient data are presented.

  9. Automatic block-matching registration to improve lung tumor localization during image-guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Robertson, Scott Patrick

    To improve relatively poor outcomes for locally-advanced lung cancer patients, many current efforts are dedicated to minimizing uncertainties in radiotherapy. This enables the isotoxic delivery of escalated tumor doses, leading to better local tumor control. The current dissertation specifically addresses inter-fractional uncertainties resulting from patient setup variability. An automatic block-matching registration (BMR) algorithm is implemented and evaluated for the purpose of directly localizing advanced-stage lung tumors during image-guided radiation therapy. In this algorithm, small image sub-volumes, termed "blocks", are automatically identified on the tumor surface in an initial planning computed tomography (CT) image. Each block is independently and automatically registered to daily images acquired immediately prior to each treatment fraction. To improve the accuracy and robustness of BMR, this algorithm incorporates multi-resolution pyramid registration, regularization with a median filter, and a new multiple-candidate-registrations technique. The result of block-matching is a sparse displacement vector field that models local tissue deformations near the tumor surface. The distribution of displacement vectors is aggregated to obtain the final tumor registration, corresponding to the treatment couch shift for patient setup correction. Compared to existing rigid and deformable registration algorithms, the final BMR algorithm significantly improves the overlap between target volumes from the planning CT and registered daily images. Furthermore, BMR results in the smallest treatment margins for the given study population. However, despite these improvements, large residual target localization errors were noted, indicating that purely rigid couch shifts cannot correct for all sources of inter-fractional variability. Further reductions in treatment uncertainties may require the combination of high-quality target localization and adaptive radiotherapy.

  10. Inter- and Intrafraction Uncertainty in Prostate Bed Image-Guided Radiotherapy

    SciTech Connect

    Huang, Kitty; Palma, David A.; Scott, Danielle; McGregor, Danielle; Gaede, Stewart; Yartsev, Slav; Bauman, Glenn; Louie, Alexander V.; Rodrigues, George

    2012-10-01

    Purpose: The goals of this study were to measure inter- and intrafraction setup error and prostate bed motion (PBM) in patients undergoing post-prostatectomy image-guided radiotherapy (IGRT) and to propose appropriate population-based three-dimensional clinical target volume to planning target volume (CTV-PTV) margins in both non-IGRT and IGRT scenarios. Methods and Materials: In this prospective study, 14 patients underwent adjuvant or salvage radiotherapy to the prostate bed under image guidance using linac-based kilovoltage cone-beam CT (kV-CBCT). Inter- and intrafraction uncertainty/motion was assessed by offline analysis of three consecutive daily kV-CBCT images of each patient: (1) after initial setup to skin marks, (2) after correction for positional error/immediately before radiation treatment, and (3) immediately after treatment. Results: The magnitude of interfraction PBM was 2.1 mm, and intrafraction PBM was 0.4 mm. The maximum inter- and intrafraction prostate bed motion was primarily in the anterior-posterior direction. Margins of at least 3-5 mm with IGRT and 4-7 mm without IGRT (aligning to skin marks) will ensure 95% of the prescribed dose to the clinical target volume in 90% of patients. Conclusions: PBM is a predominant source of intrafraction error compared with setup error and has implications for appropriate PTV margins. Based on inter- and estimated intrafraction motion of the prostate bed using pre- and post-kV-CBCT images, CBCT IGRT to correct for day-to-day variances can potentially reduce CTV-PTV margins by 1-2 mm. CTV-PTV margins for prostate bed treatment in the IGRT and non-IGRT scenarios are proposed; however, in cases with more uncertainty of target delineation and image guidance accuracy, larger margins are recommended.

  11. Calcifications Are Potential Surrogates for Prostate Localization in Image-Guided Radiotherapy

    SciTech Connect

    Zeng, Grace G. McGowan, Tom S.; Larsen, Tessa M.; Bruce, Lisa M.; Moran, Natasha K.; Tsao, Jonathan R.; MacPherson, Miller S.

    2008-11-15

    Purpose: To investigate the feasibility of using calcifications as surrogates for the prostate position during cone-beam computed tomography (CBCT) image-guided radiotherapy. Methods and Materials: The twice-weekly CBCT images taken during the treatment course of 4 patients were retrospectively studied for the stability of the calcifications. The geometric center of three fiducial markers was used as the reference. The planning CT images of 131 prostate patients recently treated with external beam radiotherapy at our center were reviewed to estimate the calcification occurrence rate. Analysis was conducted using the Varian Eclipse treatment planning system. Two patients were treated using prostate calcifications as the landmark in on-line registration. Both the Varian standard and the low-dose CBCT modes were used for imaging. Results: The calcifications were found to be stable during the treatment course. At the 95% confidence interval, the difference between the distance from an identified calcification to the fiducial markers on CBCT and the distance on the planning CT scans was 0.2 {+-} 2.0 mm, 0.8 {+-} 2.2 mm, and 0.4 {+-} 2.4 mm in the left-right, anteroposterior, and superoinferior direction, respectively. Of the 131 patients, 46 (35%) had well-defined calcifications either inside the prostate or near the borders. Our experience in treating the first 2 patients demonstrated that the calcifications are easily distinguished on low-dose scans and that calcification registration can be precisely performed. Conclusion: The results of our study have shown that calcifications can be reliable markers of prostate position and allow for precise image guidance with a low-imaging dose. With this approach, potentially about one-third of prostate patients could benefit from precise image guidance without the invasive use of markers.

  12. Real-time 3D surface-image-guided beam setup in radiotherapy of breast cancer

    SciTech Connect

    Djajaputra, David; Li Shidong

    2005-01-01

    We describe an approach for external beam radiotherapy of breast cancer that utilizes the three-dimensional (3D) surface information of the breast. The surface data of the breast are obtained from a 3D optical camera that is rigidly mounted on the ceiling of the treatment vault. This 3D camera utilizes light in the visible range therefore it introduces no ionization radiation to the patient. In addition to the surface topographical information of the treated area, the camera also captures gray-scale information that is overlaid on the 3D surface image. This allows us to visualize the skin markers and automatically determine the isocenter position and the beam angles in the breast tangential fields. The field sizes and shapes of the tangential, supraclavicular, and internal mammary gland fields can all be determined according to the 3D surface image of the target. A least-squares method is first introduced for the tangential-field setup that is useful for compensation of the target shape changes. The entire process of capturing the 3D surface data and subsequent calculation of beam parameters typically requires less than 1 min. Our tests on phantom experiments and patient images have achieved the accuracy of 1 mm in shift and 0.5 deg. in rotation. Importantly, the target shape and position changes in each treatment session can both be corrected through this real-time image-guided system.

  13. Incremental learning with selective memory (ILSM): towards fast prostate localization for image guided radiotherapy.

    PubMed

    Gao, Yaozong; Zhan, Yiqiang; Shen, Dinggang

    2013-01-01

    Image-guided radiotherapy (IGRT) requires fast and accurate localization of prostate in treatment CTs, which is challenging due to low tissue contrast and large anatomical variations across patients. On the other hand, in IGRT workflow, a series of CT images is acquired from the same patient under treatment, which contains valuable patient-specific information yet is often neglected by previous works. In this paper, we propose a novel learning framework, namely incremental learning with selective memory (ILSM), to effectively learn the patient-specific appearance characteristics from these patient-specific images. Specifically, starting with a population-based discriminative appearance model, ILSM aims to "personalize" the model to fit patient-specific appearance characteristics. Particularly, the model is personalized with two steps, backward pruning that discards obsolete population-based knowledge, and forward learning that incorporates patient-specific characteristics. By effectively combining the patient-specific characteristics with the general population statistics, the incrementally learned appearance model can localize the prostate of the specific patient much more accurately. Validated on a large dataset (349 CT scans), our method achieved high localization accuracy (DSC approximately 0.87) in 4 seconds.

  14. Image-Guided Hypofractionated Radiotherapy in Low-Risk Prostate Cancer Patients

    PubMed Central

    Valeriani, Maurizio; Carnevale, Alessia; Bonome, Paolo; Montalto, Adelaide; Nicosia, Luca; Osti, Mattia F.; De Sanctis, Vitaliana; Minniti, Giuseppe; Maurizi Enrici, Riccardo

    2014-01-01

    Aim. To evaluate efficacy and toxicity of image-guided hypofractionated radiotherapy (HFRT) in the treatment of low-risk prostate cancer. Outcomes and toxicities of this series of patients were compared to another group of 32 low-risk patients treated with conventional fractionation (CFRT). Methods. Fifty-nine patients with low-risk prostate cancer were analysed. Total dose for the prostate and proximal seminal vesicles was 60 Gy delivered in 20 fractions. Results. The median follow-up was 30 months. The actuarial 4-year overall survival, biochemical free survival, and disease specific survival were 100%, 97.4%, and 97.4%, respectively. Acute grade 1-2 gastrointestinal (GI) and genitourinary (GU) toxicity rates were 11.9% and 40.7%, respectively. Grade 1 GI and GU late toxicity rates were 8.5% and 13.6%, respectively. No grade ≥2 late toxicities were recorded. Acute grade 2-3 GU toxicity resulted significantly lower (P = 0.04) in HFRT group compared to the CFRT group. The cumulative 4-year incidence of grade 1-2 GU toxicity was significantly higher (P < 0.001) for HFRT patients. Conclusions. Our study demonstrated that hypofractionated regimen provided excellent biochemical control in favorable risk prostate cancer patients. The incidence of GI and GU toxicity was low. However, HFRT presented higher cumulative incidence of low-grade late GU toxicity than CFRT. PMID:24864248

  15. Towards inherently distortion-free MR images for image-guided radiotherapy on an MRI accelerator.

    PubMed

    Crijns, S P M; Bakker, C J G; Seevinck, P R; de Leeuw, H; Lagendijk, J J W; Raaymakers, B W

    2012-03-07

    In MR-guided interventions, it is mandatory to establish a solid relationship between the imaging coordinate system and world coordinates. This is particularly important in image-guided radiotherapy (IGRT) on an MRI accelerator, as the interaction of matter with γ-radiation cannot be visualized. In conventional acquisitions, off-resonance effects cause discrepancies between coordinate systems. We propose to mitigate this by using only phase encoding and to reduce the longer acquisitions by under-sampling and regularized reconstruction. To illustrate the performance of this acquisition in the presence of off-resonance phenomena, phantom and in vivo images are acquired using spin-echo (SE) and purely phase-encoded sequences. Data are retrospectively under-sampled and reconstructed iteratively. We observe accurate geometries in purely phase-encoded images for all cases, whereas SE images of the same phantoms display image distortions. Regularized reconstruction yields accurate phantom images under high acceleration factors. In vivo images were reconstructed faithfully while using acceleration factors up to 4. With the proposed technique, inherently undistorted images with one-to-one correspondence to world coordinates can be obtained. It is a valuable tool in geometry quality assurance, treatment planning and online image guidance. Under-sampled acquisition combined with regularized reconstruction can be used to accelerate the acquisition while retaining geometrical accuracy.

  16. Image guided, adaptive, accelerated, high dose brachytherapy as model for advanced small volume radiotherapy.

    PubMed

    Haie-Meder, Christine; Siebert, Frank-André; Pötter, Richard

    2011-09-01

    Brachytherapy has consistently provided a very conformal radiation therapy modality. Over the last two decades this has been associated with significant improvements in imaging for brachytherapy applications (prostate, gynecology), resulting in many positive advances in treatment planning, application techniques and clinical outcome. This is emphasized by the increased use of brachytherapy in Europe with gynecology as continuous basis and prostate and breast as more recently growing fields. Image guidance enables exact knowledge of the applicator together with improved visualization of tumor and target volumes as well as of organs at risk providing the basis for very individualized 3D and 4D treatment planning. In this commentary the most important recent developments in prostate, gynecological and breast brachytherapy are reviewed, with a focus on European recent and current research aiming at the definition of areas for important future research. Moreover the positive impact of GEC-ESTRO recommendations and the highlights of brachytherapy physics are discussed what altogether presents a full overview of modern image guided brachytherapy. An overview is finally provided on past and current international brachytherapy publications focusing on "Radiotherapy and Oncology". These data show tremendous increase in almost all research areas over the last three decades strongly influenced recently by translational research in regard to imaging and technology. In order to provide high level clinical evidence for future brachytherapy practice the strong need for comprehensive prospective clinical research addressing brachytherapy issues is high-lighted. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. Penile bulb dose and impotence after three-dimensional conformal radiotherapy for prostate cancer on RTOG 9406: Findings from a prospective, multi-institutional, phase I/II dose-escalation study

    SciTech Connect

    Roach, Mack . E-mail: roach@radonc17.ucsf.edu; Winter, Kathryn; Michalski, Jeffrey M.; Cox, James D.; Purdy, James A.; Bosch, Walter; Lin Xiao; Shipley, William S.

    2004-12-01

    Purpose: To assess the relationship between the dose to the bulb of the penis and the risk of impotence in men treated on Radiation Therapy Oncology Group (RTOG) 9406. Methods and materials: Men enrolled on a Phase I/II dose-escalation study, RTOG 9406, who were reported to be potent at entry and evaluable (n = 158) were selected for inclusion. Follow-up evaluations were scheduled every 3, 4, and 6 months for the first, second, and the third through fifth years, then annually. At each follow-up visit an assessment of potency status was made. Penile structures were defined by a single observer blinded to the potency status, using Web-based, on-line software. The dosimetry for penile structures was calculated at the Quality Assurance Center at Washington University and provided to RTOG Statistical Headquarters to determine whether there was a relationship between dose and impotence. Results: Patients whose median penile dose was {>=}52.5 Gy had a greater risk of impotence compared with those receiving <52.5 Gy (p = 0.039). In a multivariate analysis neither age, the dose to the prostate, nor the use of hormonal therapy correlated with the risk of impotence. Conclusions: Dose to the bulb of the penis seems to be associated with the risk of radiation-induced impotence.

  18. Inverse Relationship Between Biochemical Outcome and Acute Toxicity After Image-Guided Radiotherapy for Prostate Cancer

    SciTech Connect

    Vesprini, Danny; Catton, Charles; Jacks, Lindsay; Lockwood, Gina; Rosewall, Tara; Bayley, Andrew; Chung, Peter; Gospodarowicz, Mary; Menard, Cynthia; Milosevic, Michael; Nichol, Alan; Skala, Marketa; Warde, Padraig; Bristow, Robert G.

    2012-06-01

    Purpose: Prostate cancer patients exhibit variability in normal tissue reactions and biochemical failure. With the use of image-guided radiotherapy (IGRT), there is a greater likelihood that the differences in normal tissue and tumor response are due to biological rather than physical factors. We tested the hypothesis that prospectively scored acute toxicity is associated with biochemical failure-free rate (BFFR) in prostate cancer patients treated with IGRT. Methods and Materials: We retrospectively analyzed BFFR in 362 patients with localized prostate cancer treated with IGRT. We compared BFFR with prospectively collected Radiation Therapy Oncology Group (RTOG) maximum acute gastrointestinal (GI) and genitourinary (GU) toxicity scores. Median follow-up for all patients was 58.3 months after total radiotherapy doses of 75.6-79.8 Gy. Results: Patients reporting RTOG acute GU or GI toxicity scores of {>=}2 were considered 'sensitive' (n = 141, 39%) and patients reporting scores <2 were considered 'nonsensitive' (n = 221, 61%). When calculating biochemical failure (BF) using the American Society for Therapeutic Radiology and Oncology definition at 5 years, 76% (CI 70-82%) of the 'nonsensitive' patients were failure free, compared with only 53% (CI 43-62%) of the 'sensitive' patients (log-rank test, p < 0.0001). This difference was also observed using the Phoenix definition; 'nonsensitive' 5-year BFFR was 81% (CI 74-86%) vs. 'sensitive' BFFR was 68% (CI 58-76%; log-rank test p = 0.0012). The difference in BF between cohorts remained significant when controlled for radiation dose (75.6 vs. 79.8 Gy), prognostic stratification (T category, prostate-specific antigen, and Gleason score), and prostate volume. Conclusions: This study unexpectedly shows that prostate cancer patients who develop {>=}Grade 2 RTOG acute toxicity during radiotherapy are less likely to remain BFF at 5 years. These results deserve further study and, if validated in other large IGRT cohorts

  19. Multi-System Verification of Registrations for Image-Guided Radiotherapy in Clinical Trials

    SciTech Connect

    Cui Yunfeng; Galvin, James M.; Straube, William L.; Bosch, Walter R.; Purdy, James A.; Li, X. Allen; Xiao Ying

    2011-09-01

    Purpose: To provide quantitative information on the image registration differences from multiple systems for image-guided radiotherapy (IGRT) credentialing and margin reduction in clinical trials. Methods and Materials: Images and IGRT shift results from three different treatment systems (Tomotherapy Hi-Art, Elekta Synergy, Varian Trilogy) have been sent from various institutions to the Image-Guided Therapy QA Center (ITC) for evaluation for the Radiation Therapy Oncology Group (RTOG) trials. Nine patient datasets (five head-and-neck and four prostate) were included in the comparison, with each patient having 1-4 daily individual IGRT studies. In all cases, daily shifts were re-calculated by re-registration of the planning CT with the daily IGRT data using three independent software systems (MIMvista, FocalSim, VelocityAI). Automatic fusion was used in all calculations. The results were compared with those submitted from institutions. Similar regions of interest (ROIs) and same initial positions were used in registrations for inter-system comparison. Different slice spacings for CBCT sampling and different ROIs for registration were used in some cases to observe the variation of registration due to these factors. Results: For the 54 comparisons with head-and-neck datasets, the absolute values of differences of the registration results between different systems were 2.6 {+-} 2.1 mm (mean {+-} SD; range 0.1-8.6 mm, left-right [LR]), 1.7 {+-} 1.3 mm (0.0-4.9 mm, superior-inferior [SI]), and 1.8 {+-} 1.1 mm (0.1-4.0 mm, anterior-posterior [AP]). For the 66 comparisons in prostate cases, the differences were 1.1 {+-} 1.0 mm (0.0-4.6 mm, LR), 2.1 {+-} 1.7 mm (0.0-6.6 mm, SI), and 2.0 {+-} 1.8 mm (0.1-6.9 mm, AP). The differences caused by the slice spacing variation were relatively small, and the different ROI selections in FocalSim and MIMvista also had limited impact. Conclusion: The extent of differences was reported when different systems were used for image

  20. Five-year follow-up using a prostate stent as fiducial in image-guided radiotherapy of prostate cancer.

    PubMed

    Carl, Jesper; Sander, Lotte

    2015-06-01

    To report results from the five-year follow-up on a previously reported study using image-guided radiotherapy (IGRT) of localized or locally advanced prostate cancer (PC) and a removable prostate stent as fiducial. Patients with local or locally advanced PC were treated using five-field 3D conformal radiotherapy (3DRT). The clinical target volumes (CTV) were treated to 78 Gy in 39 fractions using daily on-line image guidance (IG). Late genito-urinary (GU) and gastro-intestinal (GI) toxicities were scored using the radiotherapy oncology group (RTOG) score and the common toxicity score of adverse events (CTC) score. Urinary symptoms were also scored using the international prostate symptom score (IPSS). Median observation time was 5.4 year. Sixty-two of the 90 patients from the original study cohort were eligible for toxicity assessment. Overall survival, cancer-specific survival and biochemical freedom from failure were 85%, 96% and 80%, respectively at five years after radiotherapy. Late toxicity GU and GI RTOG scores≥2 were 5% and 0%. Comparing pre- and post-radiotherapy IPSS scores indicate that development in urinary symptoms after radiotherapy may be complex. Prostate image-guided radiotherapy using a prostate stent demonstrated survival data comparable with recently published data. GU and GI toxicities at five-year follow-up were low and comparable to the lowest toxicity rates reported. These findings support that the precision of the prostate stent technique is at least as good as other techniques. IPSS revealed a complex development in urinary symptoms after radiotherapy.

  1. Integration between in vivo dosimetry and image guided radiotherapy for lung tumors.

    PubMed

    Piermattei, Angelo; Cilla, Savino; Grimaldi, Luca; Sabatino, Domenico; Fidanzio, Andrea; Greco, Francesca; Mameli, Alessandra; Balducci, Mario; Mattiucci, Gian Carlo; Frascino, Vincenzo; Stimato, Gerardina; Gaudino, Diego; Ramella, Sara; Trodella, Lucio; D'Onofrio, Guido; Zini, Giampaolo; Macchia, Gabriella; Digesu', Cinzia; Morganti, Alessio G; Clemente, Stefania; Cozzolino, Mariella; Pedicini, Piernicola; Fusco, Vincenzo

    2009-06-01

    The article reports a feasibility study about the potentiality of an in vivo dosimetry method for the adaptive radiotherapy of the lung tumors treated by 3D conformal radiotherapy techniques (3D CRTs). At the moment image guided radiotherapy (IGRT) has been used for this aim, but it requires taking many periodic radiological images during the treatment that increase workload and patient dose. In vivo dosimetry reported here can reduce the above efforts, alerting the medical staff for the commissioning of new radiological images for an eventual adaptive plan. The in vivo dosimetry method applied on 20 patients makes use of the transit signal St on the beam central axis measured by a small ion chamber positioned on an electronic portal imaging device (EPID) or by the EPID itself. The reconstructed in vivo dosimetry at the isocenter point Diso requires a convolution between the transit signal St and a dose reconstruction factor C that essentially depends on (i) tissue inhomogeneities along the beam central axis and (ii) the in-patient isocenter depth. The C factors, one for every gantry angle, are obtained by processing the patient's computed tomography scan. The method has been recently applied in some Italian centers to check the radiotherapy of pelvis, breast, head, and thorax treatments. In this work the dose reconstruction was carried out in five centers to check the Diso in the lung tumor during the 3D CRT, and the results have been used to detect the interfraction tumor anatomy variations that can require new CT imaging and an adaptive plan. In particular, in three centers a small ion chamber was positioned below the patient and used for the St measurement. In two centers, the St signal was obtained directly by 25 central pixels of an a-Si EPID, equipped with commercial software that enabled its use as a stable detector. A tolerance action level of +/- 6% for every checked beam was assumed. This means that when a difference greater than 6% between the predicted

  2. Toxicity after post-prostatectomy image-guided intensity-modulated radiotherapy using Australian guidelines.

    PubMed

    Chin, Stephen; Aherne, Noel J; Last, Andrew; Assareh, Hassan; Shakespeare, Thomas P

    2017-06-17

    We evaluated single institution toxicity outcomes after post-prostatectomy radiotherapy (PPRT) via image-guided intensity-modulated radiation therapy (IG-IMRT) with implanted fiducial markers following national eviQ guidelines, for which late toxicity outcomes have not been published. Prospectively collected toxicity data were retrospectively reviewed for 293 men who underwent 64-66 Gy IG-IMRT to the prostate bed between 2007 and 2015. Median follow-up after PPRT was 39 months. Baseline grade ≥2 genitourinary (GU), gastrointestinal (GI) and sexual toxicities were 20.5%, 2.7% and 43.7%, respectively, reflecting ongoing toxicity after radical prostatectomy. Incidence of new (compared to baseline) acute grade ≥2 GU and GI toxicity was 5.8% and 10.6%, respectively. New late grade ≥2 GU, GI and sexual toxicity occurred in 19.1%, 4.7% and 20.2%, respectively. However, many patients also experienced improvements in toxicities. For this reason, prevalence of grade ≥2 GU, GI and sexual toxicities 4 years after PPRT was similar to or lower than baseline (21.7%, 2.6% and 17.4%, respectively). There were no grade ≥4 toxicities. Post-prostatectomy IG-IMRT using Australian contouring guidelines appears to have tolerable acute and late toxicity. The 4-year prevalence of grade ≥2 GU and GI toxicity was virtually unchanged compared to baseline, and sexual toxicity improved over baseline. This should reassure radiation oncologists following these guidelines. Late toxicity rates of surgery and PPRT are higher than following definitive IG-IMRT, and this should be taken into account if patients are considering surgery and likely to require PPRT. © 2017 The Royal Australian and New Zealand College of Radiologists.

  3. Towards efficient biomechanical based deformable image registration of lungs for image guided radiotherapy

    PubMed Central

    Al-Mayah, Adil; Moseley, Joanne; Velec, Mike; Brock, Kristy

    2011-01-01

    Both accuracy and efficiency are critical for the implementation of biomechanical model-based deformable registration into clinical practice. The focus of this investigation is to evaluate the potential of improving the efficiency of the deformable image registration of the human lungs without loss of accuracy. Three dimensional finite element models have been developed using image data of fourteen lung cancer patients. Each model consists of two lungs, tumor, and external body. Sliding of the lungs inside the chest cavity is modeled using a frictionless surface based contact model. The effect of type of element, finite deformation and elasticity on the accuracy and computing time are investigated. Linear and quadrilateral tetrahedral elements are used with linear and nonlinear geometric analysis. Two types of material properties are applied namely: elastic and hyperelastic. The accuracy of each of the four models is examined using a number of anatomical landmarks representing the vessels bifurcation points distributed across the lungs. The registration error is not significantly affected by element type or linearity of analysis with an average vector error of around 2.8 mm. The displacement differences between linear and nonlinear analysis methods are calculated for all lungs nodes and a maximum value of 3.6 mm is found in one of the nodes near the entrance of the bronchial tree into the lungs. The 95 percentile of displacement difference ranges between 0.4 and 0.8 mm. However, the time required for the analysis is reduced from 95 min in the quadratic elements nonlinear geometry model to 3.4 min in the linear element linear geometry model. Therefore using linear tetrahedral elements with linear elastic materials and linear geometry is preferable for modeling the breathing motion of lungs for image guided radiotherapy applications. PMID:21734336

  4. Toward efficient biomechanical-based deformable image registration of lungs for image-guided radiotherapy.

    PubMed

    Al-Mayah, Adil; Moseley, Joanne; Velec, Mike; Brock, Kristy

    2011-08-07

    Both accuracy and efficiency are critical for the implementation of biomechanical model-based deformable registration in clinical practice. The focus of this investigation is to evaluate the potential of improving the efficiency of the deformable image registration of the human lungs without loss of accuracy. Three-dimensional finite element models have been developed using image data of 14 lung cancer patients. Each model consists of two lungs, tumor and external body. Sliding of the lungs inside the chest cavity is modeled using a frictionless surface-based contact model. The effect of the type of element, finite deformation and elasticity on the accuracy and computing time is investigated. Linear and quadrilateral tetrahedral elements are used with linear and nonlinear geometric analysis. Two types of material properties are applied namely: elastic and hyperelastic. The accuracy of each of the four models is examined using a number of anatomical landmarks representing the vessels bifurcation points distributed across the lungs. The registration error is not significantly affected by the element type or linearity of analysis, with an average vector error of around 2.8 mm. The displacement differences between linear and nonlinear analysis methods are calculated for all lungs nodes and a maximum value of 3.6 mm is found in one of the nodes near the entrance of the bronchial tree into the lungs. The 95 percentile of displacement difference ranges between 0.4 and 0.8 mm. However, the time required for the analysis is reduced from 95 min in the quadratic elements nonlinear geometry model to 3.4 min in the linear element linear geometry model. Therefore using linear tetrahedral elements with linear elastic materials and linear geometry is preferable for modeling the breathing motion of lungs for image-guided radiotherapy applications.

  5. Radiation Dose From Kilovoltage Cone Beam Computed Tomography in an Image-Guided Radiotherapy Procedure

    SciTech Connect

    Ding, George X. Coffey, Charles W.

    2009-02-01

    Purpose: Image-guided radiation therapy has emerged as the new paradigm in radiotherapy. This work is to provide detailed information concerning the additional imaging doses to patients' radiosensitive organs from a kilovoltage cone beam computed tomography (kV CBCT) scan procedure. Methods and Materials: The Vanderbilt-Monte-Carlo-Beam-Calibration (VMCBC; Vanderbilt University, Nashville, TN) algorithm was used to calculate radiation dose to organs resulting from a kV CBCT imaging guidance procedure. Eight patients, including 3 pediatric and 5 adult patients, were investigated. The CBCT scans in both full- and half-fan modes were studied. Results: For a head-and-neck scan in half-fan mode, dose-volume histogram analyses show mean doses of 7 and 8 cGy to the eyes, 5 and 6 cGy to the spinal cord, 5 and 6 cGy to the brain, and 18 and 23 cGy to the cervical vertebrae for an adult and a 29-month-old child, respectively. The dose from a scan in full-fan mode is 10-20% lower than that in half-fan mode. For an abdominal scan, mean doses are 3 and 7 cGy to prostate and 7 and 17 cGy to femoral heads for a large adult patient and a 31-month-old pediatric patient, respectively. Conclusions: Doses to radiosensitive organs can total 300 cGy accrued over an entire treatment course if kV CBCT scans are acquired daily. These findings provide needed data for clinicians to make informed decisions concerning additional imaging doses. The dose to bone is two to four times greater than dose to soft tissue for kV x-rays, which should be considered, especially for pediatric patients.

  6. Deep architecture neural network-based real-time image processing for image-guided radiotherapy.

    PubMed

    Mori, Shinichiro

    2017-08-01

    To develop real-time image processing for image-guided radiotherapy, we evaluated several neural network models for use with different imaging modalities, including X-ray fluoroscopic image denoising. Setup images of prostate cancer patients were acquired with two oblique X-ray fluoroscopic units. Two types of residual network were designed: a convolutional autoencoder (rCAE) and a convolutional neural network (rCNN). We changed the convolutional kernel size and number of convolutional layers for both networks, and the number of pooling and upsampling layers for rCAE. The ground-truth image was applied to the contrast-limited adaptive histogram equalization (CLAHE) method of image processing. Network models were trained to keep the quality of the output image close to that of the ground-truth image from the input image without image processing. For image denoising evaluation, noisy input images were used for the training. More than 6 convolutional layers with convolutional kernels >5×5 improved image quality. However, this did not allow real-time imaging. After applying a pair of pooling and upsampling layers to both networks, rCAEs with >3 convolutions each and rCNNs with >12 convolutions with a pair of pooling and upsampling layers achieved real-time processing at 30 frames per second (fps) with acceptable image quality. Use of our suggested network achieved real-time image processing for contrast enhancement and image denoising by the use of a conventional modern personal computer. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  7. Markerless tumor tracking using short kilovoltage imaging arcs for lung image-guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Shieh, Chun-Chien; Keall, Paul J.; Kuncic, Zdenka; Huang, Chen-Yu; Feain, Ilana

    2015-12-01

    The ability to monitor tumor motion without implanted markers is clinically advantageous for lung image-guided radiotherapy (IGRT). Existing markerless tracking methods often suffer from overlapping structures and low visibility of tumors on kV projection images. We introduce the short arc tumor tracking (SATT) method to overcome these issues. The proposed method utilizes multiple kV projection images selected from a nine-degree imaging arc to improve tumor localization, and respiratory-correlated 4D cone-beam CT (CBCT) prior knowledge to minimize the effects of overlapping anatomies. The 3D tumor position is solved as an optimization problem with prior knowledge incorporated via regularization. We retrospectively validated SATT on 11 clinical scans from four patients with central tumors. These patients represent challenging scenarios for markerless tumor tracking due to the inferior adjacent contrast. The 3D trajectories of implanted fiducial markers were used as the ground truth for tracking accuracy evaluation. In all cases, the tumors were successfully tracked at all gantry angles. Compared to standard pre-treatment CBCT guidance alone, trajectory errors were significantly smaller with tracking in all cases, and the improvements were the most prominent in the superior-inferior direction. The mean 3D tracking error ranged from 2.2-9.9 mm, which was 0.4-2.6 mm smaller compared to pre-treatment CBCT. In conclusion, we were able to directly track tumors with inferior visibility on kV projection images using SATT. Tumor localization accuracies are significantly better with tracking compared to the current standard of care of lung IGRT. Future work involves the prospective evaluation and clinical implementation of SATT.

  8. Investigation of Linac-Based Image-Guided Hypofractionated Prostate Radiotherapy

    SciTech Connect

    Pawlicki, Todd . E-mail: tpaw@stanford.edu; Kim, Gwe-Ya; Hsu, Annie; Cotrutz, Cristian; Boyer, Arthur L.; Xing Lei; King, Christopher R.; Luxton, Gary

    2007-07-01

    A hypofractionation treatment protocol for prostate cancer was initiated in our department in December 2003. The treatment regimen consists of a total dose of 36.25 Gy delivered at 7.25 Gy per fraction over 10 days. We discuss the rationale for such a prostate hypofractionation protocol and the need for frequent prostate imaging during treatment. The CyberKnife (Accuray Inc., Sunnyvale, CA), a linear accelerator mounted on a robotic arm, is currently being used as the radiation delivery device for this protocol, due to its incorporation of near real-time kV imaging of the prostate via 3 gold fiducial seeds. Recently introduced conventional linac kV imaging with intensity modulated planning and delivery may add a new option for these hypofractionated treatments. The purpose of this work is to investigate the use of intensity modulated radiotherapy (IMRT) and the Varian Trilogy Accelerator with on-board kV imaging (Varian Medical Systems Inc., Palo Alto, CA) for treatment of our hypofractionated prostate patients. The dose-volume histograms and dose statistics of 2 patients previously treated on the CyberKnife were compared to 7-field IMRT plans. A process of acquiring images to observe intrafraction prostate motion was achieved in an average time of about 1 minute and 40 seconds, and IMRT beam delivery takes about 40 seconds per field. A complete 7-field IMRT plan can therefore be imaged and delivered in 10 to 17 minutes. The Varian Trilogy Accelerator with on-board imaging and IMRT is well suited for image-guided hypofractionated prostate treatments. During this study, we have also uncovered opportunities for improvement of the on-board imaging hardware/software implementation that would further enhance performance in this regard.

  9. Markerless tumor tracking using short kilovoltage imaging arcs for lung image-guided radiotherapy

    PubMed Central

    Shieh, Chun-Chien; Keall, Paul J.; Kuncic, Zdenka; Huang, Chen-Yu; Feain, Ilana

    2015-01-01

    The ability to monitor tumor motion without implanted markers is clinically advantageous for lung image-guided radiotherapy (IGRT). Existing markerless tracking methods often suffer from overlapping structures and low visibility of tumors on kV projection images. We introduce the short arc tumor tracking (SATT) method to overcome these issues. The proposed method utilizes multiple kV projection images selected from a nine-degree imaging arc to improve tumor localization, and respiratory-correlated 4D cone-beam CT (CBCT) prior knowledge to minimize the effects of overlapping anatomies. The 3D tumor position is solved as an optimization problem with prior knowledge incorporated via regularization. We retrospectively validated SATT on 11 clinical scans from four patients with central tumors. These patients represent challenging scenarios for markerless tumor tracking due to the inferior adjacent contrast. The 3D trajectories of implanted fiducial markers were used as the ground truth for tracking accuracy evaluation. In all cases, the tumors were successfully tracked at all gantry angles. Compared to standard pre-treatment CBCT guidance alone, trajectory errors were significantly smaller with tracking in all cases, and the improvements were the most prominent in the superior-inferior (SI) direction. The mean 3D tracking error ranged from 2.2–9.9 mm, which was 0.4–2.6 mm smaller compared to pre-treatment CBCT. In conclusion, we were able to directly track tumors with inferior visibility on kV projection images using SATT. Tumor localization accuracies are significantly better with tracking compared to the current standard of care of lung IGRT. Future work involves the prospective evaluation and clinical implementation of SATT. PMID:26583772

  10. Acute Toxicity in Definitive Versus Postprostatectomy Image-Guided Radiotherapy for Prostate Cancer

    SciTech Connect

    Cheng, Jonathan C.; Schultheiss, Timothy E. Nguyen, Khanh H.; Wong, Jeffrey Y.C.

    2008-06-01

    Purpose: To assess the incidence of acute gastrointestinal (GI) and genitourinary (GU) injury and the dose-volume response in patients with clinically localized prostate cancer treated with image-guided radiotherapy using helical tomotherapy. Methods and Materials: Between November 2004 and March 2007, 146 consecutive patients with localized prostate cancer were treated with helical tomotherapy at the City of Hope Medical Center. Of the 146 patients, 70 had undergone prostatectomy. Acute GI and GU toxicities were evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Cancer of Medical scoring system. Events were scored for patients developing Grade 2 or greater morbidity within 90 days after the end of radiotherapy (RT). The dosimetric parameters included the minimal dose received by the highest 10%, 20%, 50%, 80%, and 90% of the target volume, the mean rectal dose, minimal rectal dose, maximal rectal dose, and the volume receiving {>=}45, {>=}65, and {>=}70 Gy. These variables, plus the status of radical prostatectomy, hormonal therapy, RT techniques, and medical conditions, were included in a multivariate logistic regression analysis. A goodness-of-fit evaluation was done using the Hosmer-Lemeshow statistic. Results: A dose-response function for acute GI toxicity was elicited. The acute GI Grade 2 or greater toxicity was lower in the definitive RT group than in the postoperative RT group (25% vs. 41%, p <0.05). Acute GU Grade 2 or greater toxicity was comparable between the two groups. No grade 3 or greater complications were observed. No dosimetric variable was significant for GU toxicity. For acute GI toxicity, the significant dosimetric parameters were the minimal dose received by 10%, 20%, and 50% of the target volume and the mean rectal dose; the most predictive parameter was the minimal dose received by 10% of the target volume. The dose-modifying factor was 1.2 for radical prostatectomy. Conclusion: The results of our

  11. Image-guided radiotherapy using a mobile kilovoltage x-ray device.

    PubMed

    Sorensen, Stephen P; Chow, Phillip E; Kriminski, Sergey; Medin, Paul M; Solberg, Timothy D

    2006-01-01

    A mobile isocentric C-arm kilovoltage imager has been evaluated as a potential tool for image-guided radiotherapy. The C-arm is equipped with an amorphous silicon flat panel for high-quality image acquisition. Additionally, the device is capable of cone beam computed tomography (CT) and volumetric reconstruction. This is achieved through the application of a modified Feldkamp algorithm with acquisition over a 180 degrees scan arc. The number of projections can be varied from 100 to 1000, resulting in a reconstructed volume 20 cm in diameter by 15-cm long. While acquisition time depends upon number of projections, acceptable quality images can be obtained in less than 60 seconds. Image resolution and contrast of cone-beam phantom images have been compared with images from a conventional CT scanner. The system has a spatial resolution of > or = 10 lp/cm and resolution is approximately equal in all 3 dimensions. Conversely, subject contrast is poorer than conventional CT, compromised by the increased scatter and underlying noise inherent in cone beam reconstruction, as well as the absence of filtering prior to reconstruction. The mobility of the C-arm makes it necessary to determine the C-arm position relative to the linear accelerator isocenter. Two solutions have been investigated: (1) the use of fiducial markers, embedded in the linac couch, that can subsequently be registered in the image sets; and (2), a navigation approach for infrared tracking of the C-arm relative to the linac isocenter. Observed accuracy in phantom positioning ranged from 1.0 to 1.5 mm using the navigation approach and 1.5 to 2.5 mm using the fiducial-based approach. As part of this work, the impact of respiratory motion on cone-beam image quality was evaluated, and a scheme for retrospective gating was devised. Results demonstrated that kilovoltage cone beam CT provides spatial integrity and resolution comparable to conventional CT. Cone-beam CT studies of patients undergoing radiotherapy

  12. Image-Guided Intensity-Modulated Photon Radiotherapy Using Multifractionated Regimen to Paraspinal Chordomas and Rare Sarcomas

    SciTech Connect

    Terezakis, Stephanie A. Lovelock, D. Michael; Bilsky, Mark H.; Hunt, Margaret A.; Zatcky, Joan N.P.; Yamada, Yoshiya

    2007-12-01

    Purpose: Image-guided intensity-modulated radiotherapy enables delivery of high-dose radiation to tumors close to the spinal cord. We report our experience with multifractionated regimens using image-guided intensity-modulated radiotherapy to treat gross paraspinal disease to doses beyond cord tolerance. Methods and Materials: We performed a retrospective review of 27 consecutive patients with partially resected or unresectable paraspinal tumors irradiated to >5,300 cGy in standard fractionation. Results: The median follow-up was 17.4 months (range, 2.1-47.3). Eighteen sarcomas, seven chordomas, and two ependymomas were treated. The median dose to the planning target volume was 6,600 cGy (range, 5,396-7,080) in 180- or 200-cGy fractions. The median planning target volume was 164 cm{sup 3} (range, 29-1,116). Seven patients developed recurrence at the treatment site (26%), and 6 of these patients had high-grade tumors. Three patients with recurrence had metastatic disease at the time of radiotherapy. The 2-year local control rate was 65%, and the 2-year overall survival rate was 79%. Of the 5 patients who died, 4 had metastatic disease at death. Twenty-three patients (84%) reported either no pain or improved pain at the last follow-up visit. Sixteen patients discontinued narcotic use after treatment (62.5%). Twenty-three patients (89%) had a stable or improved American Spine Injury Association score at the last follow-up visit. No patient experienced radiation-induced myelopathy. Conclusions: The dose to paraspinal tumors has traditionally been limited to respect cord tolerance. With image-guided intensity-modulated radiotherapy, greater doses of radiation delivered in multiple fractions can be prescribed with excellent target coverage, effective palliation, and acceptable toxicity and local control.

  13. Dose Escalation of Gemcitabine Is Possible With Concurrent Chest Three-Dimensional Rather Than Two-Dimensional Radiotherapy: A Phase I Trial in Patients With Stage III Non-Small-Cell Lung Cancer

    SciTech Connect

    Zinner, Ralph G. Cox, James D.; Glisson, Bonnie S.; Pisters, Katherine M.W.; Herbst, Roy S.; Kies, Merril; Hong, Waun K.; Fossella, Frank V.

    2009-01-01

    Purpose: To determine in a Phase I study the maximum tolerated dose of weekly gemcitabine concurrent with radiotherapy in locally advanced non-small-cell lung cancer (NSCLC), as well as the relationship between the volume of the esophagus irradiated and severe esophagitis. Methods and Materials: Twenty-one patients with Stage III NSCLC received gemcitabine initially at 150 mg/m{sup 2}/wk over 7 weeks concurrently with chest radiotherapy to 63 Gy in 34 fractions. The first 9 patients underwent treatment with two-dimensional (2D) radiotherapy; the remaining 12 patients, with three-dimensional conformal radiotherapy (3D-CRT) and target volume reduced to clinically apparent disease. Consolidation was 4 cycles of gemcitabine at 1000 mg/m{sup 2}/wk and cisplatin 60 mg/m{sup 2}. Results: In the 2D group, the dose-limiting toxicity, Grade 3 esophagitis, occurred in 3 of 6 patients in the 150-mg/m{sup 2}/wk cohort and 2 of 3 patients in the 125-mg/m{sup 2}/wk cohort. No cases of Grade 3 esophagitis occurred at these doses in the 3D group. At gemcitabine 190 mg/m{sup 2}/wk, 2 of 6 patients in the 3D cohort had Grade 3 esophagitis. The mean percentages of esophagus irradiated to 60 Gy were 68% in the 2D cohort and 18% in the 3D cohort. Conclusions: We could not escalate the dose of gemcitabine with concurrent radiotherapy when using 2D planning because of severe acute esophagitis. However, we could escalate the dose of gemcitabine to 190 mg/m{sup 2}/wk when using 3D planning. The Phase II dose is 150 mg/m{sup 2}/wk. Three-dimensional CRT permitted the use of higher doses of gemcitabine.

  14. Evaluation of volume change in rectum and bladder during application of image-guided radiotherapy for prostate carcinoma

    SciTech Connect

    Luna, J. A.; Rojas, J. I.

    2016-07-07

    All prostate cancer patients from Centro Médico Radioterapia Siglo XXI receive Volumetric Modulated Arc Therapy (VMAT). This therapy uses image-guided radiotherapy (IGRT) with the Cone Beam Computed Tomography (CBCT). This study compares the planned dose in the reference CT image against the delivered dose recalculate in the CBCT image. The purpose of this study is to evaluate the anatomic changes and related dosimetric effect based on weekly CBCT directly for patients with prostate cancer undergoing volumetric modulated arc therapy (VMAT) treatment. The collected data were analyzed using one-way ANOVA.

  15. Evaluation of volume change in rectum and bladder during application of image-guided radiotherapy for prostate carcinoma

    NASA Astrophysics Data System (ADS)

    Luna, J. A.; Rojas, J. I.

    2016-07-01

    All prostate cancer patients from Centro Médico Radioterapia Siglo XXI receive Volumetric Modulated Arc Therapy (VMAT). This therapy uses image-guided radiotherapy (IGRT) with the Cone Beam Computed Tomography (CBCT). This study compares the planned dose in the reference CT image against the delivered dose recalculate in the CBCT image. The purpose of this study is to evaluate the anatomic changes and related dosimetric effect based on weekly CBCT directly for patients with prostate cancer undergoing volumetric modulated arc therapy (VMAT) treatment. The collected data were analyzed using one-way ANOVA.

  16. Individualized Tamoxifen Dose Escalation: Confirmation of Feasibility, Question of Utility.

    PubMed

    Hertz, Daniel L; Rae, James M

    2016-07-01

    Tamoxifen may require metabolic activation to endoxifen for efficacy in treating hormone receptor-positive breast cancer. Dose escalation in patients with low endoxifen concentrations could enhance treatment efficacy. This approach is clinically feasible, and successfully increases endoxifen concentrations; however, it is unknown whether patients benefit from individualized tamoxifen dose escalation. Clin Cancer Res; 22(13); 3121-3. ©2016 AACRSee related article by Fox et al., p. 3164.

  17. The management of imaging dose during image-guided radiotherapy: Report of the AAPM Task Group 75

    SciTech Connect

    Murphy, Martin J.; Balter, James; Balter, Stephen; BenComo, Jose A. Jr.; Das, Indra J.; Jiang, Steve B.; Ma, C.-M.; Olivera, Gustavo H.; Rodebaugh, Raymond F.; Ruchala, Kenneth J.; Shirato, Hiroki; Yin, Fang-Fang

    2007-10-15

    Radiographic image guidance has emerged as the new paradigm for patient positioning, target localization, and external beam alignment in radiotherapy. Although widely varied in modality and method, all radiographic guidance techniques have one thing in common--they can give a significant radiation dose to the patient. As with all medical uses of ionizing radiation, the general view is that this exposure should be carefully managed. The philosophy for dose management adopted by the diagnostic imaging community is summarized by the acronym ALARA, i.e., as low as reasonably achievable. But unlike the general situation with diagnostic imaging and image-guided surgery, image-guided radiotherapy (IGRT) adds the imaging dose to an already high level of therapeutic radiation. There is furthermore an interplay between increased imaging and improved therapeutic dose conformity that suggests the possibility of optimizing rather than simply minimizing the imaging dose. For this reason, the management of imaging dose during radiotherapy is a different problem than its management during routine diagnostic or image-guided surgical procedures. The imaging dose received as part of a radiotherapy treatment has long been regarded as negligible and thus has been quantified in a fairly loose manner. On the other hand, radiation oncologists examine the therapy dose distribution in minute detail. The introduction of more intensive imaging procedures for IGRT now obligates the clinician to evaluate therapeutic and imaging doses in a more balanced manner. This task group is charged with addressing the issue of radiation dose delivered via image guidance techniques during radiotherapy. The group has developed this charge into three objectives: (1) Compile an overview of image-guidance techniques and their associated radiation dose levels, to provide the clinician using a particular set of image guidance techniques with enough data to estimate the total diagnostic dose for a specific

  18. First Clinical Release of an Online, Adaptive, Aperture-Based Image-Guided Radiotherapy Strategy in Intensity-Modulated Radiotherapy to Correct for Inter- and Intrafractional Rotations of the Prostate

    SciTech Connect

    Deutschmann, Heinz; Kametriser, Gerhard; Steininger, Philipp; Scherer, Philipp; Schoeller, Helmut; Gaisberger, Christoph; Mooslechner, Michaela; Mitterlechner, Bernhard; Weichenberger, Harald; Fastner, Gert; Wurstbauer, Karl; Jeschke, Stephan; Forstner, Rosemarie; Sedlmayer, Felix

    2012-08-01

    adaptive image-guided, intensity-modulated prostate protocol on a standard linear accelerator to correct 6 degrees of freedom of internal organ motion, allowing safe and straightforward implementation of margin reduction and dose escalation.

  19. Dose-Escalation Study of Thoracic Radiotherapy in Combination With Pemetrexed Plus Cisplatin in Japanese Patients With Locally Advanced Nonsquamous Non-Small Cell Lung Cancer: A Post Hoc Analysis of Survival and Recurrent Sites.

    PubMed

    Niho, Seiji; Nokihara, Hiroshi; Nihei, Keiji; Akimoto, Tetsuo; Sumi, Minako; Ito, Yoshinori; Yoh, Kiyotaka; Goto, Koichi; Ohmatsu, Hironobu; Horinouchi, Hidehito; Yamamoto, Noboru; Sekine, Ikuo; Kubota, Kaoru; Ohe, Yuichiro; Tamura, Tomohide

    2016-04-01

    We performed a post hoc analysis of progression-free survival (PFS), overall survival (OS), and recurrent sites in patients with locally advanced nonsquamous non-small cell lung cancer who were enrolled in a phase I trial of combination chemotherapy consisting of pemetrexed plus cisplatin with concurrent thoracic radiotherapy. Patients received pemetrexed (500 mg/m²) plus cisplatin (75 mg/m²) on day 1 every 3 weeks for 3 cycles plus concurrent thoracic radiotherapy consisting of 60 Gy (n=6) or 66 Gy (n=12); 4 to 6 weeks thereafter, patients received consolidation treatment with pemetrexed (500 mg/m) every 3 weeks for up to 3 cycles. We reviewed the medial records to collect data on progression, recurrent sites, late toxicity, and survival. No late radiation morbidity was observed. Thirteen patients (72%) exhibited disease progression: 8 patients had distant metastases, 8 patients had local recurrence (within the radiation field [n=6], outside the radiation field [n=2], and both [n=1]), and 3 patients had local recurrence plus distant metastases. The median PFS was 10.5 months (95% confidence interval [CI], 8.8-12.3), and the 3-year PFS rate was 28% (95% CI, 7.0-48.6). Ten of the 18 patients died of lung cancer. The median follow-up time for the censored cases was 42.8 months (range, 38.1 to 52.9 mo). The median OS was 27.3 months (95% CI, 13.1-41.6), and the 3-year OS rate was 50% (95% CI, 26.9-73.1). The median PFS and OS in our study were comparable to those of historical chemoradiotherapy controls.

  20. Intensity-Modulated and Image-Guided Radiotherapy in Patients with Locally Advanced Inoperable Pancreatic Cancer after Preradiation Chemotherapy

    PubMed Central

    Sinn, M.; Ganeshan, R.; Graf, R.; Pelzer, U.; Stieler, J. M.; Striefler, J. K.; Bahra, M.; Wust, P.; Riess, H.

    2014-01-01

    Background. Radiotherapy (RT) in patients with pancreatic cancer is still a controversial subject and its benefit in inoperable stages of locally advanced pancreatic cancer (LAPC), even after induction chemotherapy, remains unclear. Modern radiation techniques such as image-guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT) may improve effectiveness and reduce radiotherapy-related toxicities. Methods. Patients with LAPC who underwent radiotherapy after chemotherapy between 09/2004 and 05/2013 were retrospectively analyzed with regard to preradiation chemotherapy (PRCT), modalities of radiotherapy, and toxicities. Progression-free (PFS) and overall survival (OS) were estimated by Kaplan-Meier curves. Results. 15 (68%) women and 7 men (median age 64 years; range 40–77) were identified. Median duration of PRCT was 11.1 months (range 4.3–33.0). Six patients (27%) underwent conventional RT and 16 patients (73%) advanced IMRT and IGRT; median dosage was 50.4 (range 9–54) Gray. No grade III or IV toxicities occurred. Median PFS (estimated from the beginning of RT) was 5.8 months, 2.6 months in the conventional RT group (conv-RT), and 7.1 months in the IMRT/IGRT group (P = 0.029); median OS was 11.0 months, 4.2 months (conv-RT), and 14.0 months (IMRT/IGRT); P = 0.141. Median RT-specific PFS for patients with prolonged PRCT > 9 months was 8.5 months compared to 5.6 months for PRCT < 9 months (P = 0.293). This effect was translated into a significantly better median RT-specific overall survival of patients in the PRCT > 9 months group, with 19.0 months compared to 8.5 months in the PRCT  <  9 months group (P = 0.049). Conclusions. IGRT and IMRT after PRCT are feasible and effective options for patients with LAPC after prolonged preradiation chemotherapy. PMID:25401140

  1. Development of a four-dimensional image-guided radiotherapy system with a gimbaled X-ray head

    SciTech Connect

    Kamino, Yuichiro . E-mail: daisaku_horiuchi@mhi.co.jp; Takayama, Kenji; Kokubo, Masaki; Narita, Yuichiro; Hirai, Etsuro; Kawawda, Noriyuki; Mizowaki, Takashi; Nagata, Yasushi; Nishidai, Takehiro; Hiraoka, Masahiro

    2006-09-01

    Purpose: To develop and evaluate a new four-dimensional image-guided radiotherapy system, which enables precise setup, real-time tumor tracking, and pursuit irradiation. Methods and Materials: The system has an innovative gimbaled X-ray head that enables small-angle ({+-}2.4{sup o}) rotations (pan and tilt) along the two orthogonal gimbals. This design provides for both accurate beam positioning at the isocenter by actively compensating for mechanical distortion and quick pursuit of the target. The X-ray head is composed of an ultralight C-band linear accelerator and a multileaf collimator. The gimbaled X-ray head is mounted on a rigid O-ring structure with an on-board imaging subsystem composed of two sets of kilovoltage X-ray tubes and flat panel detectors, which provides a pair of radiographs, cone beam computed tomography images useful for image guided setup, and real-time fluoroscopic monitoring for pursuit irradiation. Results: The root mean square accuracy of the static beam positioning was 0.1 mm for 360{sup o} of O-ring rotation. The dynamic beam response and positioning accuracy was {+-}0.6 mm for a 0.75 Hz, 40-mm stroke and {+-}0.4 mm for a 2.0 Hz, 8-mm stroke. The quality of the images was encouraging for using the tomography-based setup. Fluoroscopic images were sufficient for monitoring and tracking lung tumors. Conclusions: Key functions and capabilities of our new system are very promising for precise image-guided setup and for tracking and pursuit irradiation of a moving target.

  2. High-Dose, Single-Fraction Image-Guided Intensity-Modulated Radiotherapy for Metastatic Spinal Lesions

    SciTech Connect

    Yamada, Yoshiya Bilsky, Mark H.; Lovelock, D. Michael; Venkatraman, Ennapadam S.; Toner, Sean; Johnson, Jared; Zatcky, Joan N.P.; Zelefsky, Michael J.; Fuks, Zvi

    2008-06-01

    Purpose: To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT. Methods and Materials: A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging. Results: The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed. Conclusion: High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control.

  3. Evaluation of Imaging Dose From Different Image Guided Systems During Head and Neck Radiotherapy: A Phantom Study.

    PubMed

    Cheng, Chun Shing; Jong, Wei Loong; Ung, Ngie Min; Wong, Jeannie Hsiu Ding

    2016-12-09

    This work evaluated and compared the absorbed doses to selected organs in the head and neck region from the three image guided radiotherapy systems: cone-beam computed tomography (CBCT) and kilovoltage (kV) planar imaging using the On-board Imager(®) (OBI) as well as the ExacTrac(®) X-ray system, all available on the Varian Novalis TX linear accelerator. The head and neck region of an anthropomorphic phantom was used to simulate patients' head within the imaging field. Nanodots optically stimulated luminescent dosemeters were positioned at selected sites to measure the absorbed doses. CBCT was found to be delivering the highest dose to internal organs while OBI-2D gave the highest doses to the eye lenses. The setting of half-rotation in CBCT effectively reduces the dose to the eye lenses. Daily high-quality CBCT verification was found to increase the secondary cancer risk by 0.79%.

  4. Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

    PubMed

    Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

    2016-01-01

    Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3-6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered.

  5. Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

    PubMed Central

    Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

    2016-01-01

    Aim Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients and methods Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3–6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. Results In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. Conclusion There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered. PMID:27274277

  6. Dose escalation in brachytherapy for cervical cancer: impact on (or increased need for) MRI-guided plan optimisation

    PubMed Central

    Paton, A M; Chalmers, K E; Coomber, H; Cameron, A L

    2012-01-01

    Objective The aim of this study was to assess the impact of dose escalation on the proportion of patients requiring MR image-guided optimisation rather than standard Manchester-based CT-guided planning, and the level of escalation achievable. Methods 30 patients with cervical cancer treated with external beam radiotherapy and image-guided brachytherapy (IGBT) had MR images acquired at the first fraction of IGBT. Gross tumour volume and high-risk clinical target volume (HR CTV) were contoured and treatment plans retrospectively produced for a range of total 2-Gy equivalent (EQD2) prescription doses from 66 Gyα/β=10 to 90 Gyα/β=10 (HR CTV D90). Standard Manchester system-style plans were produced, prescribed to point A and then optimised where necessary with the aim of delivering at least the prescription dose to the HR CTV D90 while respecting organ-at-risk (OAR) tolerances. Results Increasing the total EQD2 from 66 Gyα/β=10 to 90 Gyα/β=10 increased the number of plans requiring optimisation from 13.3% to 90%. After optimisation, the number of plans achieving the prescription dose ranged from 93.3% (66 Gyα/β=10) to 63.3% (90 Gyα/β=10) with the mean±standard deviation for HR CTV D90 EQD2 from 78.4±12.4 Gyα/β=10 (66 Gyα/β=10) to 94.1±19.9 Gyα/β=10 (90 Gyα/β=10). Conclusion As doses are escalated, the need for non-standard optimised planning increases, while benefits in terms of increased target doses actually achieved diminish. The maximum achievable target dose is ultimately limited by proximity of OARs. Advances in knowledge This work represents a guide for other centres in determining the highest practicable prescription doses while considering patient throughput and maintaining acceptable OAR doses. PMID:23175490

  7. Image-guided stereotactic radiotherapy in 4 dogs with intracranial neoplasia.

    PubMed

    Moon, Alaina Burkard; Heller, Heidi Barnes; Forrest, Lisa

    2016-05-01

    The purpose of this study was to describe the use, and side effects, of a novel stereotactic radiotherapy protocol using TomoTherapy(®) in 4 dogs with confirmed or suspected primary extra-axial intracranial neoplasia. Three fractions of 8 Gy were prescribed. Acute side effects were noted in 1 dog; no late effects were noted.

  8. Implementation of an image guided intensity-modulated protocol for post-prostatectomy radiotherapy: planning data and acute toxicity outcomes.

    PubMed

    Chua, Benjamin; Min, Myo; Wood, Maree; Edwards, Sarah; Hoffmann, Matthew; Greenham, Stuart; Kovendy, Andrew; McKay, Michael J; Shakespeare, Thomas P

    2013-08-01

    There is substantial interest in implementation of image-guided intensity-modulated radiotherapy (IG-IMRT) in the post-prostatectomy setting. We describe our implementation of IG-IMRT, and examine how often published organ-at-risk (OAR) constraints were met. Furthermore, we evaluate the incidence of acute genitourinary and gastrointestinal toxicities when patients were treated according to our protocol. Patients were eligible if they received post-prostatectomy radiotherapy (PPRT). Planning data were collected prospectively, and toxicity assessments were collected before, during and after treatment. Seventy-five eligible patients received either 64 Gy (19%) or 66 Gy (81%) in a single phase to the prostate bed. Suggested rectal dose-constraints of V40Gy < 60% and V60Gy < 40% were met in 64 (85%) and 75 (100%) patients, respectively. IMRT-specific rectal dose-constraints of V40Gy < 35% and V65Gy < 17% were achieved in 5 (7%) and 57 (76%) of patients. Bladder dose-constraint (V50Gy < 50%) was met in 58 (77%) patients. Two patients (3%) experienced new grade 3 genitourinary toxicity and one patient (1%) experienced new grade 3 gastroinestinal toxicity. All grade 3 toxicities had improved by 3-month review. Overall deterioration in urinary and gastrointestinal symptoms occurred in 33 (44%) and 35 (47%) of patients respectively. We report on our implementation of PPRT which takes into account nationally adopted guidelines, with a margin reduction supported by use of daily image guidance. Non-IMRT OAR constraints were met in most cases. IMRT-specific constraints were less often achieved despite margin reductions, suggesting the need for review of guidelines. Severe toxicity was rare, and most patients did not experience deterioration in urinary or bowel function attributable to radiotherapy. © 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.

  9. Use of the BrainLAB ExacTrac X-Ray 6D System in Image-Guided Radiotherapy

    SciTech Connect

    Jin, J.-Y. Yin Fangfang; Tenn, Stephen E.; Medin, Paul M.; Solberg, Timothy D.

    2008-07-01

    The ExacTrac X-Ray 6D image-guided radiotherapy (IGRT) system will be described and its performance evaluated. The system is mainly an integration of 2 subsystems: (1) an infrared (IR)-based optical positioning system (ExacTrac) and (2) a radiographic kV x-ray imaging system (X-Ray 6D). The infrared system consists of 2 IR cameras, which are used to monitor reflective body markers placed on the patient's skin to assist in patient initial setup, and an IR reflective reference star, which is attached to the treatment couch and can assist in couch movement with spatial resolution to better than 0.3 mm. The radiographic kV devices consist of 2 oblique x-ray imagers to obtain high-quality radiographs for patient position verification and adjustment. The position verification is made by fusing the radiographs with the simulation CT images using either 3 degree-of-freedom (3D) or 6 degree-of-freedom (6D) fusion algorithms. The position adjustment is performed using the infrared system according to the verification results. The reliability of the fusion algorithm will be described based on phantom and patient studies. The results indicated that the 6D fusion method is better compared to the 3D method if there are rotational deviations between the simulation and setup positions. Recently, the system has been augmented with the capabilities for image-guided positioning of targets in motion due to respiration and for gated treatment of those targets. The infrared markers provide a respiratory signal for tracking and gating of the treatment beam, with the x-ray system providing periodic confirmation of patient position relative to the gating window throughout the duration of the gated delivery.

  10. Use of the BrainLAB ExacTrac X-Ray 6D system in image-guided radiotherapy.

    PubMed

    Jin, Jian-Yue; Yin, Fang-Fang; Tenn, Stephen E; Medin, Paul M; Solberg, Timothy D

    2008-01-01

    The ExacTrac X-Ray 6D image-guided radiotherapy (IGRT) system will be described and its performance evaluated. The system is mainly an integration of 2 subsystems: (1) an infrared (IR)-based optical positioning system (ExacTrac) and (2) a radiographic kV x-ray imaging system (X-Ray 6D). The infrared system consists of 2 IR cameras, which are used to monitor reflective body markers placed on the patient's skin to assist in patient initial setup, and an IR reflective reference star, which is attached to the treatment couch and can assist in couch movement with spatial resolution to better than 0.3 mm. The radiographic kV devices consist of 2 oblique x-ray imagers to obtain high-quality radiographs for patient position verification and adjustment. The position verification is made by fusing the radiographs with the simulation CT images using either 3 degree-of-freedom (3D) or 6 degree-of-freedom (6D) fusion algorithms. The position adjustment is performed using the infrared system according to the verification results. The reliability of the fusion algorithm will be described based on phantom and patient studies. The results indicated that the 6D fusion method is better compared to the 3D method if there are rotational deviations between the simulation and setup positions. Recently, the system has been augmented with the capabilities for image-guided positioning of targets in motion due to respiration and for gated treatment of those targets. The infrared markers provide a respiratory signal for tracking and gating of the treatment beam, with the x-ray system providing periodic confirmation of patient position relative to the gating window throughout the duration of the gated delivery.

  11. Comparison of Spine, Carina, and Tumor as Registration Landmarks for Volumetric Image-Guided Lung Radiotherapy

    SciTech Connect

    Higgins, Jane Bezjak, Andrea; Franks, Kevin; Le, Lisa W.; Cho, B.C.; Payne, David; Bissonnette, Jean-Pierre

    2009-04-01

    Purpose: To assess the feasibility, reproducibility, and accuracy of volumetric lung image guidance using different thoracic landmarks for image registration. Methods and Materials: In 30 lung patients, four independent observers conducted automated and manual image registrations on Day 1 cone-beam computed tomography data sets using the spine, carina, and tumor (720 image registrations). The image registration was timed, and the couch displacements were recorded. The intraclass correlation was used to assess reproducibility, and the Bland-Altman analysis was used to compare the automatic and manual matching methods. Tumor coverage (accuracy) was assessed through grading the tumor position after image matching against the internal target volume and planning target volume. Results: The image-guided process took an average of 1 min for all techniques, with the exception of manual tumor matching, which took 4 min. Reproducibility was greatest for automatic carina matching (intraclass correlation, 0.90-0.93) and lowest for manual tumor matching (intraclass correlation, 0.07-0.43) in the left-right, superoinferior, and anteroposterior directions, respectively. The Bland-Altman analysis showed no significant difference between the automatic and manual registration methods. The tumor was within the internal target volume 62% and 60% of the time and was outside the internal target volume, but within the planning target volume, 38% and 40% of the time after automatic spine and automatic carina matching, respectively. Conclusion: For advanced lung cancer, the spine or carina can be used equally for cone-beam computed tomography image registration without compromising target coverage. The carina was more reproducible than the spine, but additional analysis is required to confirm its validation as a tumor surrogate. Soft-tissue registration is unsuitable at present, given the limitations in contrast resolution and the high interobserver variability.

  12. Moderate dose escalation with volumetric modulated arc therapy improves outcome in rectal cancer.

    PubMed

    Stuyck, Cedric; Wegge, Marilyn; Bulens, Philippe; Joye, Ines; Haustermans, Karin

    2017-08-22

    Locally advanced rectal cancer is frequently treated with a long course of preoperative chemoradiotherapy. We investigated the effect of moderate dose escalation with volumetric modulated arc therapy (VMAT) up to 50 Gy in 25 fractions compared to 3D conformal radiotherapy (3D-CRT) to 45 Gy in 25 fractions in rectal cancer patients. Dose-volume parameters, acute toxicity, and complete response rates were compared. For both groups, 65 patients were selected from our database through availability. Dose-volume parameters and acute toxicity data were compared using a Mann-Whitney U-test. Univariate and multivariate analyses correcting for tumor and nodal stage, distance to the mesorectal fascia and interval to surgery were used to compare complete response rates. Lower mean doses to the small and large bowel were observed in the VMAT group compared to the 3D-CRT group (21 Gy vs. 29 Gy [p < .001] and 26 Gy vs. 30 Gy [p = .002], respectively). Similar beneficial dose-volume parameters were observed for the bladder, sacrum and femoral heads. Furthermore, patients receiving VMAT experienced significantly less diarrhea, flatulence, non-infective cystitis, urinary frequency, dermatitis, and fatigue. In univariate analysis, a significant increase in complete response rate after moderate dose escalation with VMAT was observed (34% vs. 15%, p = .015). However, this did not remain significant when corrected for tumor and nodal stage, distance to the mesorectal fascia, and interval to surgery. Moderate dose escalation with VMAT resulted in superior dose-volume parameters compared to 3D-CRT, translating into lower acute toxicity. Additionally, improved tumor response after VMAT up to 50 Gy might contribute to a higher percentage of patients achieving a complete response.

  13. Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance

    PubMed Central

    2014-01-01

    Background Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated with daily image-guided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa). Methods A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1–2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5–7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT. Results The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p < 0.001). For GU toxicity the numbers were 41.8% and 29.7%, respectively (p = 0.011). On multivariate analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p < 0.001, HR = 11.59 [CI: 6.67-20.14]). 3DCRT was also associated with an increased risk of developing GU toxicity compared to IG-IMRT. The 3-year actuarial biochemical progression-free survival probability was 86.0% for 3DCRT and 90.3% for IG-IMRT (p = 0.386). On multivariate analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT. Conclusion The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction. PMID:24495815

  14. Impact of field number and beam angle on functional image-guided lung cancer radiotherapy planning

    NASA Astrophysics Data System (ADS)

    Tahir, Bilal A.; Bragg, Chris M.; Wild, Jim M.; Swinscoe, James A.; Lawless, Sarah E.; Hart, Kerry A.; Hatton, Matthew Q.; Ireland, Rob H.

    2017-09-01

    To investigate the effect of beam angles and field number on functionally-guided intensity modulated radiotherapy (IMRT) normal lung avoidance treatment plans that incorporate hyperpolarised helium-3 magnetic resonance imaging (3He MRI) ventilation data. Eight non-small cell lung cancer patients had pre-treatment 3He MRI that was registered to inspiration breath-hold radiotherapy planning computed tomography. IMRT plans that minimised the volume of total lung receiving  ⩾20 Gy (V20) were compared with plans that minimised 3He MRI defined functional lung receiving  ⩾20 Gy (fV20). Coplanar IMRT plans using 5-field manually optimised beam angles and 9-field equidistant plans were also evaluated. For each pair of plans, the Wilcoxon signed ranks test was used to compare fV20 and the percentage of planning target volume (PTV) receiving 90% of the prescription dose (PTV90). Incorporation of 3He MRI led to median reductions in fV20 of 1.3% (range: 0.2-9.3% p  =  0.04) and 0.2% (range: 0 to 4.1%; p  =  0.012) for 5- and 9-field arrangements, respectively. There was no clinically significant difference in target coverage. Functionally-guided IMRT plans incorporating hyperpolarised 3He MRI information can reduce the dose received by ventilated lung without comprising PTV coverage. The effect was greater for optimised beam angles rather than uniformly spaced fields.

  15. Image-guided adaptive radiotherapy for prostate and head-and-neck cancers

    NASA Astrophysics Data System (ADS)

    O'Daniel, Jennifer C.

    In the current practice of radiation therapy, daily patient alignments have been based on external skin marks or on bone. However, internal organ variation (both motion and volumetric changes) between treatment fractions can displace the treatment target, causing target underdosage and normal tissue overdosage. In order to deliver the radiation treatment as planned, more accurate knowledge of the daily internal anatomy was needed. Additionally, treatments needed to adapt to these variations by either shifting the patient to account for the daily target position or by altering the treatment plan. In this dissertation, the question of whether inter-fractional variations in internal patient anatomy combined with external set-up uncertainties produced measurable differences between planned and delivered doses for prostate and head-and-neck cancer patients was investigated. Image-guided adaptive treatment strategies to improve tumor coverage and/or reduce normal tissue dose were examined. Treatment deliveries utilizing various alignment procedures for ten prostate cancer patients and eleven head-and-neck cancer patients, each of whom received multiple CT scans over the course of treatment, were simulated. The largest prostate dose losses between planning and delivery were correlated with anterior/posterior and superior/inferior prostate displacement. Daily bone alignment sufficiently maintained target coverage for 70% of patients, ultrasound for 90%, and CT for 100%. A no-action-level correction protocol, which corrected the daily bone alignment for the systematic internal displacement of the prostate based on a pre-determined number of CT image sets, successfully improved the prostate and seminal vesicle dosimetric coverage. Three CT image sets were sufficient to accurately correct the bone alignment scheme for the prostate internal systematic shifts. For head-and-neck cancer patient treatment, setup uncertainties and internal organ variations did not greatly affect

  16. Robotic image-guided stereotactic radiotherapy, for isolated recurrent primary, lymph node or metastatic prostate cancer.

    PubMed

    Jereczek-Fossa, Barbara Alicja; Beltramo, Giancarlo; Fariselli, Laura; Fodor, Cristiana; Santoro, Luigi; Vavassori, Andrea; Zerini, Dario; Gherardi, Federica; Ascione, Carmen; Bossi-Zanetti, Isa; Mauro, Roberta; Bregantin, Achille; Bianchi, Livia Corinna; De Cobelli, Ottavio; Orecchia, Roberto

    2012-02-01

    To evaluate the outcome of robotic CyberKnife (Accuray, Sunnyvale, CA)-based stereotactic radiotherapy (CBK-SRT) for isolated recurrent primary, lymph node, or metastatic prostate cancer. Between May 2007 and December 2009, 34 consecutive patients/38 lesions were treated (15 patients reirradiated for local recurrence [P], 4 patients reirradiated for anastomosis recurrence [A], 16 patients treated for single lymph node recurrence [LN], and 3 patients treated for single metastasis [M]). In all but 4 patients, [(11)C]choline positron emission tomography/computed tomography was performed. CBK-SRT consisted of reirradiation and first radiotherapy in 27 and 11 lesions, respectively. The median CBK-SRT dose was 30 Gy in 4.5 fractions (P, 30 Gy in 5 fractions; A, 30 Gy in 5 fractions; LN, 33 Gy in 3 fractions; and M, 36 Gy in 3 fractions). In 18 patients (21 lesions) androgen deprivation was added to CBK-SRT (median duration, 16.6 months). The median follow-up was 16.9 months. Acute toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event). Late toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event and 1 Grade 2 event). Biochemical response was observed in 32 of 38 evaluable lesions. Prostate-specific antigen stabilization was seen for 4 lesions, and in 2 cases prostate-specific antigen progression was reported. The 30-month progression-free survival rate was 42.6%. Disease progression was observed for 14 lesions (5, 2, 5, and 2 in Groups P, A, LN, and M respectively). In only 3 cases, in-field progression was seen. At the time of analysis (May 2010), 19 patients are alive with no evidence of disease and 15 are alive with disease. CyberKnife-based stereotactic radiotherapy is a feasible approach for isolated recurrent primary, lymph node, or metastatic prostate cancer, offering excellent in-field tumor control and a low toxicity profile. Further investigation

  17. Robotic Image-Guided Stereotactic Radiotherapy, for Isolated Recurrent Primary, Lymph Node or Metastatic Prostate Cancer

    SciTech Connect

    Jereczek-Fossa, Barbara Alicja; Beltramo, Giancarlo; Fariselli, Laura; Fodor, Cristiana; Santoro, Luigi; Vavassori, Andrea; Zerini, Dario; Gherardi, Federica; Ascione, Carmen; Bossi-Zanetti, Isa; Mauro, Roberta; Bregantin, Achille; Bianchi, Livia Corinna; De Cobelli, Ottavio; Orecchia, Roberto

    2012-02-01

    Purpose: To evaluate the outcome of robotic CyberKnife (Accuray, Sunnyvale, CA)-based stereotactic radiotherapy (CBK-SRT) for isolated recurrent primary, lymph node, or metastatic prostate cancer. Methods and Materials: Between May 2007 and December 2009, 34 consecutive patients/38 lesions were treated (15 patients reirradiated for local recurrence [P], 4 patients reirradiated for anastomosis recurrence [A], 16 patients treated for single lymph node recurrence [LN], and 3 patients treated for single metastasis [M]). In all but 4 patients, [{sup 11}C]choline positron emission tomography/computed tomography was performed. CBK-SRT consisted of reirradiation and first radiotherapy in 27 and 11 lesions, respectively. The median CBK-SRT dose was 30 Gy in 4.5 fractions (P, 30 Gy in 5 fractions; A, 30 Gy in 5 fractions; LN, 33 Gy in 3 fractions; and M, 36 Gy in 3 fractions). In 18 patients (21 lesions) androgen deprivation was added to CBK-SRT (median duration, 16.6 months). Results: The median follow-up was 16.9 months. Acute toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event). Late toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event and 1 Grade 2 event). Biochemical response was observed in 32 of 38 evaluable lesions. Prostate-specific antigen stabilization was seen for 4 lesions, and in 2 cases prostate-specific antigen progression was reported. The 30-month progression-free survival rate was 42.6%. Disease progression was observed for 14 lesions (5, 2, 5, and 2 in Groups P, A, LN, and M respectively). In only 3 cases, in-field progression was seen. At the time of analysis (May 2010), 19 patients are alive with no evidence of disease and 15 are alive with disease. Conclusions: CyberKnife-based stereotactic radiotherapy is a feasible approach for isolated recurrent primary, lymph node, or metastatic prostate cancer, offering excellent in-field tumor

  18. Medical applications of fast 3D cameras in real-time image-guided radiotherapy (IGRT) of cancer

    NASA Astrophysics Data System (ADS)

    Li, Shidong; Li, Tuotuo; Geng, Jason

    2013-03-01

    Dynamic volumetric medical imaging (4DMI) has reduced motion artifacts, increased early diagnosis of small mobile tumors, and improved target definition for treatment planning. High speed cameras for video, X-ray, or other forms of sequential imaging allow a live tracking of external or internal movement useful for real-time image-guided radiation therapy (IGRT). However, none of 4DMI can track real-time organ motion and no camera has correlated with 4DMI to show volumetric changes. With a brief review of various IGRT techniques, we propose a fast 3D camera for live-video stereovision, an automatic surface-motion identifier to classify body or respiratory motion, a mechanical model for synchronizing the external surface movement with the internal target displacement by combination use of the real-time stereovision and pre-treatment 4DMI, and dynamic multi-leaf collimation for adaptive aiming the moving target. Our preliminary results demonstrate that the technique is feasible and efficient in IGRT of mobile targets. A clinical trial has been initiated for validation of its spatial and temporal accuracies and dosimetric impact for intensity-modulated RT (IMRT), volumetric-modulated arc therapy (VMAT), and stereotactic body radiotherapy (SBRT) of any mobile tumors. The technique can be extended for surface-guided stereotactic needle insertion in biopsy of small lung nodules.

  19. MR-CT registration using a Ni-Ti prostate stent in image-guided radiotherapy of prostate cancer

    SciTech Connect

    Korsager, Anne Sofie; Ostergaard, Lasse Riis; Carl, Jesper

    2013-06-15

    Purpose: In image-guided radiotherapy of prostate cancer defining the clinical target volume often relies on magnetic resonance (MR). The task of transferring the clinical target volume from MR to standard planning computed tomography (CT) is not trivial due to prostate mobility. In this paper, an automatic local registration approach is proposed based on a newly developed removable Ni-Ti prostate stent.Methods: The registration uses the voxel similarity measure mutual information in a two-step approach where the pelvic bones are used to establish an initial registration for the local registration.Results: In a phantom study, the accuracy was measured to 0.97 mm and visual inspection showed accurate registration of all 30 data sets. The consistency of the registration was examined where translation and rotation displacements yield a rotation error of 0.41 Degree-Sign {+-} 0.45 Degree-Sign and a translation error of 1.67 {+-} 2.24 mm.Conclusions: This study demonstrated the feasibility for an automatic local MR-CT registration using the prostate stent.

  20. Magnitude of speed of sound aberration corrections for ultrasound image guided radiotherapy for prostate and other anatomical sites

    SciTech Connect

    Fontanarosa, Davide; Meer, Skadi van der; Bloemen-van Gurp, Esther; Stroian, Gabriela; Verhaegen, Frank

    2012-08-15

    Purpose: The purpose of this work is to assess the magnitude of speed of sound (SOS) aberrations in three-dimensional ultrasound (US) imaging systems in image guided radiotherapy. The discrepancy between the fixed SOS value of 1540 m/s assumed by US systems in human soft tissues and its actual nonhomogeneous distribution in patients produces small but systematic errors of up to a few millimeters in the positions of scanned structures. Methods: A correction, provided by a previously published density-based algorithm, was applied to a set of five prostate, five liver, and five breast cancer patients. The shifts of the centroids of target structures and the change in shape were evaluated. Results: After the correction the prostate cases showed shifts up to 3.6 mm toward the US probe, which may explain largely the reported positioning discrepancies in the literature on US systems versus other imaging modalities. Liver cases showed the largest changes in volume of the organ, up to almost 9%, and shifts of the centroids up to more than 6 mm either away or toward the US probe. Breast images showed systematic small shifts of the centroids toward the US probe with a maximum magnitude of 1.3 mm. Conclusions: The applied correction in prostate and liver cancer patients shows positioning errors of several mm due to SOS aberration; the errors are smaller in breast cancer cases, but possibly becoming more important when breast tissue thickness increases.

  1. Automatic transperineal ultrasound probe positioning based on CT scan for image guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Camps, S. M.; Verhaegen, F.; Paiva Fonesca, G.; de With, P. H. N.; Fontanarosa, D.

    2017-03-01

    Image interpretation is crucial during ultrasound image acquisition. A skilled operator is typically needed to verify if the correct anatomical structures are all visualized and with sufficient quality. The need for this operator is one of the major reasons why presently ultrasound is not widely used in radiotherapy workflows. To solve this issue, we introduce an algorithm that uses anatomical information derived from a CT scan to automatically provide the operator with a patient-specific ultrasound probe setup. The first application we investigated, for its relevance to radiotherapy, is 4D transperineal ultrasound image acquisition for prostate cancer patients. As initial test, the algorithm was applied on a CIRS multi-modality pelvic phantom. Probe setups were calculated in order to allow visualization of the prostate and adjacent edges of bladder and rectum, as clinically required. Five of the proposed setups were reproduced using a precision robotic arm and ultrasound volumes were acquired. A gel-filled probe cover was used to ensure proper acoustic coupling, while taking into account possible tilted positions of the probe with respect to the flat phantom surface. Visual inspection of the acquired volumes revealed that clinical requirements were fulfilled. Preliminary quantitative evaluation was also performed. The mean absolute distance (MAD) was calculated between actual anatomical structure positions and positions predicted by the CT-based algorithm. This resulted in a MAD of (2.8±0.4) mm for prostate, (2.5±0.6) mm for bladder and (2.8±0.6) mm for rectum. These results show that no significant systematic errors due to e.g. probe misplacement were introduced.

  2. Performance characteristics of mobile MOSFET dosimeter for kilovoltage X-rays used in image guided radiotherapy

    PubMed Central

    Kumar, A. Sathish; Singh, I. Rabi Raja; Sharma, S. D.; Ravindran, B. Paul

    2015-01-01

    The main objective of this study was to investigate the characteristics of metal oxide semiconductor field effect transistor (MOSFET) dosimeter for kilovoltage (kV) X-ray beams in order to perform the in vivo dosimetry during image guidance in radiotherapy. The performance characteristics of high sensitivity MOSFET dosimeters were investigated for 80, 90, 100, 110, 120, and 125 kV X-ray beams used for imaging in radiotherapy. This study was performed using Clinac 2100 C/D medical electron linear accelerator with on-board imaging and kV cone beam computed tomography system. The characteristics studied in this work include energy dependence, angular dependence, and linearity. The X-ray beam outputs were measured as per American Association of Physicists in Medicine (AAPM) TG 61 recommendations using PTW parallel plate (PP) ionization chamber, which was calibrated in terms of air kerma (Nk) by the National Standard Laboratory. The MOSFET dosimeters were calibrated against the PP ionization chamber for all the kV X-ray beams and the calibration coefficient was found to be 0.11 cGy/mV with a standard deviation of about ±1%. The response of MOSFET was found to be energy independent for the kV X-ray energies used in this study. The response of the MOSFET dosimeter was also found independent of angle of incidence for the gantry angles in the range of 0° to 360° in-air as well as at 3 cm depth in tissue equivalent phantom. PMID:26500397

  3. Phase II Trial of Hypofractionated Image-Guided Intensity-Modulated Radiotherapy for Localized Prostate Adenocarcinoma

    SciTech Connect

    Martin, Jarad M.; Rosewall, Tara; Bayley, Andrew; Bristow, Robert; Chung, Peter; Crook, Juanita; Gospodarowicz, Mary; McLean, Michael; Menard, Cynthia; Milosevic, Michael; Warde, Padraig; Catton, Charles

    2007-11-15

    Purpose: To assess in a prospective trial the feasibility and late toxicity of hypofractionated radiotherapy (RT) for prostate cancer. Methods and Materials: Eligible patients had clinical stage T1c-2cNXM0 disease. They received 60 Gy in 20 fractions over 4 weeks with intensity-modulated radiotherapy including daily on-line image guidance with intraprostatic fiducial markers. Results: Between June 2001 and March 2004, 92 patients were treated with hypofractionated RT. The cohort had a median prostate-specific antigen value of 7.06 ng/mL. The majority had Gleason grade 5-6 (38%) or 7 (59%) disease, and 82 patients had T1c-T2a clinical staging. Overall, 29 patients had low-risk, 56 intermediate-risk, and 7 high-risk disease. Severe acute toxicity (Grade 3-4) was rare, occurring in only 1 patient. Median follow-up was 38 months. According to the Phoenix definition for biochemical failure, the rate of biochemical control at 14 months was 97%. According to the previous American Society for Therapeutic Radiology and Oncology definition, biochemical control at 3 years was 76%. The incidence of late toxicity was low, with no severe (Grade {>=}3) toxicity at the most recent assessment. Conclusions: Hypofractionated RT using 60 Gy in 20 fractions over 4 weeks with image guidance is feasible and is associated with low rates of late bladder and rectal toxicity. At early follow-up, biochemical outcome is comparable to that reported for conventionally fractionated controls. The findings are being tested in an ongoing, multicenter, Phase III trial.

  4. Dose escalation in permanent brachytherapy for prostate cancer: dosimetric and biological considerations

    NASA Astrophysics Data System (ADS)

    Li, X. Allen; Wang, Jian Z.; Stewart, Robert D.; Di Biase, Steven J.

    2003-09-01

    No prospective dose escalation study for prostate brachytherapy (PB) with permanent implants has been reported. In this work, we have performed a dosimetric and biological analysis to explore the implications of dose escalation in PB using 125I and 103Pd implants. The concept of equivalent uniform dose (EUD), proposed originally for external-beam radiotherapy (EBRT), is applied to low dose rate brachytherapy. For a given 125I or 103Pd PB, the EUD for tumour that corresponds to a dose distribution delivered by EBRT is calculated based on the linear quadratic model. The EUD calculation is based on the dose volume histogram (DVH) obtained retrospectively from representative actual patient data. Tumour control probabilities (TCPs) are also determined in order to compare the relative effectiveness of different dose levels. The EUD for normal tissue is computed using the Lyman model. A commercial inverse treatment planning algorithm is used to investigate the feasibility of escalating the dose to prostate with acceptable dose increases in the rectum and urethra. The dosimetric calculation is performed for five representative patients with different prostate sizes. A series of PB dose levels are considered for each patient using 125I and 103Pd seeds. It is found that the PB prescribed doses (minimum peripheral dose) that give an equivalent EBRT dose of 64.8, 70.2, 75.6 and 81 Gy with a fraction size of 1.8 Gy are 129, 139, 150 and 161 Gy for 125I and 103, 112, 122 and 132 Gy for 103Pd implants, respectively. Estimates of the EUD and TCP for a series of possible prescribed dose levels (e.g., 145, 160, 170 and 180 Gy for 125I and 125, 135, 145 and 155 for 103Pd implants) are tabulated. The EUD calculation was found to depend strongly on DVHs and radiobiological parameters. The dosimetric calculations suggest that the dose to prostate can be escalated without a substantial increase in both rectal and urethral dose. For example, increasing the PB prescribed dose from 145 to

  5. Preliminary results of radiation dose escalation for locally advanced nasopharyngeal carcinoma

    SciTech Connect

    Kwong, Dora L.W. . E-mail: dlwkwong@hkucc.hku.hk; Sham, Jonathan S.T.; Leung, Lucullus H.T.; Cheng, Ashley C.K.; Ng, W.M.; Kwong, Philip W.K.; Lui, W.M.; Yau, C.C.; Wu, P.M.; Wei, William; Au, Gordon

    2006-02-01

    Purpose: To study the safety and efficacy of dose escalation in tumor for locally advanced nasopharyngeal carcinoma (NPC). Methods and Materials: From September 2000 to June 2004, 50 patients with T3-T4 NPC were treated with intensity-modulated radiotherapy (IMRT). Fourteen patients had Stage III and 36 patients had Stage IVA-IVB disease. The prescribed dose was 76 Gy to gross tumor volume (GTV), 70 Gy to planning target volume (PTV), and 72 Gy to enlarged neck nodes (GTVn). All doses were given in 35 fractions over 7 weeks. Thirty-four patients also had concurrent cisplatin and induction or adjuvant PF (cisplatin and 5-fluorouracil). Results: The average mean dose achieved in GTV, GTVn, and PTV were 79.5 Gy, 75.3 Gy, and 74.6 Gy, respectively. The median follow-up was 25 months, with 4 recurrences: 2 locoregional and 2 distant failures. All patients with recurrence had IMRT alone without chemotherapy. The 2-year locoregional control rate, distant metastases-free and disease-free survivals were 95.7%, 94.2%, and 93.1%, respectively. One treatment-related death caused by adjuvant chemotherapy occurred. The 2-year overall survival was 92.1%. Conclusions: Dose escalation to 76 Gy in tumor is feasible with T3-T4 NPC and can be combined with chemotherapy. Initial results showed good local control and survival.

  6. Strategies of dose escalation in the treatment of locally advanced non-small cell lung cancer: image guidance and beyond.

    PubMed

    Chi, Alexander; Nguyen, Nam Phong; Welsh, James S; Tse, William; Monga, Manish; Oduntan, Olusola; Almubarak, Mohammed; Rogers, John; Remick, Scot C; Gius, David

    2014-01-01

    Radiation dose in the setting of chemo-radiation for locally advanced non-small cell lung cancer (NSCLC) has been historically limited by the risk of normal tissue toxicity and this has been hypothesized to correlate with the poor results in regard to local tumor recurrences. Dose escalation, as a means to improve local control, with concurrent chemotherapy has been shown to be feasible with three-dimensional conformal radiotherapy in early phase studies with good clinical outcome. However, the potential superiority of moderate dose escalation to 74 Gy has not been shown in phase III randomized studies. In this review, the limitations in target volume definition in previous studies; and the factors that may be critical to safe dose escalation in the treatment of locally advanced NSCLC, such as respiratory motion management, image guidance, intensity modulation, FDG-positron emission tomography incorporation in the treatment planning process, and adaptive radiotherapy, are discussed. These factors, along with novel treatment approaches that have emerged in recent years, are proposed to warrant further investigation in future trials in a more comprehensive and integrated fashion.

  7. Strategies of Dose Escalation in the Treatment of Locally Advanced Non-Small Cell Lung Cancer: Image Guidance and Beyond

    PubMed Central

    Chi, Alexander; Nguyen, Nam Phong; Welsh, James S.; Tse, William; Monga, Manish; Oduntan, Olusola; Almubarak, Mohammed; Rogers, John; Remick, Scot C.; Gius, David

    2014-01-01

    Radiation dose in the setting of chemo-radiation for locally advanced non-small cell lung cancer (NSCLC) has been historically limited by the risk of normal tissue toxicity and this has been hypothesized to correlate with the poor results in regard to local tumor recurrences. Dose escalation, as a means to improve local control, with concurrent chemotherapy has been shown to be feasible with three-dimensional conformal radiotherapy in early phase studies with good clinical outcome. However, the potential superiority of moderate dose escalation to 74 Gy has not been shown in phase III randomized studies. In this review, the limitations in target volume definition in previous studies; and the factors that may be critical to safe dose escalation in the treatment of locally advanced NSCLC, such as respiratory motion management, image guidance, intensity modulation, FDG–positron emission tomography incorporation in the treatment planning process, and adaptive radiotherapy, are discussed. These factors, along with novel treatment approaches that have emerged in recent years, are proposed to warrant further investigation in future trials in a more comprehensive and integrated fashion. PMID:24999451

  8. Tumor Control Outcomes After Hypofractionated and Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases From Renal Cell Carcinoma

    SciTech Connect

    Zelefsky, Michael J.; Greco, Carlo; Motzer, Robert; Magsanoc, Juan Martin; Pei Xin; Lovelock, Michael; Mechalakos, Jim; Zatcky, Joan; Fuks, Zvi; Yamada, Yoshiya

    2012-04-01

    Purpose: To report tumor local progression-free outcomes after treatment with single-dose, image-guided, intensity-modulated radiotherapy and hypofractionated regimens for extracranial metastases from renal cell primary tumors. Patients and Methods: Between 2004 and 2010, 105 lesions from renal cell carcinoma were treated with either single-dose, image-guided, intensity-modulated radiotherapy to a prescription dose of 18-24 Gy (median, 24) or hypofractionation (three or five fractions) with a prescription dose of 20-30 Gy. The median follow-up was 12 months (range, 1-48). Results: The overall 3-year actuarial local progression-free survival for all lesions was 44%. The 3-year local progression-free survival for those who received a high single-dose (24 Gy; n = 45), a low single-dose (<24 Gy; n = 14), or hypofractionation regimens (n = 46) was 88%, 21%, and 17%, respectively (high single dose vs. low single dose, p = .001; high single dose vs. hypofractionation, p < .001). Multivariate analysis revealed the following variables were significant predictors of improved local progression-free survival: 24 Gy dose compared with a lower dose (p = .009) and a single dose vs. hypofractionation (p = .008). Conclusion: High single-dose, image-guided, intensity-modulated radiotherapy is a noninvasive procedure resulting in high probability of local tumor control for metastatic renal cell cancer generally considered radioresistant according to the classic radiobiologic ranking.

  9. Image-Guided Radiotherapy via Daily Online Cone-Beam CT Substantially Reduces Margin Requirements for Stereotactic Lung Radiotherapy

    SciTech Connect

    Grills, Inga S. Hugo, Geoffrey; Kestin, Larry L.; Galerani, Ana Paula; Chao, K. Kenneth; Wloch, Jennifer; Yan Di

    2008-03-15

    Purpose: To determine treatment accuracy and margins for stereotactic lung radiotherapy with and without cone-beam CT (CBCT) image guidance. Methods and Materials: Acquired for the study were 308 CBCT of 24 patients with solitary peripheral lung tumors treated with stereotactic radiotherapy. Patients were immobilized in a stereotactic body frame (SBF) or alpha-cradle and treated with image guidance using daily CBCT. Four (T1) or five (T2/metastatic) 12-Gy fractions were prescribed to the planning target volume (PTV) edge. The PTV margin was {>=}5 mm depending on a pretreatment estimate of tumor excursion. Initial daily setup was according to SBF coordinates or tattoos for alpha-cradle cases. A CBCT was performed and registered to the planning CT using soft tissue registration of the target. The initial setup error/precorrection position, was recorded for the superior-inferior, anterior-posterior, and medial-lateral directions. The couch was adjusted to correct the tumor positional error. A second CBCT verified tumor position after correction. Patients were treated in the corrected position after the residual errors were {<=}2 mm. A final CBCT after treatment assessed intrafraction tumor displacement. Results: The precorrection systematic ({sigma}) and random errors ({sigma}) for the population ranged from 2-3 mm for SBF and 2-6 mm for alpha-cradle patients; postcorrection errors ranged from 0.4-1.0 mm. Calculated population margins were 9 to 13 mm (SBF) and 10-14 mm (cradle) precorrection, 1-2 mm (SBF), and 2-3 mm (cradle) postcorrection, and 2-4 mm (SBF) and 2-5 mm (cradle) posttreatment. Conclusions: Setup for stereotactic lung radiotherapy using a SBF or alpha-cradle alone is suboptimal. CBCT image guidance significantly improves target positioning and substantially reduces required target margins and normal tissue irradiation.

  10. [Small animal image-guided radiotherapy: A new era for preclinical studies].

    PubMed

    Delpon, G; Frelin-Labalme, A-M; Heinrich, S; Beaudouin, V; Noblet, C; Begue, M; Le Deroff, C; Pouzoulet, F; Chiavassa, S

    2016-02-01

    Preclinical external beam radiotherapy irradiations used to be delivered with a static broad beam. To promote the transfer from animal to man, the preclinical treatment techniques dedicated to the animal have been optimized to be similar to those delivered to patients in clinical practice. In this context, preclinical irradiators have been developed. Due to the small sizes of the animals, and the irradiation beams, the scaling to the small animal dimensions involves specific problems. Reducing the size and energy of the irradiation beams require very high technical performance, especially for the mechanical stability of the irradiator and the spatial resolution of the imaging system. In addition, the determination of the reference absorbed dose rate must be conducted with a specific methodology and suitable detectors. To date, three systems are used for preclinical studies in France. The aim of this article is to present these new irradiators dedicated to small animals from a physicist point of view, including the commissioning and the quality control. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  11. [Assessment of overall spatial accuracy in image guided stereotactic body radiotherapy using a spine registration method].

    PubMed

    Nakazawa, Hisato; Uchiyama, Yukio; Komori, Masataka; Hayashi, Naoki

    2014-06-01

    Stereotactic body radiotherapy (SBRT) for lung and liver tumors is always performed under image guidance, a technique used to confirm the accuracy of setup positioning by fusing planning digitally reconstructed radiographs with X-ray, fluoroscopic, or computed tomography (CT) images, using bony structures, tumor shadows, or metallic markers as landmarks. The Japanese SBRT guidelines state that bony spinal structures should be used as the main landmarks for patient setup. In this study, we used the Novalis system as a linear accelerator for SBRT of lung and liver tumors. The current study compared the differences between spine registration and target registration and calculated total spatial accuracy including setup uncertainty derived from our image registration results and the geometric uncertainty of the Novalis system. We were able to evaluate clearly whether overall spatial accuracy is achieved within a setup margin (SM) for planning target volume (PTV) in treatment planning. After being granted approval by the Hospital and University Ethics Committee, we retrospectively analyzed eleven patients with lung tumor and seven patients with liver tumor. The results showed the total spatial accuracy to be within a tolerable range for SM of treatment planning. We therefore regard our method to be suitable for image fusion involving 2-dimensional X-ray images during the treatment planning stage of SBRT for lung and liver tumors.

  12. A rapid and robust iterative closest point algorithm for image guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Barbiere, Joseph; Hanley, Joseph

    2008-03-01

    Our work presents a rapid and robust process that can analytically evaluate and correct patient setup error for head and neck radiotherapy by comparing orthogonal megavoltage portal images with digitally reconstructed radiographs. For robust data Photoshop is used to interactively segment images and registering reference contours to the transformed PI. MatLab is used for matrix computations and image analysis. The closest point distance for each PI point to a DRR point forms a set of homologous points. The translation that aligns the PI to the DRR is equal to the difference in centers of mass. The original PI points are transformed and the process repeated with an Iterative Closest Point algorithm until the transformation change becomes negligible. Using a 3.00 GHz processor the calculation of the 2500x1750 CPD matrix takes about 150 sec per iteration. Standard down sampling to about 1000 DRR and 250 PI points significantly reduces that time. We introduce a local neighborhood matrix consisting of a small subset of the DRR points in the vicinity of each PI point to further reduce the CPD matrix size. Our results demonstrate the effects of down sampling on accuracy. For validation, analytical detailed results are displayed as a histogram.

  13. Optimization and quality assurance of an image-guided radiation therapy system for intensity-modulated radiation therapy radiotherapy.

    PubMed

    Tsai, Jen-San; Micaily, Bizhan; Miyamoto, Curtis

    2012-01-01

    To develop a quality assurance (QA) of XVI cone beam system (XVIcbs) for its optimal imaging-guided radiotherapy (IGRT) implementation, and to construe prostate tumor margin required for intensity-modulated radiation therapy (IMRT) if IGRT is unavailable. XVIcbs spatial accuracy was explored with a humanoid phantom; isodose conformity to lesion target with a rice phantom housing a soap as target; image resolution with a diagnostic phantom; and exposure validation with a Radcal ion chamber. To optimize XVIcbs, rotation flexmap on coincidency between gantry rotational axis and that of XVI cone beam scan was investigated. Theoretic correlation to image quality of XVIcbs rotational axis stability was elaborately studied. Comprehensive QA of IGRT using XVIcbs has initially been explored and then implemented on our general IMRT treatments, and on special IMRT radiotherapies such as head and neck (H and N), stereotactic radiation therapy (SRT), stereotactic radiosurgery (SRS), and stereotactic body radiotherapy (SBRT). Fifteen examples of prostate setup accounted for 350 IGRT cone beam system were analyzed. IGRT accuracy results were in agreement ± 1 mm. Flexmap 0.25 mm met the manufacturer's specification. Films confirmed isodose coincidence with target (soap) via XVIcbs, otherwise not. Superficial doses were measured from 7.2-2.5 cGy for anatomic diameters 15-33 cm, respectively. Image quality was susceptible to rotational stability or patient movement. IGRT using XVIcbs on general IMRT treatments such as prostate, SRT, SRS, and SBRT for setup accuracy were verified; and subsequently coordinate shifts corrections were recorded. The 350 prostate IGRT coordinate shifts modeled to Gaussian distributions show central peaks deviated off the isocenter by 0.6 ± 3.0 mm, 0.5 ± 4.5 mm in the X(RL)- and Z(SI)-coordinates, respectively; and 2.0 ± 3.0 mm in the Y(AP)-coordinate as a result of belly and bladder capacity variations. Sixty-eight percent of confidence was within

  14. Optimization and quality assurance of an image-guided radiation therapy system for intensity-modulated radiation therapy radiotherapy

    SciTech Connect

    Tsai, Jen-San; Micaily, Bizhan; Miyamoto, Curtis

    2012-10-01

    To develop a quality assurance (QA) of XVI cone beam system (XVIcbs) for its optimal imaging-guided radiotherapy (IGRT) implementation, and to construe prostate tumor margin required for intensity-modulated radiation therapy (IMRT) if IGRT is unavailable. XVIcbs spatial accuracy was explored with a humanoid phantom; isodose conformity to lesion target with a rice phantom housing a soap as target; image resolution with a diagnostic phantom; and exposure validation with a Radcal ion chamber. To optimize XVIcbs, rotation flexmap on coincidency between gantry rotational axis and that of XVI cone beam scan was investigated. Theoretic correlation to image quality of XVIcbs rotational axis stability was elaborately studied. Comprehensive QA of IGRT using XVIcbs has initially been explored and then implemented on our general IMRT treatments, and on special IMRT radiotherapies such as head and neck (H and N), stereotactic radiation therapy (SRT), stereotactic radiosurgery (SRS), and stereotactic body radiotherapy (SBRT). Fifteen examples of prostate setup accounted for 350 IGRT cone beam system were analyzed. IGRT accuracy results were in agreement {+-} 1 mm. Flexmap 0.25 mm met the manufacturer's specification. Films confirmed isodose coincidence with target (soap) via XVIcbs, otherwise not. Superficial doses were measured from 7.2-2.5 cGy for anatomic diameters 15-33 cm, respectively. Image quality was susceptible to rotational stability or patient movement. IGRT using XVIcbs on general IMRT treatments such as prostate, SRT, SRS, and SBRT for setup accuracy were verified; and subsequently coordinate shifts corrections were recorded. The 350 prostate IGRT coordinate shifts modeled to Gaussian distributions show central peaks deviated off the isocenter by 0.6 {+-} 3.0 mm, 0.5 {+-} 4.5 mm in the X(RL)- and Z(SI)-coordinates, respectively; and 2.0 {+-} 3.0 mm in the Y(AP)-coordinate as a result of belly and bladder capacity variations. Sixty-eight percent of confidence was

  15. SU-E-J-205: Monte Carlo Modeling of Ultrasound Probes for Real-Time Ultrasound Image-Guided Radiotherapy

    SciTech Connect

    Hristov, D; Schlosser, J; Bazalova, M; Chen, J

    2014-06-01

    Purpose: To quantify the effect of ultrasound (US) probe beam attenuation for radiation therapy delivered under real-time US image guidance by means of Monte Carlo (MC) simulations. Methods: MC models of two Philips US probes, an X6-1 matrix-array transducer and a C5-2 curved-array transducer, were built based on their CT images in the EGSnrc BEAMnrc and DOSXYZnrc codes. Due to the metal parts, the probes were scanned in a Tomotherapy machine with a 3.5 MV beam. Mass densities in the probes were assigned based on an electron density calibration phantom consisting of cylinders with mass densities between 0.2–8.0 g/cm{sup 3}. Beam attenuation due to the probes was measured in a solid water phantom for a 6 MV and 15 MV 15x15 cm{sup 2} beam delivered on a Varian Trilogy linear accelerator. The dose was measured with the PTW-729 ionization chamber array at two depths and compared to MC simulations. The extreme case beam attenuation expected in robotic US image guided radiotherapy for probes in upright position was quantified by means of MC simulations. Results: The 3.5 MV CT number to mass density calibration curve was found to be linear with R{sup 2} > 0.99. The maximum mass densities were 4.6 and 4.2 g/cm{sup 3} in the C5-2 and X6-1 probe, respectively. Gamma analysis of the simulated and measured doses revealed that over 98% of measurement points passed the 3%/3mm criteria for both probes and measurement depths. The extreme attenuation for probes in upright position was found to be 25% and 31% for the C5-2 and X6-1 probe, respectively, for both 6 and 15 MV beams at 10 cm depth. Conclusion: MC models of two US probes used for real-time image guidance during radiotherapy have been built. As a Result, radiotherapy treatment planning with the imaging probes in place can now be performed. J Schlosser is an employee of SoniTrack Systems, Inc. D Hristov has financial interest in SoniTrack Systems, Inc.

  16. Prospective Study of Cone-Beam Computed Tomography Image-Guided Radiotherapy for Prone Accelerated Partial Breast Irradiation

    SciTech Connect

    Jozsef, Gabor; DeWyngaert, J. Keith; Becker, Stewart J.; Lymberis, Stella; Formenti, Silvia C.

    2011-10-01

    Purpose: To report setup variations during prone accelerated partial breast irradiation (APBI). Methods: New York University (NYU) 07-582 is an institutional review board-approved protocol of cone-beam computed tomography (CBCT) to deliver image-guided ABPI in the prone position. Eligible are postmenopausal women with pT1 breast cancer excised with negative margins and no nodal involvement. A total dose of 30 Gy in five daily fractions of 6 Gy are delivered to the planning target volume (the tumor cavity with 1.5-cm margin) by image-guided radiotherapy. Patients are set up prone, on a dedicated mattress, used for both simulation and treatment. After positioning with skin marks and lasers, CBCTs are performed and the images are registered to the planning CT. The resulting shifts (setup corrections) are recorded in the three principal directions and applied. Portal images are taken for verification. If they differ from the planning digital reconstructed radiographs, the patient is reset, and a new CBCT is taken. Results: 70 consecutive patients have undergone a total of 343 CBCTs: 7 patients had four of five planned CBCTs performed. Seven CBCTs (2%) required to be repeated because of misalignment in the comparison between portal and digital reconstructed radiograph image after the first CBCT. The mean shifts and standard deviations in the anterior-posterior (AP), superior-inferior (SI), and medial-lateral (ML) directions were -0.19 (0.54), -0.02 (0.33), and -0.02 (0.43) cm, respectively. The average root mean squares of the daily shifts were 0.50 (0.28), 0.29 (0.17), and 0.38 (0.20). A conservative margin formula resulted in a recommended margin of 1.26, 0.73, 0.96 cm in the AP, SI, and ML directions. Conclusion: CBCTs confirmed that the NYU prone APBI setup and treatment technique are reproducible, with interfraction variation comparable to those reported for supine setup. The currently applied margin (1.5 cm) adequately compensates for the setup variation detected.

  17. Localization Accuracy of the Clinical Target Volume During Image-Guided Radiotherapy of Lung Cancer

    SciTech Connect

    Hugo, Geoffrey D.; Weiss, Elisabeth; Badawi, Ahmed; Orton, Matthew

    2011-10-01

    Purpose: To evaluate the position and shape of the originally defined clinical target volume (CTV) over the treatment course, and to assess the impact of gross tumor volume (GTV)-based online computed tomography (CT) guidance on CTV localization accuracy. Methods and Materials: Weekly breath-hold CT scans were acquired in 17 patients undergoing radiotherapy. Deformable registration was used to propagate the GTV and CTV from the first weekly CT image to all other weekly CT images. The on-treatment CT scans were registered rigidly to the planning CT scan based on the GTV location to simulate online guidance, and residual error in the CTV centroids and borders was calculated. Results: The mean GTV after 5 weeks relative to volume at the beginning of treatment was 77% {+-} 20%, whereas for the prescribed CTV, it was 92% {+-} 10%. The mean absolute residual error magnitude in the CTV centroid position after a GTV-based localization was 2.9 {+-} 3.0 mm, and it varied from 0.3 to 20.0 mm over all patients. Residual error of the CTV centroid was associated with GTV regression and anisotropy of regression during treatment (p = 0.02 and p = 0.03, respectively; Spearman rank correlation). A residual error in CTV border position greater than 2 mm was present in 77% of patients and 50% of fractions. Among these fractions, residual error of the CTV borders was 3.5 {+-} 1.6 mm (left-right), 3.1 {+-} 0.9 mm (anterior-posterior), and 6.4 {+-} 7.5 mm (superior-inferior). Conclusions: Online guidance based on the visible GTV produces substantial error in CTV localization, particularly for highly regressing tumors. The results of this study will be useful in designing margins for CTV localization or for developing new online CTV localization strategies.

  18. Variation of neck position with image-guided radiotherapy for head and neck cancer.

    PubMed

    Ove, Roger; Cavalieri, Ronaldo; Noble, Darin; Russo, Suzanne M

    2012-02-01

    An understanding of the setup variation of the low neck in relation to the upper neck is necessary to define appropriate planning margins, while treating the full neck with intensity-modulated radiotherapy (IMRT) technique. The setup of 20 sequential head and neck cancer patients was studied. Daily position verification was performed with a computed tomography (CT) on rails. An upper neck point was defined as the anterior-most portion of the cervical spine on the lowest CT cut on which both styloid processes are visible. A low neck point was defined as the anterior-most portion of the cervical spine on the lowest CT cut on which the thyroid gland was visible bilaterally. This procedure was carried out on the planning CT and on each daily treatment CT. The variation of the low neck was analyzed, assuming perfect alignment of the upper neck anatomy. Daily treatment CT of upper neck anterior cervical spine points were normalized to the planning CT. Relative to this coordinate system, the low neck cervical spine point was displaced an average of 3.08 mm anteriorly, ±0.17 mm. There was no systematic lateral or craniocaudal displacement. Random setup errors resulted in low neck standard deviations of 3.9 mm (anteroposterior), 3.3 mm (lateral), and 2.6 mm (craniocaudal). Position variation in the low neck varied in excess of the planning margins. There was a systematic anterior displacement. Random setup error was greater than expected. The results suggest that the neck volumes located distant from the region of fusion should be drawn with larger planning margins.

  19. Image-Guided Radiotherapy Using a Modified Industrial Micro-CT for Preclinical Applications

    PubMed Central

    Felix, Manuela C.; Fleckenstein, Jens; Kirschner, Stefanie; Hartmann, Linda; Wenz, Frederik; Brockmann, Marc A.

    2015-01-01

    Purpose/Objective Although radiotherapy is a key component of cancer treatment, its implementation into pre-clinical in vivo models with relatively small target volumes is frequently omitted either due to technical complexity or expected side effects hampering long-term observational studies. We here demonstrate how an affordable industrial micro-CT can be converted into a small animal IGRT device at very low costs. We also demonstrate the proof of principle for the case of partial brain irradiation of mice carrying orthotopic glioblastoma implants. Methods/Materials A commercially available micro-CT originally designed for non-destructive material analysis was used. It consists of a CNC manipulator, a transmission X-ray tube (10–160 kV) and a flat-panel detector, which was used together with custom-made steel collimators (1–5 mm aperture size). For radiation field characterization, an ionization chamber, water-equivalent slab phantoms and radiochromic films were used. A treatment planning tool was implemented using a C++ application. For proof of principle, NOD/SCID/γc−/− mice were orthotopically implanted with U87MG high-grade glioma cells and irradiated using the novel setup. Results The overall symmetry of the radiation field at 150 kV was 1.04±0.02%. The flatness was 4.99±0.63% and the penumbra widths were between 0.14 mm and 0.51 mm. The full width at half maximum (FWHM) ranged from 1.97 to 9.99 mm depending on the collimator aperture size. The dose depth curve along the central axis followed a typical shape of keV photons. Dose rates measured were 10.7 mGy/s in 1 mm and 7.6 mGy/s in 5 mm depth (5 mm collimator aperture size). Treatment of mice with a single dose of 10 Gy was tolerated well and resulted in central tumor necrosis consistent with therapeutic efficacy. Conclusion A conventional industrial micro-CT can be easily modified to allow effective small animal IGRT even of critical target volumes such as the brain. PMID:25993010

  20. Image-Guided Radiotherapy for Left-Sided Breast Cancer Patients: Geometrical Uncertainty of the Heart

    SciTech Connect

    Topolnjak, Rajko; Borst, Gerben R.; Nijkamp, Jasper

    2012-03-15

    Purpose: To quantify the geometrical uncertainties for the heart during radiotherapy treatment of left-sided breast cancer patients and to determine and validate planning organ at risk volume (PRV) margins. Methods and Materials: Twenty-two patients treated in supine position in 28 fractions with regularly acquired cone-beam computed tomography (CBCT) scans for offline setup correction were included. Retrospectively, the CBCT scans were reconstructed into 10-phase respiration correlated four-dimensional scans. The heart was registered in each breathing phase to the planning CT scan to establish the respiratory heart motion during the CBCT scan ({sigma}{sub resp}). The average of the respiratory motion was calculated as the heart displacement error for a fraction. Subsequently, the systematic ({Sigma}), random ({sigma}), and total random ({sigma}{sub tot}={radical}({sigma}{sup 2}+{sigma}{sub resp}{sup 2})) errors of the heart position were calculated. Based on the errors a PRV margin for the heart was calculated to ensure that the maximum heart dose (D{sub max}) is not underestimated in at least 90% of the cases (M{sub heart} = 1.3{Sigma}-0.5{sigma}{sub tot}). All analysis were performed in left-right (LR), craniocaudal (CC), and anteroposterior (AP) directions with respect to both online and offline bony anatomy setup corrections. The PRV margin was validated by accumulating the dose to the heart based on the heart registrations and comparing the planned PRV D{sub max} to the accumulated heart D{sub max}. Results: For online setup correction, the cardiac geometrical uncertainties and PRV margins were N-Ary-Summation = 2.2/3.2/2.1 mm, {sigma} = 2.1/2.9/1.4 mm, and M{sub heart} = 1.6/2.3/1.3 mm for LR/CC/AP, respectively. For offline setup correction these were N-Ary-Summation = 2.4/3.7/2.2 mm, {sigma} = 2.9/4.1/2.7 mm, and M{sub heart} = 1.6/2.1/1.4 mm. Cardiac motion induced by breathing was {sigma}{sub resp} = 1.4/2.9/1.4 mm for LR/CC/AP. The PRV D{sub max

  1. Dosimetric impact of setup errors in head and neck cancer patients treated by image-guided radiotherapy

    PubMed Central

    Kaur, Inderjit; Rawat, Sheh; Ahlawat, Parveen; Kakria, Anjali; Gupta, Gourav; Saxena, Upasna; Mishra, Manindra Bhushan

    2016-01-01

    To assess and analyze the impact of setup uncertainties on target volume coverage and doses to organs at risk (OAR) in head and neck cancer (HNC) patients treated by image-guided radiotherapy (IGRT). Translational setup errors in 25 HNC patients were observed by kilovoltage cone beam computed tomography (kV CBCT). Two plans were generated. Plan one – the original plan which was the initially optimized and approved plan of the patient. All patients were treated according to their respective approved plans at a defined isocenter. Plan two – the plan sum which was the sum of all plans recalculated at a different isocenter according to setup errors in x, y, and z-direction. Plan sum was created to evaluate doses that would have been received by planning target volume (PTV) and OARs if setup errors were not corrected. These 2 plans were analyzed and compared in terms of target volume coverage and doses to OARs. A total 503 kV CBCT images were acquired for evaluation of setup errors in 25 HNC patients. The systematic (mean) and random errors (standard deviation) combined for 25 patients in x, y, and z directions were 0.15 cm, 0.21 cm, and 0.19 cm and 0.09 cm, 0.12 cm, and 0.09 cm, respectively. The study showed that there was a significant difference in PTV coverage between 2 plans. The doses to various OARs showed a nonsignificant increase in the plan sum. The correction of translational setup errors is essential for IGRT treatment in terms of delivery of planned optimal doses to target volume. PMID:27217627

  2. Establishment of linear accelerator-based image guided radiotherapy for orthotopic 4T1 mouse mammary tumor model

    PubMed Central

    Lee, Seung-Heon; Kim, Ji-Young; Nam, Jeong-Seok; Choi, Jinho; Lee, Seok-Ho; Sung, Ki-Hoon; Ahn, So-Hyun

    2014-01-01

    This study was conducted to assess the feasibility of image guided radiotherapy (IGRT) for orthotopic 4T1 mouse mammary tumor using linear accelerator (LINAC). Eighteen Balb/C mice were inoculated with 4T1 cells on left mammary fat pad and nine of them were irradiated using LINAC. Tumors, planning target volumes (PTV), bowels adjacent to tumors, bones and lungs were delineated on planning CT images. IGRT plans were generated to irradiate prescription dose to at least 90% of the PTV and then compared with conventional 2-dimensional plans with anterior-posterior and posterior-anterior beams with 5 mm margins (2D AP/PA plan). Homemade dose-build-up-cradle was designed to encompass mouse bed for homogeneous dose build up. To confirm the irradiated dose, tumor doses were measured using diode detector placed on the surface of tumors. Plan comparison demonstrated equivalent doses to PTV while sparing more doses to normal tissues including bowel (from 90.9% to 40.5%, median value of mean doses) and bone marrow (from 12.9% to 4.7%, median value of mean doses) than 2D AP/PA plan. Quality assurance using diode detector confirmed that IGRT could deliver 95.3-105.3% of the planned doses to PTV. Tumors grew 505.2-1185.8% (mean 873.3%) in the control group and 436.1-771.8% (mean 615.5%) in the irradiated group. These results demonstrate that LINAC-based IGRT provides a reliable approach with accurate dose delivery in the radiobiological study for orthotropic tumor model maintaining tumor microenvironment. PMID:24999360

  3. Predictors of Local Control After Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases

    SciTech Connect

    Greco, Carlo; Zelefsky, Michael J.; Lovelock, Michael; Fuks, Zvi; Hunt, Margie; Rosenzweig, Kenneth; Zatcky, Joan; Kim, Balem; Yamada, Yoshiya

    2011-03-15

    Purpose: To report tumor local control after treatment with single-dose image-guided intensity-modulated radiotherapy (SD-IGRT) to extracranial metastatic sites. Methods and Materials: A total of 126 metastases in 103 patients were treated with SD-IGRT to prescription doses of 18-24 Gy (median, 24 Gy) between 2004 and 2007. Results: The overall actuarial local relapse-free survival (LRFS) rate was 64% at a median follow-up of 18 months (range, 2-45 months). The median time to failure was 9.6 months (range, 1-23 months). On univariate analysis, LRFS was significantly correlated with prescription dose (p = 0.029). Stratification by dose into high (23 to 24 Gy), intermediate (21 to 22 Gy), and low (18 to 20 Gy) dose levels revealed highly significant differences in LRFS between high (82%) and low doses (25%) (p < 0.0001). Overall, histology had no significant effect on LRFS (p = 0.16). Renal cell histology displayed a profound dose-response effect, with 80% LRFS at the high dose level (23 to 24 Gy) vs. 37% with low doses ({<=}22 Gy) (p = 0.04). However, for patients who received the high dose level, histology was not a statistically significant predictor of LRFS (p = 0.90). Target organ (bone vs. lymph node vs. soft tissues) (p = 0.5) and planning target volume size (p = 0.55) were not found to be associated with long-term LRFS probability. Multivariate Cox regression analysis confirmed prescription dose to be a significant predictor of LRFS (p = 0.003). Conclusion: High-dose SD-IGRT is a noninvasive procedure resulting in high probability of local tumor control. Single-dose IGRT may be effectively used to locally control metastatic deposits regardless of histology and target organ, provided sufficiently high doses (> 22 Gy) of radiation are delivered.

  4. SU-D-9A-07: Imaging Dose and Cancer Risk in Image-Guided Radiotherapy of Cancers

    SciTech Connect

    Zhou, L; Bai, S; Zhang, Y; Ming, X; Zhang, Y; Deng, J

    2014-06-01

    Purpose: To systematically evaluate the imaging doses and cancer risks associated with various imaging procedures involving ionizing radiation during image-guided radiotherapy of an increasingly large number of cancer patients. Methods: 141 patients (52 brain cases, 47 thoracic cases, 42 abdominal cases, aged 3 to 91 years old) treated between October 2009 and March 2010 were included in this IRB-approved retrospective study. During the whole radiotherapy course, each patient underwent at least one type of imaging procedures, i.e., kV portal, MV portal and kVCBCT, besides CT simulations. Based on Monte Carlo modeling and particle transport in human anatomy of various dimensions, the correlations between the radiation doses to the various organs-at-risk (OARs) at the head, the thoracic and the abdominal regions and one's weight, circumference, scan mAs and kVp have been obtained and used to estimate the radiation dose from a specific imaging procedure. The radiation-induced excess relative risk (ERR) was then estimated with BEIR VII formulism based on one's gender, age and radiation dose. 1+ ERR was reported in this study as relative cancer risk. Results: For the whole cohort of 141 patients, the mean imaging doses from various imaging procedures were 8.3 cGy to the brain, 10.5 cGy to the lungs and 19.2 cGy to the red bone marrow, respectively. Accordingly, the cancer risks were 1.140, 1.369 and 2.671, respectively. In comparison, MV portal deposited largest doses to the lungs while kVCBCT delivered the highest doses to the red bone marrow. Conclusion: The compiled imaging doses to a patient during his/her treatment course were patient-specific and site-dependent, varying from 1.2 to 263.5 cGy on average, which were clinically significant and should be included in the treatment planning and overall decision-making. Our results indicated the necessity of personalized imaging to maximize its clinical benefits while reducing the associated cancer risks. Sichuan

  5. SU-E-J-144: MRI Visualization of a Metallic Fiducial Marker Used for Image Guided Prostate Radiotherapy

    SciTech Connect

    Yee, S; Krauss, D; Yan, D

    2014-06-01

    Purpose: Unlike on the daily CBCT used for the image-guided radiation therapy, the visualization of an implantable metallic fiducial marker on the planning MRI images has been a challenge due to the inherent insensitivity of metal in MRI, and very thin (∼ 1 mm or less) diameter. Here, an MRI technique to visualize a marker used for prostate cancer radiotherapy is reported. Methods: During the MRI acquisitions, a multi-shot turbo spin echo (TSE) technique (TR=3500 ms, TE=8.6 ms, ETL=17, recon voxel=0.42x0.42x3.5 mm3) was acquired in Philips 3T Ingenia together with a T2-weighted multi-shot TSE (TR=5381 ms, TE=110 ms, ETL=17, recon voxel=0.47×0.47×3 mm3) and a balanced turbo field echo (bTFE, flip angle 60, TR=2.76 ms, TE=1.3 ms, 0.85×0.85×3 mm3, NSA=4). In acquiring the MRI to visualize the fiducial marker, a particular emphasis was made to improve the spatial resolution and visibility in the generally dark, inhomogeneous prostate area by adjusting the slice profile ordering and TE values of TSE acquisition (in general, the lower value of TE in TSE acquisition generates a brighter signal but at the cost of high spatial resolution since the k-space, responsible for high spatial resolution, is filled with noisier data). Results: While clearly visible in CT, the marker was not visible in either T2-weighted TSE or bTFE, although the image qualities of both images were superior. In the new TSE acquisition (∼ a proton-density weighted image) adjusted by changing the profile ordering and the TE value, the marker was visible as a negative (but clear) contrast in the magnitude MRI, and as a positive contrast in the imaginary image of the phase-sensitive MRI. Conclusion: A metallic fiducial marker used for image guidance before prostate cancer radiotherapy can be made visible in MRI, which may facilitate more use of MRI in planning and guiding such radiation therapy.

  6. [Image-guided radiotherapy].

    PubMed

    de Crevoisier, R; Chauvet, B; Barillot, I; Lafond, C; Mahé, M; Delpon, G

    2016-09-01

    The IGRT is described in its various equipment and implementation. IGRT can be based either on ionizing radiation generating 2D imaging (MV or kV) or 3D imaging (CBCT or MV-CT) or on non-ionizing radiation (ultrasound, optical imaging, MRI or radiofrequency). Adaptive radiation therapy is then presented in its principles of implementation. The function of the technicians for IGRT is then presented and the possible dose delivered by the on-board imaging is discussed. The quality control of IGRT devices is finally described.

  7. SU-E-J-10: Imaging Dose and Cancer Risk in Image-Guided Radiotherapy of Cancers

    SciTech Connect

    Zhou, L; Bai, S; Zhang, Y; Deng, J

    2015-06-15

    Purpose: To systematically evaluate imaging doses and cancer risks to organs-at-risk as a Result of cumulative doses from various radiological imaging procedures in image-guided radiotherapy (IGRT) in a large cohort of cancer patients. Methods: With IRB approval, imaging procedures (computed tomography, kilo-voltage portal imaging, megavoltage portal imaging and kilo-voltage cone-beam computed tomography) of 4832 cancer patients treated during 4.5 years were collected with their gender, age and circumference. Correlations between patient’s circumference and Monte Carlo simulated-organ dose were applied to estimate organ doses while the cancer risks were reported as 1+ERR using BEIR VII models. Results: 80 cGy or more doses were deposited to brain, lungs and RBM in 273 patients (maximum 136, 278 and 267 cGy, respectively), due largely to repetitive imaging procedures and non-personalized imaging settings. Regardless of gender, relative cancer risk estimates for brain, lungs, and RBM were 3.4 (n = 55), 2.6 (n = 49), 1.8 (n = 25) for age group of 0–19; 1.2 (n = 87), 1.4 (n = 98), 1.3 (n = 51) for age group of 20–39; 1.0 (n = 457), 1.1 (n = 880), 1.8 (n=360) for age group of 40–59; 1.0 (n = 646), 1.1 (n = 1400), 2.3 (n = 716) for age group of 60–79 and 1.0 (n = 108),1.1 (n = 305),1.6 (n = 147) for age group of 80–99. Conclusion: The cumulative imaging doses and associated cancer risks from multi-imaging procedures were patient-specific and site-dependent, with up to 2.7 Gy imaging dose deposited to critical structures in some pediatric patients. The associated cancer risks in brain and lungs for children of age 0 to 19 were 2–3 times larger than those for adults. This study indicated a pressing need for personalized imaging protocol to maximize its clinical benefits while reducing associated cancer risks. Sichuan University Scholarship.

  8. Personalized Assessment of kV Cone Beam Computed Tomography Doses in Image-guided Radiotherapy of Pediatric Cancer Patients

    SciTech Connect

    Zhang Yibao; Yan Yulong; Nath, Ravinder; Bao Shanglian; Deng Jun

    2012-08-01

    Purpose: To develop a quantitative method for the estimation of kV cone beam computed tomography (kVCBCT) doses in pediatric patients undergoing image-guided radiotherapy. Methods and Materials: Forty-two children were retrospectively analyzed in subgroups of different scanned regions: one group in the head-and-neck and the other group in the pelvis. Critical structures in planning CT images were delineated on an Eclipse treatment planning system before being converted into CT phantoms for Monte Carlo simulations. A benchmarked EGS4 Monte Carlo code was used to calculate three-dimensional dose distributions of kVCBCT scans with full-fan high-quality head or half-fan pelvis protocols predefined by the manufacturer. Based on planning CT images and structures exported in DICOM RT format, occipital-frontal circumferences (OFC) were calculated for head-and-neck patients using DICOMan software. Similarly, hip circumferences (HIP) were acquired for the pelvic group. Correlations between mean organ doses and age, weight, OFC, and HIP values were analyzed with SigmaPlot software suite, where regression performances were analyzed with relative dose differences (RDD) and coefficients of determination (R{sup 2}). Results: kVCBCT-contributed mean doses to all critical structures decreased monotonically with studied parameters, with a steeper decrease in the pelvis than in the head. Empirical functions have been developed for a dose estimation of the major organs at risk in the head and pelvis, respectively. If evaluated with physical parameters other than age, a mean RDD of up to 7.9% was observed for all the structures in our population of 42 patients. Conclusions: kVCBCT doses are highly correlated with patient size. According to this study, weight can be used as a primary index for dose assessment in both head and pelvis scans, while OFC and HIP may serve as secondary indices for dose estimation in corresponding regions. With the proposed empirical functions, it is possible

  9. Patient-Specific Three-Dimensional Concomitant Dose From Cone Beam Computed Tomography Exposure in Image-Guided Radiotherapy

    SciTech Connect

    Spezi, Emiliano; Downes, Patrick; Jarvis, Richard; Radu, Emil; Staffurth, John

    2012-05-01

    Purpose: The purpose of the present study was to quantify the concomitant dose received by patients undergoing cone beam computed tomography (CBCT) scanning in different clinical scenarios as a part of image-guided radiotherapy (IGRT) procedures. Methods and Materials: We calculated the three-dimensional concomitant dose received as a result of CBCT scans in 6 patients representing different clinical scenarios: two pelvis, two head and neck, and two chest. We assessed the effect that a daily on-line IGRT strategy would have on the patient dose distribution, assuming 40 CBCT scans throughout the treatment course. The additional dose to the planning target volume margin region was also estimated. Results: In the pelvis, a single CBCT scan delivered a mean dose to the femoral heads of 2-6 cGy and the rectum of 1-2 cGy. An additional dose to the planning target volume was within 1-3 cGy. In the chest, the mean dose to the planning target volume varied from 2.5 to 5 cGy. The lung and spinal cord planning organ at risk volume received {<=}4 cGy and {<=}5 cGy, respectively. In the head and neck, a single CBCT scan delivered a mean dose of 0.3 cGy, with bony structures receiving 0.5-0.8 cGy. The femoral heads received an additional dose of 1.5-2.5 Gy. A reduction of 20-30% in the mean dose to the organs at risk was achieved using bowtie filtration. In the head and neck, the dose to the eyes and brainstem was eliminated by decreasing the craniocaudal field size. Conclusions: The additional dose from on-line IGRT procedures can be clinically relevant. The organ dose can be significantly reduced with the use of appropriate patient-specific settings. The concomitant dose from CBCT should be accounted for and the acquisition settings optimized for optimal IGRT strategies on a patient basis.

  10. Dose-Escalated Robotic SBRT for Stage I-II Prostate Cancer.

    PubMed

    Meier, Robert

    2015-01-01

    Stereotactic body radiotherapy (SBRT) is the precise external delivery of very high-dose radiotherapy to targets in the body, with treatment completed in one to five fractions. SBRT should be an ideal approach for organ-confined prostate cancer because (I) dose-escalation should yield improved rates of cancer control; (II) the unique radiobiology of prostate cancer favors hypofractionation; and (III) the conformal nature of SBRT minimizes high-dose radiation delivery to immediately adjacent organs, potentially reducing complications. This approach is also more convenient for patients, and is cheaper than intensity-modulated radiotherapy (IMRT). Several external beam platforms are capable of delivering SBRT for early-stage prostate cancer, although most of the mature reported series have employed a robotic non-coplanar platform (i.e., CyberKnife). Several large studies report 5-year biochemical relapse rates which compare favorably to IMRT. Rates of late GU toxicity are similar to those seen with IMRT, and rates of late rectal toxicity may be less than with IMRT and low-dose rate brachytherapy. Patient-reported quality of life (QOL) outcomes appear similar to IMRT in the urinary domain. Bowel QOL may be less adversely affected by SBRT than with other radiation modalities. After 5 years of follow-up, SBRT delivered on a robotic platform is yielding outcomes at least as favorable as IMRT, and may be considered appropriate therapy for stage I-II prostate cancer.

  11. Dose-Escalated Robotic SBRT for Stage I–II Prostate Cancer

    PubMed Central

    Meier, Robert

    2015-01-01

    Stereotactic body radiotherapy (SBRT) is the precise external delivery of very high-dose radiotherapy to targets in the body, with treatment completed in one to five fractions. SBRT should be an ideal approach for organ-confined prostate cancer because (I) dose-escalation should yield improved rates of cancer control; (II) the unique radiobiology of prostate cancer favors hypofractionation; and (III) the conformal nature of SBRT minimizes high-dose radiation delivery to immediately adjacent organs, potentially reducing complications. This approach is also more convenient for patients, and is cheaper than intensity-modulated radiotherapy (IMRT). Several external beam platforms are capable of delivering SBRT for early-stage prostate cancer, although most of the mature reported series have employed a robotic non-coplanar platform (i.e., CyberKnife). Several large studies report 5-year biochemical relapse rates which compare favorably to IMRT. Rates of late GU toxicity are similar to those seen with IMRT, and rates of late rectal toxicity may be less than with IMRT and low-dose rate brachytherapy. Patient-reported quality of life (QOL) outcomes appear similar to IMRT in the urinary domain. Bowel QOL may be less adversely affected by SBRT than with other radiation modalities. After 5 years of follow-up, SBRT delivered on a robotic platform is yielding outcomes at least as favorable as IMRT, and may be considered appropriate therapy for stage I–II prostate cancer. PMID:25905037

  12. [Comparison of vacuum bag fixation and Orfit rack with thermoplastic membrane fixation for image-guided cervical cancer radiotherapy].

    PubMed

    Li, Y B; Wang, Y L; Zhuo, Y H

    2017-06-23

    the vacuum bag fixation and the Orfit rack with thermoplastic membrane fixation are suitable for the cone-beam CT image-guided radiotherapy of cervical cancer patients. However, the displacement in the left and right directions of the vacuum bag fixation is smaller than the Orfit rack with thermoplastic membrane fixation. During the period of treatment, the mean value of the difference of displacement in the anterior and posterior directions of the Orfit rack with thermoplastic membrane fixation is mild, which can be used individually by the patients with a flexible body and good tolerance.

  13. Dose escalation studies with caspofungin against Candida glabrata.

    PubMed

    Domán, Marianna; Kovács, Renátó; Perlin, David S; Kardos, Gábor; Gesztelyi, Rudolf; Juhász, Béla; Bozó, Aliz; Majoros, László

    2015-09-01

    Echinocandins are recommended as first-line agents against invasive fungal infections caused by Candida glabrata, which still carry a high mortality rate. Dose escalation of echinocandins has been suggested to improve the clinical outcome against C. glabrata. To address this possibility, we performed in vitro and in vivo experiments with caspofungin against four WT C. glabrata clinical isolates, a drug-susceptible ATCC 90030 reference strain and two echinocandin-resistant strains with known FKS mutations. MIC values for the clinical isolates in RPMI 1640 were ≤ 0.03 mg l(-1 ) but increased to 0.125-0.25 mg l(-1 )in RPMI 1640+50% serum. In RPMI 1640+50% serum, the replication of C. glabrata was weaker than in RPMI 1640.Caspofungin in RPMI 1640 at 1 and 4 mg l(-1) showed a fungicidal effect within 7 h against three of the four clinical isolates but was only fungistatic at 16 and 32 mg l(-1) (paradoxically decreased killing activity). In RPMI 1640+50% serum, caspofungin at ≥ 1 mg l(-1) was rapidly fungicidal (within 3.31 h) against three of the four isolates. In a profoundly neutropenic murine model, all caspofungin doses (1, 2, 3, 5 and 20 mg kg(-1) daily) decreased the fungal tissue burdens significantly (P < 0.05-0.001) without statistical differences between doses, but the mean fungal tissue burdens never fell below 105 cells (g tissue)(-1). The echinocandin-resistant strains were highly virulent in animal models and all doses were ineffective. These results confirm the clinical experience that caspofungin dose escalation does not improve efficacy.

  14. Increasing Use of Dose-Escalated External Beam Radiation Therapy for Men With Nonmetastatic Prostate Cancer

    SciTech Connect

    Swisher-McClure, Samuel; Mitra, Nandita; Woo, Kaitlin; Smaldone, Marc; Uzzo, Robert; Bekelman, Justin E.

    2014-05-01

    Purpose: To examine recent practice patterns, using a large national cancer registry, to understand the extent to which dose-escalated external beam radiation therapy (EBRT) has been incorporated into routine clinical practice for men with prostate cancer. Methods and Materials: We conducted a retrospective observational cohort study using the National Cancer Data Base, a nationwide oncology outcomes database in the United States. We identified 98,755 men diagnosed with nonmetastatic prostate cancer between 2006 and 2011 who received definitive EBRT and classified patients into National Comprehensive Cancer Network (NCCN) risk groups. We defined dose-escalated EBRT as total prescribed dose of ≥75.6 Gy. Using multivariable logistic regression, we examined the association of patient, clinical, and demographic characteristics with the use of dose-escalated EBRT. Results: Overall, 81.6% of men received dose-escalated EBRT during the study period. The use of dose-escalated EBRT did not vary substantially by NCCN risk group. Use of dose-escalated EBRT increased from 70.7% of patients receiving treatment in 2006 to 89.8% of patients receiving treatment in 2011. On multivariable analysis, year of diagnosis and use of intensity modulated radiation therapy were significantly associated with receipt of dose-escalated EBRT. Conclusions: Our study results indicate that dose-escalated EBRT has been widely adopted by radiation oncologists treating prostate cancer in the United States. The proportion of patients receiving dose-escalated EBRT increased nearly 20% between 2006 and 2011. We observed high utilization rates of dose-escalated EBRT within all disease risk groups. Adoption of intensity modulated radiation therapy was strongly associated with use of dose-escalated treatment.

  15. [Patient positioning using in-room kV CT for image-guided radiotherapy (IGRT) of prostate cancer].

    PubMed

    Kliton, Jorgo; Agoston, Péter; Major, Tibor; Polgár, Csaba

    2012-09-01

    automatic and manual image registrations were 0.31 cm and 0.26 cm in LAT, 0.27 cm and 0.27 cm in LONG and 0.24 cm and 0.33 cm in VERT directions, respectively. In case of manual image co-registration, the required PTV to CTV margins to cover at least 95% of the CTVs with at least 95% percent of the prescribed dose were calculated to 0.93 cm in LAT, 0.65 cm in LONG, and 0.89 cm in VERT directions. Patients set up can be verified with manual image co-registration based on soft tissues around the prostate using a kV CT-on-rails system installed in the treatment room. The difference between automatic and manual image co-registration was significant in LAT direction. A PTV to CTV margin <1 cm seems to be appropriate to cover the CTVs in image-guided prostate radiotherapy. These findings support our recent clinical protocol.

  16. Evaluations of an adaptive planning technique incorporating dose feedback in image-guided radiotherapy of prostate cancer

    SciTech Connect

    Liu Han; Wu Qiuwen

    2011-12-15

    treatment course, then 11 patients fail. If the same criteria is assessed at the end of each week (every five fractions), then 14 patients fail, with three patients failing the 1st or 2nd week but passing at the end. The average dose deficit from these 14 patients was 4.4%. They improved to 2% after the weekly compensation. Out of these 14 patients who needed dose compensation, ten passed the dose criterion after weekly dose compensation, three patients failed marginally, and one patient still failed the criterion significantly (10% deficit), representing 3.6% of the patient population. A more aggressive compensation frequency (every three fractions) could successfully reduce the dose deficit to the acceptable level for this patient. The average number of required dose compensation re-planning per patient was 0.82 (0.79) per patient for schedule A (B) delivery strategy. The doses to OARs were not significantly different from the online IG only plans without dose compensation. Conclusions: We have demonstrated the effectiveness of offline dose compensation technique in image-guided radiotherapy for prostate cancer. It can effectively account for residual uncertainties which cannot be corrected through online IG. Dose compensation allows further margin reduction and critical organs sparing.

  17. Dose Escalation for Metastatic Spinal Cord Compression in Patients With Relatively Radioresistant Tumors

    SciTech Connect

    Rades, Dirk; Freundt, Katja; Meyners, Thekla; Bajrovic, Amira; Basic, Hiba; Karstens, Johann H.; Adamietz, Irenaeus A.; Wildfang, Ingeborg; Rudat, Volker; Schild, Steven E.; Dunst, Juergen

    2011-08-01

    Purpose: Radiotherapy alone is the most common treatment for metastatic spinal cord compression (MSCC) from relatively radioresistant tumors such as renal cell carcinoma, colorectal cancer, and malignant melanoma. However, the results of the 'standard' regimen 30 Gy/10 fractions need to be improved with respect to functional outcome. This study investigated whether a dose escalation beyond 30 Gy can improve treatment outcomes. Methods and Materials: A total of 91 patients receiving 30 Gy/10 fractions were retrospectively compared to 115 patients receiving higher doses (37.5 Gy/15 fractions, 40 Gy/20 fractions) for motor function and local control of MSCC. Ten further potential prognostic factors were evaluated: age, gender, tumor type, performance status, number of involved vertebrae, visceral or other bone metastases, interval from tumor diagnosis to radiotherapy, pretreatment ambulatory status, and time developing motor deficits before radiotherapy. Results: Motor function improved in 18% of patients after 30 Gy and in 22% after higher doses (p = 0.81). On multivariate analysis, functional outcome was associated with visceral metastases (p = 0.030), interval from tumor diagnosis to radiotherapy (p = 0.010), and time developing motor deficits (p < 0.001). The 1-year local control rates were 76% after 30 Gy and 80% after higher doses, respectively (p = 0.64). On multivariate analysis, local control was significantly associated with visceral metastases (p = 0.029) and number of involved vertebrae (p = 0.043). Conclusions: Given the limitations of a retrospective study, escalation of the radiation dose beyond 30 Gy/10 fractions did not significantly improve motor function and local control of MSCC in patients with relatively radioresistant tumors.

  18. Comparison of Effects Between Central and Peripheral Stage I Lung Cancer Using Image-Guided Stereotactic Body Radiotherapy via Helical Tomotherapy.

    PubMed

    He, Jian; Huang, Yan; Shi, Shiming; Hu, Yong; Zeng, Zhaochong

    2015-12-01

    Lung cancer is a common malignant tumor with high morbidity and mortality. Here we compared the effects and outcome between central and peripheral stage I lung cancer using image-guided stereotactic body radiotherapy. From June 2011 to July 2013, a total of 33 patients with stage I lung cancer were enrolled. A total of 50 Gy in 10 fractions or 60 Gy in 10 fractions was delivered in the central arm (n = 18), while 50 Gy in 5 fractions in the peripheral arm (n = 15). Statistical analyses were performed using logistic regression analysis and Kaplan-Meier method. The mean follow-up time was 38.1 months. Three-month, 1-, 2-, and 3-year overall response rates were 66.7%, 83.3%, 61.1%, and 72.2% and 66.7%, 80%, 80%, and 80% in the central and peripheral arms, respectively. Three-year local control rates (94.4% vs 93.3%, P = .854), regional control rates (94.4% vs 86.7%, P = .412), and distant control rates (64.2% vs 61.7%, P = .509) had no differences between the central and the peripheral arms. Grade 2 radiation pneumonitis was observed in 6 of 18 patients in the central arm and in 1 of 15 patients in the peripheral arm (P = .92). Grade 2 radiation esophagitis was 5.7% in the central arm, while none occurred in the peripheral arm (P = .008). Five (15.1%) of all patients felt slight fatigue during radiotherapy. Other major complications were not observed. In conclusion, helical image-guided stereotactic body radiotherapy for central stage I lung cancer is safe and effective compared to peripheral stage I lung cancer.

  19. A Phase I Dose Escalation Study of Hypofractionated IMRT Field-in-Field Boost for Newly Diagnosed Glioblastoma Multiforme

    SciTech Connect

    Monjazeb, Arta M.; Ayala, Deandra; Jensen, Courtney; Case, L. Douglas; Bourland, J. Daniel; Ellis, Thomas L.; McMullen, Kevin P.; Chan, Michael D.; Tatter, Stephen B.; Lesser, Glen J.; Shaw, Edward G.

    2012-02-01

    Objectives: To describe the results of a Phase I dose escalation trial for newly diagnosed glioblastoma multiforme (GBM) using a hypofractionated concurrent intensity-modulated radiotherapy (IMRT) boost. Methods: Twenty-one patients were enrolled between April 1999 and August 2003. Radiotherapy consisted of daily fractions of 1.8 Gy with a concurrent boost of 0.7 Gy (total 2.5 Gy daily) to a total dose of 70, 75, or 80 Gy. Concurrent chemotherapy was not permitted. Seven patients were enrolled at each dose and dose limiting toxicities were defined as irreversible Grade 3 or any Grade 4-5 acute neurotoxicity attributable to radiotherapy. Results: All patients experienced Grade 1 or 2 acute toxicities. Acutely, 8 patients experienced Grade 3 and 1 patient experienced Grade 3 and 4 toxicities. Of these, only two reversible cases of otitis media were attributable to radiotherapy. No dose-limiting toxicities were encountered. Only 2 patients experienced Grade 3 delayed toxicity and there was no delayed Grade 4 toxicity. Eleven patients requiring repeat resection or biopsy were found to have viable tumor and radiation changes with no cases of radionecrosis alone. Median overall and progression-free survival for this cohort were 13.6 and 6.5 months, respectively. One- and 2-year survival rates were 57% and 19%. At recurrence, 15 patients received chemotherapy, 9 underwent resection, and 5 received radiotherapy. Conclusions: Using a hypofractionated concurrent IMRT boost, we were able to safely treat patients to 80 Gy without any dose-limiting toxicity. Given that local failure still remains the predominant pattern for GBM patients, a trial of dose escalation with IMRT and temozolomide is warranted.

  20. Dosimetric evaluation of the OneDose MOSFET for measuring kilovoltage imaging dose from image-guided radiotherapy procedures

    SciTech Connect

    Ding, George X.; Coffey, Charles W.

    2010-09-15

    Purpose: The purpose of this study is to investigate the feasibility of using a single-use dosimeter, OneDose MOSFET designed for in vivo patient dosimetry, for measuring the radiation dose from kilovoltage (kV) x rays resulting from image-guided procedures. Methods: The OneDose MOSFET dosimeters were precalibrated by the manufacturer using Co-60 beams. Their energy response and characteristics for kV x rays were investigated by using an ionization chamber, in which the air-kerma calibration factors were obtained from an Accredited Dosimetry Calibration Laboratory (ADCL). The dosimetric properties have been tested for typical kV beams used in image-guided radiation therapy (IGRT). Results: The direct dose reading from the OneDose system needs to be multiplied by a correction factor ranging from 0.30 to 0.35 for kilovoltage x rays ranging from 50 to 125 kVp, respectively. In addition to energy response, the OneDose dosimeter has up to a 20% reduced sensitivity for beams (70-125 kVp) incident from the back of the OneDose detector. Conclusions: The uncertainty in measuring dose resulting from a kilovoltage beam used in IGRT is approximately 20%; this uncertainty is mainly due to the sensitivity dependence of the incident beam direction relative to the OneDose detector. The ease of use may allow the dosimeter to be suitable for estimating the dose resulting from image-guided procedures.

  1. Squamous-cell carcinoma of the anus: progress in radiotherapy treatment.

    PubMed

    Glynne-Jones, Rob; Tan, David; Hughes, Robert; Hoskin, Peter

    2016-07-01

    Chemoradiotherapy is the standard-of-care treatment of squamous-cell carcinoma of the anus (SCCA), and this has not changed in decades. Radiation doses of 50-60 Gy, as used in many phase III trials, result in substantial late morbidities and fail to control larger and node-positive tumours. Technological advances in radiation therapy are improving patient outcomes and quality of life, and should be applied to patients with SCCA. Modern techniques such as intensity-modulated radiotherapy (IMRT), rotational IMRT, image-guided radiotherapy using cone-beam CT, and stereotactic techniques have enabled smaller margins and highly conformal plans, resulting in decreased radiation doses to the organs at risk and ensuring a shorter overall treatment time. In this Perspectives article, the use of novel approaches to target delineation, optimized radiotherapy techniques, adaptive radiotherapy, dose-escalation with external-beam radiotherapy (EBRT) or brachytherapy, and the potential for modified fractionation are discussed in the context of SCCA.

  2. Prostate Dose Escalation by Innovative Inverse Planning-Driven IMRT

    DTIC Science & Technology

    2006-11-01

    be correlated with internal anatomy motion. Fluoroscopy and the cine model electronic-portal-imaging device (a) (EPID) have been proposed as a means...institutions). Fast- cine MRI is ical and planning target volume (CTV and PTV, respec- also becoming increasingly available and may offer phy- tively...utilizes high-frequency (I - 10 Image-guided radiation therapy 0 L. XING et al. 93 Fig. I. Cine MR images at inhale and exhale phases for a liver cancer

  3. Decision regret in men undergoing dose-escalated radiation therapy for prostate cancer.

    PubMed

    Steer, Anna N; Aherne, Noel J; Gorzynska, Karen; Hoffman, Matthew; Last, Andrew; Hill, Jacques; Shakespeare, Thomas P

    2013-07-15

    Decision regret (DR) is a negative emotion associated with medical treatment decisions, and it is an important patient-centered outcome after therapy for localized prostate cancer. DR has been found to occur in up to 53% of patients treated for localized prostate cancer, and it may vary depending on treatment modality. DR after modern dose-escalated radiation therapy (DE-RT) has not been investigated previously, to our knowledge. Our primary aim was to evaluate DR in a cohort of patients treated with DE-RT. We surveyed 257 consecutive patients with localized prostate cancer who had previously received DE-RT, by means of a validated questionnaire. There were 220 responses (85.6% response rate). Image-guided intensity modulated radiation therapy was given in 85.0% of patients and 3-dimensional conformal radiation therapy in 15.0%. Doses received included 73.8 Gy (34.5% patients), 74 Gy (53.6%), and 76 Gy (10.9%). Neoadjuvant androgen deprivation (AD) was given in 51.8% of patients and both neoadjuvant and adjuvant AD in 34.5%. The median follow-up time was 23 months (range, 12-67 months). In all, 3.8% of patients expressed DR for their choice of treatment. When asked whether they would choose DE-RT or AD again, only 0.5% probably or definitely would not choose DE-RT again, compared with 8.4% for AD (P<.01). Few patients treated with modern DE-RT express DR, with regret appearing to be lower than in previously published reports of patients treated with radical prostatectomy or older radiation therapy techniques. Patients experienced more regret with the AD component of treatment than with the radiation therapy component, with implications for informed consent. Further research should investigate regret associated with individual components of modern therapy, including AD, radiation therapy and surgery. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  4. Decision Regret in Men Undergoing Dose-Escalated Radiation Therapy for Prostate Cancer

    SciTech Connect

    Steer, Anna N.; Aherne, Noel J.; Gorzynska, Karen; Hoffman, Matthew; Last, Andrew; Hill, Jacques; Shakespeare, Thomas P.

    2013-07-15

    Purpose: Decision regret (DR) is a negative emotion associated with medical treatment decisions, and it is an important patient-centered outcome after therapy for localized prostate cancer. DR has been found to occur in up to 53% of patients treated for localized prostate cancer, and it may vary depending on treatment modality. DR after modern dose-escalated radiation therapy (DE-RT) has not been investigated previously, to our knowledge. Our primary aim was to evaluate DR in a cohort of patients treated with DE-RT. Methods and Materials: We surveyed 257 consecutive patients with localized prostate cancer who had previously received DE-RT, by means of a validated questionnaire. Results: There were 220 responses (85.6% response rate). Image-guided intensity modulated radiation therapy was given in 85.0% of patients and 3-dimensional conformal radiation therapy in 15.0%. Doses received included 73.8 Gy (34.5% patients), 74 Gy (53.6%), and 76 Gy (10.9%). Neoadjuvant androgen deprivation (AD) was given in 51.8% of patients and both neoadjuvant and adjuvant AD in 34.5%. The median follow-up time was 23 months (range, 12-67 months). In all, 3.8% of patients expressed DR for their choice of treatment. When asked whether they would choose DE-RT or AD again, only 0.5% probably or definitely would not choose DE-RT again, compared with 8.4% for AD (P<.01). Conclusion: Few patients treated with modern DE-RT express DR, with regret appearing to be lower than in previously published reports of patients treated with radical prostatectomy or older radiation therapy techniques. Patients experienced more regret with the AD component of treatment than with the radiation therapy component, with implications for informed consent. Further research should investigate regret associated with individual components of modern therapy, including AD, radiation therapy and surgery.

  5. Dose-escalated radiation therapy is associated with better overall survival in patients with bone metastases from solid tumors: a propensity score-matched study.

    PubMed

    Chou, Yung-Chih; Lin, Chien-Yu; Pai, Ping-Ching; Tseng, Chen-Kan; Hsieh, Cheng-En; Chang, Kai-Ping; Hsu, Cheng-Lung; Liao, Chun-Ta; Wang, Chun-Chieh; Chin, Shy-Chyi; Yen, Tzu-Chen; Ho, Tsung-Ying; Hong, Ji-Hong; Lei, Kin-Fong; Chang, Joseph Tung-Chieh; Tsang, Ngan-Ming

    2017-09-01

    We aimed to compare the overall survival (OS) of patients with bone metastases (BM) from solid tumors after standard-dose radiotherapy ([RT]; 30 Gy administered in 10 fractions; EQD2Gy  = 32.5 Gy) and dose-escalated RT (EQD2Gy  > 32.5 Gy). We retrospectively reviewed the clinical charts of 1795 patients (median age, 62.3 years; age range, 18-96 years) with BM from solid tumors who were referred for RT to our institute between 2000 and 2013. These patients were assigned to the standard-dose (n = 1125; 63%) and dose-escalated (n = 670; 37%) RT groups. OS, estimated as the duration between the first RT session and death, served as the main outcome measure. The dose-escalated RT group had a significantly better OS than the standard-dose RT group (P = 0.000). After allowing potential confounders in multivariate analysis, the RT dose retained its independent association with OS (hazard ratio [HR], 0.837; 95% confidence interval [CI], 0.753-0.929, P = 0.001). After propensity score matching of the baseline characteristics of both groups, RT dose retained its independent association with OS (HR, 0.887; 95% CI, 0.737-0.951; P = 0.011) on multivariate analysis. Dose-escalated RT exerted more favorable effects on OS in patients with non-lung cancer, those without multiple metastases, those without symptoms, and those with favorable prognosis. Dose-escalated RT was significantly associated with better OS in patients with BM from solid malignancies, particularly among those with non-lung cancer, those without multiple metastases, those without symptoms, and those with favorable prognosis. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  6. Can we avoid dose escalation for intermediate-risk prostate cancer in the setting of short-course neoadjuvant androgen deprivation?

    PubMed

    Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

    2016-01-01

    Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve the outcomes in patients with intermediate-risk prostate cancer. Despite this, there are only few reports evaluating DE-EBRT for patients with intermediate-risk prostate cancer receiving neoadjuvant ADT, and virtually no studies investigating dose escalation >74 Gy in this setting. We aimed to determine whether DE-EBRT >74 Gy improved the outcomes for patients with intermediate-risk prostate cancer who received neoadjuvant ADT. In our institution, patients with intermediate-risk prostate cancer were treated with neoadjuvant ADT and DE-EBRT, with doses sequentially increasing from 74 Gy to 76 Gy and then to 78 Gy between 2006 and 2012. We identified 435 patients treated with DE-EBRT and ADT, with a median follow-up of 70 months. For the 74 Gy, 76 Gy, and 78 Gy groups, five-year biochemical disease-free survival rates were 95.0%, 97.8%, and 95.3%, respectively; metastasis-free survival rates were 99.1%, 100.0%, and 98.6%, respectively; and prostate cancer-specific survival rate was 100% for all three dose levels. There was no significant benefit for dose escalation either on univariate or multivariate analysis for any outcome. There was no benefit for DE-EBRT >74 Gy in our cohort of intermediate-risk prostate cancer patients treated with neoadjuvant ADT. Given the higher risks of toxicity associated with dose escalation, it may be feasible to omit dose escalation in this group of patients. Randomized studies evaluating dose de-escalation should be considered.

  7. Can we avoid dose escalation for intermediate-risk prostate cancer in the setting of short-course neoadjuvant androgen deprivation?

    PubMed Central

    Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

    2016-01-01

    Background Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve the outcomes in patients with intermediate-risk prostate cancer. Despite this, there are only few reports evaluating DE-EBRT for patients with intermediate-risk prostate cancer receiving neoadjuvant ADT, and virtually no studies investigating dose escalation >74 Gy in this setting. We aimed to determine whether DE-EBRT >74 Gy improved the outcomes for patients with intermediate-risk prostate cancer who received neoadjuvant ADT. Findings In our institution, patients with intermediate-risk prostate cancer were treated with neoadjuvant ADT and DE-EBRT, with doses sequentially increasing from 74 Gy to 76 Gy and then to 78 Gy between 2006 and 2012. We identified 435 patients treated with DE-EBRT and ADT, with a median follow-up of 70 months. For the 74 Gy, 76 Gy, and 78 Gy groups, five-year biochemical disease-free survival rates were 95.0%, 97.8%, and 95.3%, respectively; metastasis-free survival rates were 99.1%, 100.0%, and 98.6%, respectively; and prostate cancer-specific survival rate was 100% for all three dose levels. There was no significant benefit for dose escalation either on univariate or multivariate analysis for any outcome. Conclusion There was no benefit for DE-EBRT >74 Gy in our cohort of intermediate-risk prostate cancer patients treated with neoadjuvant ADT. Given the higher risks of toxicity associated with dose escalation, it may be feasible to omit dose escalation in this group of patients. Randomized studies evaluating dose de-escalation should be considered. PMID:27073327

  8. Successful treatment of a 67-year-old woman with urethral adenocarcinoma with the use of external beam radiotherapy and image guided adaptive interstitial brachytherapy

    PubMed Central

    Mujkanovic, Jasmin; Tanderup, Kari; Agerbæk, Mads; Bisgaard, Ulla; Høyer, Søren; Lindegaard, Jacob Christian

    2016-01-01

    Primary urethral cancer (PUC) is a very rare disease. This case report illustrates a successful treatment approach of a 67-year-old woman with a urethral adenocarcinoma selected for an organ preserving treatment with external beam radiotherapy (EBRT) and interstitial brachytherapy (BT) boost, using the GEC-ESTRO target concept originally designed for locally advanced cervical cancer (LACC). Treatment included EBRT with 45 Gy in 25 fractions followed by image guided adaptive interstitial BT (IGABT) with a pulsed-dose-rate (PDR) BT boost with 30 Gy in 50 hourly pulses. The D90 for CTVHR was 79.1 Gy in EQD23. At 24 months follow-up, the patient was recurrence free and without treatment related side effects. PMID:27895686

  9. Accuracy in automatic image registration between MV cone beam computed tomography and planning kV computed tomography in image guided radiotherapy.

    PubMed

    Kanakavelu, Nithya; Samuel, E James Jebaseelan

    2016-01-01

    To verify the accuracy of automatic image registration (IR) between the planning kilo voltage computed tomography (kV CT) and megavoltage cone beam computed tomography (MV CBCT) datasets using phantom and patient images. The automatic IR between MV CBCT and planning kV CT is a fast solution for performing online image guided radiotherapy (IGRT). The IR accuracy has to be verified periodically as it directly affects patient setup accuracy. The automatic IR accuracy was evaluated using image quality phantom acquired with different kV CT slice thickness, different MV CBCT acquisition MUs and reconstruction slice size and thickness. The IR accuracy was also evaluated on patient images on different anatomical sites such as brain, head & neck, thorax and pelvis. The uncertainty in the automatic registration was assessed by introducing known offset to kV CT dataset and compared with the registration results. The result with the phantom images was within 2 mm in all three translational directions. The accuracy in automatic IR using patient images was within 2 mm in most of the cases. 3 mm planning kV CT slice thickness was sufficient to perform automatic IR successfully within 2 mm accuracy. The MV CBCT reconstruction parameters such as slice thickness and slice size had no effect on the registration accuracy. This study shows that the automatic IR is accurate within 2 mm and provides confidence in performing them between planning kV CT and MV CBCT image datasets for online image guided radiotherapy.

  10. Hypofractionated stereotactic body radiotherapy for primary and metastatic liver tumors using the novalis image-guided system: preliminary results regarding efficacy and toxicity.

    PubMed

    Iwata, Hiromitsu; Shibamoto, Yuta; Hashizume, Chisa; Mori, Yoshimasa; Kobayashi, Tatsuya; Hayashi, Naoki; Kosaki, Katsura; Ishikawa, Tetsuya; Kuzuya, Teiji; Utsunomiya, Setsuo

    2010-12-01

    www.tcrt.org The purpose of this study was to evaluate the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for primary and metastatic liver tumors using the Novalis image-guided radiotherapy system. After preliminarily treating liver tumors using the Novalis system from July 2006, we started a protocol-based study in February 2008. Eighteen patients (6 with primary hepatocellular carcinoma and 12 with metastatic liver tumor) were treated with 55 or 50 Gy, depending upon their planned dose distribution and liver function, delivered in 10 fractions over 2 weeks. Four non-coplanar and three coplanar static beams were used. Patient age ranged from 54 to 84 years (median: 72 years). The Child-Pugh classification was Grade A in 17 patients and Grade B in 1. Tumor diameter ranged from 12 to 35 mm (median: 23 mm). Toxicities were evaluated according to the Common Terminology Criteria of Adverse Events version 4.0, and radiation-induced liver disease (RILD) was defined by Lawrence's criterion. The median follow-up period was 14.5 months. For all patients, the 1-year overall survival and local control rates were 94% and 86%, respectively. A Grade 1 liver enzyme change was observed in 5 patients, but no RILD or chronic liver dysfunction was observed. SBRT using the Novalis image-guided system is safe and effective for treating primary and metastatic liver tumors. Further investigation of SBRT for liver tumors is warranted. In view of the acceptable toxicity observed with this protocol, we have moved to a new protocol to shorten the overall treatment time and escalate the dose.

  11. Dose Escalation for Prostate Cancer Using the Three-Dimensional Conformal Dynamic Arc Technique: Analysis of 542 Consecutive Patients

    SciTech Connect

    Jereczek-Fossa, Barbara A. Vavassori, Andrea; Fodor, Cristiana; Santoro, Luigi; Zerini, Dario; Cattani, Federica; Garibaldi, Cristina; Cambria, Raffaella; Fodor, Andrei; Boboc, Genoveva Ionela; Vitolo, Viviana; Ivaldi, Giovanni Battista; Musi, Gennaro; De Cobelli, Ottavio; Orecchia, Roberto

    2008-07-01

    Purpose: To present the results of dose escalation using three-dimensional conformal dynamic arc radiotherapy (3D-ART) for prostate cancer. Methods and Materials: Five hundred and forty two T1-T3N0M0 prostate cancer patients were treated with 3D-ART. Dose escalation (from 76 Gy/38 fractions to 80 Gy/40 fractions) was introduced in September 2003; 32% of patients received 80 Gy. In 366 patients, androgen deprivation was added to 3D-ART. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and Houston definition (nadir + 2) were used for toxicity and biochemical failure evaluation, respectively. Median follow-up was 25 months. Results: Acute toxicity included rectal (G1-2 28.9%; G3 0.5%) and urinary events (G1-2 57.9%; G3-4 2.4%). Late toxicity included rectal (G1-2 15.8%; G3-4 3.1%) and urinary events (G1-2 26.9%; G3-4 1.6%). Two-year failure-free survival and overall survival rates were 94.1% and 97.9%, respectively. Poor prognostic group (GS, iPSA, T), transurethral prostate resection, and dose >76 Gy showed significant association to high risk of progression in multivariate analysis (p = 0.014, p = 0.045, and p 0.04, respectively). The negative effect of dose >76 Gy was not observed (p 0.10), when the analysis was limited to 353 patients treated after September 2003 (when dose escalation was introduced). Higher dose was not associated with higher late toxicity. Conclusions: Three-dimensional-ART is a feasible modality allowing for dose escalation (no increase in toxicity has been observed with higher doses). However, the dose increase from 76 to 80 Gy was not associated with better tumor outcome. Further investigation is warranted for better understanding of the dose effect for prostate cancer.

  12. Holmium-166 radioembolisation in patients with unresectable, chemorefractory liver metastases (HEPAR trial): a phase 1, dose-escalation study.

    PubMed

    Smits, Maarten L J; Nijsen, Johannes F W; van den Bosch, Maurice A A J; Lam, Marnix G E H; Vente, Maarten A D; Mali, Willem P T M; van Het Schip, Alfred D; Zonnenberg, Bernard A

    2012-10-01

    The efficacy of radioembolisation for the treatment of liver tumours depends on the selective distribution of radioactive microspheres to tumorous tissue. The distribution of holmium-166 ((166)Ho) poly(L-lactic acid) microspheres can be visualised in vivo by both single-photon-emission CT (SPECT) and MRI. In this phase 1 clinical trial, we aimed to assess the safety and the maximum tolerated radiation dose (MTRD) of (166)Ho-radioembolisation in patients with liver metastases. Between Nov 30, 2009, and Sept 19, 2011, patients with unresectable, chemorefractory liver metastases were enrolled in the Holmium Embolization Particles for Arterial Radiotherapy (HEPAR) trial. Patients were treated with intra-arterial (166)Ho-radioembolisation in cohorts of three patients, with escalating aimed whole-liver absorbed doses of 20, 40, 60, and 80 Gy. Cohorts were extended to a maximum of six patients if dose-limiting toxicity occurred. Patients were assigned a dose in the order of study entry, with dose escalation until dose-limiting toxicity was encountered in at least two patients of a dose cohort. Clinical or laboratory toxicities were scored according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 3.0. The primary endpoint was the MTRD. Analyses were per protocol. This study is registered with ClinicalTrials.gov, number NCT01031784. 15 patients underwent (166)Ho-radioembolisation at doses of 20 Gy (n=6), 40 Gy (n=3), 60 Gy (n=3), and 80 Gy (n=3). Mean estimated whole-liver absorbed doses were 18 Gy (SD 2) for the 20 Gy cohort, 35 Gy (SD 1) for the 40 Gy cohort, 58 Gy (SD 3) for the 60 Gy cohort, and 73 Gy (SD 4) for the 80 Gy cohort. The 20 Gy cohort was extended to six patients because of the occurrence of dose-limiting toxicity in one patient (pulmonary embolism). In the 80 Gy cohort, dose-limiting toxicity occurred in two patients: grade 4 thrombocytopenia, grade 3 leucopenia, and grade 3 hypoalbuminaemia in one patient, and

  13. [F-18]-fluorodeoxyglucose positron emission tomography for targeting radiation dose escalation for patients with glioblastoma multiforme: Clinical outcomes and patterns of failure

    SciTech Connect

    Douglas, James G. . E-mail: drjay@u.washington.edu; Stelzer, Keith J.; Mankoff, David A.; Tralins, Kevin S.; Krohn, Kenneth A.; Muzi, Mark; Silbergeld, Daniel L.; Rostomily, Robert C.; Scharnhorst, Jeffrey B.S.; Spence, Alexander M.

    2006-03-01

    Purpose: [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging for brain tumors has been shown to identify areas of active disease. Radiation dose escalation in the treatment of glioblastoma multiforme may lead to improved disease control. Based on these premises, we initiated a prospective study of FDG-PET for the treatment planning of radiation dose escalation for the treatment of glioblastoma multiforme. Methods and Materials: Forty patients were enrolled. Patients were treated with standard conformal fractionated radiotherapy with volumes defined by MRI imaging. When patients reached a dose of 45-50.4 Gy, they underwent FDG-PET imaging for boost target delineation, for an additional 20 Gy (2 Gy per fraction) to a total dose of 79.4 Gy (n = 30). Results: The estimated 1-year and 2-year overall survival (OS) for the entire group was 70% and 17%, respectively, with a median overall survival of 70 weeks. The estimated 1-year and 2-year progression-free survival (PFS) was 18% and 3%, respectively, with a median of 24 weeks. No significant improvements in OS or PFS were observed for the study group in comparison to institutional historical controls. Conclusions: Radiation dose escalation to 79.4 Gy based on FDG-PET imaging demonstrated no improvement in OS or PFS. This study establishes the feasibility of integrating PET metabolic imaging into radiotherapy treatment planning.

  14. [Clinical experience in image-guided ultra-conformal hypofractionated radiotherapy in case of metastatic diseases at the University of Pécs].

    PubMed

    László, Zoltán; Boronkai, Árpád; Lõcsei, Zoltán; Kalincsák, Judit; Szappanos, Szabolcs; Farkas, Róbert; Al Farhat, Yousuf; Sebestyén, Zsolt; Sebestyén, Klára; Kovács, Péter; Csapó, László; Mangel, László

    2015-06-01

    With the development of radiation therapy technology, the utilization of more accurate patient fixation, inclusion of PET/CT image fusion into treatment planning, 3D image-guided radiotherapy, and intensity-modulated dynamic arc irradiation, the application of hypofractionated stereotactic radiotherapy can be extended to specified extracranial target volumes, and so even to the treatment of various metastases. Between October 2012 and August 2014 in our institute we performed extracranial, hypofractionated, image-többguided radiotherapy with RapidArc system for six cases, and 3D conformal multifield technique for one patient with Novalis TX system in case of different few-numbered and slow-growing metastases. For the precise definition of the target volumes we employed PET/CT during the treatment planning procedure. Octreotid scan was applied in one carcinoid tumour patient. Considering the localisation of the metastases and the predictable motion of the organs, we applied 5 to 20 mm safety margin during the contouring procedure. The average treatment volume was 312 cm3. With 2.5-3 Gy fraction doses we delivered 39-45 Gy total dose, and the treatment duration was 2.5 to 3 weeks. The image guidance was carried out via ExacTrac, and kV-Cone Beam CT equipment based on an online protocol, therefore localisation differences were corrected before every single treatment. The patients tolerated the treatments well without major (Gr>2) side effects. Total or near total regression of the metastases was observed at subsequent control examinations in all cases (the median follow-up time was 5 months). According to our first experience, extracranial, imageguided hypofractionated radiotherapy is well-tolerated by patients and can be effectively applied in the treatment of slow-growing and few-numbered metastases.

  15. Evaluation of inter- and intrafractional motion of liver tumors using interstitial markers and implantable electromagnetic radiotransmitters in the context of image-guided radiotherapy (IGRT) - the ESMERALDA trial.

    PubMed

    Habermehl, Daniel; Naumann, Patrick; Bendl, Rolf; Oelfke, Uwe; Nill, Simeon; Debus, Jürgen; Combs, Stephanie E

    2015-07-14

    With the development of more conformal and precise radiation techniques such as Intensity-Modulated Radiotherapy (IMRT), Stereotactic Body Radiotherapy (SBRT) and Image-Guided Radiotherapy (IGRT), patients with hepatic tumors could be treated with high local doses by sparing normal liver tissue. However, frequently occurring large HCC tumors are still a dosimetric challenge in spite of modern high sophisticated RT modalities. This interventional clinical study has been set up to evaluate the value of different fiducial markers, and to use the modern imaging methods for further treatment optimization using physical and informatics approaches. Surgically implanted radioopaque or electromagnetic markers are used to detect tumor local-ization during radiotherapy. The required markers for targeting and observation during RT can be implanted in a previously defined optimal position during the oncologically indicated operation. If there is no indication for a surgical resection or open biopsy, markers may be inserted into the liver or tumor tissue by using ultrasound-guidance. Primary study aim is the detection of the patients' anatomy at the time of RT by observation of the marker position during the indicated irradiation (IGRT). Secondary study aims comprise detection and recording of 3D liver and tumor motion during RT. Furthermore, the study will help to develop technical strategies and mechanisms based on the recorded information on organ motion to avoid inaccurate dose application resulting from fast organ motion and deformation. This is an open monocentric non-randomized, prospective study for the evaluation of organ motion using interstitial markers or implantable radiotransmitter. The trial will evaluate the full potential of different fiducial markers to further optimize treatment of moving targets, with a special focus on liver lesions.

  16. Tissue feature-based intra-fractional motion tracking for stereoscopic x-ray image guided radiotherapy.

    PubMed

    Xie, Yaoqin; Xing, Lei; Gu, Jia; Liu, Wu

    2013-06-07

    Real-time knowledge of tumor position during radiation therapy is essential to overcome the adverse effect of intra-fractional organ motion. The goal of this work is to develop a tumor tracking strategy by effectively utilizing the inherent image features of stereoscopic x-ray images acquired during dose delivery. In stereoscopic x-ray image guided radiation delivery, two orthogonal x-ray images are acquired either simultaneously or sequentially. The essence of markerless tumor tracking is the reliable identification of inherent points with distinct tissue features on each projection image and their association between two images. The identification of the feature points on a planar x-ray image is realized by searching for points with high intensity gradient. The feature points are associated by using the scale invariance features transform descriptor. The performance of the proposed technique is evaluated by using images of a motion phantom and four archived clinical cases acquired using either a CyberKnife equipped with a stereoscopic x-ray imaging system, or a LINAC equipped with an onboard kV imager and an electronic portal imaging device. In the phantom study, the results obtained using the proposed method agree with the measurements to within 2 mm in all three directions. In the clinical study, the mean error is 0.48 ± 0.46 mm for four patient data with 144 sequential images. In this work, a tissue feature-based tracking method for stereoscopic x-ray image guided radiation therapy is developed. The technique avoids the invasive procedure of fiducial implantation and may greatly facilitate the clinical workflow.

  17. Tissue feature-based intra-fractional motion tracking for stereoscopic x-ray image guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Xie, Yaoqin; Xing, Lei; Gu, Jia; Liu, Wu

    2013-06-01

    Real-time knowledge of tumor position during radiation therapy is essential to overcome the adverse effect of intra-fractional organ motion. The goal of this work is to develop a tumor tracking strategy by effectively utilizing the inherent image features of stereoscopic x-ray images acquired during dose delivery. In stereoscopic x-ray image guided radiation delivery, two orthogonal x-ray images are acquired either simultaneously or sequentially. The essence of markerless tumor tracking is the reliable identification of inherent points with distinct tissue features on each projection image and their association between two images. The identification of the feature points on a planar x-ray image is realized by searching for points with high intensity gradient. The feature points are associated by using the scale invariance features transform descriptor. The performance of the proposed technique is evaluated by using images of a motion phantom and four archived clinical cases acquired using either a CyberKnife equipped with a stereoscopic x-ray imaging system, or a LINAC equipped with an onboard kV imager and an electronic portal imaging device. In the phantom study, the results obtained using the proposed method agree with the measurements to within 2 mm in all three directions. In the clinical study, the mean error is 0.48 ± 0.46 mm for four patient data with 144 sequential images. In this work, a tissue feature-based tracking method for stereoscopic x-ray image guided radiation therapy is developed. The technique avoids the invasive procedure of fiducial implantation and may greatly facilitate the clinical workflow.

  18. Dose Escalation during the First Year of Long-Term Opioid Therapy for Chronic Pain

    PubMed Central

    Henry, Stephen G.; Wilsey, Barth L.; Melnikow, Joy A.; Iosif, Ana-Maria

    2014-01-01

    OBJECTIVE To identify patient factors and health care utilization patterns associated with dose escalation during the first year of long-term opioid therapy for chronic pain DESIGN Retrospective cohort study using electronic health record data SETTING University health system SUBJECTS Opioid naïve adults with musculoskeletal pain who received a new outpatient opioid prescription between July 1, 2011 and June 30, 2012 and stayed on opioids for one year METHODS Mixed-effects regression was used to estimate patients’ rate of opioid dose escalation. Demographics, clinical characteristics, and healthcare utilization for patients with and without dose escalation were compared. RESULTS Twenty-three (9%) of 246 patients in the final cohort experienced dose escalation (defined as an increase in mean daily opioid dose of ≥30 mg morphine equivalents over 1 year). Compared to patients without dose escalation, patients with escalation had higher rates of substance use diagnoses (17% versus 1%, P = 0.01) and more total outpatient encounters (51 versus 35, P = 0.002) over 1 year. Differences in outpatient encounters were largely due to more non face-to-face encounters (e.g., telephone calls, emails) among patients with dose escalation. Differences in age, race, concurrent benzodiazepine use, and mental health diagnoses between patients with and without dose escalation were not statistically significant. Primary care clinicians prescribed 89% of opioid prescriptions. CONCLUSIONS Dose escalation during the first year of long-term opioid therapy is associated with higher rates of substance use disorders and more frequent outpatient encounters, especially non face-to-face encounters. PMID:25529548

  19. [Image guided radiotherapy with the Cone Beam CT kV (Elekta): experience of the Léon Bérard centre].

    PubMed

    Pommier, P; Gassa, F; Lafay, F; Claude, L

    2009-09-01

    Image guide radiotherapy with the Cone Beam CT kV (CBCT-kV) developed by Elekta has been implemented at the centre Léon Bérard in November 2006. The treatment procedure is presented and detailed for prostate cancer IGRT and non small cell lung cancer (NSCLC) stereotactic radiotherapy (SRT). CBCT-kV is routinely used for SRT, selected paediatric cancers, all prostate carcinomas, primitive brain tumours and head and neck cancers that do not require nodes irradiation. Thirty-five to 40 patients are treated within a daily 11-hours period. The general procedure for 3D images acquisition and their analysis is described. The CBCT-kV permitted to identify about 10% of prostate cancer patients for whom a positioning with bone-based 2D images only would have led to an unacceptable dose distribution for at least one session. SRT is now used routinely for inoperable NSCLC. The easiness of implementing CBCT-kV imaging and its expected medical benefit should lead to a rapid diffusion of this technology that is also submitted to prospective and multicentric medico-economical evaluations.

  20. Image-Guided Radiotherapy (IGRT) for Prostate Cancer Comparing kV Imaging of Fiducial Markers With Cone Beam Computed Tomography (CBCT)

    SciTech Connect

    Barney, Brandon M.; Lee, R. Jeffrey; Handrahan, Diana; Welsh, Keith T.; Cook, J. Taylor; Sause, William T.

    2011-05-01

    Purpose: To present our single-institution experience with image-guided radiotherapy comparing fiducial markers and cone-beam computed tomography (CBCT) for daily localization of prostate cancer. Methods and Materials: From April 2007 to October 2008, 36 patients with prostate cancer received intensity-modulated radiotherapy with daily localization by use of implanted fiducials. Orthogonal kilovoltage (kV) portal imaging preceded all 1244 treatments. Cone-beam computed tomography images were also obtained before 286 treatments (23%). Shifts in the anterior-posterior (AP), superior-inferior (SI), and left-right (LR) dimensions were made from kV fiducial imaging. Cone-beam computed tomography shifts based on soft tissues were recorded. Shifts were compared by use of Bland-Altman limits of agreement. Mean and standard deviation of absolute differences were also compared. A difference of 5 mm or less was acceptable. Subsets including start date, body mass index, and prostate size were analyzed. Results: Of 286 treatments, 81 (28%) resulted in a greater than 5.0-mm difference in one or more dimensions. Mean differences in the AP, SI, and LR dimensions were 3.4 {+-} 2.6 mm, 3.1 {+-} 2.7 mm, and 1.3 {+-} 1.6 mm, respectively. Most deviations occurred in the posterior (fiducials, 78%; CBCT, 59%), superior (79%, 61%), and left (57%, 63%) directions. Bland-Altman 95% confidence intervals were -4.0 to 9.3 mm for AP, -9.0 to 5.3 mm for SI, and -4.1 to 3.9 mm for LR. The percentages of shift agreements within {+-}5 mm were 72.4% for AP, 72.7% for SI, and 97.2% for LR. Correlation between imaging techniques was not altered by time, body mass index, or prostate size. Conclusions: Cone-beam computed tomography and kV fiducial imaging are similar; however, more than one-fourth of CBCT and kV shifts differed enough to affect target coverage. This was even more pronounced with smaller margins (3 mm). Fiducial imaging requires less daily physician input, is less time-consuming, and is

  1. Performance of a Novel Repositioning Head Frame for Gamma Knife Perfexion and Image-Guided Linac-Based Intracranial Stereotactic Radiotherapy

    SciTech Connect

    Ruschin, Mark; Nayebi, Nazanin; Carlsson, Per; Brown, Kevin

    2010-09-01

    Purpose: To evaluate the geometric positioning and immobilization performance of a vacuum bite-block repositioning head frame (RHF) system for Perfexion (PFX-SRT) and linac-based intracranial image-guided stereotactic radiotherapy (SRT). Methods and Materials: Patients with intracranial tumors received linac-based image-guided SRT using the RHF for setup and immobilization. Three hundred thirty-three fractions of radiation were delivered in 12 patients. The accuracy of the RHF was estimated for linac-based SRT with online cone-beam CT (CBCT) and for PFX-SRT with a repositioning check tool (RCT) and offline CBCT. The RCT's ability to act as a surrogate for anatomic position was estimated through comparison to CBCT image matching. Immobilization performance was evaluated daily with pre- and postdose delivery CBCT scans and RCT measurements. Results: The correlation coefficient between RCT- and CBCT-reported displacements was 0.59, 0.75, 0.79 (Right, Superior, and Anterior, respectively). For image-guided linac-based SRT, the mean three-dimensional (3D) setup error was 0.8 mm with interpatient ({Sigma}) and interfraction ({sigma}) variations of 0.1 and 0.4 mm, respectively. For PFX-SRT, the initial, uncorrected mean 3D positioning displacement in stereotactic coordinates was 2.0 mm, with {Sigma} = 1.1 mm and {sigma} = 0.8 mm. Considering only RCT setups <1mm (PFX action level) the mean 3D positioning displacement reduced to 1.3 mm, with {Sigma} = 0.9 mm and {sigma} = 0.4 mm. The largest contributing systematic uncertainty was in the superior-inferior direction (mean displacement = -0.5 mm; {Sigma} = 0.9 mm). The largest mean rotation was 0.6{sup o} in pitch. The mean 3D intrafraction motion was 0.4 {+-} 0.3 mm. Conclusion: The RHF provides excellent immobilization for intracranial SRT and PFX-SRT. Some small systematic uncertainties in stereotactic positioning exist and must be considered when generating PFX-SRT treatment plans. The RCT provides reasonable surrogacy

  2. Performance of a novel repositioning head frame for gamma knife perfexion and image-guided linac-based intracranial stereotactic radiotherapy.

    PubMed

    Ruschin, Mark; Nayebi, Nazanin; Carlsson, Per; Brown, Kevin; Tamerou, Messeret; Li, Winnie; Laperriere, Normand; Sahgal, Arjun; Cho, Young-Bin; Ménard, Cynthia; Jaffray, David

    2010-09-01

    To evaluate the geometric positioning and immobilization performance of a vacuum bite-block repositioning head frame (RHF) system for Perfexion (PFX-SRT) and linac-based intracranial image-guided stereotactic radiotherapy (SRT). Patients with intracranial tumors received linac-based image-guided SRT using the RHF for setup and immobilization. Three hundred thirty-three fractions of radiation were delivered in 12 patients. The accuracy of the RHF was estimated for linac-based SRT with online cone-beam CT (CBCT) and for PFX-SRT with a repositioning check tool (RCT) and offline CBCT. The RCT's ability to act as a surrogate for anatomic position was estimated through comparison to CBCT image matching. Immobilization performance was evaluated daily with pre- and postdose delivery CBCT scans and RCT measurements. The correlation coefficient between RCT- and CBCT-reported displacements was 0.59, 0.75, 0.79 (Right, Superior, and Anterior, respectively). For image-guided linac-based SRT, the mean three-dimensional (3D) setup error was 0.8 mm with interpatient (Sigma) and interfraction (sigma) variations of 0.1 and 0.4 mm, respectively. For PFX-SRT, the initial, uncorrected mean 3D positioning displacement in stereotactic coordinates was 2.0 mm, with Sigma = 1.1 mm and sigma = 0.8 mm. Considering only RCT setups <1mm (PFX action level) the mean 3D positioning displacement reduced to 1.3 mm, with Sigma = 0.9 mm and sigma = 0.4 mm. The largest contributing systematic uncertainty was in the superior-inferior direction (mean displacement = -0.5 mm; Sigma = 0.9 mm). The largest mean rotation was 0.6 degrees in pitch. The mean 3D intrafraction motion was 0.4 +/- 0.3 mm. The RHF provides excellent immobilization for intracranial SRT and PFX-SRT. Some small systematic uncertainties in stereotactic positioning exist and must be considered when generating PFX-SRT treatment plans. The RCT provides reasonable surrogacy for internal anatomic displacement. Copyright (c) 2010 Elsevier Inc

  3. Postradiotherapy PSA nadirs fail to support dose escalation study in patients with pretreatment PSA values < 10 ng/ml.

    PubMed

    Herold, D; Hanks, G; Movsas, B; Hanlon, A

    1997-01-01

    With three-dimensional conformal therapy, doses > 75 Gy have been delivered to the prostate with acceptable levels of morbidity; however, higher doses do appear to increase late gastrointestinal (GI) and genitourinary (GU) morbidity. Because patients with pretreatment prostate-specific antigen (PSA) values < 10 ng/ml can achieve 3-year actuarial bNED control rates of 90% after treatment with external beam radiotherapy to doses < 71 Gy, one might question the need for further dose escalation in this population. In this report, we examined the relationship between dose and PSA nadir for 90 patients with pretreatment PSA values < 10 ng/ml entered into a dose escalation study from March 1987 to October 1992. We wanted to see if nadir response data would predict a different outcome from our 3-year bNED control reports. All patients were treated with external beam radiotherapy to ICRU reporting point doses of 6,598 cGy to 7,895 cGy (median of 7,068 cGy). Minimum follow-up was 36 months (median, 47 months). Seven hundred thirty-nine posttreatment PSA nadir values were analyzed, yielding an average of 8.2 values per patient. Estimates of rates of bNED control and time to reach a posttreatment PSA of 1.0 ng/ml were calculated using the Kaplan-Meier product limit method. The log-rank test was used to evaluate differences in rates according to dose levels. Linear regression and Cox proportional hazard modeling were used to relate dose to bNED control on a continuum. Escalating doses from 66 to 79 Gy failed to increase the percentage of patients achieving nadir values < 1 ng/ml and similarly failed to increase the 3-year actuarial bNED control. Linear regression (P = .81) and the chi-square test of association (P = .23) supported the lack of a dose effect on nadir continuously and categorically, respectively, and the Cox regression model supported the conclusion that dose on a continuum has no effect on bNED control (P = .34). Furthermore, time to reach a posttreatment PSA

  4. Do We Need Daily Image-Guided Radiotherapy by Megavoltage Computed Tomography in Head and Neck Helical Tomotherapy? The Actual Delivered Dose to the Spinal Cord

    SciTech Connect

    Duma, Marciana Nona; Kampfer, Severin; Schuster, Tibor; Aswathanarayana, Nandana; Fromm, Laura-Sophie; Molls, Michael; Andratschke, Nicolaus; Geinitz, Hans

    2012-09-01

    Purpose: To quantify the actual delivered dose to the cervical spinal cord with different image-guided radiotherapy (IGRT) approaches during head and neck (HN) cancer helical tomotherapy. Methods and Materials: Twenty HN patients (HNpts) treated with bilateral nodal irradiation were analyzed. Daily megavoltage computed tomography MVCT) scans were performed for setup purposes. The maximum dose on the planning CT scan (plan-Dmax) and the magnitude and localization of the actual delivered Dmax (a-Dmax) were analyzed for four scenarios: daily image-guided radiotherapy (dIGRT), twice weekly IGRT (2 Multiplication-Sign WkIGRT), once weekly IGRT (1 Multiplication-Sign WkIGRT), and no IGRT at all (non-IGRT). The spinal cord was recontoured on 236 MVCTs for each scenario (total, 944 fractions), and the delivered dose was recalculated for each fraction (fx) separately. Results: Fifty-one percent of the analyzed fx for dIGRT, 56% of the analyzed fx for the 2 Multiplication-Sign WkIGRT, 62% of the analyzed fx for the 1 Multiplication-Sign WkIGRT, and 63% of the analyzed fx for the non-IGRT scenarios received a higher a-Dmax than the plan-Dmax. The median increase of dose in these fx was 3.3% more for dIGRT, 5.8% more for 2 Multiplication-Sign WkIGRT, 10.0% more for 1 Multiplication-Sign WkIGRT, and 9.5% more for non-IGRT than the plan-Dmax. The median spinal cord volumes receiving a higher dose than the plan-Dmax were 0.02 cm{sup 3} for dIGRT, 0.11 cm{sup 3} for 2 Multiplication-Sign WkIGRT, 0.31 cm{sup 3} for 1 Multiplication-Sign WkIGRT, and 0.22 cm{sup 3} for non-IGRT. Differences between the dIGRT and all other scenarios were statistically significant (p < 0.05). Conclusions: Compared to the Dmax of the initial plan, daily IGRT had the smallest increase in dose. Furthermore, daily IGRT had the lowest proportion of fractions and the smallest volumes affected by a dose that was higher than the planned dose. For patients treated with doses close to the tolerance dose of the

  5. A Study on Target Positioning Error and Its Impact on Dose Variation in Image-Guided Stereotactic Body Radiotherapy for the Spine

    SciTech Connect

    Kim, Siyong Jin, Hosang; Yang, Huey; Amdur, Robert J.

    2009-04-01

    Purpose: To investigate the amount of target positioning error and evaluate its dosimetric impact during image-guided stereotactic body radiotherapy for single-fraction spine treatment. Methods and Materials: A prescription dose of 15 Gy and five to nine coplanar intensity-modulated beams were used. The patient was immobilized with a custom-fit vacuum mold, and the target was localized with a volumetric cone-beam CT image. A robotic couch with six degrees of freedom was used for target adjustment. For evaluation a cone-beam CT image was obtained at the end of treatment. Both target positioning error and its dosimetric impact were investigated for the first 9 cases. Results: For cases studied, translational errors were 0.9 {+-} 0.5 mm (lateral), 1.2 {+-} 0.9 mm (longitudinal), 0.7 {+-} 0.6 mm (vertical), and 1.8 {+-} 1.0 mm (vector), and rotational errors were 1.6 deg. {+-} 1.3 deg. (pitch), 0.8 deg. {+-} 0.9 deg. (roll), and 0.8 deg. {+-} 0.4{sup o} (yaw). For the clinical target volume, D{sub 95} (dose to 95% of target volume), D{sub 90}, D{sub max}, and D{sub mean} were evaluated. Only 1 case showed significant dose variations, reaching up to 18% in D{sub 95}. The spinal cord dose was evaluated by observing D{sub 0.1} (dose to 0.1 cm{sup 3}), D{sub 0.5}, D{sub 1.0}, and D{sub max}. Although 1 case showed a dose change reaching up to 30% in D{sub max}, cord dose was within the planning tolerance limit in all but 2 cases (3% higher in one and 0.4% higher in the other). Conclusion: The implemented image-guided stereotactic body radiotherapy provides precise target localization. However, despite reasonably precise spatial precision, dosimetric perturbation can be significant because of both extremely steep dose gradients and close distances between the target and the spinal cord.

  6. Image-guided intensity-modulated radiotherapy for prostate cancer: Dose constraints for the anterior rectal wall to minimize rectal toxicity

    SciTech Connect

    Peterson, Jennifer L.; Buskirk, Steven J.; Heckman, Michael G.; Diehl, Nancy N.; Bernard, Johnny R.; Tzou, Katherine S.; Casale, Henry E.; Bellefontaine, Louis P.; Serago, Christopher; Kim, Siyong; Vallow, Laura A.; Daugherty, Larry C.; Ko, Stephen J.

    2014-04-01

    Rectal adverse events (AEs) are a major concern with definitive radiotherapy (RT) treatment for prostate cancer. The anterior rectal wall is at the greatest risk of injury as it lies closest to the target volume and receives the highest dose of RT. This study evaluated the absolute volume of anterior rectal wall receiving a high dose to identify potential ideal dose constraints that can minimize rectal AEs. A total of 111 consecutive patients with Stage T1c to T3a N0 M0 prostate cancer who underwent image-guided intensity-modulated RT at our institution were included. AEs were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The volume of anterior rectal wall receiving 5 to 80 Gy in 2.5-Gy increments was determined. Multivariable Cox regression models were used to identify cut points in these volumes that led to an increased risk of early and late rectal AEs. Early AEs occurred in most patients (88%); however, relatively few of them (13%) were grade ≥2. At 5 years, the cumulative incidence of late rectal AEs was 37%, with only 5% being grade ≥2. For almost all RT doses, we identified a threshold of irradiated absolute volume of anterior rectal wall above which there was at least a trend toward a significantly higher rate of AEs. Most strikingly, patients with more than 1.29, 0.73, or 0.45 cm{sup 3} of anterior rectal wall exposed to radiation doses of 67.5, 70, or 72.5 Gy, respectively, had a significantly increased risk of late AEs (relative risks [RR]: 2.18 to 2.72; p ≤ 0.041) and of grade ≥ 2 early AEs (RR: 6.36 to 6.48; p = 0.004). Our study provides evidence that definitive image-guided intensity-modulated radiotherapy (IG-IMRT) for prostate cancer is well tolerated and also identifies dose thresholds for the absolute volume of anterior rectal wall above which patients are at greater risk of early and late complications.

  7. Polymeric micelles as a diagnostic tool for image-guided drug delivery and radiotherapy of HER2 overexpressing breast cancer

    NASA Astrophysics Data System (ADS)

    Hoang, Nu Bryan

    Block copolymer micelles have emerged as a viable formulation strategy with several drugs relying on this technology in clinical evaluation. To date, information on the tumor penetration and intratumoral distribution of block copolymer micelles (BCM) has been quite limited. Thus, there is impetus to develop a radiolabeled formulation that can be used to gain invaluable insight into the intratumoral distribution of the BCMs. This information could then be used to direct formulation strategies as a means to optimize treatment outcomes. This thesis describes the synthesis and characterization of a targeted block copolymer micelle system based on poly(ethylene glycol)-block -poly(epsilon-caprolactone) labeled with the radionuclide Indium-111 (111In). The incorporation of the imageable component, 111In permits pursuit of image-guided drug delivery for real-time monitoring of tumor localization and intratumoral distribution. Intracellular trafficking of drugs and therapies such as Auger electron emitting radionuclides to perinuclear and nuclear regions of cells is critical to realizing their full therapeutic potential. HER2 specific antibodies (trastuzumab fab fragments) and nuclear localization signal peptides were conjugated to the surface of the BCMs to direct uptake in HER2 expressing cells and subsequent localization in the cell nucleus. Cell uptake was HER2 density dependent, confirming receptor-mediated internalization of the BCMs. Importantly, conjugation of NLS resulted in a significant increase in nuclear uptake of the radionuclide 111In. Successful nuclear targeting was shown to improve the antiproliferative effect of the Auger electrons. In addition, a significant radiation enhancement effect was observed by concurrent delivery of low-dose MTX and 111In in all breast cancer cell lines evaluated. Imaging enabled the accurate quantification of the specific tumor uptake of the micelles and visualization of their degree of tumor penetration in relation to

  8. Assessment of contrast enhanced respiration managed cone-beam CT for image guided radiotherapy of intrahepatic tumors

    SciTech Connect

    Jensen, Nikolaj K. G.; Stewart, Errol; Lock, Michael; Fisher, Barbara; Kozak, Roman; Chen, Jeff; Lee, Ting-Yim; Wong, Eugene

    2014-05-15

    Purpose: Contrast enhancement and respiration management are widely used during image acquisition for radiotherapy treatment planning of liver tumors along with respiration management at the treatment unit. However, neither respiration management nor intravenous contrast is commonly used during cone-beam CT (CBCT) image acquisition for alignment prior to radiotherapy. In this study, the authors investigate the potential gains of injecting an iodinated contrast agent in combination with respiration management during CBCT acquisition for liver tumor radiotherapy. Methods: Five rabbits with implanted liver tumors were subjected to CBCT with and without motion management and contrast injection. The acquired CBCT images were registered to the planning CT to determine alignment accuracy and dosimetric impact. The authors developed a simulation tool for simulating contrast-enhanced CBCT images from dynamic contrast enhanced CT imaging (DCE-CT) to determine optimal contrast injection protocols. The tool was validated against contrast-enhanced CBCT of the rabbit subjects and was used for five human patients diagnosed with hepatocellular carcinoma. Results: In the rabbit experiment, when neither motion management nor contrast was used, tumor centroid misalignment between planning image and CBCT was 9.2 mm. This was reduced to 2.8 mm when both techniques were employed. Tumors were not visualized in clinical CBCT images of human subjects. Simulated contrast-enhanced CBCT was found to improve tumor contrast in all subjects. Different patients were found to require different contrast injections to maximize tumor contrast. Conclusions: Based on the authors’ animal study, respiration managed contrast enhanced CBCT improves IGRT significantly. Contrast enhanced CBCT benefits from patient specific tracer kinetics determined from DCE-CT.

  9. X-ray volumetric imaging in image-guided radiotherapy: The new standard in on-treatment imaging

    SciTech Connect

    McBain, Catherine A.; Henry, Ann M. . E-mail: catherine.mcbain@christie-tr.nwest.nhs.uk; Sykes, Jonathan; Amer, Ali; Marchant, Tom; Moore, Christopher M.; Davies, Julie; Stratford, Julia; McCarthy, Claire; Porritt, Bridget; Williams, Peter; Khoo, Vincent S.; Price, Pat

    2006-02-01

    Purpose: X-ray volumetric imaging (XVI) for the first time allows for the on-treatment acquisition of three-dimensional (3D) kV cone beam computed tomography (CT) images. Clinical imaging using the Synergy System (Elekta, Crawley, UK) commenced in July 2003. This study evaluated image quality and dose delivered and assessed clinical utility for treatment verification at a range of anatomic sites. Methods and Materials: Single XVIs were acquired from 30 patients undergoing radiotherapy for tumors at 10 different anatomic sites. Patients were imaged in their setup position. Radiation doses received were measured using TLDs on the skin surface. The utility of XVI in verifying target volume coverage was qualitatively assessed by experienced clinicians. Results: X-ray volumetric imaging acquisition was completed in the treatment position at all anatomic sites. At sites where a full gantry rotation was not possible, XVIs were reconstructed from projection images acquired from partial rotations. Soft-tissue definition of organ boundaries allowed direct assessment of 3D target volume coverage at all sites. Individual image quality depended on both imaging parameters and patient characteristics. Radiation dose ranged from 0.003 Gy in the head to 0.03 Gy in the pelvis. Conclusions: On-treatment XVI provided 3D verification images with soft-tissue definition at all anatomic sites at acceptably low radiation doses. This technology sets a new standard in treatment verification and will facilitate novel adaptive radiotherapy techniques.

  10. [Postoperative radiotherapy of prostate cancer].

    PubMed

    Guérif, S; Latorzeff, I; Lagrange, J-L; Hennequin, C; Supiot, S; Garcia, A; François, P; Soulié, M; Richaud, P; Salomon, L

    2014-10-01

    Between 10 and 40% of patients who have undergone a radical prostatectomy may have a biologic recurrence. Local or distant failure represents the possible patterns of relapse. Patients at high-risk for local relapse have extraprostatic disease, positive surgical margins or seminal vesicles infiltration or high Gleason score at pathology. Three phase-III randomized clinical trials have shown that, for these patients, adjuvant irradiation reduces the risk of tumoral progression without higher toxicity. Salvage radiotherapy for late relapse allows a disease control in 60-70% of the cases. Several research in order to improve the therapeutic ratio of the radiotherapy after prostatectomy are evaluate in the French Groupe d'Étude des Tumeurs Urogénitales (Gétug) and of the French association of urology (Afu). The Gétug-Afu 17 trial will provide answers to the question of the optimal moment for postoperative radiotherapy for pT3-4 R1 pN0 Nx patients, with the objective of comparing an immediate treatment to a differed early treatment initiated at biological recurrence. The Gétug-Afu 22 questions the place of a short hormonetherapy combined with image-guided, intensity-modulated radiotherapy (IMRT) in adjuvant situation for a detectable prostate specific antigen (PSA). The implementation of a multicenter quality control within the Gétug-Afu in order to harmonize a modern postoperative radiotherapy will allow the development of a dose escalation IMRT after surgery.

  11. Setup Variations in Radiotherapy of Anal Cancer: Advantages of Target Volume Reduction Using Image-Guided Radiation Treatment

    SciTech Connect

    Chen Yijen; Suh, Steve; Nelson, Rebecca A.; Liu An; Pezner, Richard D.; Wong, Jeffrey Y.C.

    2012-09-01

    Purpose: To define setup variations in the radiation treatment (RT) of anal cancer and to report the advantages of image-guided RT (IGRT) in terms of reduction of target volume and treatment-related side effects. Methods and Materials: Twelve consecutive patients with anal cancer treated by combined chemoradiation by use of helical tomotherapy from March 2007 to November 2008 were selected. With patients immobilized and positioned in place, megavoltage computed tomography (MVCT) scans were performed before each treatment and were automatically registered to planning CT scans. Patients were shifted per the registration data and treated. A total of 365 MVCT scans were analyzed. The primary site received a median dose of 55 Gy. To evaluate the potential dosimetric advantage(s) of IGRT, cases were replanned according to Radiation Therapy Oncology Group 0529, with and without adding recommended setup variations from the current study. Results: Significant setup variations were observed throughout the course of RT. The standard deviations for systematic setup correction in the anterior-posterior (AP), lateral, and superior-inferior (SI) directions and roll rotation were 1.1, 3.6, and 3.2 mm, and 0.3 Degree-Sign , respectively. The average random setup variations were 3.8, 5.5, and 2.9 mm, and 0.5 Degree-Sign , respectively. Without daily IGRT, margins of 4.9, 11.1, and 8.5 mm in the AP, lateral, and SI directions would have been needed to ensure that the planning target volume (PTV) received {>=}95% of the prescribed dose. Conversely, daily IGRT required no extra margins on PTV and resulted in a significant reduction of V15 and V45 of intestine and V10 of pelvic bone marrow. Favorable toxicities were observed, except for acute hematologic toxicity. Conclusions: Daily MVCT scans before each treatment can effectively detect setup variations and thereby reduce PTV margins in the treatment of anal cancer. The use of concurrent chemotherapy and IGRT provided favorable

  12. Intermediate-risk prostate cancer patients treated with androgen deprivation therapy and a hypofractionated radiation regimen with or without image guided radiotherapy

    PubMed Central

    2013-01-01

    Background To evaluate the efficacy of hypofractionated radiotherapy (HyRT) with or without image guided radiotherapy (IGRT) in intermediate risk prostate cancer. Methods 105 patients were treated with HyRT, 43,8 Gy and 54,75 Gy were delivered to the seminal vescicles and to the prostate, respectively; 3,65 Gy/fraction three times weekly. All patients underwent 9 months hormonal therapy. Patient position was verified with daily kV cone beam CT in 69 patients (IGRT group). Acute and late toxicities were evaluated according to RTOG scale. Biochemical relapse was defined using PSA nadir + 2 ng/mL. The data were prospectively collected and retrospectively analyzed to evaluate the efficacy of IGRT. Results After a median follow-up of 31 months the actuarial 3-year bNED was 93,7%. During RT, 10.5% and 7.6% of patients developed ≥Grade 2 rectal and urinary toxicities, respectively. The cumulative incidence of ≥Grade 2 late rectal and urinary toxicities at 3 years were 6,9%, and 10,8%, respectively. The incidence of ≥Grade 2 late rectal toxicities was significant reduced in the IGRT group (1,6% vs. 14,5%, p=0,021). Two patients developed Grade 3 urethral obstruction and one patient developed grade 3 rectal bleeding. Conclusions HyRT represents a well-tolerated treatment able to achieve a high bNED. The use of daily IGRT is beneficial for reducing the incidence of late toxicities. PMID:23759081

  13. Tumor Control Outcomes Following Hypofractionated and Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases from Renal Cell Carcinoma

    PubMed Central

    Zelefsky, Michael J; Greco, Carlo; Motzer, Robert; Magsanoc, Juan Martin; Pei, Xin; Lovelock, Michael; Mechalakos, Jim; Zatcky, Joan; Fuks, Zvi; Yamada, Yoshiya

    2014-01-01

    Purpose To report tumor local progression-free outcomes following treatment with single-dose image-guided intensity-modulated radiotherapy (SD-IGRT) and hypofractionated regimens for extracranial metastases from renal cell primary tumors. Methods and Materials Between 2004 and 2010, a total of 105 lesions from renal cell carcinomas were treated with either SD-IGRT to prescription doses of 18–24 Gy (median, 24 Gy) or hypofractionation (3 or 5 fractions) with prescription doses ranging between 20 and 30 Gy. The median follow-up was 12 months (range, 1–48 months). Results The overall 3-year actuarial local progression-free survival (LPFS) for all lesions was 44%. The 3-year LPFS for those who received high single-dose (24 Gy; n = 45), low single-dose (< 24 Gy; n = 14), and hypofractionation regimens (n = 46) were 88%, 21%, and 17%, respectively (high single dose versus low single dose, p = 0.001; high single dose versus hypofractionation, p < 0.001). Multivariate analysis revealed the following variables as significant predictors of improved LPFS: dose of 24 Gy compared with lower dose (p = 0.009), and single dose versus hypofractionation (p = 0.008). Conclusion High-dose SD-IGRT is a non-invasive procedure resulting in high probability of local tumor control for metastatic renal cell cancers, generally considered radioresistant according to classical radiobiological ranking. PMID:21596489

  14. SU-E-T-306: Study of the Reduction Technique for the Secondary Cancer Risk Due to Cone Beam CT in Image Guided Radiotherapy

    SciTech Connect

    Sung, J; Kim, D; Kim, D; Chung, W; Baek, T; Lee, H; Yoon, M

    2014-06-01

    Purpose: This study evaluated the effectiveness of a thin lead sheet based simple shielding method for imaging doses from cone beam computed tomography (CBCT) in image-guided radiotherapy (IGRT). Methods: The entire body, except for the region scanned by CBCT, was shielded by wrapping in a 2 mm lead sheet. Reduction of secondary doses from CBCT was measured using a radio-photoluminescence glass dosimeter (RPLGD) placed inside an anthropomorphic phantom and changes in secondary cancer risk due to the shielding effect were estimated using BEIR VII model. Results: Doses to out-of-field organs for head-and-neck, chest, and pelvis scans were decreased 15∼100 %, 23∼90 %, and 23∼98 %, respectively, and the average reductions in lifetime secondary cancer risk due to the 2 mm lead shielding were 1.61, 10.4, and 12.8 persons per 100,000, respectively. Conclusion: This study suggests that a simple thin lead sheet based shielding method results in a non-negligible reduction of secondary doses to out-of-field regions for CBCT.

  15. Effect of Patient Set-up and Respiration motion on Defining Biological Targets for Image-Guided Targeted Radiotherapy

    NASA Astrophysics Data System (ADS)

    McCall, Keisha C.

    Identification and monitoring of sub-tumor targets will be a critical step for optimal design and evaluation of cancer therapies in general and biologically targeted radiotherapy (dose-painting) in particular. Quantitative PET imaging may be an important tool for these applications. Currently radiotherapy planning accounts for tumor motion by applying geometric margins. These margins create a motion envelope to encompass the most probable positions of the tumor, while also maintaining the appropriate tumor control and normal tissue complication probabilities. This motion envelope is effective for uniform dose prescriptions where the therapeutic dose is conformed to the external margins of the tumor. However, much research is needed to establish the equivalent margins for non-uniform fields, where multiple biological targets are present and each target is prescribed its own dose level. Additionally, the size of the biological targets and close proximity make it impractical to apply planning margins on the sub-tumor level. Also, the extent of high dose regions must be limited to avoid excessive dose to the surrounding tissue. As such, this research project is an investigation of the uncertainty within quantitative PET images of moving and displaced dose-painting targets, and an investigation of the residual errors that remain after motion management. This included characterization of the changes in PET voxel-values as objects are moved relative to the discrete sampling interval of PET imaging systems (SPECIFIC AIM 1). Additionally, the repeatability of PET distributions and the delineating dose-painting targets were measured (SPECIFIC AIM 2). The effect of imaging uncertainty on the dose distributions designed using these images (SPECIFIC AIM 3) has also been investigated. This project also included analysis of methods to minimize motion during PET imaging and reduce the dosimetric impact of motion/position-induced imaging uncertainty (SPECIFIC AIM 4).

  16. Prospective assessment of the quality of life before, during and after image guided intensity modulated radiotherapy for prostate cancer.

    PubMed

    Sveistrup, Joen; Mortensen, Ole Steen; Bjørner, Jakob B; Engelholm, Svend Aage; Munck Af Rosenschöld, Per; Petersen, Peter Meidahl

    2016-09-07

    Radiotherapy (RT) in combination with androgen deprivation therapy (ADT) for prostate cancer (PCa) carries a risk of gastrointestinal (GI) and genitourinary toxicity, which might affect the quality of life (QoL). The purpose of this study was to assess the QoL in patients with PCa before, during and after radiotherapy (RT) and to compare the QoL 1 year after RT to a normal population. The QoL was evaluated prospectively by the self-administered questionnaire SF-36 in 87 patients with PCa. The SF-36 was completed before RT (baseline), at start of RT, at end of RT and 1 year after RT. A mixed model analysis was used to determine the changes in QoL at each time point compared to baseline. The patients' QoL 1 year after RT was compared to a normal population consisting of 462 reference subjects matched on age and education. One year after RT, patients reported significantly less pain and significantly fewer limitations due to their physical health compared to baseline. Compared to the normal population, patients reported significantly less pain 1 year after RT. However, patients also reported significantly less vitality, worse mental health as well as significantly more limitations due to physical and mental health 1 year after RT compared to the normal population. In this study, patients with PCa did not experience significant impairment in the QoL 1 year after RT compared to baseline. However, patients reported significantly worse mental health before, during and 1 year after RT compared to the normal population.

  17. Rotation to methadone after opioid dose escalation: How should individualization of dosing occur?

    PubMed

    Zimmermann, Camilla; Seccareccia, Dori; Booth, Christopher M; Cottrell, Wayne

    2005-01-01

    Methadone is a synthetic opioid agonist and N-methyl-D-aspartate (NMDA) receptor antagonist that is being increasingly used in pain management, particularly for pain that is resistant to conventional opioids. We describe two patients with neurotoxic side effects on escalating doses of parenteral hydromorphone with uncontrolled cancer pain who were successfully converted to oral methadone at a dose much smaller than predicted. The phenomenon of increasing pain despite opioid dose escalation is discussed and the rationale for the use of methadone in this situation is described. While methadone is useful for patients with unremitting pain on another opioid, existing conversion regimens do not specifically take into account the setting of dose escalation. Clinical guidelines for rotation to methadone after dose escalation of the previous opioid are needed to avoid toxicity including respiratory depression. A possible conversion method for rotation to methadone for patients with escalating pain and opioid use is suggested.

  18. Clinical Feasibility of Using an EPID in cine Mode for Image-Guided Verification of Stereotactic Body Radiotherapy

    SciTech Connect

    Berbeco, Ross I.

    2007-09-01

    Purpose: To introduce a novel method for monitoring tumor location during stereotactic body radiotherapy (SBRT) while the treatment beam is on by using a conventional electronic portal imaging device (EPID). Methods and Materials: In our clinic, selected patients were treated under a phase I institutional review board-approved SBRT protocol for limited hepatic metastases from solid tumors. Before treatment planning multiple gold fiducial markers were implanted on the periphery of the tumor. During treatment the EPID was used in cine mode to collect the exit radiation and produce a sequence of images for each field. An in-house program was developed for calculating the location of the fiducials and their relative distance to the planned locations. Results: Three case studies illustrate the utility of the technique. Patient A exhibited a systematic shift of 4 mm during one of the treatment beams. Patient B showed an inferior drift of the target of approximately 1 cm from the time of setup to the end of the fraction. Patient C had a poor setup on the first day of treatment that was quantified and accounted for on subsequent treatment days. Conclusions: Target localization throughout each treatment beam can be quickly assessed with the presented technique. Treatment monitoring with an EPID in cine mode is shown to be a clinically feasible and useful tool.

  19. Outcome of Elderly Patients with Meningioma after Image-Guided Stereotactic Radiotherapy: A Study of 100 Cases

    PubMed Central

    Budach, Volker; Graaf, Lukas; Gollrad, Johannes; Badakhshi, Harun

    2015-01-01

    Introduction. Incidence of meningioma increases with age. Surgery has been the mainstay treatment. Elderly patients, however, are at risk of severe morbidity. Therefore, we conducted this study to analyze long-term outcomes of linac-based fractionated stereotactic radiotherapy (FSRT) for older adults (aged ≥65 years) with meningioma and determine prognostic factors. Materials and Methods. Between October 1998 and March 2009, 100 patients (≥65, median age, 71 years) were treated with FSRT for meningioma. Two patients were lost to follow-up. Eight patients each had grade I and grade II meningiomas, and five patients had grade III meningiomas. The histology was unknown in 77 cases (grade 0). Results. The median follow-up was 37 months, and 3-year, 5-year, and 10-year progression-free survival (PFS) rates were 93.7%, 91.1%, and 82%. Patients with grade 0/I meningioma showed 3- and 5-year PFS rates of 98.4% and 95.6%. Patients with grade II or III meningiomas showed 3-year PFS rates of 36%. 93.8% of patients showed local tumor control. Multivariate analysis did not indicate any significant prognostic factors. Conclusion. FSRT may play an important role as a noninvasive and safe method in the clinical management of older patients with meningioma. PMID:26101778

  20. SU-E-J-12: An Image-Guided Soft Robotic Patient Positioning System for Maskless Head-And-Neck Cancer Radiotherapy: A Proof-Of-Concept Study

    SciTech Connect

    Ogunmolu, O; Gans, N; Jiang, S; Gu, X

    2015-06-15

    Purpose: We propose a surface-image-guided soft robotic patient positioning system for maskless head-and-neck radiotherapy. The ultimate goal of this project is to utilize a soft robot to realize non-rigid patient positioning and real-time motion compensation. In this proof-of-concept study, we design a position-based visual servoing control system for an air-bladder-based soft robot and investigate its performance in controlling the flexion/extension cranial motion on a mannequin head phantom. Methods: The current system consists of Microsoft Kinect depth camera, an inflatable air bladder (IAB), pressured air source, pneumatic valve actuators, custom-built current regulators, and a National Instruments myRIO microcontroller. The performance of the designed system was evaluated on a mannequin head, with a ball joint fixed below its neck to simulate torso-induced head motion along flexion/extension direction. The IAB is placed beneath the mannequin head. The Kinect camera captures images of the mannequin head, extracts the face, and measures the position of the head relative to the camera. This distance is sent to the myRIO, which runs control algorithms and sends actuation commands to the valves, inflating and deflating the IAB to induce head motion. Results: For a step input, i.e. regulation of the head to a constant displacement, the maximum error was a 6% overshoot, which the system then reduces to 0% steady-state error. In this initial investigation, the settling time to reach the regulated position was approximately 8 seconds, with 2 seconds of delay between the command start of motion due to capacitance of the pneumatics, for a total of 10 seconds to regulate the error. Conclusion: The surface image-guided soft robotic patient positioning system can achieve accurate mannequin head flexion/extension motion. Given this promising initial Result, the extension of the current one-dimensional soft robot control to multiple IABs for non-rigid positioning control

  1. Definition and visualisation of regions of interest in post-prostatectomy image-guided intensity modulated radiotherapy

    SciTech Connect

    Bell, Linda J Cox, Jennifer; Eade, Thomas; Rinks, Marianne; Kneebone, Andrew

    2014-09-15

    Standard post-prostatectomy radiotherapy (PPRT) image verification uses bony anatomy alignment. However, the prostate bed (PB) moves independently of bony anatomy. Cone beam computed tomography (CBCT) can be used to soft tissue match, so radiation therapists (RTs) must understand pelvic anatomy and PPRT clinical target volumes (CTV). The aims of this study are to define regions of interest (ROI) to be used in soft tissue matching image guidance and determine their visibility on planning CT (PCT) and CBCT. Published CTV guidelines were used to select ROIs. The PCT scans (n = 23) and CBCT scans (n = 105) of 23 post-prostatectomy patients were reviewed. Details on ROI identification were recorded. Eighteen patients had surgical clips. All ROIs were identified on PCTs at least 90% of the time apart from mesorectal fascia (MF) (87%) due to superior image quality. When surgical clips are present, the seminal vesicle bed (SVB) was only seen in 2.3% of CBCTs and MF was unidentifiable. Most other structures were well identified on CBCT. The anterior rectal wall (ARW) was identified in 81.4% of images and penile bulb (PB) in 68.6%. In the absence of surgical clips, the MF and SVB were always identified; the ARW was identified in 89.5% of CBCTs and PB in 73.7%. Surgical clips should be used as ROIs when present to define SVB and MF. In the absence of clips, SVB, MF and ARW can be used. RTs must have a strong knowledge of soft tissue anatomy and PPRT CTV to ensure coverage and enable soft tissue matching.

  2. Technical feasibility of integrating 7 T anatomical MRI in image-guided radiotherapy of glioblastoma: a preparatory study.

    PubMed

    Compter, Inge; Peerlings, Jurgen; Eekers, Daniëlle B P; Postma, Alida A; Ivanov, Dimo; Wiggins, Christopher J; Kubben, Pieter; Küsters, Benno; Wesseling, Pieter; Ackermans, Linda; Schijns, Olaf E M G; Lambin, Philippe; Hoffmann, Aswin L

    2016-06-01

    The use of 7 Tesla (T) magnetic resonance imaging (MRI) has recently shown great potential for high-resolution soft-tissue neuroimaging and visualization of microvascularization in glioblastoma (GBM). We have designed a clinical trial to explore the value of 7 T MRI in radiation treatment of GBM. For this aim we performed a preparatory study to investigate the technical feasibility of incorporating 7 T MR images into the neurosurgical navigation and radiotherapy treatment planning (RTP) systems via qualitative and quantitative assessment of the image quality. The MR images were acquired with a Siemens Magnetom 7 T whole-body scanner and a Nova Medical 32-channel head coil. The 7 T MRI pulse sequences included magnetization-prepared two rapid acquisition gradient echoes (MP2RAGE), T2-SPACE, SPACE-FLAIR and gradient echo sequences (GRE). A pilot study with three healthy volunteers and an anthropomorphic 3D phantom was used to assess image quality and geometrical image accuracy. The MRI scans were well tolerated by the volunteers. Susceptibility artefacts were observed in both the cortex and subcortical white matter at close proximity to air-tissue interfaces. Regional loss of signal and contrast could be minimized by the use of dielectric pads. Image transfer and processing did not degrade image quality. The system-related spatial uncertainty of geometrical distortion-corrected MP2RAGE pulse sequences was ≤2 mm. Integration of high-quality and geometrically-reliable 7 T MR images into neurosurgical navigation and RTP software is technically feasible and safe.

  3. Intrafraction Variation of Mean Tumor Position During Image-Guided Hypofractionated Stereotactic Body Radiotherapy for Lung Cancer

    SciTech Connect

    Shah, Chirag; Grills, Inga S.; Kestin, Larry L.; McGrath, Samuel; Ye Hong; Martin, Shannon K.; Yan Di

    2012-04-01

    Purpose: Prolonged delivery times during daily cone-beam computed tomography (CBCT)-guided lung stereotactic body radiotherapy (SBRT) introduce concerns regarding intrafraction variation (IFV) of the mean target position (MTP). The purpose of this study was to evaluate the magnitude of the IFV-MTP and to assess target margins required to compensate for IFV and postonline CBCT correction residuals. Patient, treatment, and tumor characteristics were analyzed with respect to their impact on IFV-MTP. Methods and Materials: A total of 126 patients with 140 tumors underwent 659 fractions of lung SBRT. Dose prescribed was 48 or 60 Gy in 12 Gy fractions. Translational target position correction of the MTP was performed via onboard CBCT. IFV-MTP was measured as the difference in MTP between the postcorrection CBCT and the posttreatment CBCT excluding residual error. Results: IFV-MTP was 0.2 {+-} 1.8 mm, 0.1 {+-} 1.9 mm, and 0.01 {+-} 1.5 mm in the craniocaudal, anteroposterior, and mediolateral dimensions and the IFV-MTP vector was 2.3 {+-} 2.1 mm. Treatment time and excursion were found to be significant predictors of IFV-MTP. An IFV-MTP vector greater than 2 and 5 mm was seen in 40.8% and 7.2% of fractions, respectively. IFV-MTP greater than 2 mm was seen in heavier patients with larger excursions and longer treatment times. Significant differences in IFV-MTP were seen between immobilization devices. The stereotactic frame immobilization device was found to be significantly less likely to have an IFV-MTP vector greater than 2 mm compared with the alpha cradle, BodyFIX, and hybrid immobilization devices. Conclusions: Treatment time and respiratory excursion are significantly associated with IFV-MTP. Significant differences in IFV-MTP were found between immobilization devices. Target margins for IFV-MTP plus post-correction residuals are dependent on immobilization device with 5-mm uniform margins being acceptable for the frame immobilization device.

  4. Esophageal Cancer Dose Escalation Using a Simultaneous Integrated Boost Technique

    SciTech Connect

    Welsh, James; Palmer, Matthew B.; Ajani, Jaffer A.; Liao Zhongxing; Swisher, Steven G.; Hofstetter, Wayne L.; Allen, Pamela K.; Settle, Steven H.; Gomez, Daniel; Likhacheva, Anna; Cox, James D.; Komaki, Ritsuko

    2012-01-01

    Purpose: We previously showed that 75% of radiation therapy (RT) failures in patients with unresectable esophageal cancer are in the gross tumor volume (GTV). We performed a planning study to evaluate if a simultaneous integrated boost (SIB) technique could selectively deliver a boost dose of radiation to the GTV in patients with esophageal cancer. Methods and Materials: Treatment plans were generated using four different approaches (two-dimensional conformal radiotherapy [2D-CRT] to 50.4 Gy, 2D-CRT to 64.8 Gy, intensity-modulated RT [IMRT] to 50.4 Gy, and SIB-IMRT to 64.8 Gy) and optimized for 10 patients with distal esophageal cancer. All plans were constructed to deliver the target dose in 28 fractions using heterogeneity corrections. Isodose distributions were evaluated for target coverage and normal tissue exposure. Results: The 50.4 Gy IMRT plan was associated with significant reductions in mean cardiac, pulmonary, and hepatic doses relative to the 50.4 Gy 2D-CRT plan. The 64.8 Gy SIB-IMRT plan produced a 28% increase in GTV dose and comparable normal tissue doses as the 50.4 Gy IMRT plan; compared with the 50.4 Gy 2D-CRT plan, the 64.8 Gy SIB-IMRT produced significant dose reductions to all critical structures (heart, lung, liver, and spinal cord). Conclusions: The use of SIB-IMRT allowed us to selectively increase the dose to the GTV, the area at highest risk of failure, while simultaneously reducing the dose to the normal heart, lung, and liver. Clinical implications warrant systematic evaluation.

  5. SU-E-J-47: Development of a High-Precision, Image-Guided Radiotherapy, Multi- Purpose Radiation Isocenter Quality-Assurance Calibration and Checking System

    SciTech Connect

    Liu, C; Yan, G; Helmig, R; Lebron, S; Kahler, D

    2014-06-01

    Purpose: To develop a system that can define the radiation isocenter and correlate this information with couch coordinates, laser alignment, optical distance indicator (ODI) settings, optical tracking system (OTS) calibrations, and mechanical isocenter walkout. Methods: Our team developed a multi-adapter, multi-purpose quality assurance (QA) and calibration device that uses an electronic portal imaging device (EPID) and in-house image-processing software to define the radiation isocenter, thereby allowing linear accelerator (Linac) components to be verified and calibrated. Motivated by the concept that each Linac component related to patient setup for image-guided radiotherapy based on cone-beam CT should be calibrated with respect to the radiation isocenter, we designed multiple concentric adapters of various materials and shapes to meet the needs of MV and KV radiation isocenter definition, laser alignment, and OTS calibration. The phantom's ability to accurately define the radiation isocenter was validated on 4 Elekta Linacs using a commercial ball bearing (BB) phantom as a reference. Radiation isocenter walkout and the accuracy of couch coordinates, ODI, and OTS were then quantified with the device. Results: The device was able to define the radiation isocenter within 0.3 mm. Radiation isocenter walkout was within ±1 mm at 4 cardinal angles. By switching adapters, we identified that the accuracy of the couch position digital readout, ODI, OTS, and mechanical isocenter walkout was within sub-mm. Conclusion: This multi-adapter, multi-purpose isocenter phantom can be used to accurately define the radiation isocenter and represents a potential paradigm shift in Linac QA. Moreover, multiple concentric adapters allowed for sub-mm accuracy for the other relevant components. This intuitive and user-friendly design is currently patent pending.

  6. SU-E-J-151: Dosimetric Evaluation of DIR Mapped Contours for Image Guided Adaptive Radiotherapy with 4D Cone-Beam CT

    SciTech Connect

    Balik, S; Weiss, E; Williamson, J; Hugo, G; Jan, N; Zhang, L; Roman, N; Christensen, G

    2014-06-01

    Purpose: To estimate dosimetric errors resulting from using contours deformably mapped from planning CT to 4D cone beam CT (CBCT) images for image-guided adaptive radiotherapy of locally advanced non-small cell lung cancer (NSCLC). Methods: Ten locally advanced non-small cell lung cancer (NSCLC) patients underwent one planning 4D fan-beam CT (4DFBCT) and weekly 4DCBCT scans. Multiple physicians delineated the gross tumor volume (GTV) and normal structures in planning CT images and only GTV in CBCT images. Manual contours were mapped from planning CT to CBCTs using small deformation, inverse consistent linear elastic (SICLE) algorithm for two scans in each patient. Two physicians reviewed and rated the DIR-mapped (auto) and manual GTV contours as clinically acceptable (CA), clinically acceptable after minor modification (CAMM) and unacceptable (CU). Mapped normal structures were visually inspected and corrected if necessary, and used to override tissue density for dose calculation. CTV (6mm expansion of GTV) and PTV (5mm expansion of CTV) were created. VMAT plans were generated using the DIR-mapped contours to deliver 66 Gy in 33 fractions with 95% and 100% coverage (V66) to PTV and CTV, respectively. Plan evaluation for V66 was based on manual PTV and CTV contours. Results: Mean PTV V66 was 84% (range 75% – 95%) and mean CTV V66 was 97% (range 93% – 100%) for CAMM scored plans (12 plans); and was 90% (range 80% – 95%) and 99% (range 95% – 100%) for CA scored plans (7 plans). The difference in V66 between CAMM and CA was significant for PTV (p = 0.03) and approached significance for CTV (p = 0.07). Conclusion: The quality of DIR-mapped contours directly impacted the plan quality for 4DCBCT-based adaptation. Larger safety margins may be needed when planning with auto contours for IGART with 4DCBCT images. Reseach was supported by NIH P01CA116602.

  7. Interfractional Prostate Shifts: Review of 1870 Computed Tomography (CT) Scans Obtained During Image-Guided Radiotherapy Using CT-on-Rails for the Treatment of Prostate Cancer

    SciTech Connect

    Wong, James R. Gao Zhanrong; Uematsu, Minoru; Merrick, Scott; Machernis, Nolan P.; Chen, Timothy; Cheng, C.W.

    2008-12-01

    Purpose: To review 1870 CT scans of interfractional prostate shift obtained during image-guided radiotherapy. Methods and Materials: A total of 1870 pretreatment CT scans were acquired with CT-on-rails, and the corresponding shift data for 329 patients with prostate cancer were analyzed. Results: Of the 1870 scans reviewed, 44% required no setup adjustments in the anterior-posterior (AP) direction, 14% had shifts of 3-5 mm, 29% had shifts of 6-10 mm, and 13% had shifts of >10 mm. In the superior-inferior direction, 81% had no adjustments, 2% had shifts of 3-5 mm, 15% had shifts of 6-10 mm, and 2% had shifts of >10 mm. In the left-right direction, 65% had no adjustment, 13% had shifts of 3-5 mm, 17% had shifts of 6-10 mm, and 5% had shifts of >10 mm. Further analysis of the first 66 consecutive patients divided into three groups according to body mass index indicates that the shift in the AP direction for the overweight subgroup was statistically larger than those for the control and obese subgroups (p < 0.05). The interfractional shift in the lateral direction for the obese group (1 SD, 5.5 mm) was significantly larger than those for the overweight and control groups (4.1 and 2.9 mm, respectively) (p < 0.001). Conclusions: These data demonstrate that there is a significantly greater shift in the AP direction than in the lateral and superior-inferior directions for the entire patient group. Overweight and obese patient groups show a significant difference from the control group in terms of prostate shift.

  8. Residual Seminal Vesicle Displacement in Marker-Based Image-Guided Radiotherapy for Prostate Cancer and the Impact on Margin Design

    SciTech Connect

    Smitsmans, Monique H.P.; Bois, Josien de; Sonke, Jan-Jakob; Catton, Charles N.; Jaffray, David A.; Lebesque, Joos V.; Herk, Marcel van

    2011-06-01

    Purpose: The objectives of this study were to quantify residual interfraction displacement of seminal vesicles (SV) and investigate the efficacy of rotation correction on SV displacement in marker-based prostate image-guided radiotherapy (IGRT). We also determined the effect of marker registration on the measured SV displacement and its impact on margin design. Methods and Materials: SV displacement was determined relative to marker registration by using 296 cone beam computed tomography scans of 13 prostate cancer patients with implanted markers. SV were individually registered in the transverse plane, based on gray-value information. The target registration error (TRE) for the SV due to marker registration inaccuracies was estimated. Correlations between prostate gland rotations and SV displacement and between individual SV displacements were determined. Results: The SV registration success rate was 99%. Displacement amounts of both SVs were comparable. Systematic and random residual SV displacements were 1.6 mm and 2.0 mm in the left-right direction, respectively, and 2.8 mm and 3.1 mm in the anteroposterior (AP) direction, respectively. Rotation correction did not reduce residual SV displacement. Prostate gland rotation around the left-right axis correlated with SV AP displacement (R{sup 2} = 42%); a correlation existed between both SVs for AP displacement (R{sup 2} = 62%); considerable correlation existed between random errors of SV displacement and TRE (R{sup 2} = 34%). Conclusions: Considerable residual SV displacement exists in marker-based IGRT. Rotation correction barely reduced SV displacement, rather, a larger SV displacement was shown relative to the prostate gland that was not captured by the marker position. Marker registration error partly explains SV displacement when correcting for rotations. Correcting for rotations, therefore, is not advisable when SV are part of the target volume. Margin design for SVs should take these uncertainties into

  9. Scapula alata in early breast cancer patients enrolled in a randomized clinical trial of post-surgery short-course image-guided radiotherapy

    PubMed Central

    2012-01-01

    Background Scapula alata (SA) is a known complication of breast surgery associated with palsy of the serratus anterior, but it is seldom mentioned. We evaluated the risk factors associated with SA and the relationship of SA with ipsilateral shoulder/arm morbidity in a series of patients enrolled in a trial of post-surgery radiotherapy (RT). Methods The trial randomized women with completely resected stage I-II breast cancer to short-course image-guided RT, versus conventional RT. SA, arm volume and shoulder-arm mobility were measured prior to RT and at one to three months post-RT. Shoulder/arm morbidities were computed as a post-RT percentage change relative to pre-RT measurements. Results Of 119 evaluable patients, 13 (= 10.9%) had pre-RT SA. Age younger than 50 years old, a body mass index less than 25 kg/m2, and axillary lymph node dissection were significant risk factors, with odds ratios of 4.8 (P = 0.009), 6.1 (P = 0.016), and 6.1 (P = 0.005), respectively. Randomization group was not significant. At one to three months’ post-RT, mean arm volume increased by 4.1% (P = 0.036) and abduction decreased by 8.6% (P = 0.046) among SA patients, but not among non-SA patients. SA resolved in eight, persisted in five, and appeared in one patient. Conclusion The relationship of SA with lower body mass index suggests that SA might have been underestimated in overweight patients. Despite apparent resolution of SA in most patients, pre-RT SA portended an increased risk of shoulder/arm morbidity. We argue that SA warrants further investigation. Incidentally, the observation of SA occurring after RT in one patient represents the second case of post-RT SA reported in the literature. PMID:22591589

  10. Positron Emission Tomography for Pre-Clinical Sub-Volume Dose Escalation

    NASA Astrophysics Data System (ADS)

    Bass, Christopher Paul

    Purpose: This dissertation focuses on establishment of pre-clinical methods facilitating the use of PET imaging for selective sub-volume dose escalation. Specifically the problems addressed are 1.) The difficulties associated with comparing multiple PET images, 2.) The need for further validation of novel PET tracers before their implementation in dose escalation schema and 3.) The lack of concrete pre-clinical data supporting the use of PET images for guidance of selective sub-volume dose escalations. Methods and materials: In order to compare multiple PET images the confounding effects of mispositioning and anatomical change between imaging sessions needed to be alleviated. To mitigate the effects of these sources of error, deformable image registration was employed. A deformable registration algorithm was selected and the registration error was evaluated via the introduction of external fiducials to the tumor. Once a method for image registration was established, a procedure for validating the use of novel PET tracers with FDG was developed. Nude mice were used to perform in-vivo comparisons of the spatial distributions of two PET tracers, FDG and FLT. The spatial distributions were also compared across two separate tumor lines to determine the effects of tumor morphology on spatial distribution. Finally, the research establishes a method for acquiring pre-clinical data supporting the use of PET for image-guidance in selective dose escalation. Nude mice were imaged using only FDG PET/CT and the resulting images were used to plan PET-guided dose escalations to a 5 mm sub-volume within the tumor that contained the highest PET tracer uptake. These plans were then delivered using the Small Animal Radiation Research Platform (SARRP) and the efficacy of the PET-guided plans was observed. Results and Conclusions: The analysis of deformable registration algorithms revealed that the BRAINSFit B-spline deformable registration algorithm available in SLICER3D was capable of

  11. Image-Guided Stereotactic Body Radiotherapy for Lung Tumors Using BodyLoc With Tomotherapy: Clinical Implementation and Set-Up Accuracy

    SciTech Connect

    Zhou Jining Uhl, Barry; Dewitt, Kelly; Young, Mark; Taylor, Brian; Fei Dingyu; Lo, Y-C

    2010-04-01

    We investigated the use of a BodyLoc immobilization and stereotactic localization device combined with TomoTherapy megavoltage CT (MVCT) in lung stereotactic body radiotherapy (SBRT) to reduce set-up uncertainty and treatment time. Eight patients treated with 3-5 fractions of SBRT were retrospectively analyzed. A BodyLoc localizer was used in both CT simulation for localization and the initial patient treatment set-up. Patients were immobilized with a vacuum cushion on the back and a thermoplastic body cast on the anterior body. Pretreatment MVCT from the TomoTherapy unit was fused with the planning kilovoltage CT (KVCT) before each fraction of treatment to determine interfractional set-up error. The comparison of two MVCTs during a fraction of treatment resulted in the intrafractional uncertainty of the treatment. A total of 224 target isocenter shifts were analyzed to assess these inter- and intrafractional tumor motions. We found that for interfractional shifts, the mean set-up errors and standard deviations were -1.1 {+-} 2.8 mm, -2.5 {+-} 8.7 mm, and 4.1 {+-} 2.6 mm, for lateral, longitudinal, and vertical variation, respectively; the mean setup rotational variation was -0.3 {+-} 0.7 deg.; and the maximum motion was 13.5 mm in the longitudinal direction. For intrafractional shifts, the mean set-up errors and standard deviations were -0.1 {+-} 0.7 mm, -0.3 {+-} 2.0 mm, and 0.5 {+-} 1.1 mm for the lateral, longitudinal, and vertical shifts, respectively; the mean rotational variation was 0.1 {+-} 0.2 deg.; and the maximum motion was 3.8 mm in the longitudinal direction. There was no correlation among patient characteristics, set-up uncertainties, and isocenter shifts, and the interfractional set-up uncertainties were larger than the intrafractional isocenter shift. The results of this study suggested that image-guided stereotactic body radiotherapy using the BodyLoc immobilization system with TomoTherapy can improve treatment accuracy.

  12. Treatment outcomes and patterns of radiologic appearance after hypofractionated image-guided radiotherapy delivered with helical tomotherapy (HHT) for lung tumours.

    PubMed

    Arcangeli, Stefano; Falcinelli, Lorenzo; Bracci, Stefano; Greco, Alessandro; Monaco, Alessia; Dognini, Jessica; Chiostrini, Cinzia; Bellavita, Rita; Aristei, Cynthia; Donato, Vittorio

    2017-03-01

    To evaluate treatment outcomes and patterns of CT lung injury after hypofractionated image-guided radiotherapy delivered with helical tomotherapy (HHT) in a series of inoperable lung lesions. 68 patients who were medically inoperable (69 lesions) without evidence of viable extrathoracic disease were included. Dose prescription was driven by tumour location (hilar/pericentral vs peripheral) and/or target volume. 52% of the lesions received a biological equivalent dose (BED10) ≥100 Gy. Assessment of tumour response was based on the Response Evaluation Criteria in Solid Tumours 1.1 criteria coupled with fluorine-18 fludeoxyglucose/positron emission tomography-CT. Toxicity monitoring was focused on treatment-related pulmonary adverse events according to the Common Terminology Criteria for Adverse Events v. 4.0. Acute and late events were classified as radiation pneumonitis (RP) and radiation fibrosis (RF), respectively. Survival curves were calculated using the Kaplan-Meier method. Univariate and multivariate analyses of survival were performed using the Cox proportional hazards model. After a median follow-up of 12 months (range, 3-31 months), no instances of ≥Grade 4 RP was documented, and clinically severe (Grade 3) RP occurred in 5.8% of the patients. 2 (3%) patients developed a late severe (≥Grade 3) symptomatic RF. No specific pattern of CT lung injury was demonstrated, in both acute and late settings. Median overall survival (OS) and progression-free survival (PFS) for the entire population were 30.8 and 14.1 months, respectively. At multivariate analysis (MVA), BED10 ≥ 100 Gy and KPS ≥ 90 emerged as significant prognostic factors for OS (p = 0.01 and p = 0.001, respectively), and BED10 ≥ 100 Gy for PFS (p = 0.02). Our findings show that HHT adjusted for tumour location and/or target volume is an effective treatment with an acceptable toxicity profile in patients who are medically inoperable with lung tumours and is not

  13. The impact of 18 F-FET PET-CT on target definition in image-guided stereotactic radiotherapy in patients with skull base lesions.

    PubMed

    Badakhshi, Harun; Graf, Reinhold; Prasad, Vikas; Budach, Volker

    2014-06-25

    as targets for Image-guided stereotactic Radiotherapy. This has to be investigated prospectively in larger cohorts.

  14. Accuracy and efficiency of an infrared based positioning and tracking system for patient set-up and monitoring in image guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Jia, Jing; Xu, Gongming; Pei, Xi; Cao, Ruifen; Hu, Liqin; Wu, Yican

    2015-03-01

    monitoring during image guided radiotherapy treatments.

  15. SU-E-J-14: A Novel Approach to Evaluate the Dosimetric Effect of Rectal Variation During Image Guided Prostate Radiotherapy

    SciTech Connect

    Murray, J; McQuaid, D; Dunlop, A; Nill, S; Gulliford, S; Buettner, F; Hall, E; Dearnaley, D

    2014-06-01

    Purpose: Deformable registration establishes the spatial correspondence back to the reference image in order to accumulate dose. However, in prostate radiotherapy the changing shape and volume of the rectum present a challenge to accurate deformable registration and consequently calculation of delivered dose. We explored an alternative approach to calculating accumulated dose to the rectum, independent of deformable registration. Methods: This study was performed on three patients who received online image-guided radiotherapy (IGRT) with daily CBCT (XVI-system,Elekta) and target localization using intraprostatic fiducials. On each CBCT, the rectum was manually contoured and bulk density assignments were made allowing dose to be calculated for each fraction. Dose-surface maps (DSM) were generated (MATLAB,Mathworks,Natick,MA) by considering the rectum as a cylinder and sampling the dose at 21-equispaced points on each CT slice. The cylinder was “cut” at the posterior-most position on each CT and unfolded to generate a DSM. These were normalised in the longitudinal direction by interpolation creating maps of 21×21 pixels. A DSM was produced for each CBCT and the dose was accumulated. Results: The mean accumulated delivered rectal surface dose was on average 7.5(+/−3.5)% lower than the planned dose. The dose difference maps consistently show that the greatest variation in dose between planned and delivered dose is away from where the rectal surface is adjacent to the prostate. Conclusion: Estimation of dose accumulation using DSM provides an alternative method for determining actual delivered dose to the rectum. The dose difference is greatest in areas away from the region where the rectal surface abuts the prostate, the region where set-up is verified. The change in size and shape of the rectum was shown to resultin a change in the accumulated dose compared to the planned dose and this will have an impact on determining the relationships between dose delivered

  16. A Phase I clinical and pharmacology study using amifostine as a radioprotector in dose-escalated whole liver radiation therapy

    PubMed Central

    Feng, Mary; Smith, David E.; Normolle, Daniel P.; Knol, James A.; Pan, Charlie C.; Ben-Josef, Edgar; Lu, Zheng; Feng, Meihua R.; Chen, Jun; Ensminger, William; Lawrence, Theodore S.

    2011-01-01

    PURPOSE Diffuse intrahepatic tumors are difficult to control. Whole liver radiotherapy has been limited by toxicity, most notably radiation-induced liver disease (RILD). Amifostine is a prodrug free-radical scavenger that selectively protects normal tissues and, in a preclinical model of intrahepatic cancer, systemic amifostine reduced normal liver radiation damage without compromising tumor effect.(1) We hypothesized that amifostine would permit escalation of whole liver radiation dose to potentially control microscopic disease. We also aimed to characterize the pharmacokinetics of amifostine and its active metabolite WR-1065 to optimize timing of radiotherapy. METHODS AND MATERIALS We conducted a radiation dose escalation trial for patients with diffuse, intrahepatic cancer treated with whole liver radiation and intravenous amifostine. Radiation dose was assigned using the Time-to-Event Continual Reassessment Method. A companion pharmacokinetic study was performed. RESULTS 23 patients were treated, with a maximum dose of 40 Gy. Using a logistical regression model, compared to our previously treated patients, amifostine increased liver tolerance by 3.3 ± 1.1 Gy (p=0.007) (approximately 10%) with similar response rates. Peak concentrations of WR-1065 were 25 μM with an elimination half life of 1.5 hours; these levels are consistent with radioprotective effects of amifostine in patients. CONCLUSION These findings demonstrate for the first time that amifostine is a normal liver radioprotector. They further suggest that it may be useful to combine amifostine with fractionated or stereotactic body radiation therapy for patients with focal intrahepatic cancer. PMID:22440042

  17. Functional Image-Guided Radiotherapy Planning in Respiratory-Gated Intensity-Modulated Radiotherapy for Lung Cancer Patients With Chronic Obstructive Pulmonary Disease

    SciTech Connect

    Kimura, Tomoki; Nishibuchi, Ikuno; Murakami, Yuji; Kenjo, Masahiro; Kaneyasu, Yuko; Nagata, Yasushi

    2012-03-15

    Purpose: To investigate the incorporation of functional lung image-derived low attenuation area (LAA) based on four-dimensional computed tomography (4D-CT) into respiratory-gated intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) in treatment planning for lung cancer patients with chronic obstructive pulmonary disease (COPD). Methods and Materials: Eight lung cancer patients with COPD were the subjects of this study. LAA was generated from 4D-CT data sets according to CT values of less than than -860 Hounsfield units (HU) as a threshold. The functional lung image was defined as the area where LAA was excluded from the image of the total lung. Two respiratory-gated radiotherapy plans (70 Gy/35 fractions) were designed and compared in each patient as follows: Plan A was an anatomical IMRT or VMAT plan based on the total lung; Plan F was a functional IMRT or VMAT plan based on the functional lung. Dosimetric parameters (percentage of total lung volume irradiated with {>=}20 Gy [V20], and mean dose of total lung [MLD]) of the two plans were compared. Results: V20 was lower in Plan F than in Plan A (mean 1.5%, p = 0.025 in IMRT, mean 1.6%, p = 0.044 in VMAT) achieved by a reduction in MLD (mean 0.23 Gy, p = 0.083 in IMRT, mean 0.5 Gy, p = 0.042 in VMAT). No differences were noted in target volume coverage and organ-at-risk doses. Conclusions: Functional IGRT planning based on LAA in respiratory-guided IMRT or VMAT appears to be effective in preserving a functional lung in lung cancer patients with COPD.

  18. Fiducial marker guided prostate radiotherapy: a review.

    PubMed

    O'Neill, Angela G M; Jain, Suneil; Hounsell, Alan R; O'Sullivan, Joe M

    2016-12-01

    Image-guided radiotherapy (IGRT) is an essential tool in the accurate delivery of modern radiotherapy techniques. Prostate radiotherapy positioned using skin marks or bony anatomy may be adequate for delivering a relatively homogeneous whole-pelvic radiotherapy dose, but these surrogates are not reliable when using reduced margins, dose escalation or hypofractionated stereotactic radiotherapy. Fiducial markers (FMs) for prostate IGRT have been in use since the 1990s. They require surgical implantation and provide a surrogate for the position of the prostate gland. A variety of FMs are available and they can be used in a number of ways. This review aimed to establish the evidence for using prostate FMs in terms of feasibility, implantation procedures, types of FMs used, FM migration, imaging modalities used and the clinical impact of FMs. A search strategy was defined and a literature search was carried out in Medline. Inclusion and exclusion criteria were applied, which resulted in 50 articles being included in this review. The evidence demonstrates that FMs provide a more accurate surrogate for the position of the prostate than either external skin marks or bony anatomy. A combination of FM alignment and soft-tissue analysis is currently the most effective and widely available approach to ensuring accuracy in prostate IGRT. FM implantation is safe and well tolerated. FM migration is possible but minimal. Standardization of all techniques and procedures in relation to the use of prostate FMs is required. Finally, a clinical trial investigating a non-surgical alternative to prostate FMs is introduced.

  19. Development of an ultrasmall C-band linear accelerator guide for a four-dimensional image-guided radiotherapy system with a gimbaled x-ray head.

    PubMed

    Kamino, Yuichiro; Miura, Sadao; Kokubo, Masaki; Yamashita, Ichiro; Hirai, Etsuro; Hiraoka, Masahiro; Ishikawa, Junzo

    2007-05-01

    We are developing a four-dimensional image-guided radiotherapy system with a gimbaled x-ray head. It is capable of pursuing irradiation and delivering irradiation precisely with the help of an agile moving x-ray head on the gimbals. Requirements for the accelerator guide were established, system design was developed, and detailed design was conducted. An accelerator guide was manufactured and basic beam performance and leakage radiation from the accelerator guide were evaluated at a low pulse repetition rate. The accelerator guide including the electron gun is 38 cm long and weighs about 10 kg. The length of the accelerating structure is 24.4 cm. The accelerating structure is a standing wave type and is composed of the axial-coupled injector section and the side-coupled acceleration cavity section. The injector section is composed of one prebuncher cavity, one buncher cavity, one side-coupled half cavity, and two axial coupling cavities. The acceleration cavity section is composed of eight side-coupled nose reentrant cavities and eight coupling cavities. The electron gun is a diode-type gun with a cerium hexaboride (CeB6) direct heating cathode. The accelerator guide can be operated without any magnetic focusing device. Output beam current was 75 mA with a transmission efficiency of 58%, and the average energy was 5.24 MeV. Beam energy was distributed from 4.95 to 5.6 MeV. The beam profile, measured 88 mm from the beam output hole on the axis of the accelerator guide, was 0.7 mm X 0.9 mm full width at half maximum (FWHM) width. The beam loading line was 5.925 (MeV)-Ib (mA) X 0.00808 (MeV/mA), where Ib is output beam current. The maximum radiation leakage of the accelerator guide at 100 cm from the axis of the accelerator guide was calculated as 0.33 cGy/min at the rated x-ray output of 500 cGy/min from the measured value. This leakage requires no radiation shielding for the accelerator guide itself per IEC 60601-2-1.

  20. Adaptive Image-Guided Radiotherapy (IGRT) Eliminates the Risk of Biochemical Failure Caused by the Bias of Rectal Distension in Prostate Cancer Treatment Planning: Clinical Evidence

    SciTech Connect

    Park, Sean S.; Yan Di; McGrath, Samuel; Dilworth, Joshua T.; Liang Jian; Ye Hong; Krauss, Daniel J.; Martinez, Alvaro A.; Kestin, Larry L.

    2012-07-01

    Purpose: Rectal distension has been shown to decrease the probability of biochemical control. Adaptive image-guided radiotherapy (IGRT) corrects for target position and volume variations, reducing the risk of biochemical failure while yielding acceptable rates of gastrointestinal (GI)/genitourinary (GU) toxicities. Methods and Materials: Between 1998 and 2006, 962 patients were treated with computed tomography (CT)-based offline adaptive IGRT. Patients were stratified into low (n = 400) vs. intermediate/high (n = 562) National Comprehensive Cancer Network (NCCN) risk groups. Target motion was assessed with daily CT during the first week. Electronic portal imaging device (EPID) was used to measure daily setup error. Patient-specific confidence-limited planning target volumes (cl-PTV) were then constructed, reducing the standard PTV and compensating for geometric variation of the target and setup errors. Rectal volume (RV), cross-sectional area (CSA), and rectal volume from the seminal vesicles to the inferior prostate (SVP) were assessed on the planning CT. The impact of these volumetric parameters on 5-year biochemical control (BC) and chronic Grades {>=}2 and 3 GU and GI toxicity were examined. Results: Median follow-up was 5.5 years. Median minimum dose covering cl-PTV was 75.6 Gy. Median values for RV, CSA, and SVP were 82.8 cm{sup 3}, 5.6 cm{sup 2}, and 53.3 cm{sup 3}, respectively. The 5-year BC was 89% for the entire group: 96% for low risk and 83% for intermediate/high risk (p < 0.001). No statistically significant differences in BC were seen with stratification by RV, CSA, and SVP in quartiles. Maximum chronic Grades {>=}2 and 3 GI toxicities were 21.2% and 2.9%, respectively. Respective values for GU toxicities were 15.5% and 4.3%. No differences in GI or GU toxicities were noted when patients were stratified by RV. Conclusions: Incorporation of adaptive IGRT reduces the risk of geometric miss and results in excellent biochemical control that is

  1. Setup deviations for whole-breast radiotherapy with TomoDirect: A comparison of weekly and biweekly image-guided protocols

    NASA Astrophysics Data System (ADS)

    Jung, Jae Hong; Jung, Joo-Young; Bae, Sun Hyun; Moon, Seong Kwon; Cho, Kwang Hwan

    2016-10-01

    The purpose of this study was to compare patient setup deviations for different image-guided protocols (weekly vs. biweekly) that are used in TomoDirect three-dimensional conformal radiotherapy (TD-3DCRT) for whole-breast radiation therapy (WBRT). A total of 138 defined megavoltage computed tomography (MVCT) image sets from 46 breast cancer cases were divided into two groups based on the imaging acquisition times: weekly or biweekly. The mean error, three-dimensional setup displacement error (3D-error), systematic error (Σ), and random error (σ) were calculated for each group. The 3D-errors were 4.29 ± 1.11 mm and 5.02 ± 1.85 mm for the weekly and biweekly groups, respectively; the biweekly error was 14.6% higher than the weekly error. The systematic errors in the roll angle and the x, y, and z directions were 0.48°, 1.72 mm, 2.18 mm, and 1.85 mm for the weekly protocol and 0.21°, 1.24 mm, 1.39 mm, and 1.85 mm for the biweekly protocol. Random errors in the roll angle and the x, y, and z directions were 25.7%, 40.6%, 40.0%, and 40.8% higher in the biweekly group than in the weekly group. For the x, y, and z directions, the distributions of the treatment frequency at less than 5 mm were 98.6%, 91.3%, and 94.2% in the weekly group and 94.2%, 89.9%, and 82.6% in the biweekly group. Moreover, the roll angles with 0 - 1° were 79.7% and 89.9% in the weekly and the biweekly groups, respectively. Overall, the evaluation of setup deviations for the two protocols revealed no significant differences (p > 0.05). Reducing the frequency of MVCT imaging could have promising effects on imaging doses and machine times during treatment. However, the biweekly protocol was associated with increased random setup deviations in the treatment. We have demonstrated a biweekly protocol of TD-3DCRT for WBRT, and we anticipate that our method may provide an alternative approach for considering the uncertainties in the patient setup.

  2. A product of independent beta probabilities dose escalation design for dual-agent phase I trials.

    PubMed

    Mander, Adrian P; Sweeting, Michael J

    2015-04-15

    Dual-agent trials are now increasingly common in oncology research, and many proposed dose-escalation designs are available in the statistical literature. Despite this, the translation from statistical design to practical application is slow, as has been highlighted in single-agent phase I trials, where a 3 + 3 rule-based design is often still used. To expedite this process, new dose-escalation designs need to be not only scientifically beneficial but also easy to understand and implement by clinicians. In this paper, we propose a curve-free (nonparametric) design for a dual-agent trial in which the model parameters are the probabilities of toxicity at each of the dose combinations. We show that it is relatively trivial for a clinician's prior beliefs or historical information to be incorporated in the model and updating is fast and computationally simple through the use of conjugate Bayesian inference. Monotonicity is ensured by considering only a set of monotonic contours for the distribution of the maximum tolerated contour, which defines the dose-escalation decision process. Varied experimentation around the contour is achievable, and multiple dose combinations can be recommended to take forward to phase II. Code for R, Stata and Excel are available for implementation.

  3. SU-C-202-04: Adapting Biologically Optimized Dose Escalation Based On Mid-Treatment PET/CT for Non-Small-Cell Lung Cancer

    SciTech Connect

    Zhang, P; Kuo, L; Yorke, E; Hu, Y; Lockney, N; Mageras, G; Deasy, J; Rimner, A

    2016-06-15

    Purpose: To develop a biological modeling strategy which incorporates the response observed on the mid-treatment PET/CT into a dose escalation design for adaptive radiotherapy of non-small-cell lung cancer. Method: FDG-PET/CT was acquired midway through standard fractionated treatment and registered to pre-treatment planning PET/CT to evaluate radiation response of lung cancer. Each mid-treatment PET voxel was assigned the median SUV inside a concentric 1cm-diameter sphere to account for registration and imaging uncertainties. For each voxel, the planned radiation dose, pre- and mid-treatment SUVs were used to parameterize the linear-quadratic model, which was then utilized to predict the SUV distribution after the full prescribed dose. Voxels with predicted post-treatment SUV≥2 were identified as the resistant target (response arm). An adaptive simultaneous integrated boost was designed to escalate dose to the resistant target as high as possible, while keeping prescription dose to the original target and lung toxicity intact. In contrast, an adaptive target volume was delineated based only on the intensity of mid-treatment PET/CT (intensity arm), and a similar adaptive boost plan was optimized. The dose escalation capability of the two approaches was compared. Result: Images of three patients were used in this planning study. For one patient, SUV prediction indicated complete response and no necessary dose escalation. For the other two, resistant targets defined in the response arm were multifocal, and on average accounted for 25% of the pre-treatment target, compared to 67% in the intensity arm. The smaller response arm targets led to a 6Gy higher mean target dose in the adaptive escalation design. Conclusion: This pilot study suggests that adaptive dose escalation to a biologically resistant target predicted from a pre- and mid-treatment PET/CT may be more effective than escalation based on the mid-treatment PET/CT alone. More plans and ultimately clinical

  4. Potential for dose-escalation and reduction of risk in pancreatic cancer using IMRT optimization with lexicographic ordering and gEUD-based cost functions

    SciTech Connect

    Spalding, Aaron C.; Jee, Kyung-Wook; Vineberg, Karen; Jablonowski, Marla; Fraass, Benedick A.; Pan, Charlie C.; Lawrence, Theodore S.; Ten Haken, Randall K.; Ben-Josef, Edgar

    2007-02-15

    Radiotherapy for pancreatic cancer is limited by the tolerance of local organs at risk (OARs) and frequent overlap of the planning target volume (PTV) and OAR volumes. Using lexicographic ordering (LO), a hierarchical optimization technique, with generalized equivalent uniform dose (gEUD) cost functions, we studied the potential of intensity modulated radiation therapy (IMRT) to increase the dose to pancreatic tumors and to areas of vascular involvement that preclude surgical resection [surgical boost volume (SBV)]. We compared 15 forward planned three-dimensional conformal (3DCRT) and IMRT treatment plans for locally advanced unresectable pancreatic cancer. We created IMRT plans optimized using LO with gEUD-based cost functions that account for the contribution of each part of the resulting inhomogeneous dose distribution. LO-IMRT plans allowed substantial PTV dose escalation compared with 3DCRT; median increase from 52 Gy to 66 Gy (a=-5,p<0.005) and median increase from 50 Gy to 59 Gy (a=-15,p<0.005). LO-IMRT also allowed increases to 85 Gy in the SBV, regardless of a value, along with significant dose reductions in OARs. We conclude that LO-IMRT with gEUD cost functions could allow dose escalation in pancreas tumors with concomitant reduction in doses to organs at risk as compared with traditional 3DCRT.

  5. Radiotherapy in Glioblastoma: the Past, the Present and the Future.

    PubMed

    Gzell, C; Back, M; Wheeler, H; Bailey, D; Foote, M

    2017-01-01

    The aim of this review is to explore the changing utility of radiotherapy in the treatment of patients with glioblastoma over the past 60 years. Together with surgery, radiotherapy has always been the cornerstone of treatment of glioblastoma, but techniques have significantly advanced over this time. The exploration of early two-dimensional techniques, investigation of dose escalation, concomitant chemotherapy and modern techniques, including intensity-modulated radiotherapy, image-guided radiotherapy, and volumetric-modulated arc therapy will be covered. In addition, current controversies including decreasing margin size, re-irradiation, treatment of elderly patients, and novel imaging tracers will be discussed. Future directions including immunotherapy and tumour treating fields are examined. Radiotherapy-based treatments cannot rely solely on advances in chemotherapy or immunotherapy to improve the overall survival of patients with glioblastoma. Radiation oncology needs to continue to develop and improve the delivery, target definition, and dose of radiotherapy to these patients to improve their survival and the toxicity associated with treatment.

  6. Image-guided brachytherapy (IGBT) combined with whole pelvic intensity-modulated radiotherapy (WP-IMRT) for locally advanced cervical cancer: a prospective study from Chiang Mai University Hospital, Thailand

    PubMed Central

    Wanwilairat, Somsak; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Tippanya, Damrongsak; Nopnop, Wannapa; Galalae, Razvan; Chitapanarux, Imjai

    2013-01-01

    Purpose A report of preliminary results and toxicity profiles using image-guided brachytherapy (IGBT) combined with whole pelvic intensity-modulated radiation therapy (WP-IMRT) for locally advanced cervical cancer. Material and methods Fifteen patients with locally advanced cervical cancer were enrolled into the study. WP-IMRT was used to treat the Clinical Target Volume (CTV) with a dose of 45 Gy in 25 fractions. Concurrent cisplatin (40 mg/m2) was prescribed during radiotherapy (RT) on weekly basis. IGBT using computed tomography was performed at the dose of 7 Gy × 4 fractions to the High-Risk Clinical Target Volume (HR-CTV). Results The mean cumulative doses – in terms of equivalent dose of 2 Gy (EQD2) – of IGBT plus WP-IMRT to HR-CTV, bladder, rectum, and sigmoid colon were 88.3, 85.0, 68.2 and 73.6 Gy, respectively. In comparison with standard (point A prescription) dose-volume histograms, volume-based image-guided brachytherapy improved the cumulative doses for bladder of 67%, rectum of 47% and sigmoid of 46%. At the median follow-up time of 14 months, the local control, metastasis-free survival and overall survival rates were 93%, 100% and 93%, respectively. No grade 3-4 acute and late toxicities were observed. Conclusion The combination of image-guided brachytherapy and intensity-modulated radiotherapy improved the dose distribution to tumor volumes and avoided overdose in OARs which could be converted in excellent local control and toxicity profiles. PMID:23634150

  7. A Phase I Clinical and Pharmacology Study Using Amifostine as a Radioprotector in Dose-escalated Whole Liver Radiation Therapy

    SciTech Connect

    Feng, Mary; Smith, David E.; Normolle, Daniel P.; Knol, James A.; Pan, Charlie C.; Ben-Josef, Edgar; Lu Zheng; Feng, Meihua R.; Chen Jun; Ensminger, William; Lawrence, Theodore S.

    2012-08-01

    Purpose: Diffuse intrahepatic tumors are difficult to control. Whole-liver radiotherapy has been limited by toxicity, most notably radiation-induced liver disease. Amifostine is a prodrug free-radical scavenger that selectively protects normal tissues and, in a preclinical model of intrahepatic cancer, systemic amifostine reduced normal liver radiation damage without compromising tumor effect. We hypothesized that amifostine would permit escalation of whole-liver radiation dose to potentially control microscopic disease. We also aimed to characterize the pharmacokinetics of amifostine and its active metabolite WR-1065 to optimize timing of radiotherapy. Methods and Materials: We conducted a radiation dose-escalation trial for patients with diffuse, intrahepatic cancer treated with whole-liver radiation and intravenous amifostine. Radiation dose was assigned using the time-to-event continual reassessment method. A companion pharmacokinetic study was performed. Results: Twenty-three patients were treated, with a maximum dose of 40 Gy. Using a logistical regression model, compared with our previously treated patients, amifostine increased liver tolerance by 3.3 {+-} 1.1 Gy (p = 0.007) (approximately 10%) with similar response rates. Peak concentrations of WR-1065 were 25 {mu}M with an elimination half-life of 1.5 h; these levels are consistent with radioprotective effects of amifostine in patients. Conclusion: These findings demonstrate for the first time that amifostine is a normal liver radioprotector. They further suggest that it may be useful to combine amifostine with fractionated or stereotactic body radiation therapy for patients with focal intrahepatic cancer.

  8. Initial application of a geometric QA tool for integrated MV and kV imaging systems on three image guided radiotherapy systems.

    PubMed

    Mao, Weihua; Speiser, Michael; Medin, Paul; Papiez, Lech; Solberg, Timothy; Xing, Lei

    2011-05-01

    Several linacs with integrated kilovoltage (kV) imaging have been developed for delivery of image guided radiation therapy (IGRT). High geometric accuracy and coincidence of kV imaging systems and megavoltage (MV) beam delivery are essential for successful image guidance. A geometric QA tool has been adapted for routine QA for evaluating and characterizing the geometric accuracy of kV and MV cone-beam imaging systems. The purpose of this work is to demonstrate the application of methodology to routine QA across three IGRT-dedicated linac platforms. It has been applied to a Varian Trilogy (Varian Medical Systems, Palo Alto, CA), an Elekta SynergyS (Elekta, Stockholm, Sweden), and a Brainlab Vero (Brainlab AG, Feldkirchen, Germany). Both the Trilogy and SynergyS linacs are equipped with a retractable kV x-ray tube and a flat panel detector. The Vero utilizes a rotating, rigid ring structure integrating a MV x-ray head mounted on orthogonal gimbals, an electronic portal imaging device (EPID), two kV x-ray tubes, and two fixed flat panel detectors. This dual kV imaging system provides orthogonal radiographs, CBCT images, and real-time fluoroscopic monitoring. Two QA phantoms were built to suit different field sizes. Projection images of a QA phantom were acquired using MV and kV imaging systems at a series of gantry angles. Software developed for this study was used to analyze the projection images and calculate nine geometric parameters for each projection. The Trilogy was characterized five times over one year, while the SynergyS was characterized four times and the Vero once. Over 6500 individual projections were acquired and analyzed. Quantitative geometric parameters of both MV and kV imaging systems, as well as the isocenter consistency of the imaging systems, were successfully evaluated. A geometric tool has been successfully implemented for calibration and QA of integrated kV and MV across a variety of radiotherapy platforms. X-ray source angle deviations up to

  9. Radiobiological Determination of Dose Escalation and Normal Tissue Toxicity in Definitive Chemoradiation Therapy for Esophageal Cancer

    SciTech Connect

    Warren, Samantha; Partridge, Mike; Carrington, Rhys; Hurt, Chris; Crosby, Thomas; Hawkins, Maria A.

    2014-10-01

    Purpose: This study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity. Methods and Materials: Twenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm{sup 3}. A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA{sub 62.5}) was compared to a standard dose plan of 50 Gy/25 fractions (RA{sub 50}). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared. Results: Clinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA{sub 50}) to 56.3% (RA{sub 62.5}), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA{sub 50}) versus 5.6% (RA{sub 62.5}) P<.001 and median lung NTCP 6.5% (RA{sub 50}) versus 7.5% (RA{sub 62.5}) P<.001. Conclusions: Dose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.

  10. Commissioning and quality assurance of the X-ray volume Imaging system of an image-guided radiotherapy capable linear accelerator

    PubMed Central

    Muralidhar, K. R.; Murthy, P. Narayana; Kumar, Rajneesh

    2008-01-01

    An Image-Guided Radiotherapy–capable linear accelerator (Elekta Synergy) was installed at our hospital, which is equipped with a kV x-ray volume imaging (XVI) system and electronic portal imaging device (iViewGT). The objective of this presentation is to describe the results of commissioning measurements carried out on the XVI facility to verify the manufacturer's specifications and also to evolve a QA schedule which can be used to test its performance routinely. The QA program consists of a series of tests (safety features, geometric accuracy, and image quality). These tests were found to be useful to assess the performance of the XVI system and also proved that XVI system is very suitable for image-guided high-precision radiation therapy. PMID:19893694

  11. Phase I dose escalation of doxorubicin chemotherapy in tumor-bearing equidae.

    PubMed

    Théon, A P; Pusterla, N; Magdesian, K G; Wilson, W D

    2013-01-01

    There is no information on the use of doxorubicin in horses with tumors. To determine dose-limiting toxicosis (DLT) and maximum tolerated dose (MTD) of doxorubicin in tumor-bearing horses. Seventeen horses with 34 localized or multicentric advanced tumors. Two-stage dose-ranging design involving intrapatient and interpatient dose escalation. Treatment protocol included 6 treatment cycles given at 3-week intervals with dosages ranging from 40 to 85 mg/m(2). Clinical signs, hematologic, and nonhematologic changes were evaluated. Total doses ranged from 1,127 to 2,900 mg in 12 horses that completed the assigned treatment protocols. The MTD was 75 mg/m(2). Hypersensitivity reactions and neutropenia were dose limiting. Hypersensitivity was dose-dependent but schedule invariant. Neutropenia was dose- and cycle-dependent but dose-escalation schedule invariant. Cardiotoxicity was not observed. The recommended dosage of doxorubicin to treat horses is 70 mg/m(2) given at 3-week intervals as single agent. Adjunctive treatment with antihistamines and nonsteroidal anti-inflammatory drugs is recommended to control hypersensitivity. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  12. An Hourly Dose-Escalation Desensitization Protocol for Aspirin-Exacerbated Respiratory Disease.

    PubMed

    Chen, Justin R; Buchmiller, Brett L; Khan, David A

    2015-01-01

    Aspirin desensitization followed by maintenance therapy effectively improves symptom control in patients with aspirin exacerbated respiratory disease (AERD). The majority of current desensitization protocols use 3-hour dosing intervals and often require 2 to 3 days to complete. We evaluated hourly dose escalations in a subset of patients with chronic rhinosinusitis, nasal polyps, and asthma who historically reacted to aspirin within 1 hour or were avoiding aspirin with the goal of developing a safe and efficient desensitization protocol. Fifty-seven aspirin desensitizations were performed under the hourly protocol. All patients had refractory nasal polyposis as an indication for aspirin desensitization. The clinical characteristics of each subject were analyzed in relation to aspects of his or her reactions during the procedure. Ninety-eight percent of study patients were successfully treated under the hourly protocol, including those with a history of severe reactions and intubation. None required further medication than is available in an outpatient allergy clinic. A total of 96% of reactors recorded a bronchial or naso-ocular reaction within 1 hour of the preceding dose. Of the total patients on this protocol, 40% were able to complete the procedure in a single day, and 60% within 2 days. Patients with AERD who have a history of symptoms less than 1 hour after aspirin exposure can be safely desensitized with a 1-hour dose-escalation protocol that can often be completed in a single day. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  13. A Phase I Dose-Escalation Study (ISIDE-BT-1) of Accelerated IMRT With Temozolomide in Patients With Glioblastoma

    SciTech Connect

    Morganti, Alessio G.; Balducci, Mario; Salvati, Maurizio; Esposito, Vincenzo; Romanelli, Pantaleo; Ferro, Marica; Calista, Franco; Digesu, Cinzia; Macchia, Gabriella; Ianiri, Massimo; Deodato, Francesco; Cilla, Savino; Piermattei, Angelo M.P.; Valentini, Vincenzo; Cellini, Numa; Cantore, Gian Paolo

    2010-05-01

    Purpose: To determine the maximum tolerated dose (MTD) of fractionated intensity-modulated radiotherapy (IMRT) with temozolomide (TMZ) in patients with glioblastoma. Methods and Materials: A Phase I clinical trial was performed. Eligible patients had surgically resected or biopsy-proven glioblastoma. Patients started TMZ (75 mg/day) during IMRT and continued for 1 year (150-200 mg/day, Days 1-5 every 28 days) or until disease progression. Clinical target volume 1 (CTV1) was the tumor bed +- enhancing lesion with a 10-mm margin; CTV2 was the area of perifocal edema with a 20-mm margin. Planning target volume 1 (PTV1) and PTV2 were defined as the corresponding CTV plus a 5-mm margin. IMRT was delivered in 25 fractions over 5 weeks. Only the dose for PTV1 was escalated (planned dose escalation: 60 Gy, 62.5 Gy, 65 Gy) while maintaining the dose for PTV2 (45 Gy, 1.8 Gy/fraction). Dose limiting toxicities (DLT) were defined as any treatment-related nonhematological adverse effects rated as Grade >=3 or any hematological toxicity rated as >=4 by Radiation Therapy Oncology Group (RTOG) criteria. Results: Nineteen consecutive glioblastoma were treated with step-and-shoot IMRT, planned with the inverse approach (dose to the PTV1: 7 patients, 60 Gy; 6 patients, 62.5 Gy; 6 patients, 65 Gy). Five coplanar beams were used to cover at least 95% of the target volume with the 95% isodose line. Median follow-up time was 23 months (range, 8-40 months). No patient experienced DLT. Grade 1-2 treatment-related neurologic and skin toxicity were common (11 and 19 patients, respectively). No Grade >2 late neurologic toxicities were noted. Conclusion: Accelerated IMRT to a dose of 65 Gy in 25 fractions is well tolerated with TMZ at a daily dose of 75 mg.

  14. SU-E-T-500: Dose Escalation Strategy for Lung Cancer Patients Using a Biologically- Guided Target Definition

    SciTech Connect

    Shusharina, N; Khan, F; Choi, N; Sharp, G

    2014-06-01

    Purpose: Dose escalation strategy for lung cancer patients can lead to late symptoms such as pneumonitis and cardiac injury. We propose a strategy to increase radiation dose for improving local tumor control while simultaneously striving to minimize the injury of organs at risk (OAR). Our strategy is based on defining a small, biologically-guided target volume for receiving additional radiation dose. Methods: 106 patients with lung cancer treated with radiotherapy were selected for patients diagnosed with stage II and III disease. Previous research has shown that 50% of the maximum SUV threshold in FDG-PET imaging is appropriate for delineation of the most aggressive part of a tumor. After PET- and CT-derived targets were contoured, an IMRT treatment plan was designed to deliver 60 Gy to the GTV as delineated on a 4D CT (Plan 1). A second plan was designed with additional dose of 18 Gy to the PET-derived volume (Plan 2). A composite plan was generated by the addition of Plan 1 and Plan 2. Results: Plan 1 was compared to the composite plan and increases in OAR dose were assessed. For seven patients on average, lung V5 was increased by 1.4% and V20 by 4.2% for ipsilateral lung and by 13.5% and 7% for contralateral lung. For total lung, V5 and V20 were increased by 4.5% and 4.8% respectively. Mean lung dose was increased by 9.7% for the total lung. The maximum dose to the spinal cord increased by 16% on average. For the heart, V20 increased by 4.2% and V40 by 5.2%. Conclusion: It seems feasible that an additional 18 Gy of radiation dose can be delivered to FDG PET-derived subvolume of the CT-based GTV of the primary tumor without significant increase in total dose to the critical organs such as lungs, spinal cord and heart.

  15. Clinical applications of image guided-intensity modulated radiation therapy (IG-IMRT) for conformal avoidance of normal tissue

    NASA Astrophysics Data System (ADS)

    Gutierrez, Alonso Navar

    2007-12-01

    Recent improvements in imaging technology and radiation delivery have led to the development of advanced treatment techniques in radiotherapy which have opened the door for novel therapeutic approaches to improve the efficacy of radiation cancer treatments. Among these advances is image-guided, intensity modulated radiation therapy (IG-IMRT), in which imaging is incorporated to aid in inter-/intra-fractional target localization and to ensure accurate delivery of precise and highly conformal dose distributions. In principle, clinical implementation of IG-IMRT should improve normal tissue sparing and permit effective biological dose escalation thus widening the radiation therapeutic window and lead to increases in survival through improved local control of primary neoplastic diseases. Details of the development of three clinical applications made possible solely with IG-IMRT radiation delivery techniques are presented: (1) Laparoscopically implanted tissue expander radiotherapy (LITE-RT) has been developed to enhance conformal avoidance of normal tissue during the treatment of intra-abdominopelvic cancers. LITE-RT functions by geometrically displacing surrounding normal tissue and isolating the target volume through the interfractional inflation of a custom-shaped tissue expander throughout the course of treatment. (2) The unique delivery geometry of helical tomotherapy, a novel form of IG-IMRT, enables the delivery of composite treatment plan m which whole brain radiotherapy (WBRT) with hippocampal avoidance, hypothesized to reduce the risk of memory function decline and improve the patient's quality of life, and simultaneously integrated boost to multiple brain metastases to improve intracranial tumor control is achieved. (3) Escalation of biological dose to targets through integrated, selective subvolume boosts have been shown to efficiently increase tumor dose without significantly increasing normal tissue dose. Helical tomotherapy was used to investigate the

  16. SU-E-T-622: Identification and Improvement of Patients Eligible for Dose Escalation with Matched Plans

    SciTech Connect

    Bush, K; Holcombe, C; Kapp, D; Buyyounouski, M; Hancock, S; Xing, L; Atwood, T; King, M

    2014-06-15

    Purpose: Radiation-therapy dose-escalation beyond 80Gy may improve tumor control rates for patients with localized prostate cancer. Since toxicity remains a concern, treatment planners must achieve dose-escalation while still adhering to dose-constraints for surrounding structures. Patientmatching is a machine-learning technique that identifies prior patients that dosimetrically match DVH parameters of target volumes and critical structures prior to actual treatment planning. We evaluated the feasibility of patient-matching in (1)identifying candidates for safe dose-escalation; and (2)improving DVH parameters for critical structures in actual dose-escalated plans. Methods: We analyzed DVH parameters from 319 historical treatment plans to determine which plans could achieve dose-escalation (8640cGy) without exceeding Zelefsky dose-constraints (rectal and bladder V47Gy<53%, and V75.6Gy<30%, max-point dose to rectum of 8550cGy, max dose to PTV< 9504cGy). We then estimated the percentage of cases that could achieve safe dose-escalation using software that enables patient matching (QuickMatch, Siris Medical, Mountain View, CA). We then replanned a case that had violated DVH constraints with DVH parameters from patient matching, in order to determine whether this previously unacceptable plan could be made eligible with this automated technique. Results: Patient-matching improved the percentage of patients eligible for dose-escalation from 40% to 63% (p=4.7e-4, t-test). Using a commercial optimizer augmented with patient-matching, we demonstrated a case where patient-matching improved the toxicity-profile such that dose-escalation would have been possible; this plan was rapidly achieved using patientmatching software. In this patient, all lower-dose constraints were met with both the denovo and patient-matching plan. In the patient-matching plan, maximum dose to the rectum was 8385cGy, while the denovo plan failed to meet the maximum rectal constraint at 8571c

  17. Sorafenib Dose Escalation is Not Uniformly Associated with Blood Pressure Elevations in Normotensive Patients with Advanced Malignancies

    PubMed Central

    Karovic, Sanja; Wen, Yujia; Karrison, Theodore G.; Bakris, George L.; Levine, Matthew R.; House, Larry K.; Wu, Kehua; Thomeas, Vasiliki; Rudek, Michelle A.; Wright, John J.; Cohen, Ezra E.W.; Fleming, Gini F.; Ratain, Mark J.; Maitland, Michael L.

    2014-01-01

    Hypertension with vascular endothelial growth factor (VEGF) receptor inhibitors is associated with superior treatment outcomes for advanced cancer patients. To determine whether increased doses of sorafenib cause incremental increases in blood pressure (BP) we measured 12-hour ambulatory BP in 41 normotensive advanced solid tumor patients in a randomized dose escalation study. After 7 days’ sorafenib (400mg BID) mean diastolic BP (DBP) increased in both study groups. After dose escalation, group A (400mg TID) had marginally significant further increase in 12-hour mean DBP (p=0.053) but group B (600mg BID) did not achieve statistically significant increases (p=0.25). Within groups, individuals varied in BP response to sorafenib dose escalation, but these differences did not correlate with changes in steady state plasma sorafenib concentrations. These findings in normotensive patients suggest BP is a complex pharmacodynamic biomarker of VEGF inhibition. Patients have intrinsic differences in sensitivity to the BP elevating effects of sorafenib. PMID:24637941

  18. Do selective radiation dose escalation and tumour hypoxia status impact the loco-regional tumour control after radio-chemotherapy of head & neck tumours? The ESCALOX protocol.

    PubMed

    Pigorsch, Steffi U; Wilkens, Jan J; Kampfer, Severin; Kehl, Victoria; Hapfelmeier, Alexander; Schläger, Christian; Bier, Henning; Schwaiger, Markus; Combs, Stephanie E

    2017-03-01

    Standard of care primary treatment of carcinoma of locally advanced squamous cell head and neck cancer (LAHNSCC) consists of platinum-based concomitant chemo-irradiation. Despite progress in the treatment of LAHNSCC using modern radiotherapy techniques the outcome remains still poor. Using IMRT with SIB the escalation of total dose to the GTV is possible with the aim to improve clinical outcome. This study tests the hypothesis if radiation dose escalation to the GTV improves 2-year-LRC and -OS after concomitant chemo-irradiation. The ESCALOX trial is a prospective randomized phase III study using cisplatin chemo-irradiation and the SIB-IMRT concept in patients with LAHNSCC of the oral cavity, oropharynx or hypopharynx to escalate the total dose to the GTV up to 80.5 Gy. Chemotherapy is planned either in the 1(st) and 5(th) week (cisplatin 20 mg/m(2)/d d 1-5 and d 29-33) or weekly (cisplatin 40 mg/m(2)/d) during RT. RT is delivered as SIB with total doses of 80.5 Gy/70.0 Gy/56.0 Gy with 2.3 Gy/2.0 Gy and 1.6 Gy in the experimental arm and in the control arm with 70.0 Gy/56.0 Gy with 2.0 Gy and 1.6 Gy. A pre-study with dose escalation up to 77.0 Gy/70.0 Gy/56.0 Gy with 2.2 Gy/2.0 Gy and 1.6 Gy is demanded by the German federal office of radiation protection (BfS). In the translational part of the trial 100 of the randomised patients will be investigated by 18-F-FMiso-PET-CT for the presence and behaviour of tumor hypoxia twice in the week before treatment start. The primary endpoint of the pre-study is acute radiation induced toxicity. Primary endpoint of the main trial is 2-year-LRC. By using the dose escalation up to 80.5 Gy to the GTV of the primary tumor and lymph nodes > 2 cm a LRC benefit of 15% at 2 years should be expected. The ESCALOX trial is supported by Deutsche Forschungsgemeinschaft (DFG); Grant No.: MO-363/4-1. ClinicalTrials.gov Identifier: NCT 01212354 , EudraCT-No.: 2010-021139-15.

  19. Caspofungin dose escalation for invasive candidiasis due to resistant Candida albicans.

    PubMed

    Wiederhold, Nathan P; Najvar, Laura K; Bocanegra, Rosie A; Kirkpatrick, William R; Patterson, Thomas F

    2011-07-01

    Previous in vivo studies have reported caspofungin dose escalation to be effective against Candida glabrata with reduced susceptibility. We hypothesized that higher doses of caspofungin would be effective against invasive candidiasis caused by the more virulent species Candida albicans, including isolates resistant to this echinocandin. Immunocompetent mice were inoculated with one of three C. albicans isolates, including one susceptible and two resistant isolates with different FKS1 hot spot 1 point mutations. Mice received daily caspofungin treatment for 7 days and were then followed off therapy for 2 weeks to assess survival. Kidney tissue and blood were collected, and fungal burden and serum (1 → 3)-β-D-glucan were measured. Significant differences in virulence were observed among the three C. albicans isolates, which translated into differences in responses to caspofungin. The most virulent of the resistant isolates studied (isolate 43001; Fks1p F641S) did not respond to caspofungin doses of up to 10 mg/kg of body weight, as there were no differences in survival (survival range, 0 to 12% with treatment), tissue burden, or (1 → 3)-β-D-glucan concentration compared to those for untreated controls. Higher doses of caspofungin did improve survival against the second resistant isolate (53264; Fks1p S645P) that demonstrated reduced virulence (5 and 10 mg/kg; 80% survival). In contrast, caspofungin doses as low as 1 mg/kg improved survival (85 to 95%) and reduced tissue burden and (1 → 3)-β-D-glucan concentration against the susceptible isolate (ATCC 90028). These data suggest that caspofungin dose escalation for invasive candidiasis may not be consistently effective against resistant C. albicans isolates, and this may be associated with the virulence of the strain.

  20. The Role of Age on Dose Limiting Toxicities (DLTs) in Phase I Dose-escalation Trials

    PubMed Central

    Schwandt, A; Harris, P. J.; Hunsberger, S.; Deleporte, A.; Smith, G. L.; Vulih, D.; Anderson, B. D.; Ivy, S. P.

    2016-01-01

    Purpose Elderly oncology patients are not enrolled in early phase trials in proportion to the numbers of geriatric patients with cancer. There may be concern that elderly patients will not tolerate investigational agents as well as younger patients resulting in a disproportionate number of dose-limiting toxicities (DLTs). Recent single-institution studies provide conflicting data on the relationship between age and DLT. Experimental Design We retrospectively reviewed data about patients treated on single-agent, dose-escalation, phase I clinical trials sponsored by the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute. Patients’ dose levels were described as percentage of maximum tolerated dose (%MTD), the highest dose level at which <33% of patients had a DLT, or recommended phase II dose (RP2D). Mixed-effect logistic regression models were used to analyze relationships between the probability of a DLT and age and other explanatory variables. Results Increasing dose, increasing age, and worsening performance status (PS) were significantly related to an increased probability of a DLT in this model (p<0.05). There was no association between dose level administered and age (p=0.57). Conclusions This analysis of phase I dose-escalation trials involving over 500 patients older than 70 years of age, is the largest reported. As age and dose level increased and PS worsened, the probability of a DLT increased. While increasing age was associated with occurrence of DLT, this risk remained within accepted thresholds of risk for phase I trials. There was no evidence of age bias on enrollment of patients on low or high dose levels. PMID:25028396

  1. Successful Within-patient Dose Escalation of Olipudase Alfa in Acid Sphingomyelinase Deficiency

    PubMed Central

    Wasserstein, Melissa P.; Jones, Simon A.; Soran, Handrean; Diaz, George A.; Lippa, Natalie; Thurberg, Beth L.; Culm-Merdek, Kerry; Shamiyeh, Elias; Inguilizian, Haig; Cox, Gerald F.; Puga, Ana Cristina

    2015-01-01

    Background Olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is an investigational enzyme replacement therapy (ERT) for patients with ASM deficiency [ASMD; Niemann-Pick Disease (NPD) A and B]. This open-label phase 1b study assessed the safety and tolerability of olipudase alfa using within-patient dose escalation to gradually debulk accumulated sphingomyelin and mitigate the rapid production of metabolites, which can be toxic. Secondary objectives were pharmacokinetics, pharmacodynamics, and exploratory efficacy. Methods Five adults with nonneuronopathic ASMD (NPD B) received escalating doses (0.1 to 3.0 mg/kg) of olipudase alfa intravenously every 2 weeks for 26 weeks. Results All patients successfully reached 3.0 mg/kg without serious or severe adverse events. One patient repeated a dose (2.0 mg/kg) and another had a temporary dose reduction (1.0 to 0.6 mg/kg). Most adverse events (97%) were mild and all resolved without sequelae. The most common adverse events were headache, arthralgia, nausea and abdominal pain. Two patients experienced single acute phase reactions. No patient developed hypersensitivity or anti-olipudase alfa antibodies. The mean circulating half-life of olipudase alfa ranged from 20.9 to 23.4 hours across doses without accumulation. Ceramide, a sphingomyelin catabolite, rose transiently in plasma after each dose, but decreased over time. Reductions in sphingomyelin storage, spleen and liver volumes, and serum chitotriosidase activity, as well as improvements in infiltrative lung disease, lipid profiles, platelet counts, and quality of life assessments, were observed. Conclusions This study provides proof-of-concept for the safety and efficacy of within-patient dose escalation of olipudase alfa in patients with nonneuronopathic ASMD. PMID:26049896

  2. Strategy for stochastic dose-rate induced enhanced elimination of malignant tumour without dose escalation.

    PubMed

    Paul, Subhadip; Roy, Prasun Kumar

    2016-09-01

    The efficacy of radiation therapy, a primary modality of cancer treatment, depends in general upon the total radiation dose administered to the tumour during the course of therapy. Nevertheless, the delivered radiation also irradiates normal tissues and dose escalation procedure often increases the elimination of normal tissue as well. In this article, we have developed theoretical frameworks under the premise of linear-quadratic-linear (LQL) model using stochastic differential equation and Jensen's inequality for exploring the possibility of attending to the two therapeutic performance objectives in contraposition-increasing the elimination of prostate tumour cells and enhancing the relative sparing of normal tissue in fractionated radiation therapy, within a prescribed limit of total radiation dose. Our study predicts that stochastic temporal modulation in radiation dose-rate appreciably enhances prostate tumour cell elimination, without needing dose escalation in radiation therapy. However, constant higher dose-rate can also enhance the elimination of tumour cells. In this context, we have shown that the sparing of normal tissue with stochastic dose-rate is considerably more than the sparing of normal tissue with the equivalent constant higher dose-rate. Further, by contrasting the stochastic dose-rate effects under LQL and linear-quadratic (LQ) models, we have also shown that the LQ model over-estimates stochastic dose-rate effect in tumour and under-estimates the stochastic dose-rate effect in normal tissue. Our study indicates the possibility of utilizing stochastic modulation of radiation dose-rate for designing enhanced radiation therapy protocol for cancer.

  3. Mesalamine dose escalation reduces fecal calprotectin in patients with quiescent ulcerative colitis.

    PubMed

    Osterman, Mark T; Aberra, Faten N; Cross, Raymond; Liakos, Steven; McCabe, Robert; Shafran, Ira; Wolf, Douglas; Hardi, Robert; Nessel, Lisa; Brensinger, Colleen; Gilroy, Erin; Lewis, James D

    2014-11-01

    Among patients with quiescent ulcerative colitis (UC), lower fecal concentrations of calprotectin are associated with lower rates of relapse. We performed an open-label, randomized controlled trial to investigate whether increasing doses of mesalamine reduce concentrations of fecal calprotectin (FC) in patients with quiescent UC. We screened 119 patients with UC in remission on the basis of Simple Clinical Colitis Activity Index scores, FC >50 μg/g, and intake of no more than 3 g/day mesalamine. Participants taking mesalamine formulations other than multimatrix mesalamine were switched to multimatrix mesalamine (2.4 g/day) for 6 weeks; 52 participants were then randomly assigned (1:1) to a group that continued its current dose of mesalamine (controls, n = 26) or a group that increased its dose by 2.4 g/day for 6 weeks (n = 26). The primary outcome was continued remission with FC <50 μg/g. Secondary outcomes were continued remission with FC <100 μg/g or <200 μg/g (among patients with pre-randomization values above these levels). The primary outcome was achieved by 3.8% of controls and 26.9% of the dose escalation group (P = .0496). More patients in the dose escalation group reduced FC to below 100 μg/g (P = .04) and 200 μg/g (P = .005). Among the patients who were still in remission after the randomization phase, clinical relapse occurred sooner in patients with FC >200 μg/g compared with those with FC <200 μg/g (P = .01). Among patients with quiescent UC and increased levels of FC, increasing the dose of mesalamine by 2.4 g/day reduced fecal concentrations of calprotectin to those associated with lower rates of relapse. Clinicaltrials.gov number: NCT00652145. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  4. Iranian Low-dose Escalating Prophylaxis Regimen in Children with Severe Hemophilia A and B.

    PubMed

    Eshghi, Peyman; Sadeghi, Elham; Tara, S Zahra; Habibpanah, Behnaz; Hantooshzadeh, Razieh

    2017-01-01

    Establishing an appropriate prophylaxis regimen for children with hemophilia is a critical challenge in developing countries. Barriers including availability and affordability, catheter-related complications, and inhibitor development risks have led to the introduction of new tailored prophylaxis regimens in different countries. This study emphasizes on the benefits of the Iranian low-dose escalating prophylaxis regimen in a Hemophilia Comprehensive Care Center in Iran. Referred patients with hemophilia less than 15 years of age, who were subject to prophylaxis regimen, are studied retrospectively. A once-weekly prophylaxis regimen of 25 IU/kg was started for the patients primarily. Their prophylaxis regimen was changed to 25 IU/kg twice a week and then 3 times a week when they experienced 3 joint bleedings, 4 soft tissue bleedings, or a 1 life-threatening bleed without a specific trauma history. Overall, 25 patients with severe hemophilia and at least 6-month history of on-demand (OD) treatment were studied. A mean of 1754 IU/kg/yr of coagulation factors, used for OD and prophylaxis purposes, was sufficient to decrease the mean annual bleeding rate (ABR) to 1.86 after prophylaxis. It also reduced the mean hospitalization days and the mean number of target joints to 0.24 and 0.16, respectively. Overall, 19 (76%) patients were continuing their once-weekly regimen at the end of the follow-up. None of the patients needed 3-times-a-week regimen or central venous catheterization and none developed inhibitors in the follow-up. Benefits of the Iranian low-dose escalating prophylaxis regimen prove equal to some of the previous 3-times-a-week prophylaxis regimens in reducing the ABR and hospitalizations.

  5. Radiation Therapy Dose Escalation for Glioblastoma Multiforme in the Era of Temozolomide

    SciTech Connect

    Badiyan, Shahed N.; Markovina, Stephanie; Simpson, Joseph R.; Robinson, Clifford G.; DeWees, Todd; Tran, David D.; Linette, Gerry; Jalalizadeh, Rohan; Dacey, Ralph; Rich, Keith M.; Chicoine, Michael R.; Dowling, Joshua L.; Leuthardt, Eric C.; Zipfel, Gregory J.; Kim, Albert H.; Huang, Jiayi

    2014-11-15

    Purpose: To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme (GBM), compared with standard-dose radiation therapy (SDRT). Methods and Materials: Adult patients aged <70 years with biopsy-proven GBM were treated with SDRT (60 Gy at 2 Gy per fraction) or with HDRT (>60 Gy) and TMZ from 2000 to 2012. Biological equivalent dose at 2-Gy fractions was calculated for the HDRT assuming an α/β ratio of 5.6 for GBM. Results: Eighty-one patients received SDRT, and 128 patients received HDRT with a median (range) biological equivalent dose at 2-Gy fractions of 64 Gy (61-76 Gy). Overall median follow-up time was 1.10 years, and for living patients it was 2.97 years. Actuarial 5-year overall survival (OS) and progression-free survival (PFS) rates for patients that received HDRT versus SDRT were 12.4% versus 13.2% (P=.71), and 5.6% versus 4.1% (P=.54), respectively. Age (P=.001) and gross total/near-total resection (GTR/NTR) (P=.001) were significantly associated with PFS on multivariate analysis. Younger age (P<.0001), GTR/NTR (P<.0001), and Karnofsky performance status ≥80 (P=.001) were associated with improved OS. On subset analyses, HDRT failed to improve PFS or OS for those aged <50 years or those who had GTR/NTR. Conclusion: Moderate radiation therapy dose escalation above 60 Gy with concurrent TMZ does not seem to improve clinical outcomes for patients with GBM.

  6. The effect of a slower than standard dose escalation scheme for dipyridamole on headaches in secondary prevention therapy of strokes: a randomized, open-label trial (DOSE).

    PubMed

    de Vos-Koppelaar, N C Martine; Kerkhoff, Henk; de Vogel, Ed M; Zock, Elles; Dieleman, Hetty G

    2014-01-01

    Combination therapy with acetylsalicylic acid and dipyridamole is first-line treatment in secondary prevention of strokes. Approximately 40% of patients report headache as a side effect of dipyridamole. Dose escalation of dipyridamole reduces this side effect. In practice, different dose escalation schemes are used. In theory, slower dose escalation than a standard scheme reduces headaches even more. This study aimed to find the best dose escalation scheme for prevention of headaches as a side effect of dipyridamole in the secondary prevention of strokes. In this randomized, open-label, 4-week trial, 114 patients who had an ischemic stroke or transient ischemic attack were randomized to receive either a standard or slow dose escalation scheme of dipyridamole. Participants were asked to report the four most common side effects of dipyridamole in a study diary on study days 1, 3, 5, 7, 14, 21 and 28. They were asked to score headache intensity on a visual analog scale (VAS). Participants were unaware that the trial was focused on headaches. Primary end point was to determine if a slow dose escalation scheme reduces the percentage of patients with headaches. Secondary objective was to determine the number of patients who discontinued treatment with dipyridamole because of headaches. Overall 37 patients (38%) of the final population reported headache, 19 (39%) in the standard dose escalation group and 18 (37%) in the slow dose escalation group (p = 1.0). In the standard dose escalation group patients scored headaches (VAS >4) on an average of 3.3 days and patients in the slow dose escalation group on 3.6 days (p = 0.82). Mean VAS scores on study days 1, 3, 5, 7, 14 and 21 ranged from 1.4 to 3.7 in both groups. These scores did not differ significantly. However, on day 28 patients scored a significantly lower mean VAS score in the standard dose escalation group than in the slow dose escalation group (2.5 vs. 4.8; p = 0.05). In the standard dose escalation group 6

  7. Long-Term Failure Patterns and Survival in a Randomized Dose-Escalation Trial for Prostate Cancer. Who Dies of Disease?

    SciTech Connect

    Kuban, Deborah A.; Levy, Lawrence B.; Cheung, M. Rex; Lee, Andrew K.; Choi, Seungtaek; Frank, Steven; Pollack, Alan

    2011-04-01

    Purpose: To report long-term failure patterns and survival in a randomized radiotherapy dose escalation trial for prostate cancer. Materials and Methods: A total of 301 patients with Stage T1b-T3 prostate cancer treated to 70 Gy versus 78 Gy now have a median follow-up of 9 years. Failure patterns and survival were compared between dose levels. The cumulative incidence of death from prostate cancer versus other causes was examined and regression analysis was used to establish predictive factors. Results: Patients with pretreatment prostate-specific antigen (PSA) >10 ng/mL or high-risk disease had higher biochemical and clinical failures rates when treated to 70 Gy. These patients also had a significantly higher risk of dying of prostate cancer. Patients <70 years old at treatment died of prostate cancer nearly three times more frequently than of other causes when they were radiated to 70 Gy, whereas those treated to 78 Gy died of other causes more frequently. Patients age 70 or older treated to 70 Gy died of prostate cancer as often as other causes, and those receiving 78 Gy never died of prostate cancer within 10 years of follow-up. In regression analysis, factors predicting for death from prostate cancer were pretreatment PSA >10.5 ng/mL, Gleason score 9 and 10, recurrence within 2.6 years of radiation, and doubling time of <3.6 months at the time of recurrence. Conclusions: Moderate dose escalation (78 Gy) decreases biochemical and clinical failure as well as prostate cancer death in patients with pretreatment PSA >10 ng/mL or high-risk disease.

  8. SU-E-J-219: Quantitative Evaluation of Motion Effects On Accuracy of Image-Guided Radiotherapy with Fiducial Markers Using CT Imaging

    SciTech Connect

    Ali, I; Oyewale, S; Ahmad, S; Algan, O; Alsbou, N

    2014-06-01

    Purpose: To investigate quantitatively patient motion effects on the localization accuracy of image-guided radiation with fiducial markers using axial CT (ACT), helical CT (HCT) and cone-beam CT (CBCT) using modeling and experimental phantom studies. Methods: Markers with different lengths (2.5 mm, 5 mm, 10 mm, and 20 mm) were inserted in a mobile thorax phantom which was imaged using ACT, HCT and CBCT. The phantom moved with sinusoidal motion with amplitudes ranging 0–20 mm and a frequency of 15 cycles-per-minute. Three parameters that include: apparent marker lengths, center position and distance between the centers of the markers were measured in the different CT images of the mobile phantom. A motion mathematical model was derived to predict the variations in the previous three parameters and their dependence on the motion in the different imaging modalities. Results: In CBCT, the measured marker lengths increased linearly with increase in motion amplitude. For example, the apparent length of the 10 mm marker was about 20 mm when phantom moved with amplitude of 5 mm. Although the markers have elongated, the center position and the distance between markers remained at the same position for different motion amplitudes in CBCT. These parameters were not affected by motion frequency and phase in CBCT. In HCT and ACT, the measured marker length, center and distance between markers varied irregularly with motion parameters. The apparent lengths of the markers varied with inverse of the phantom velocity which depends on motion frequency and phase. Similarly the center position and distance between markers varied inversely with phantom speed. Conclusion: Motion may lead to variations in maker length, center position and distance between markers using CT imaging. These effects should be considered in patient setup using image-guided radiation therapy based on fiducial markers matching using 2D-radiographs or volumetric CT imaging.

  9. Phase Ib, Dose Escalation Study of Oral LDE225 in Combination With BKM120 in Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2016-02-18

    Dose Escalation; Safety; Preliminary Efficacy; Advanced Solid Tumors; Metastatic Breast Cancer; Advanced Pancreatic Adenocarcinoma; Metastatic Colorectal Cancer; Recurrent Glioblastoma Multiforme; Gastric Cancer; Gastroesophageal Junction Cancer; Triple Negative Metastatic Breast Cancer; Hormone Receptor Positive (ER+/PR+, and Her2-) Metastatic Breast Cancer

  10. High Dose-Per-Fraction Irradiation of Limited Lung Volumes Using an Image-Guided, Highly Focused Irradiator: Simulating Stereotactic Body Radiotherapy Regimens in a Small-Animal Model

    SciTech Connect

    Cho, Jaeho; Kodym, Reinhard; Seliounine, Serguei

    2010-07-01

    Purpose: To investigate the underlying biology associated with stereotactic body radiotherapy (SBRT), both in vivo models and image-guided, highly focal irradiation systems are necessary. Here, we describe such an irradiation system and use it to examine normal tissue toxicity in a small-animal model at lung volumes similar to those associated with human therapy. Methods and Materials: High-dose radiation was delivered to a small volume of the left lung of C3H/HeJCr mice using a small-animal stereotactic irradiator. The irradiator has a collimation mechanism to produce focal radiation beams, an imaging subsystem consisting of a fluorescent screen coupled to a charge-coupled device camera, and a manual positioning stage. Histopathologic examination and micro-CT were used to evaluate the radiation response. Results: Focal obliteration of the alveoli by fibrous connective tissue, hyperplasia of the bronchiolar epithelium, and presence of a small number of inflammatory cells are the main reactions to low-volume/high-dose irradiation of the mouse lung. The tissue response suggested a radiation dose threshold for early phase fibrosis lying between 40 and 100 Gy. The irradiation system satisfied our requirements of high-dose-rate, small beam diameter, and precise localization and verification. Conclusions: We have established an experimental model and image-guided animal irradiation system for the study of high dose per fraction irradiations such as those used with SBRT at volumes analogous to those used in human beings. It will also allow the targeting of specific anatomical structures of the thorax or ultimately, orthotopic tumors of the lung.

  11. High dose-per-fraction irradiation of limited lung volumes using an image-guided, highly focused irradiator: simulating stereotactic body radiotherapy regimens in a small-animal model.

    PubMed

    Cho, Jaeho; Kodym, Reinhard; Seliounine, Serguei; Richardson, James A; Solberg, Timothy D; Story, Michael D

    2010-07-01

    To investigate the underlying biology associated with stereotactic body radiotherapy (SBRT), both in vivo models and image-guided, highly focal irradiation systems are necessary. Here, we describe such an irradiation system and use it to examine normal tissue toxicity in a small-animal model at lung volumes similar to those associated with human therapy. High-dose radiation was delivered to a small volume of the left lung of C3H/HeJCr mice using a small-animal stereotactic irradiator. The irradiator has a collimation mechanism to produce focal radiation beams, an imaging subsystem consisting of a fluorescent screen coupled to a charge-coupled device camera, and a manual positioning stage. Histopathologic examination and micro-CT were used to evaluate the radiation response. Focal obliteration of the alveoli by fibrous connective tissue, hyperplasia of the bronchiolar epithelium, and presence of a small number of inflammatory cells are the main reactions to low-volume/high-dose irradiation of the mouse lung. The tissue response suggested a radiation dose threshold for early phase fibrosis lying between 40 and 100 Gy. The irradiation system satisfied our requirements of high-dose-rate, small beam diameter, and precise localization and verification. We have established an experimental model and image-guided animal irradiation system for the study of high dose per fraction irradiations such as those used with SBRT at volumes analogous to those used in human beings. It will also allow the targeting of specific anatomical structures of the thorax or ultimately, orthotopic tumors of the lung. (c) 2010 Elsevier Inc. All rights reserved.

  12. IL-6 is an independent predictive factor of drug survival after dose escalation of infliximab in patients with rheumatoid arthritis.

    PubMed

    Takasugi, Koji; Nishida, Keiichiro; Natsumeda, Masamitsu; Yamashita, Misuzu; Yamamoto, Wataru; Ezawa, Kazuhiko

    2017-08-22

    We aimed to investigate factors predictive of increased serum infliximab (IFX) concentration with improvement of disease activity, as well as better 1-year continuation rate after dose escalation, in patients with rheumatoid arthritis (RA) who showed inadequate response to 3 mg/kg IFX. Among 42 patients allotted to receive 3 mg/kg IFX, 13 patients showed adequate response (DAS28 < 3.2) and 29 patients required dose escalation to 4.5 or 6 mg/kg after inadequate response (DAS28 ≥ 3.2) to 3 mg/kg IFX. DAS28, mHAQ, serum level of CRP, interleukin (IL)-6, IL-17, anti-infliximab antibody (AIA) titers and IFX concentration before and on average 2.7 months after dose escalation were examined to explore the baseline factors predictive of a clinically beneficial increase of serum IFX concentration and drug survival. One year after IFX dose escalation, 25 patients completed the study protocol, and 16 patients (64%) continued to show a good response for one year, while 9 patients (36%) required switching of biologics because of inadequate response. Multivariate analyses revealed that a serum IL-6 level of less than 4.0 pg/mL at baseline was the only factor predictive of a clinically beneficial increase of serum IFX concentration in patients who required dose escalation. Receiver operating characteristic analysis revealed that 5.16 pg/mL of IL-6 was the cut-off value with sensitivity 0.833 and specificity of 0.769 (95%CI for AUC: 0.712-1.006). In patients with IL-6 levels of less than 5.16 pg/mL at baseline, the serum IFX concentration significantly increased after dose escalation with adequate response. The 1-year drug survival rates of patients with IL-6 levels less than 5.16 pg/mL and in those with levels greater than or equal to 5.16 pg/mL at baseline were 83.3% and 30.8%, respectively (log-rank test, p = .011). The results of our study indicated that a baseline serum level of IL-6 below 5.16 pg/mL might be a predictive factor for a

  13. Age, gender, and earlier opioid requirement associations with the rate of dose escalation in long-term opioid therapy.

    PubMed

    Han, Huijun; Kass, Philip H; Wilsey, Barth L; Li, Chin-Shang

    2013-01-01

    To examine the association of risk factors, age, gender, and earlier opioid requirement with the rate of dose escalation in long-term opioid therapy. This is a retrospective cohort study of 1,922 individuals identified from California's prescription drug monitoring program database who continuously used opioids from 1999 to 2007. A linear mixed-effects model was used to examine the association of age, gender, and baseline dose requirement with the rate of subsequent opioid dose change. Because of different reporting requirements before and after January 1, 2005, the analyses were conducted separately for patients' opioid use in two periods (6 years between 1999 and 2004 and 3 years between 2005 and 2007). Both the 6-year and the 3-year data showed a significant age association, with younger patients having a higher rate of dose escalation than older patients (p = 0.021 and <0.0001, respectively). Females had a lower rate of dose escalation than males, although the result did not achieve statistical significance in the 6-year data (p = 0.165 and 0.013, respectively). The higher the dose requirement a patient had at baseline, the lower the rate of dose escalation (p < 0.0001 in both periods). Age, gender, and earlier dose requirement were associated with the rate of dose change in 9-year long-term opioid therapy. Patients aged 75-100 years, being female or having large dose requirement at an earlier stage of therapy may experience a slower dose escalation or even dose decline.

  14. Adalimumab Maintenance Treatment in Ulcerative Colitis: Outcomes by Prior Anti-TNF Use and Efficacy of Dose Escalation.

    PubMed

    Taxonera, Carlos; Iglesias, Eva; Muñoz, Fernando; Calvo, Marta; Barreiro-de Acosta, Manuel; Busquets, David; Calvet, Xavier; Rodríguez, Antonio; Pajares, Ramón; Gisbert, Javier P; López-Serrano, Pilar; Pérez-Calle, José Luís; Ponferrada, Ángel; De la Coba, Cristóbal; Bermejo, Fernando; Chaparro, María; Olivares, David; Alba, Cristina; Fernández-Blanco, Ignacio

    2017-02-01

    The impact of prior anti-TNF use on "real-life" outcomes of adalimumab therapy in ulcerative colitis (UC) is not well known. To compare the influence of prior anti-TNF use on the outcomes of adalimumab maintenance treatment in UC patients. We also assessed the effectiveness of adalimumab dose escalation. This retrospective multicenter cohort study included consecutive UC who advanced to an adalimumab maintenance regimen. Patients in whom adalimumab was discontinued prior to week eight of treatment were excluded. The co-primary efficacy endpoints were the cumulative probabilities of adalimumab failure-free survival and colectomy-free survival. We also assessed the need for and the effectiveness of adalimumab dose escalation. Of 184 UC on maintenance treatment with adalimumab, 116 (63%) had previous anti-TNF use. After a median follow-up of 23 months (interquartile range 13-49), 112 patients (60%) maintained corticosteroid-free clinical response. Sixty-nine patients (37%) had adalimumab failure, and 22 (12%) needed colectomy. Anti-TNF-naïve patients had significantly lower adjusted rates of adalimumab failure (hazard ratio [HR] 0.65; p < 0.001), adalimumab dose escalation (HR 0.35; p = 0.002), and need for colectomy (HR 0.26; p < 0.004). Seventy-six patients (41%) needed dose escalation after secondary loss of response, and 47% of these regained response after escalation. Short-term response after escalation was identified as a significant predictor of colectomy avoidance (HR 0.53; p = 0.007). In this "real-life" cohort of UC patients on maintenance treatment with adalimumab, anti-TNF-naïve patients had significantly better long-term outcomes. Adalimumab dose escalation enabled recovery of response in nearly half of patients.

  15. [Focal dose escalation in the treatment of prostate cancer : Long-term results of HDR brachytherapy].

    PubMed

    Cordes, J; Broschk, J; Sommerauer, M; Jocham, D; Merseburger, A S; Melchert, C; Kovács, G

    2017-02-01

    We prospectively examined the effect and the safety of intensity-modulated HDR brachytherapy (IMBT) with focal dose escalation. A total of 139 patients undergoing primary therapy for prostate cancer and 11 patients with recurrence were included. Data analysis focused on the following factors: date of primary diagnosis, Gleason score, initial prostate-specific antigen (PSA) value, PSA nadir, volume of the prostate in the transrectal ultrasound, biopsy of the prostate gland, androgen deprivation, chemotherapy, uroflowmetry, pre- and postoperative post-void residual urine (PVR), number of the needles in the prostate lobes and analysis of follow-up data. In the primary therapy group, 87.6 % of the patients had a PSA of 0-4 ng/ml at the time of follow-up, while in the recurrence group 81.8 % of patients were within this range. Overall, 55.8 % of patients in the primary group had a PSA nadir under 0.1 ng/ml, 37.2 % under 1 ng/ml, 5.8 % under 5 ng/ml and 1.2 % (1 patient) over 5 ng/ml. In the recurrence group, 100 % had a PSA nadir under 0.1 ng/dl. Fifty patients of the primary group reported grade 1 toxicity (Common Toxicity Criteria): 29 localized to the bladder and 21 to the rectum. Seventeen patients had grade 2 toxicity of the bladder and 1 patient had grade 3 toxicity of the bladder. Finally there was one grade 4 toxicity due to perforation of the sigmoid colon. In the recurrence group, 3 patients with grade 1 toxicity were observed (2 bladder and 1 bowl). Also 3 patients had grade 2 toxicity of the bladder, 1 patient had a grade 3 bladder toxicity and 1 patient had grade 4 toxicity due to bowl fistula. There were no grade 5 toxicities. The modifications of the "Kiel method" with focal dose escalation was proven as effective in locally advanced prostate carcinoma and in local recurrences of the disease with low level toxicity.

  16. Imaged-guided liver stereotactic body radiotherapy using VMAT and real-time adaptive tumor gating. Concerns about technique and preliminary clinical results.

    PubMed

    Llacer-Moscardo, Carmen; Riou, Olivier; Azria, David; Bedos, Ludovic; Ailleres, Norbert; Quenet, Francois; Rouanet, Philippe; Ychou, Marc; Fenoglietto, Pascal

    2017-01-01

    Motion management is a major challenge in abdominal SBRT. We present our study of SBRT for liver tumors using intrafraction motion review (IMR) allowing simultaneous KV information and MV delivery to synchronize the beam during gated RapidArc treatment. Between May 2012 and March 2015, 41 patients were treated by liver SBRT using gated RapidArc technique in a Varian Novalis Truebeam STx linear accelerator. PTV was created by expanding 5 mm from the ITV. Dose prescription ranged from 40 to 50 Gy in 5-10 fractions. The prescribed dose and fractionation were chosen depending on hepatic function and dosimetric results. Thirty-four patients with a minimal follow-up of six months were analyzed for local control and toxicity. Accuracy for tumor repositioning was evaluated for the first ten patients. With a median follow-up of 13 months, the treatment was well tolerated and no patient presented RILD, perforation or gastrointestinal bleeding. Acute toxicity was found in 3 patients with G1 abdominal pain, 2 with G1 nausea, 10 with G1 asthenia and 1 with G2 asthenia. 6 patients presented asymptomatic transitory perturbation of liver enzymes. In-field local control was 90.3% with 7 complete responses, 14 partial responses and 7 stabilisations. 3 patients evolved "in field". 12 patients had an intrahepatic progression "out of field". Mean intrafraction deviation of fiducials in the craneo-caudal direction was 0.91 mm (0-6 mm). The clinical tolerance and oncological outcomes were favorable when using image-guided liver SBRT with real-time adaptive tumor gating.

  17. Geant4 simulation of the Elekta XVI kV CBCT unit for accurate description of potential late toxicity effects of image-guided radiotherapy.

    PubMed

    Brochu, F M; Burnet, N G; Jena, R; Plaistow, R; Parker, M A; Thomas, S J

    2014-12-21

    This paper describes the modelisation of the Elekta XVI Cone Beam Computed Tomography (CBCT) machine components with Geant4 and its validation against calibration data taken for two commonly used machine setups. Preliminary dose maps of simulated CBCTs coming from this modelisation work are presented. This study is the first step of a research project, GHOST, aiming to improve the understanding of late toxicity risk in external beam radiotherapy patients by simulating dose depositions integrated from different sources (imaging, treatment beam) over the entire treatment plan. The second cancer risk will then be derived from different models relating irradiation dose and second cancer risk.

  18. Geant4 simulation of the Elekta XVI kV CBCT unit for accurate description of potential late toxicity effects of image-guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Brochu, F. M.; Burnet, N. G.; Jena, R.; Plaistow, R.; Parker, M. A.; Thomas, S. J.

    2014-12-01

    This paper describes the modelisation of the Elekta XVI Cone Beam Computed Tomography (CBCT) machine components with Geant4 and its validation against calibration data taken for two commonly used machine setups. Preliminary dose maps of simulated CBCTs coming from this modelisation work are presented. This study is the first step of a research project, GHOST, aiming to improve the understanding of late toxicity risk in external beam radiotherapy patients by simulating dose depositions integrated from different sources (imaging, treatment beam) over the entire treatment plan. The second cancer risk will then be derived from different models relating irradiation dose and second cancer risk.

  19. Biological equivalent dose studies for dose escalation in the stereotactic synchrotron radiation therapy clinical trials

    SciTech Connect

    Prezado, Y.; Fois, G.; Edouard, M.; Nemoz, C.; Renier, M.; Requardt, H.; Esteve, F.; Adam, JF.; Elleaume, H.; Bravin, A.

    2009-03-15

    Synchrotron radiation is an innovative tool for the treatment of brain tumors. In the stereotactic synchrotron radiation therapy (SSRT) technique a radiation dose enhancement specific to the tumor is obtained. The tumor is loaded with a high atomic number (Z) element and it is irradiated in stereotactic conditions from several entrance angles. The aim of this work was to assess dosimetric properties of the SSRT for preparing clinical trials at the European Synchrotron Radiation Facility (ESRF). To estimate the possible risks, the doses received by the tumor and healthy tissues in the future clinical conditions have been calculated by using Monte Carlo simulations (PENELOPE code). The dose enhancement factors have been determined for different iodine concentrations in the tumor, several tumor positions, tumor sizes, and different beam sizes. A scheme for the dose escalation in the various phases of the clinical trials has been proposed. The biological equivalent doses and the normalized total doses received by the skull have been calculated in order to assure that the tolerance values are not reached.

  20. Caffeine in Parkinson's disease: a pilot open-label, dose-escalation study.

    PubMed

    Altman, Robert D; Lang, Anthony E; Postuma, Ronald B

    2011-11-01

    Epidemiologic studies consistently find an inverse association between caffeine use and PD. Numerous explanations exist, but are difficult to evaluate as caffeine's symptomatic effect and tolerability in PD are unknown. We designed an open-label, 6-week dose-escalation study of caffeine to establish dose tolerability and evaluate potential motor/nonmotor benefits. Caffeine was started at 200 mg daily and was increased to a maximum of 1,000 mg. Of 25 subjects, 20 tolerated 200 mg, 17 tolerated 400 mg, 7 tolerated 800 mg, and 3 tolerated 1,000 mg. The most common adverse events were gastrointestinal discomfort, anxiety, and worsening/emerging tremor. At 400 mg daily, we found potential improvements in motor manifestations and somnolence (UPDRS III: -4.5 ± 4.6, P = 0.003; Epworth: -2.0 ± 3.0, P = 0.015). Maximum dose tolerability for caffeine in PD appears to be 100 to 200 mg BID. We found pilot preliminary evidence that caffeine may improve some motor and nonmotor aspects of PD, which must be confirmed in longer term, placebo-controlled, clinical trials. Copyright © 2011 Movement Disorder Society.

  1. Phase I dose escalation trial of feverfew with standardized doses of parthenolide in patients with cancer.

    PubMed

    Curry, Eardie A; Murry, Daryl J; Yoder, Christy; Fife, Karen; Armstrong, Victoria; Nakshatri, Harikrishna; O'Connell, Michael; Sweeney, Christopher J

    2004-08-01

    Feverfew is a botanical product that contains parthenolide. Parthenolide has in vitro and in vivo anti-tumor and anti-angiogenic activity. Feverfew has been used extensively without any formal pharmacokinetic analysis. A Phase I trial was conducted to evaluate the pharmacokinetics and toxicity of parthenolide given as a component of "feverfew." Feverfew (Tanacet trade mark ) was administered as a daily oral tablet in a 28-day cycle. A starting dose of 1 mg per day was explored with subsequent dose escalations to 2, 3, and 4 mg. Assessment of plasma pharmacokinetics was performed on patients accrued to the trial. Solid phase extraction and mass spectroscopy were used to evaluate parthenolide plasma concentrations. The limit of detection for parthenolide in plasma was 0.5 ng/ml. Patients were evaluated for response after every two cycles. Feverfew given on this schedule had no significant toxicity, and the maximum tolerated dose was not reached. When parthenolide was administered at doses up to 4 mg as a daily oral capsule in the feverfew preparation, there was not detectable concentration in the plasma. Because of this, parthenolide pharmacokinetics were not able to be completed. Feverfew, with up to 4 mg of parthenolide, given daily as an oral tablet is well tolerated without dose-limiting toxicity, but does not provide detectable plasma concentrations. Purification of parthenolide for administration of higher doses will be needed.

  2. Interfractional Seminal Vesicle Motion Relative to the Prostate Gland for Image-guided Radiotherapy for Prostate Cancer with/without Androgen Deprivation Therapy: A Retrospective Cohort Study.

    PubMed

    Waki, Takahiro; Katsui, Kuniaki; Mitsuhashi, Toshiharu; Ogata, Takeshi; Katayama, Norihisa; Takemoto, Mitsuhiro; Nasu, Yasutomo; Kumon, Hiromi; Kanazawa, Susumu

    2017-02-01

    We investigated differences in seminal vesicle (SV) length and interfractional SV motion relative to the prostate gland in prostate cancer patients. We compared 32 patients who received androgen deprivation therapy (ADT) before radiotherapy with 12 patients receiving radiotherapy alone at Okayama University Hospital in August 2008-July 2011. We examined the right and left SVs' length and motion by computed tomography (CT) to determine the ADT's effects and analyzed 347 CT scans in a multiple linear regression model. The ADT patients' SV length was significantly shorter than the non-ADT patients'. The differences in right and left SV lengths between the ADT and non-ADT patients were 6.8 mm (95% CI 2.0-11.7 mm) and 7.2 mm (95% CI 3.1- 11.3 mm) respectively in an adjusted regression model. SV motion did not differ between the ADT and non- ADT patients in terms of interfractional motion of the SV tips and the SVs' center relative to the prostate gland. The ADT patients had significantly shorter SVs compared to the non-ADT patients, but no difference in SV motion was observed. SV interfractional motion should thus be compensated using the same planning margins, regardless of whether ADT is used.

  3. Nanomedicines for image-guided cancer therapy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Zheng, Jinzi

    2016-09-01

    Imaging technologies are being increasingly employed to guide the delivery of cancer therapies with the intent to increase their performance and efficacy. To date, many patients have benefited from image-guided treatments through prolonged survival and improvements in quality of life. Advances in nanomedicine have enabled the development of multifunctional imaging agents that can further increase the performance of image-guided cancer therapy. Specifically, this talk will focus on examples that demonstrate the benefits and application of nanomedicine in the context of image-guide surgery, personalized drug delivery, tracking of cell therapies and high precision radiotherapy delivery.

  4. SU-E-J-55: End-To-End Effectiveness Analysis of 3D Surface Image Guided Voluntary Breath-Holding Radiotherapy for Left Breast

    SciTech Connect

    Lin, M; Feigenberg, S

    2015-06-15

    Purpose To evaluate the effectiveness of using 3D-surface-image to guide breath-holding (BH) left-side breast treatment. Methods Two 3D surface image guided BH procedures were implemented and evaluated: normal-BH, taking BH at a comfortable level, and deep-inspiration-breath-holding (DIBH). A total of 20 patients (10 Normal-BH and 10 DIBH) were recruited. Patients received a BH evaluation using a commercialized 3D-surface- tracking-system (VisionRT, London, UK) to quantify the reproducibility of BH positions prior to CT scan. Tangential 3D/IMRT plans were conducted. Patients were initially setup under free-breathing (FB) condition using the FB surface obtained from the untaged CT to ensure a correct patient position. Patients were then guided to reach the planned BH position using the BH surface obtained from the BH CT. Action-levels were set at each phase of treatment process based on the information provided by the 3D-surface-tracking-system for proper interventions (eliminate/re-setup/ re-coaching). We reviewed the frequency of interventions to evaluate its effectiveness. The FB-CBCT and port-film were utilized to evaluate the accuracy of 3D-surface-guided setups. Results 25% of BH candidates with BH positioning uncertainty > 2mm are eliminated prior to CT scan. For >90% of fractions, based on the setup deltas from3D-surface-trackingsystem, adjustments of patient setup are needed after the initial-setup using laser. 3D-surface-guided-setup accuracy is comparable as CBCT. For the BH guidance, frequency of interventions (a re-coaching/re-setup) is 40%(Normal-BH)/91%(DIBH) of treatments for the first 5-fractions and then drops to 16%(Normal-BH)/46%(DIBH). The necessity of re-setup is highly patient-specific for Normal-BH but highly random among patients for DIBH. Overall, a −0.8±2.4 mm accuracy of the anterior pericardial shadow position was achieved. Conclusion 3D-surface-image technology provides effective intervention to the treatment process and ensures

  5. SU-E-J-44: A Novel Approach to Quantify Patient Setup and Target Motion for Real-Time Image-Guided Radiotherapy (IGRT)

    SciTech Connect

    Li, S; Charpentier, P; Sayler, E; Micaily, B; Miyamoto, C; Geng, J

    2015-06-15

    Purpose Isocenter shifts and rotations to correct patient setup errors and organ motion cannot remedy some shape changes of large targets. We are investigating new methods in quantification of target deformation for realtime IGRT of breast and chest wall cancer. Methods Ninety-five patients of breast or chest wall cancer were accrued in an IRB-approved clinical trial of IGRT using 3D surface images acquired at daily setup and beam-on time via an in-room camera. Shifts and rotations relating to the planned reference surface were determined using iterative-closest-point alignment. Local surface displacements and target deformation are measured via a ray-surface intersection and principal component analysis (PCA) of external surface, respectively. Isocenter shift, upper-abdominal displacement, and vectors of the surface projected onto the two principal components, PC1 and PC2, were evaluated for sensitivity and accuracy in detection of target deformation. Setup errors for some deformed targets were estimated by superlatively registering target volume, inner surface, or external surface in weekly CBCT or these outlines on weekly EPI. Results Setup difference according to the inner-surface, external surface, or target volume could be 1.5 cm. Video surface-guided setup agreed with EPI results to within < 0.5 cm while CBCT results were sometimes (∼20%) different from that of EPI (>0.5 cm) due to target deformation for some large breasts and some chest walls undergoing deep-breath-hold irradiation. Square root of PC1 and PC2 is very sensitive to external surface deformation and irregular breathing. Conclusion PCA of external surfaces is quick and simple way to detect target deformation in IGRT of breast and chest wall cancer. Setup corrections based on the target volume, inner surface, and external surface could be significant different. Thus, checking of target shape changes is essential for accurate image-guided patient setup and motion tracking of large deformable

  6. Magnitude of shift of tumor position as a function of moderated deep inspiration breath-hold: An analysis of pooled data of lung patients with active breath control in image-guided radiotherapy

    PubMed Central

    Muralidhar, K. R.; Murthy, P. Narayana; Mahadev, D. Shankar; Subramanyam, K.; Sudarshan, G.; Raju, A. Krishnam

    2008-01-01

    The purpose of this study was to evaluate the reproducibility and magnitude of shift of tumor position by using active breathing control and iView-GT for patients with lung cancer with moderate deep-inspiration breath-hold (mDIBH) technique. Eight patients with 10 lung tumors were studied. CT scans were performed in the breath-holding phase. Moderate deep-inspiration breath-hold under spirometer-based monitoring system was used. Few important bony anatomic details were delineated by the radiation oncologist. To evaluate the interbreath-hold reproducibility of the tumor position, we compared the digital reconstruction radiographs (DRRs) from planning system with the DRRs from the iView-GT in the machine room. We measured the shift in x, y, and z directions. The reproducibility was defined as the difference between the bony landmarks from the DRR of the planning system and those from the DRR of the iView-GT. The maximum shift of the tumor position was 3.2 mm, 3.0 mm, and 2.9 mm in the longitudinal, lateral, and vertical directions. In conclusion, the moderated deep-inspiration breath-hold method using a spirometer is feasible, with relatively good reproducibility of the tumor position for image-guided radiotherapy in lung cancers. PMID:19893708

  7. Image-Guided Radiotherapy for Prostate Cancer: A Prospective Trial of Concomitant Boost Using Indium-111-Capromab Pendetide (ProstaScint) Imaging

    SciTech Connect

    Wong, William W.; Schild, Steven E.; Vora, Sujay A.; Ezzell, Gary A.; Nguyen, Ba D.; Ram, Panol C.; Roarke, Michael C.

    2011-11-15

    Purpose: To evaluate, in a prospective study, the use of {sup 111}In-capromab pendetide (ProstaScint) scan to guide the delivery of a concomitant boost to intraprostatic region showing increased uptake while treating the entire gland with intensity-modulated radiotherapy for localized prostate cancer. Methods and Materials: From September 2002 to November 2005, 71 patients were enrolled. Planning pelvic CT and {sup 111}In-capromab pendetide scan images were coregistered. The entire prostate gland received 75.6 Gy/42 fractions, whereas areas of increased uptake in {sup 111}In-capromab pendetide scan received 82 Gy. For patients with T3/T4 disease, or Gleason score {>=}8, or prostate-specific antigen level >20 ng/mL, 12 months of adjuvant androgen deprivation therapy was given. In January 2005 the protocol was modified to give 6 months of androgen deprivation therapy to patients with a prostate-specific antigen level of 10-20 ng/mL or Gleason 7 disease. Results: Thirty-one patients had low-risk, 30 had intermediate-risk, and 10 had high-risk disease. With a median follow-up of 66 months, the 5-year biochemical control rates were 94% for the entire cohort and 97%, 93%, and 90% for low-, intermediate-, and high-risk groups, respectively. Maximum acute and late urinary toxicities were Grade 2 for 38 patients (54%) and 28 patients (39%) and Grade 3 for 1 and 3 patients (4%), respectively. One patient had Grade 4 hematuria. Maximum acute and late gastrointestinal toxicities were Grade 2 for 32 patients (45%) and 15 patients (21%), respectively. Most of the side effects improved with longer follow-up. Conclusion: Concomitant boost to areas showing increased uptake in {sup 111}In-capromab pendetide scan to 82 Gy using intensity-modulated radiotherapy while the entire prostate received 75.6 Gy was feasible and tolerable, with 94% biochemical control rate at 5 years.

  8. SU-E-CAMPUS-J-04: Image Guided Radiation Therapy (IGRT): Review of Technical Standards and Credentialing in Radiotherapy Clinical Trials

    SciTech Connect

    Giaddui, T; Chen, W; Yu, J; Gong, Y; Galvin, J; Xiao, Y; Cui, Y; Yin, F; Craig, T; Dawson, L; Al-Hallaq, H; Chmura, S

    2014-06-15

    Purpose: To review IGRT credentialing experience and unexpected technical issues encountered in connection with advanced radiotherapy technologies as implemented in RTOG clinical trials. To update IGRT credentialing procedures with the aim of improving the quality of the process, and to increase the proportion of IGRT credentialing compliance. To develop a living disease site-specific IGRT encyclopedia. Methods: Numerous technical issues were encountered during the IGRT credentialing process. The criteria used for credentialing review were based on: image quality; anatomy included in fused data sets and shift results. Credentialing requirements have been updated according to the AAPM task group reports for IGRT to ensure that all required technical items are included in the quality review process. Implementation instructions have been updated and expanded for recent protocols. Results: Technical issues observed during the credentialing review process include, but are not limited to: poor quality images; inadequate image acquisition region; poor data quality; shifts larger than acceptable; no soft tissue surrogate. The updated IGRT credentialing process will address these issues and will also include the technical items required from AAPM: TG 104; TG 142 and TG 179 reports. An instruction manual has been developed describing a remote credentialing method for reviewers. Submission requirements are updated, including images/documents as well as facility questionnaire. The review report now includes summary of the review process and the parameters that reviewers check. We have reached consensus on the minimum IGRT technical requirement for a number of disease sites. RTOG 1311(NRG-BR002A Phase 1 Study of Stereotactic Body Radiotherapy (SBRT) for the Treatment of Multiple Metastases) is an example, here; the protocol specified the minimum requirement for each anatomical sites (with/without fiducials). Conclusion: Technical issues are identified and reported. IGRT

  9. SU-C-18A-04: 3D Markerless Registration of Lung Based On Coherent Point Drift: Application in Image Guided Radiotherapy

    SciTech Connect

    Nasehi Tehrani, J; Wang, J; Guo, X; Yang, Y

    2014-06-01

    Purpose: This study evaluated a new probabilistic non-rigid registration method called coherent point drift for real time 3D markerless registration of the lung motion during radiotherapy. Method: 4DCT image datasets Dir-lab (www.dir-lab.com) have been used for creating 3D boundary element model of the lungs. For the first step, the 3D surface of the lungs in respiration phases T0 and T50 were segmented and divided into a finite number of linear triangular elements. Each triangle is a two dimensional object which has three vertices (each vertex has three degree of freedom). One of the main features of the lungs motion is velocity coherence so the vertices that creating the mesh of the lungs should also have features and degree of freedom of lung structure. This means that the vertices close to each other tend to move coherently. In the next step, we implemented a probabilistic non-rigid registration method called coherent point drift to calculate nonlinear displacement of vertices between different expiratory phases. Results: The method has been applied to images of 10-patients in Dir-lab dataset. The normal distribution of vertices to the origin for each expiratory stage were calculated. The results shows that the maximum error of registration between different expiratory phases is less than 0.4 mm (0.38 SI, 0.33 mm AP, 0.29 mm RL direction). This method is a reliable method for calculating the vector of displacement, and the degrees of freedom (DOFs) of lung structure in radiotherapy. Conclusions: We evaluated a new 3D registration method for distribution set of vertices inside lungs mesh. In this technique, lungs motion considering velocity coherence are inserted as a penalty in regularization function. The results indicate that high registration accuracy is achievable with CPD. This method is helpful for calculating of displacement vector and analyzing possible physiological and anatomical changes during treatment.

  10. Development of image quality assurance measures of the ExacTrac localization system using commercially available image evaluation software and hardware for image-guided radiotherapy.

    PubMed

    Stanley, Dennis N; Papanikolaou, Nikos; Gutierrez, Alonso N

    2014-11-01

    Quality assurance (QA) of the image quality for image-guided localization systems is crucial to ensure accurate visualization and localization of target volumes. In this study, a methodology was developed to assess and evaluate the constancy of the high-contrast spatial resolution, dose, energy, contrast, and geometrical accuracy of the BrainLAB ExacTrac system. An in-house fixation device was constructed to hold the QCkV-1 phantom firmly and reproducibly against the face of the flat panel detectors. Two image sets per detector were acquired using ExacTrac preset console settings over a period of three months. The image sets were analyzed in PIPSpro and the following metrics were recorded: high-contrast spatial resolution (f30,f40,f50 (lp/mm)), noise, and contrast-to-noise ratio. Geometrical image accuracy was evaluated by assessing the length between to predetermined points of the QCkV-1 phantom. Dose and kVp were recorded using the Unfors RaySafe Xi R/F Detector. The kVp and dose were evaluated for the following: Cranial Standard (CS) (80 kV,80 mA,80 ms), Thorax Standard (TS) (120 kV,160 mA,160 ms), Abdomen Standard (AS) (120 kV,160 mA,130 ms), and Pelvis Standard (PS) (120 kV,160 mA,160 ms). With regard to high-contrast spatial resolution, the mean values of the f30 (lp/mm), f40 (lp/mm) and f50 (lp/mm) for the left detector were 1.39±0.04,1.24±0.05, and 1.09±0.04, respectively, while for the right detector they were 1.38±0.04,1.22±0.05, and 1.09±0.05, respectively. Mean CNRs for the left and right detectors were 148±3 and 143±4, respectively. For geometrical accuracy, both detectors had a measured image length of the QCkV-1 of 57.9±0.5mm. The left detector showed dose measurements of 20.4±0.2μGy(CS), 191.8±0.7μGy(TS), 154.2±0.7μGy(AS), and 192.2±0.6μGy(PS), while the right detector showed 20.3±0.3μGy(CS), 189.7±0.8μGy(TS), 151.0±0.7μGy(AS), and 189.7±0.8μGy(PS), respectively. For X-ray energy, the left detector (right X-ray tube) had

  11. Development of image quality assurance measures of the ExacTrac localization system using commercially available image evaluation software and hardware for image-guided radiotherapy.

    PubMed

    Stanley, Dennis N; Papanikolaou, Nikos; Gutiérrez, Alonso N

    2014-11-08

    Quality assurance (QA) of the image quality for image-guided localization systems is crucial to ensure accurate visualization and localization of target volumes. In this study, a methodology was developed to assess and evaluate the constancy of the high-contrast spatial resolution, dose, energy, contrast, and geometrical accuracy of the BrainLAB ExacTrac system. An in-house fixation device was constructed to hold the QCkV-1 phantom firmly and reproducibly against the face of the flat panel detectors. Two image sets per detector were acquired using ExacTrac preset console settings over a period of three months. The image sets were analyzed in PIPSpro and the following metrics were recorded: high-contrast spatial resolution (f30, f40, f50 (lp/mm)), noise, and contrast-to-noise ratio. Geometrical image accu- racy was evaluated by assessing the length between to predetermined points of the QCkV-1 phantom. Dose and kVp were recorded using the Unfors RaySafe Xi R/F Detector. The kVp and dose were evaluated for the following: Cranial Standard (CS) (80 kV,80 mA,80 ms), Thorax Standard (TS) (120 kV,160 mA,160 ms), Abdomen Standard (AS) (120 kV,160 mA,130 ms), and Pelvis Standard (PS) (120 kV,160 mA,160 ms). With regard to high-contrast spatial resolution, the mean values of the f30 (lp/mm), f40 (lp/mm) and f50 (lp/mm) for the left detector were 1.39 ± 0.04, 1.24 ± 0.05, and 1.09 ± 0.04, respectively, while for the right detector they were 1.38 ± 0.04, 1.22 ± 0.05, and 1.09 ± 0.05, respectively. Mean CNRs for the left and right detectors were 148 ± 3 and 143 ± 4, respectively. For geometrical accuracy, both detectors had a measured image length of the QCkV-1 of 57.9 ± 0.5 mm. The left detector showed dose measurements of 20.4 ± 0.2 μGy (CS), 191.8 ± 0.7 μGy (TS), 154.2 ± 0.7 μGy (AS), and 192.2 ± 0.6 μGy (PS), while the right detector showed 20.3 ± 0.3 μGy (CS), 189.7 ± 0.8 μGy (TS), 151.0 ± 0.7 μGy (AS), and 189.7 ± 0.8 μGy (PS), respectively. For X

  12. Biological dose escalation and hypofractionation: what is there to be gained and how will it best be done?

    PubMed

    Tree, A C; Alexander, E J; Van As, N J; Dearnaley, D P; Khoo, V

    2013-08-01

    The evidence supporting dose escalation for localised prostate cancer is widely accepted, but in tandem with improvements in biochemical control, dose escalation increases side-effects. In a scenario where most patients achieve control of their cancer, quality of life concerns predominate. Here we examine the biological ways in which an effective dose can be escalated without an unacceptable increase in toxicity. Possible avenues include exploiting the unusual radiobiology of prostate cancer by hypofractionation, the use of image guidance, adaptive planning and prostate motion management. We await with anticipation the results of large randomised trials of hypofractionation, moderate and profound, to establish whether we can further improve the balance between cure and quality of life.

  13. New-onset depression following stable, slow, and rapid rate of prescription opioid dose escalation.

    PubMed

    Salas, Joanne; Scherrer, Jeffrey F; Schneider, Frank David; Sullivan, Mark D; Bucholz, Kathleen K; Burroughs, Thomas; Copeland, Laurel A; Ahmedani, Brian K; Lustman, Patrick J

    2017-02-01

    Recent studies suggest that longer durations of opioid use, independent of maximum morphine equivalent dose (MED) achieved, is associated with increased risk of new-onset depression (NOD). Conversely, other studies, not accounting for duration, found that higher MED increased probability of depressive symptoms. To determine whether rate of MED increase is associated with NOD, a retrospective cohort analysis of Veterans Health Administration data (2000-2012) was conducted. Eligible patients were new, chronic (>90 days) opioid users, aged 18 to 80, and without depression diagnoses for 2 years before start of follow-up (n = 7051). Mixed regression models of MED across follow-up defined 4 rate of dose change categories: stable, decrease, slow increase, and rapid increase. Cox proportional hazard models assessed the relationship of rate of dose change and NOD, controlling for pain, duration of use, maximum MED, and other confounders using inverse probability of treatment-weighted propensity scores. Incidence rate for NOD was 14.1/1000PY (person-years) in stable rate, 13.0/1000PY in decreasing, 19.3/1000PY in slow increasing, and 27.5/1000PY in rapid increasing dose. Compared with stable rate, risk of NOD increased incrementally for slow (hazard ratio = 1.22; 95% confidence interval: 1.05-1.42) and rapid (hazard ratio = 1.58; 95% confidence interval: 1.30-1.93) rate of dose increase. Faster rates of MED escalation contribute to NOD, independent of maximum dose, pain, and total opioid duration. Dose escalation may be a proxy for loss of control or undetected abuse known to be associated with depression. Clinicians should avoid rapid dose increase when possible and discuss risk of depression with patients if dose increase is warranted for pain.

  14. Prospective, Randomized Study of Radiation Dose Escalation With Combined Proton-Photon Therapy for Benign Meningiomas.

    PubMed

    Sanford, Nina N; Yeap, Beow Y; Larvie, Mykol; Daartz, Juliane; Munzenrider, John E; Liebsch, Norbert J; Fullerton, Barbara; Pan, Elizabeth; Loeffler, Jay S; Shih, Helen A

    2017-07-12

    To assess the outcomes of benign meningiomas (BM) treated to two radiation dose levels. We randomly assigned patients (1:1) with incompletely resected or recurrent BM to 2 radiation doses: 55.8 Gy(relative biological effectiveness [RBE]) and 63.0 Gy(RBE) of fractionated combined proton-photon radiation therapy. The primary endpoint was local control with hypothesis of improved tumor control with higher dose. Secondary endpoints included progression-free survival, overall survival, and rates of treatment-related toxicities. Between 1991 and 2000, 47 patients were randomized. Three patients were excluded for nonbenign histology; therefore, 44 patients were analyzed: 22 who received 55.8 Gy(RBE) and 22 who received 63.0 Gy(RBE). The median follow-up was 17.1 years. Local control for the entire cohort was 98% at 10 years and 90% at 15 years. Of the 5 patients with local recurrence, 4 occurred after 10 years of follow-up, and 3 were in the lower dose group (P=.322). In the modified intention to treat analysis, there was no difference in progression-free survival (P=.234) and overall survival (P=.271) between arms. A total of 26 patients (59%) experienced a grade 2 or higher late toxicity, including 9 patients (20%) incurring a cerebrovascular accident (CVA), 7 of which were deemed at least possibly attributable to irradiation. The median time between completion of radiation therapy and CVA was 5.6 years (range, 1.4-14.0 years). Fractionated combined proton-photon radiation therapy is effective for BM, with no apparent benefit in dose escalation. Further investigation is needed to better define the risk of late toxicities, including CVA after cranial radiation therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Dose Escalated Liver Stereotactic Body Radiation Therapy at the Mean Respiratory Position

    SciTech Connect

    Velec, Michael; Moseley, Joanne L.; Dawson, Laura A.; Brock, Kristy K.

    2014-08-01

    Purpose: The dosimetric impact of dose probability based planning target volume (PTV) margins for liver cancer patients receiving stereotactic body radiation therapy (SBRT) was compared with standard PTV based on the internal target volume (ITV). Plan robustness was evaluated by accumulating the treatment dose to ensure delivery of the intended plan. Methods and Materials: Twenty patients planned on exhale CT for 27 to 50 Gy in 6 fractions using an ITV-based PTV and treated free-breathing were retrospectively evaluated. Isotoxic, dose escalated plans were created on midposition computed tomography (CT), representing the mean breathing position, using a dose probability PTV. The delivered doses were accumulated using biomechanical deformable registration of the daily cone beam CT based on liver targeting at the exhale or mean breathing position, for the exhale and midposition CT plans, respectively. Results: The dose probability PTVs were on average 38% smaller than the ITV-based PTV, enabling an average ± standard deviation increase in the planned dose to 95% of the PTV of 4.0 ± 2.8 Gy (9 ± 5%) on the midposition CT (P<.01). For both plans, the delivered minimum gross tumor volume (GTV) doses were greater than the planned nominal prescribed dose in all 20 patients and greater than the planned dose to 95% of the PTV in 18 (90%) patients. Nine patients (45%) had 1 or more GTVs with a delivered minimum dose more than 5 Gy higher with the midposition CT plan using dose probability PTV, compared with the delivered dose with the exhale CT plan using ITV-based PTV. Conclusions: For isotoxic liver SBRT planned and delivered at the mean respiratory, reduced dose probability PTV enables a mean escalation of 4 Gy (9%) in 6 fractions over ITV-based PTV. This may potentially improve local control without increasing the risk of tumor underdosing.

  16. Dose Escalation and Dosimetry of First in Human Alpha Radioimmunotherapy with 212Pb-TCMC-trastuzumab

    PubMed Central

    Meredith, Ruby; Torgue, Julien; Shen, Sui; Fisher, Darrell R.; Banaga, Eileen; Bunch, Patty; Morgan, Desiree; Fan, Jinda; Straughn, J. Michael

    2015-01-01

    Our purpose was to study the safety, distribution, pharmacokinetics, immunogenicity and tumor response of intraperitoneal (IP) 212Pb-TCMC-trastuzumab (TCMC is S-2-(4-isothiocyantobenzl)-1, 4, 7, 10-tetraaza-1, 4, 7, 10=tetra (2-carbamoylmethl) cyclododecane) in patients with HER-2 expressing malignancy. Methods In a standard 3+3 Phase 1 design for dose escalation, 212Pb-TCMC-trastuzumab was delivered IP less than 4 hours after giving 4mg/kg IV trastuzumab to patients with peritoneal carcinomatosis who had failed standard therapies. Results Five dosage levels (7.4, 9.6, 12.6, 16.3, 21.1 MBq/m2) showed minimal toxicity at >1 year for the first group and >4 months for others. The lack of substantial toxicity was consistent with the dosimetry assessments (mean equivalent dose to marrow = 0.18 mSv/MBq). Radiation dosimetry assessment was performed using pharmacokinetics data obtained in the initial cohort (n=3). Limited redistribution of radioactivity out of the peritoneal cavity to circulating blood, which cleared via urinary excretion and no specific uptake in major organs was observed in 24 hours. Maximum serum concentration of the radiolabeled antibody was 22.9% at 24h (decay corrected to injection time) and 500 Bq/mL (decay corrected to collection time). Non-decay corrected cumulative urinary excretion was ≤6% in 24h (2.3 half lives). Dose rate measurements performed at 1m from the patient registered less than 5μSv/hr (using portable detectors) in the latest cohort, significantly less than what is normally observed using nuclear medicine imaging agents. Anti-drug antibody assays performed on serum from the first 4 cohorts were all negative. Conclusions Five dose levels of IP 212Pb-TCMC-trastuzumab treatment of patients with peritoneal carcinomatosis showed little agent related toxicity, consistent with the dosimetry calculations. PMID:25157044

  17. Dose escalated liver stereotactic body radiation therapy at the mean respiratory position.

    PubMed

    Velec, Michael; Moseley, Joanne L; Dawson, Laura A; Brock, Kristy K

    2014-08-01

    The dosimetric impact of dose probability based planning target volume (PTV) margins for liver cancer patients receiving stereotactic body radiation therapy (SBRT) was compared with standard PTV based on the internal target volume (ITV). Plan robustness was evaluated by accumulating the treatment dose to ensure delivery of the intended plan. Twenty patients planned on exhale CT for 27 to 50 Gy in 6 fractions using an ITV-based PTV and treated free-breathing were retrospectively evaluated. Isotoxic, dose escalated plans were created on midposition computed tomography (CT), representing the mean breathing position, using a dose probability PTV. The delivered doses were accumulated using biomechanical deformable registration of the daily cone beam CT based on liver targeting at the exhale or mean breathing position, for the exhale and midposition CT plans, respectively. The dose probability PTVs were on average 38% smaller than the ITV-based PTV, enabling an average ± standard deviation increase in the planned dose to 95% of the PTV of 4.0 ± 2.8 Gy (9 ± 5%) on the midposition CT (P<.01). For both plans, the delivered minimum gross tumor volume (GTV) doses were greater than the planned nominal prescribed dose in all 20 patients and greater than the planned dose to 95% of the PTV in 18 (90%) patients. Nine patients (45%) had 1 or more GTVs with a delivered minimum dose more than 5 Gy higher with the midposition CT plan using dose probability PTV, compared with the delivered dose with the exhale CT plan using ITV-based PTV. For isotoxic liver SBRT planned and delivered at the mean respiratory, reduced dose probability PTV enables a mean escalation of 4 Gy (9%) in 6 fractions over ITV-based PTV. This may potentially improve local control without increasing the risk of tumor underdosing. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Dose-Escalation Study for Cardiac Radiosurgery in a Porcine Model

    SciTech Connect

    Blanck, Oliver; Bode, Frank; Gebhard, Maximilian; Hunold, Peter; Brandt, Sebastian; Bruder, Ralf; Grossherr, Martin; Vonthein, Reinhard; Rades, Dirk; Dunst, Juergen

    2014-07-01

    Purpose: To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation. Methods and Materials: Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm{sup 3}). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination. Results: Transmural scarring of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy. Conclusions: Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.

  19. Cost of dose escalation in people with rheumatoid arthritis treated with tumour necrosis factor inhibitors across Europe.

    PubMed

    Holden, Sarah E; Currie, Craig J; Lennon, Martin; Reynolds, Alan V; Moots, Robert J

    2016-01-01

    The aim of this study was to calculate the marginal cost of dose escalation in people with rheumatoid arthritis treated with tumour necrosis factor (TNF) inhibitors across Europe. The proportion of people who escalate their dose of TNF inhibitor and the average percentage increase in TNF inhibitor cost associated with escalators versus non-escalators was calculated from previously published estimates, weighted by the sample size for each study. The number of people with rheumatoid arthritis treated with TNF inhibitors and the corresponding total drug sales were obtained for five European countries from Decision Resources' Pharmacor Market Forecast. Method 1 assumed that total sales of a TNF inhibitor represented the cost of an escalator multiplied by the number of escalators plus the cost of a non-escalator multiplied by the number of non-escalators. Method 2 assumed that the drug cost per day used to forecast total sales was calculated using the dose of TNF inhibitor used by non-escalators. The marginal cost of TNF inhibitor dose escalation was estimated by multiplying the difference in cost between escalators and non-escalators by the number of escalators. The estimated increase in TNF inhibitor costs associated with dose escalation in people with rheumatoid arthritis across five European countries (Germany, France, UK, Spain and Italy) was €51.5-54.4 million for adalimumab, €44.8-52.8 million for infliximab and €5.8-5.9 million for etanercept. Dose escalation of the TNF inhibitors adalimumab, etanercept and infliximab in people with rheumatoid arthritis has resulted in an increase in TNF inhibitor costs across five European countries.

  20. Long-Term Response and Possible Cure of Patients With B-Cell Malignancies With Dose-Escalated Rituximab

    PubMed Central

    Jacobs, Lauren M.; Wiernik, Peter H.; Dutcher, Janice P.; Muxi, Pablo

    2017-01-01

    Rituximab (R), a chimeric monoclonal antibody targeting CD20 antigen on B-cells, has become a standard of care in the treatment of B-cell malignancies, most often in conjunction with cytotoxic chemotherapy. Activity has been demonstrated in many subtypes of B-cell lymphoma, including diffuse large cell lymphoma, follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), lymphocyte-predominant Hodgkin lymphoma, and Waldenström macroglobulinemia (WM). Additionally, dose escalation of R as a single agent has demonstrated improved activity in previously treated/poor prognosis CLL. We present 4 cases of B-cell malignancy (2 CLL variants/MCL, 1 FL, 1 WM) who received dose-escalated R as a single agent and achieved complete response (3 patients) and stable disease/partial response (1 patient) of 6.5+ to 15+ years duration. They have been off treatment for 6.5+ to 15+ years. Toxicity was minimal, with initial infusion reactions similar to those observed with standard dose infusions. There were no serious treatment-related adverse events or infections. Dose escalated R as a single agent may possibly be curative for some patients with B-cell malignancies, unlike the standard empiric dose of 375 mg/m2, and deserves further study. PMID:28203581

  1. WE-G-BRB-02: The Role of Program Project Grants in Study of 3D Conformal Therapy, Dose Escalation and Motion Management

    SciTech Connect

    Fraass, B.

    2015-06-15

    Over the past 20 years the NIH has funded individual grants, program projects grants, and clinical trials which have been instrumental in advancing patient care. The ways that each grant mechanism lends itself to the different phases of translating research into clinical practice will be described. Major technological innovations, such as IMRT and proton therapy, have been advanced with R01-type and P01-type funding and will be discussed. Similarly, the role of program project grants in identifying and addressing key hypotheses on the potential of 3D conformal therapy, normal tissue-guided dose escalation and motion management will be described. An overview will be provided regarding how these technological innovations have been applied to multi-institutional NIH-sponsored trials. Finally, the panel will discuss regarding which research questions should be funded by the NIH to inspire the next advances in radiation therapy. Learning Objectives: Understand the different funding mechanisms of the NIH Learn about research advances that have led to innovation in delivery Review achievements due to NIH-funded program project grants in radiotherapy over the past 20 years Understand example advances achieved with multi-institutional clinical trials NIH.

  2. Image-guided intensity-modulated radiotherapy for refractory bilateral breast cancer in a patient with extensive cutaneous metastasis in the chest and abdominal walls

    PubMed Central

    Lu, Yueh-Feng; Lin, Yu-Chin; Chen, Kuo-Hsin; Shueng, Pei-Wei; Yeh, Hsin-Pei; Hsieh, Chen-Hsi

    2016-01-01

    Treatment for bilateral breast cancer with chest wall and abdominal skin invasion normally involves conventional radiotherapy (RT); however, conventional RT provides inadequate target volume coverage and excessive treatment of large volumes of normal tissue. Helical tomotherapy (HT) has the ability to deliver continuous craniocaudal irradiation that suppresses junction problems and provides good conformity of dose distribution. A 47-year-old female with stage IV bilateral breast cancer with chest wall and pectoralis major muscle invasion, lymphadenopathy, bilateral pleural effusion, and multiple bone metastases received chemotherapy and target therapy beginning in January 2014; 4 months after the initiation of chemotherapy, computed tomography revealed progression of chest and abdominal wall invasion. A total dose of 70.2 Gy was delivered to both breasts, the chest wall, the abdominal wall, and the bilateral supraclavicular nodal areas in 39 fractions via HT. The total planning target volume was 4,533.29 cm3. The percent of lung volume receiving at least 20 Gy (V20) was 28%, 22%, and 25% for the right lung, left lung, and whole lung, respectively. The mean dose to the heart was 8.6 Gy. Follow-up computed tomography revealed complete response after the RT course. Grade 1 dysphagia, weight loss, grade 2 neutropenia, and grade 3 dermatitis were noted during the RT course. Pain score decreased from 6 to 1. No cardiac, pulmonary, liver, or intestinal toxicity developed during treatment or follow-up. Concurrent HT with or without systemic treatment could be a safe salvage therapy for chemorefractory locally advanced breast cancer patients with extensive cutaneous metastasis. PMID:27284253

  3. FIRE: an open-software suite for real-time 2D/3D image registration for image guided radiotherapy research

    NASA Astrophysics Data System (ADS)

    Furtado, H.; Gendrin, C.; Spoerk, J.; Steiner, E.; Underwood, T.; Kuenzler, T.; Georg, D.; Birkfellner, W.

    2016-03-01

    Radiotherapy treatments have changed at a tremendously rapid pace. Dose delivered to the tumor has escalated while organs at risk (OARs) are better spared. The impact of moving tumors during dose delivery has become higher due to very steep dose gradients. Intra-fractional tumor motion has to be managed adequately to reduce errors in dose delivery. For tumors with large motion such as tumors in the lung, tracking is an approach that can reduce position uncertainty. Tumor tracking approaches range from purely image intensity based techniques to motion estimation based on surrogate tracking. Research efforts are often based on custom designed software platforms which take too much time and effort to develop. To address this challenge we have developed an open software platform especially focusing on tumor motion management. FLIRT is a freely available open-source software platform. The core method for tumor tracking is purely intensity based 2D/3D registration. The platform is written in C++ using the Qt framework for the user interface. The performance critical methods are implemented on the graphics processor using the CUDA extension. One registration can be as fast as 90ms (11Hz). This is suitable to track tumors moving due to respiration (~0.3Hz) or heartbeat (~1Hz). Apart from focusing on high performance, the platform is designed to be flexible and easy to use. Current use cases range from tracking feasibility studies, patient positioning and method validation. Such a framework has the potential of enabling the research community to rapidly perform patient studies or try new methods.

  4. Real-time intensity based 2D/3D registration using kV-MV image pairs for tumor motion tracking in image guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Furtado, H.; Steiner, E.; Stock, M.; Georg, D.; Birkfellner, W.

    2014-03-01

    Intra-fractional respiratorymotion during radiotherapy is one of themain sources of uncertainty in dose application creating the need to extend themargins of the planning target volume (PTV). Real-time tumormotion tracking by 2D/3D registration using on-board kilo-voltage (kV) imaging can lead to a reduction of the PTV. One limitation of this technique when using one projection image, is the inability to resolve motion along the imaging beam axis. We present a retrospective patient study to investigate the impact of paired portal mega-voltage (MV) and kV images, on registration accuracy. We used data from eighteen patients suffering from non small cell lung cancer undergoing regular treatment at our center. For each patient we acquired a planning CT and sequences of kV and MV images during treatment. Our evaluation consisted of comparing the accuracy of motion tracking in 6 degrees-of-freedom(DOF) using the anterior-posterior (AP) kV sequence or the sequence of kV-MV image pairs. We use graphics processing unit rendering for real-time performance. Motion along cranial-caudal direction could accurately be extracted when using only the kV sequence but in AP direction we obtained large errors. When using kV-MV pairs, the average error was reduced from 3.3 mm to 1.8 mm and the motion along AP was successfully extracted. The mean registration time was of 190+/-35ms. Our evaluation shows that using kVMV image pairs leads to improved motion extraction in 6 DOF. Therefore, this approach is suitable for accurate, real-time tumor motion tracking with a conventional LINAC.

  5. Local Setup Errors in Image-Guided Radiotherapy for Head and Neck Cancer Patients Immobilized With a Custom-Made Device

    SciTech Connect

    Giske, Kristina; Stoiber, Eva M.; Schwarz, Michael; Stoll, Armin; Muenter, Marc W.; Timke, Carmen; Roeder, Falk; Debus, Juergen; Huber, Peter E.; Thieke, Christian; Bendl, Rolf

    2011-06-01

    Purpose: To evaluate the local positioning uncertainties during fractionated radiotherapy of head-and-neck cancer patients immobilized using a custom-made fixation device and discuss the effect of possible patient correction strategies for these uncertainties. Methods and Materials: A total of 45 head-and-neck patients underwent regular control computed tomography scanning using an in-room computed tomography scanner. The local and global positioning variations of all patients were evaluated by applying a rigid registration algorithm. One bounding box around the complete target volume and nine local registration boxes containing relevant anatomic structures were introduced. The resulting uncertainties for a stereotactic setup and the deformations referenced to one anatomic local registration box were determined. Local deformations of the patients immobilized using our custom-made device were compared with previously published results. Several patient positioning correction strategies were simulated, and the residual local uncertainties were calculated. Results: The patient anatomy in the stereotactic setup showed local systematic positioning deviations of 1-4 mm. The deformations referenced to a particular anatomic local registration box were similar to the reported deformations assessed from patients immobilized with commercially available Aquaplast masks. A global correction, including the rotational error compensation, decreased the remaining local translational errors. Depending on the chosen patient positioning strategy, the remaining local uncertainties varied considerably. Conclusions: Local deformations in head-and-neck patients occur even if an elaborate, custom-made patient fixation method is used. A rotational error correction decreased the required margins considerably. None of the considered correction strategies achieved perfect alignment. Therefore, weighting of anatomic subregions to obtain the optimal correction vector should be investigated in the

  6. [Comparison of setup accuracy between ExacTrac X-ray 6 dimensions and cone-beam computed tomography for intracranial and pelvic image-guided radiotherapy].

    PubMed

    Kudo, Tsuyoshi; Ono, Kaoru; Furukawa, Kengo; Fujimoto, Sachie; Akagi, Yukio; Koyama, Tadashi; Hirokawa, Yutaka

    2012-01-01

    The aim of this study was to compare the setup difference measured with ExacTrac X-ray 6D (ETX6D) and cone-beam computed tomography (CBCT) for non-invasive fractionated radiotherapy. Setup data were collected on a Novalis Tx treatment unit for both a head phantom and patients with intracranial tumors and a pelvic phantom and patients with prostate cancer. Initially, setup was done for a phantom using ETX6D. Secondly, a treatment couch was shifted or rotated by each already known value. Thirdly, ETX6D and CBCT scans were obtained. Finally, setup difference was determined: the registrations of ETX6D images with the corresponding digitally reconstructed radiographs using ETX6D fusion, and registrations of CBCT images with the planning CT using online 6D fusion. The setup difference between ETX6D and CBCT was compared. The impact of shifts and rotations on the difference was evaluated. Patients' setup data was similarly analyzed. In phantom experiments, the root mean square (RMS) of difference of the shift and rotation was less than 0.45 mm for translations, and 0.17 degrees for rotations. In intracranial patients' data, the RMS of that was 0.55 mm and 0.44 degree, respectively. In prostate cancer patients' data, the RMS of that was 0.77 mm and 0.79 degree, respectively. In this study, we observed modest setup differences between ETX6D and CBCT. These differences were generally less than 1.00 mm for translations, and 1.00 degrees for rotations, respectively.

  7. Evaluation of overall setup accuracy and adequate setup margins in pelvic image-guided radiotherapy: Comparison of the male and female patients

    SciTech Connect

    Laaksomaa, Marko; Kapanen, Mika; Tulijoki, Tapio; Peltola, Seppo; Hyödynmaa, Simo; Kellokumpu-Lehtinen, Pirkko-Liisa

    2014-04-01

    We evaluated adequate setup margins for the radiotherapy (RT) of pelvic tumors based on overall position errors of bony landmarks. We also estimated the difference in setup accuracy between the male and female patients. Finally, we compared the patient rotation for 2 immobilization devices. The study cohort included consecutive 64 male and 64 female patients. Altogether, 1794 orthogonal setup images were analyzed. Observer-related deviation in image matching and the effect of patient rotation were explicitly determined. Overall systematic and random errors were calculated in 3 orthogonal directions. Anisotropic setup margins were evaluated based on residual errors after weekly image guidance. The van Herk formula was used to calculate the margins. Overall, 100 patients were immobilized with a house-made device. The patient rotation was compared against 28 patients immobilized with CIVCO's Kneefix and Feetfix. We found that the usually applied isotropic setup margin of 8 mm covered all the uncertainties related to patient setup for most RT treatments of the pelvis. However, margins of even 10.3 mm were needed for the female patients with very large pelvic target volumes centered either in the symphysis or in the sacrum containing both of these structures. This was because the effect of rotation (p ≤ 0.02) and the observer variation in image matching (p ≤ 0.04) were significantly larger for the female patients than for the male patients. Even with daily image guidance, the required margins remained larger for the women. Patient rotations were largest about the lateral axes. The difference between the required margins was only 1 mm for the 2 immobilization devices. The largest component of overall systematic position error came from patient rotation. This emphasizes the need for rotation correction. Overall, larger position errors and setup margins were observed for the female patients with pelvic cancer than for the male patients.

  8. Comparison of Localization Performance with Implanted Fiducial Markers and Cone-Beam Computed Tomography for On-line Image-Guided Radiotherapy of the Prostate

    PubMed Central

    Moseley, Douglas J; White, Elizabeth A; Wiltshire, Kirsty L; Rosewall, Tara; Sharpe, Michael B; Siewerdsen, Jeffrey H; Bissonnette, Jean-Pierre; Gospodarowicz, Mary; Warde, Padraig; Catton, Charles N; Jaffray, David A

    2007-01-01

    Purpose To assess the accuracy of kV cone-beam CT (CBCT) based setup corrections as compared to orthogonal MV portal image-based corrections for patients undergoing external-beam radiotherapy of the prostate. Method and Materials Daily cone-beam CT volumetric images were acquired after setup for patients with three intra-prostatic fiducial markers. The estimated couch shifts were compared retrospectively to patient adjustments based on two orthogonal MV portal images (the current clinical standard of care in our institution). The CBCT soft-tissue based shifts were also estimated by digitally removing the gold markers in each projection to suppress the artifacts in the reconstructed volumes. A total of 256 volumetric images for 15 patients were analyzed. Results The Pearson coefficient of correlation for the patient position shifts using fiducial markers in MV vs kV was (R2 = 0.95, 0.84, 0.81) in the L/R, A/P and S/I directions respectively. The correlation using soft-tissue matching was ((R2 = 0.90, 0.49, 0.51) in the L/R, A/P and S/I directions. A Bland-Altman analysis showed no significant trends in the data. The percentage of shifts within a +/−3mm tolerance (the clinical action level) was (99.7, 95.5, 91.3) for fiducial marker matching and (99.5, 70.3, 78.4) for soft-tissue matching. Conclusions Cone-beam CT is an accurate and precise tool for image-guidance. It provides an equivalent means of patient setup correction for prostate patients with implanted gold fiducial markers. Use of the additional information provided by the visualization of soft-tissue structures is an active area of research. PMID:17293243

  9. Comparison of localization performance with implanted fiducial markers and cone-beam computed tomography for on-line image-guided radiotherapy of the prostate

    SciTech Connect

    Moseley, Douglas J. . E-mail: douglas.moseley@rmp.uhn.on.ca; White, Elizabeth A.; Wiltshire, Kirsty L.; Rosewall, Tara; Sharpe, Michael B.; Siewerdsen, Jeffrey H.; Bissonnette, Jean-Pierre; Gospodarowicz, Mary; Warde, Padraig; Catton, Charles N.; Jaffray, David A.

    2007-03-01

    Purpose: The aim of this work was to assess the accuracy of kilovoltage (kV) cone-beam computed tomography (CBCT)-based setup corrections as compared with orthogonal megavoltage (MV) portal image-based corrections for patients undergoing external-beam radiotherapy of the prostate. Methods and Materials: Daily cone-beam CT volumetric images were acquired after setup for patients with three intraprostatic fiducial markers. The estimated couch shifts were compared retrospectively to patient adjustments based on two orthogonal MV portal images (the current clinical standard of care in our institution). The CBCT soft-tissue based shifts were also estimated by digitally removing the gold markers in each projection to suppress the artifacts in the reconstructed volumes. A total of 256 volumetric images for 15 patients were analyzed. Results: The Pearson coefficient of correlation for the patient position shifts using fiducial markers in MV vs. kV was (R{sup 2} = 0.95, 0.84, 0.81) in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. The correlation using soft-tissue matching was as follows: R{sup 2} = 0.90, 0.49, 0.51 in the LR, AP and SI directions. A Bland-Altman analysis showed no significant trends in the data. The percentage of shifts within a {+-}3-mm tolerance (the clinical action level) was 99.7%, 95.5%, 91.3% for fiducial marker matching and 99.5%, 70.3%, 78.4% for soft-tissue matching. Conclusions: Cone-beam CT is an accurate and precise tool for image guidance. It provides an equivalent means of patient setup correction for prostate patients with implanted gold fiducial markers. Use of the additional information provided by the visualization of soft-tissue structures is an active area of research.

  10. FDG-PET/CT Predicts Outcome in Oropharingeal Carcinoma Patients Undergoing Intensity Modulated Radiation Therapy with Dose Escalation to FDG-avid Tumour Volumes.

    PubMed

    Mapelli, Paola; Broggi, Sara; Incerti, Elena; Alongi, Pierpaolo; Kirienko, Margarita; Fiorino, Claudio; Dell Oca, Italo; Fallanca, Federico; Vanoli, Emilia Giovanna; Di Muzio, Nadia Gisella; Gianolli, Luigi; Picchio, Maria

    2017-08-24

    To evaluate the predictive value of FDG-PET/CT parameters on outcome of oropharyngeal squamocellular cancer (OSCC) patients undergoing helical tomotherapy (HTT), with dose escalation to FDG-PET/CT positive tumour volumes using the simultaneous integrated boost (SIB) technique. We analysed 41 patients studied by FDG-PET/CT and treated with radical intent between 2005 and 2014 for OSCC. HTT-SIB was delivered in 30 fractions concomitantly: 69 Gy, as SIB, to the PET-positive volume (biological target volume - BTV-PET), both to the primary tumour (T) and lymph nodes (N), 66 Gy to the T and positive N, 54 Gy to the laterocervical nodes at risk. Selected PET parameters were recovered: maximum and mean standardized uptake values (SUVmax and SUVmean, respectively), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) obtained with different thresholds (40-50-60% of the SUVmax) for T and N. The correlation between these parameters and the 3-year overall (OS), cancer specific (CSS), disease free (DFS), local relapse free for T and N (LRFS-T and LRFS-N) and distant metastasis free (DMFS) survivals was investigated. The median follow-up was 37 months (range: 3-125). The 3-year OS, CSS, DFS, LRFST, LRFS-N and DMFS were 86%, 88%, 76%, 83%, 88% and 91%, respectively. BTVT+ N>30.9cc and BTV-T>22.4cc were correlated with CSS (p=0.02) and OS (p=0.006) respectively; TLG-T-60>34.6cc was correlated with CSS (p=0.04) and OS (p=0.01). MTV-T-60>4.4cc could predict a higher risk of relapse/death (CSS: p=0.033; hazard ratio (HR) =10.92; OS: p=0.01; HR=16.4; LRFS-T: p=0.02; HR=13.90; LRFS-T+N: p=0.03; HR=6.50). PET parameters predicted survival outcomes and may be considered in the future in the implementation of more personalized treatment schedules in patients affected by OSCC undergoing radiotherapy. FDG-PET/CT dose escalated HTT-SIB allowed very promising 3-year disease control rates in OSCC patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. SU-E-T-69: A Radiobiological Investigation of Dose Escalation in Lower Oesophageal Tumours with a Focus On Gastric Toxicity

    SciTech Connect

    Carrington, R; Staffurth, J; Spezi, E; Crosby, T; Warren, S; Partridge, M; Hawkins, M

    2015-06-15

    The incidence of lower third oesophageal tumours is increasing in most Western populations. With the role of radiotherapy dose escalation being identified as a research priority in improving outcomes, it is important to quantify the increased toxicity that this may pose to sites such as the lower oesophagus. This study therefore aims to investigate the feasibility of lower oesophageal dose escalation with a focus on stomach tissue toxicity.The original 3D-conformal plans (50Gy3D) from 10 patients in the SCOPE1 trial were reviewed and compared to two RapidArc plans created retrospectively to represent the treatment arms of the forthcoming SCOPE2 trial: 50GyRA and 60GyRA (50Gy to PTV1 with a simultaneously integrated boost of 60Gy to PTV2). The stomach was contoured as stomach wall and dose constraints set according to QUANTEC. Normal tissue complication probability (NTCP) was estimated for the stomach wall for an endpoint of gastric bleeding. There was a mean increase of 5.93% in NTCP from 50Gy3D to 60GyRA and a mean increase of 8.15% in NTCP from the 50GyRA to 60GyRA. With NTCP modelling restricted to volumes outside PTV2, there was a mean decrease of 0.92% in NTCP from the 50Gy3D to 60GyRA, and a mean increase of 2.25% from 50GyRA to 60GyRA. There was a strong correlation between the NTCP and Stomach Wall/PTV1 overlap volume for all plans (R=0.80, 0.77 and 0.77 for 60GyRA, 50GyRA and 50Gy3D respectively). There was also a strong correlation between NTCP and the Stomach Wall/PTV2 overlap volume for 60GyRA (R= 0.82).Radiobiological modelling suggests that increasing the prescribed dose to 60Gy may be associated with a significantly increased risk of toxicity to the stomach within the boost volume. It is recommended that stomach toxicity be closely monitored prospectively when treating patients with lower oesophageal tumours in the forthcoming SCOPE 2 trial. Rhys Carrington received a PhD studentship grant from Cancer Research Wales. Grant number: 2445; Dr Warren and

  12. Radiation Dose Escalation in Esophageal Cancer Revisited: A Contemporary Analysis of the National Cancer Data Base, 2004 to 2012.

    PubMed

    Brower, Jeffrey V; Chen, Shuai; Bassetti, Michael F; Yu, Menggang; Harari, Paul M; Ritter, Mark A; Baschnagel, Andrew M

    2016-12-01

    To evaluate the effect of radiation dose escalation on overall survival (OS) for patients with nonmetastatic esophageal cancer treated with concurrent radiation and chemotherapy. Patients diagnosed with stage I to III esophageal cancer treated from 2004 to 2012 were identified from the National Cancer Data Base. Patients who received concurrent radiation and chemotherapy with radiation doses of ≥50 Gy and did not undergo surgery were included. OS was compared using Cox proportional hazards regression and propensity score matching. A total of 6854 patients were included; 3821 (55.7%) received 50 to 50.4 Gy and 3033 (44.3%) received doses >50.4 Gy. Univariate analysis revealed no significant difference in OS between patients receiving 50 to 50.4 Gy and those receiving >50.4 Gy (P=.53). The dose analysis, binned as 50 to 50.4, 51 to 54, 55 to 60, and >60 Gy, revealed no appreciable difference in OS within any group compared with 50 to 50.4 Gy. Subgroup analyses investigating the effect of dose escalation by histologic type and in the setting of intensity modulated radiation therapy also failed to reveal a benefit. Propensity score matching confirmed the absence of a statistically significant difference in OS among the dose levels. The factors associated with improved OS on multivariable analysis included female sex, lower Charlson-Deyo comorbidity score, private insurance, cervical/upper esophagus location, squamous cell histologic type, lower T stage, and node-negative status (P<.01 for all analyses). In this large national cohort, dose escalation >50.4 Gy did not result in improved OS among patients with stage I to III esophageal cancer treated with definitive concurrent radiation and chemotherapy. These data suggest that despite advanced contemporary treatment techniques, OS for patients with esophageal cancer remains unaltered by escalation of radiation dose >50.4 Gy, consistent with the results of the INT-0123 trial. Furthermore, these data highlight

  13. Incidence of Secondary Cancer Development After High-Dose Intensity-Modulated Radiotherapy and Image-Guided Brachytherapy for the Treatment of Localized Prostate Cancer

    SciTech Connect

    Zelefsky, Michael J.; Housman, Douglas M.; Pei Xin; Alicikus, Zumre; Magsanoc, Juan Martin; Dauer, Lawrence T.; St Germain, Jean; Yamada, Yoshiya; Kollmeier, Marisa; Cox, Brett; Zhang Zhigang

    2012-07-01

    Purpose: To report the incidence and excess risk of second malignancy (SM) development compared with the general population after external beam radiotherapy (EBRT) and brachytherapy to treat prostate cancer. Methods and Materials: Between 1998 and 2001, 1,310 patients with localized prostate cancer were treated with EBRT (n = 897) or brachytherapy (n = 413). We compared the incidence of SMs in our patients with that of the general population extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results data set combined with the 2000 census data. Results: The 10-year likelihood of SM development was 25% after EBRT and 15% after brachytherapy (p = .02). The corresponding 10-year likelihood for in-field SM development in these groups was 4.9% and 1.6% (p = .24). Multivariate analysis showed that EBRT vs. brachytherapy and older age were the only significant predictors for the development of all SMs (p = .037 and p = .030), with a trend for older patients to develop a SM. The increased incidence of SM for EBRT patients was explained by the greater incidence of skin cancer outside the radiation field compared with that after brachytherapy (10.6% and 3.3%, respectively, p = .004). For the EBRT group, the 5- and 10-year mortality rate was 1.96% and 5.1% from out-of field cancer, respectively; for in-field SM, the corresponding mortality rates were 0.1% and 0.7%. Among the brachytherapy group, the 5- and 10-year mortality rate related to out-of field SM was 0.8% and 2.7%, respectively. Our observed SM rates after prostate RT were not significantly different from the cancer incidence rates in the general population. Conclusions: Using modern sophisticated treatment techniques, we report low rates of in-field bladder and rectal SM risks after prostate cancer RT. Furthermore, the likelihood of mortality secondary to a SM was unusual. The greater rate of SM observed with EBRT vs. brachytherapy was related to a small, but significantly increased

  14. Safety and Dose Escalation Study of Intravenous Zinc Supplementation in Pediatric Critical Illness.

    PubMed

    Cvijanovich, Natalie Z; King, Janet C; Flori, Heidi R; Gildengorin, Ginny; Vinks, Alexander A; Wong, Hector R

    2016-08-01

    Critically ill children have low plasma zinc (pZn), correlating with organ failure. Since Zn influences inflammation, immune function, and glucose control, Zn supplementation is a plausible therapeutic modality. We sought to determine a safe dose of intravenous (IV) Zn to restore pZn in critically ill children. Stepwise dose escalation study of IV Zn supplementation at a tertiary children's hospital. All children (<10 years) admitted to the pediatric intensive care unit with a Pediatric Risk of Mortality III score >5, or ≥1 new organ failure were eligible. After consent, patients were sequentially enrolled into 4 dosing groups: (1) no zinc, (2) Zn250: 250 mcg/kg/d ZnSO4, (3) Zn500: 500 mcg/kg/d ZnSO4, or (4) Zn750: 750 mcg/kg/d ZnSO4 ZnSO4 was administered 3 times daily for 7 days. pZn was measured at baseline, end of first ZnSO4 infusion, 1 hour postinfusion, and 7 hours postinfusion on day 1, then daily through days 2-7. Interleukin-6 (IL-6), C-reactive protein (CRP), and lymphocyte subsets were measured on days 1 and 3. Glucose was measured 3 times daily for 7 days. Twenty-four patients were enrolled. Baseline demographics were similar among groups. Baseline pZn was low in all patients (mean [SD], 41.8 [16.0] mcg/dL). pZn increased over the study period in supplemented groups; however, mean pZn in the Zn750 group exceeded the 50th percentile. pZn was not associated with IL-6, CRP, or lymphocyte subsets among groups. Degree of hyperglycemia did not differ among groups. No patient had a study-related adverse event. IV zinc supplementation at 500 mcg/kg/d restores pZn to near the 50th percentile and is well tolerated. © 2015 American Society for Parenteral and Enteral Nutrition.

  15. Feasibility Study of Intra-patient Sorafenib Dose-Escalation or Re-Escalation in Patients with Previously Treated Advanced Solid Tumors

    PubMed Central

    Semrad, Thomas J.; Eddings, Courtney; Pan, Chong-Xian; Lau, Derick H.; Gandara, David; Beckett, Laurel; Lara, Primo N.

    2014-01-01

    Purpose To determine if intra-patient dose escalation of the multi-targeted kinase inhibitor sorafenib is feasible in patients with advanced pretreated solid malignancies. Methods An intra-patient dose escalation scheme starting at 400 mg BID was employed in this prospective trial. Doses were escalated to 600 mg BID for the second cycle and to 800 mg BID for the third cycle in the absence of grade 3+ adverse events. In the event of grade 3+ adverse events during cycle 1, doses were reduced to 400 mg daily through cycle 2. Dose re-escalation for cycle 3 was allowed in the absence of grade 3+ adverse events during cycle 2. Further dose escalation was prohibited. The primary endpoint was the overall percentage of patients tolerating dose escalation to 600 mg BID through cycle 2 or tolerating re-escalation to 400 mg BID through cycle 3. Results Fifty eligible patients with various solid tumors and a median of 3 prior therapies were enrolled. Eleven patients (22%) tolerated primary dose escalation or re-escalation. Only 14 patients (28%) completed cycle 1 without dose modification or discontinuing treatment. Seven of 13 patients tolerated primary dose escalation through cycle 2. Four of 5 patients tolerated dose re-escalation through cycle 3. Reasons for escalation failure included tumor progression (42%) and adverse events (26%). Common grade 3+ adverse events included hand-foot skin reaction, hypertension, and hypophosphatemia. Conclusions Intra-patient dose escalation and/or re-escalation of sorafenib were not feasible in pretreated solid tumor patients. Sorafenib dose escalation remains an investigational approach. PMID:22015991

  16. Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation

    PubMed Central

    Krishnan, Sunil; Chadha, Awalpreet S.; Suh, Yelin; Chen, Hsiang-Chun; Rao, Arvind; Das, Prajnan; Minsky, Bruce D.; Mahmood, Usama; Delclos, Marc E.; Sawakuchi, Gabriel O.; Beddar, Sam; Katz, Matthew H.; Fleming, Jason B.; Javle, Milind M.; Varadhachary, Gauri R.; Wolff, Robert A.; Crane, Christopher H.

    2016-01-01

    Purpose To review outcomes of locally advanced pancreatic cancer (LAPC) patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with curative intent. Methods and Materials A total of 200 patients with LAPC were treated with induction chemotherapy followed by chemoradiation between 2006 and 2014. Of these, 47 (24%) having tumors >1 cm from the luminal organs were selected for dose-escalated IMRT (biologically effective dose [BED] >70 Gy) using a simultaneous integrated boost technique, inspiration breath hold, and computed tomographic image guidance. Fractionation was optimized for coverage of gross tumor and luminal organ sparing. A 2- to 5-mm margin around the gross tumor volume was treated using a simultaneous integrated boost with a microscopic dose. Overall survival (OS), recurrence-free survival (RFS), local-regional and distant RFS, and time to local-regional and distant recurrence, calculated from start of chemoradiation, were the outcomes of interest. Results Median radiation dose was 50.4 Gy (BED = 59.47 Gy) with a concurrent capecitabine-based (86%) regimen. Patients who received BED >70 Gy had a superior OS (17.8 vs 15.0 months, P = .03), which was preserved throughout the follow-up period, with estimated OS rates at 2 years of 36% versus 19% and at 3 years of 31% versus 9% along with improved local-regional RFS (10.2 vs 6.2 months, P = .05) as compared with those receiving BED ≤70 Gy. Degree of gross tumor volume coverage did not seem to affect outcomes. No additional toxicity was observed in the high-dose group. Higher dose (BED) was the only predictor of improved OS on multivariate analysis. Conclusion Radiation dose escalation during consolidative chemoradiation therapy after induction chemotherapy for LAPC patients improves OS and local-regional RFS. PMID:26972648

  17. Nomogram to predict rectal toxicity following prostate cancer radiotherapy

    PubMed Central

    Delobel, Jean-Bernard; Ospina, Juan David; Beckendorf, Véronique; Chira, Ciprian; Zhu, Jian; Bossi, Alberto; Messai, Taha; Acosta, Oscar; Castelli, Joël; de Crevoisier, Renaud

    2017-01-01

    Background To identify predictors of acute and late rectal toxicity following prostate cancer radiotherapy (RT), while integrating the potential impact of RT technique, dose escalation, and moderate hypofractionation, thus enabling us to generate a nomogram for individual prediction. Methods In total, 972 patients underwent RT for localized prostate cancer, to a total dose of 70 Gy or 80 Gy, using two different fractionations (2 Gy or 2.5 Gy/day), by means of several RT techniques (3D conformal RT [3DCRT], intensity-modulated RT [IMRT], or image-guided RT [IGRT]). Multivariate analyses were performed to identify predictors of acute and late rectal toxicity. A nomogram was generated based on the logistic regression model used to predict the 3-year rectal toxicity risk, with its accuracy assessed by dividing the cohort into training and validation subgroups. Results Mean follow-up for the entire cohort was 62 months, ranging from 6 to 235. The rate of acute Grade ≥2 rectal toxicity was 22.2%, decreasing when combining IMRT and IGRT, compared to 3DCRT (RR = 0.4, 95%CI: 0.3–0.6, p<0.01). The 5-year Grade ≥2 risks for rectal bleeding, urgency/tenesmus, diarrhea, and fecal incontinence were 9.9%, 4.5%, 2.8%, and 0.4%, respectively. The 3-year Grade ≥2 risk for overall rectal toxicity increased with total dose (p<0.01, RR = 1.1, 95%CI: 1.0–1.1) and dose per fraction (2Gy vs. 2.5Gy) (p = 0.03, RR = 3.3, 95%CI: 1.1–10.0), and decreased when combining IMRT and IGRT (RR = 0.50, 95% CI: 0.3–0.8, p<0.01). Based on these three parameters, a nomogram was generated. Conclusions Dose escalation and moderate hypofractionation increase late rectal toxicity. IMRT combined with IGRT markedly decreases acute and late rectal toxicity. Performing combined IMRT and IGRT can thus be envisaged for dose escalation and moderate hypofractionation. Our nomogram predicts the 3-year rectal toxicity risk by integrating total dose, fraction dose, and RT technique. PMID:28640871

  18. Is Androgen Deprivation Therapy Necessary in All Intermediate-Risk Prostate Cancer Patients Treated in the Dose Escalation Era?

    SciTech Connect

    Castle, Katherine O.; Hoffman, Karen E.; Levy, Lawrence B.; Lee, Andrew K.; Choi, Seungtaek; Nguyen, Quynh N.; Frank, Steven J.; Pugh, Thomas J.; McGuire, Sean E.; Kuban, Deborah A.

    2013-03-01

    Purpose: The benefit of adding androgen deprivation therapy (ADT) to dose-escalated radiation therapy (RT) for men with intermediate-risk prostate cancer is unclear; therefore, we assessed the impact of adding ADT to dose-escalated RT on freedom from failure (FFF). Methods: Three groups of men treated with intensity modulated RT or 3-dimensional conformal RT (75.6-78 Gy) from 1993-2008 for prostate cancer were categorized as (1) 326 intermediate-risk patients treated with RT alone, (2) 218 intermediate-risk patients treated with RT and ≤6 months of ADT, and (3) 274 low-risk patients treated with definitive RT. Median follow-up was 58 months. Recursive partitioning analysis based on FFF using Gleason score (GS), T stage, and pretreatment PSA concentration was applied to the intermediate-risk patients treated with RT alone. The Kaplan-Meier method was used to estimate 5-year FFF. Results: Based on recursive partitioning analysis, intermediate-risk patients treated with RT alone were divided into 3 prognostic groups: (1) 188 favorable patients: GS 6, ≤T2b or GS 3+4, ≤T1c; (2) 71 marginal patients: GS 3+4, T2a-b; and (3) 68 unfavorable patients: GS 4+3 or T2c disease. Hazard ratios (HR) for recurrence in each group were 1.0, 2.1, and 4.6, respectively. When intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT, the greatest benefit from ADT was seen for the unfavorable intermediate-risk patients (FFF, 74% vs 94%, respectively; P=.005). Favorable intermediate-risk patients had no significant benefit from the addition of ADT to RT (FFF, 94% vs 95%, respectively; P=.85), and FFF for favorable intermediate-risk patients treated with RT alone approached that of low-risk patients treated with RT alone (98%). Conclusions: Patients with favorable intermediate-risk prostate cancer did not benefit from the addition of ADT to dose-escalated RT, and their FFF was nearly as good as patients with low-risk disease

  19. The impact of image-guided radiation therapy on the dose distribution in prostate cancer using deformable registration

    NASA Astrophysics Data System (ADS)

    Schaly, Bryan

    Dosimetric uncertainties due to variable anatomy and beam setup variability pose a significant limitation in modern precision radiotherapy. These uncertainties may lead to discrepancies between the planned and actual dose distribution delivered to the patient. This may have an adverse impact on the treatment outcome in terms of recurrent tumour growth and/or causing complications in normal tissues. This work investigates the hypothesis that image-guided radiation therapy is needed to reduce the detrimental effects of changes in anatomy on the delivered dose distribution in cancer patients. To test this hypothesis, a deformable model is developed to enable the quantification of dose differences due to patient repositioning and variable anatomy. The deformable model is based on contour-driven thin-plate splines to track the position of tissue elements within the patient. This is combined with recalculation of the treatment plan using frequent computed tomography (CT) image data acquired at different times during treatment. It is demonstrated using a clinical prostate case that dose differences in the rectum and bladder are significant (˜25%) after a multiple fraction treatment. The deformable model is validated using phantom and clinical prostate CT data. A mathematical phantom is used to demonstrate that the accuracy in tracking the dose delivered to a tissue element is 3--4% in high dose gradient regions. Ten prostate cancer patients with radio-opaque markers implanted in the prostate and seminal vesicles are used to demonstrate that the deformable model is accurate (˜2.5 mm) to within the intra-observer contouring variability. The impact of correcting for setup uncertainty and inter-fraction tumour motion is explored by comparing treatment scenarios that would employ current image guidance technology to conventional treatment (i.e., alignment to external markers). This work demonstrates that geographic tumour miss is remedied using image-guided treatment and day

  20. 45 or 50 Gy, Which is the Optimal Radiotherapy Pelvic Dose in Locally Advanced Cervical Cancer in the Perspective of Reaching Magnetic Resonance Image-guided Adaptive Brachytherapy Planning Aims?

    PubMed

    Mazeron, R; Petit, C; Rivin, E; Limkin, E; Dumas, I; Maroun, P; Annede, P; Martinetti, F; Seisen, T; Lefkopoulos, D; Chargari, C; Haie-Meder, C

    2016-03-01

    In locally advanced cervical cancer, the dose delivered results from the sum of external beam radiotherapy and brachytherapy, and is limited by the surrounding organs at risk. The balance between both techniques influences the total dose delivered to the high-risk clinical target volume (HR-CTV). The aim of the present study was to compare the ability of reaching different planning aims after external beam radiotherapy pelvic doses of 45 Gy in 25 fractions or 50.4 Gy in 28 fractions, both considered as standard prescriptions. The optimised plans of 120 patients treated with pelvic chemoradiation followed by magnetic resonance image-guided intracavitary brachytherapy were reviewed. The doses per pulse were calculated, and the number of pulses required to reach the planning aims, or a limiting dose constraint to organs at risk, was calculated. All doses were converted to 2-Gy equivalents. Three scenarios were applied consisting of different sets of planning aims: 85 and 60 Gy for the HR-CTV and the intermediate-risk CTV (IR-CTV) D90 (minimal dose received by 90% of the volume) in scenario 1, 90 and 60 Gy, respectively, for scenarios 2 and 3. For organs at risk, dose constraints were 90, 75 and 75 Gy to the bladder, rectum and sigmoid D2cm(3), respectively, in scenarios 1 and 2, and 80, 65 and 70 Gy in scenario 3. A similar HR-CTV D90 could have been reached in scenarios 1 and 2 according to both pelvic doses. In scenario 3, a higher mean HR-CTV could have been reached in the 45 Gy arm (83.5 ± 8.0 versus 82.4 ± 8.0, P < 0.0001). The mean D2cm(3) of organs at risk was systematically and significantly increased after a delivery of 50.4 Gy to the pelvis, from 0.9 to 2.89 Gy. The proportions of plans reaching planning aims were 85.8, 72.5 and 42.5% after 45 Gy and 85.5, 67.5 and 33.3% after 50.4 Gy according to scenarios 1, 2 and 3, respectively. According to scenario 3, 50.4 Gy, the reachable HR-CTV D90 was higher in 30% of the cases, by 2 Gy in two

  1. Effects of voluntary dose escalation in a placebo-controlled, flexible-dose trial of fesoterodine in subjects with overactive bladder.

    PubMed

    Staskin, David; Khullar, Vik; Michel, Martin C; Morrow, Jon D; Sun, Franklin; Guan, Zhonghong; Dmochowski, Roger

    2011-11-01

    To characterize the response to fesoterodine treatment for overactive bladder (OAB) in subjects who did or did not choose to dose escalate in a flexible-dose study. Subjects were randomized to fesoterodine 4  mg or placebo. At week 2, subjects could remain on 4  mg (non-escalators) or choose to increase to 8  mg (escalators) for the remaining 10 weeks (sham escalation for placebo). Subjects completed 3-day bladder diaries at baseline, week 2 and week 12 noting micturitions, urgency episodes, and urgency urinary incontinence (UUI) episodes. Sixty-three per cent of 438 subjects randomized to fesoterodine and 73% of 445 randomized to placebo dose escalated. At baseline, fesoterodine escalators had significantly more micturitions and urgency episodes than fesoterodine non-escalators (P < 0.001); at week 2, before dose escalation, diary-dry rate and improvement in micturitions and urgency episodes were significantly greater among fesoterodine non-escalators versus escalators (P < 0.001); and by week 12, after dose escalation, diary-dry rate and improvements in micturitions and UUI episodes were similar between fesoterodine non-escalators and escalators (P > 0.05). The placebo escalator group did not demonstrate a similar response over placebo non-escalators following the dose escalation decision point. A rapid and robust response to fesoterodine 4  mg was demonstrated in non-escalators. Subjects who chose to dose escalate to fesoterodine 8  mg at week 2 showed significant improvement by week 12 versus baseline and week 2 (prior to escalation), as well as versus placebo. Dose escalation to 8  mg fesoterodine provided subjects with efficacy and tolerability similar to those who were satisfied with the 4-mg dose. Copyright © 2011 Wiley Periodicals, Inc.

  2. Factors associated with dose escalation of fesoterodine for treatment of overactive bladder in people >65 years of age: A post hoc analysis of data from the SOFIA study.

    PubMed

    Wagg, Adrian; Darekar, Amanda; Arumi, Daniel; Khullar, Vik; Oelke, Matthias

    2015-06-01

    To investigate factors which may influence dose escalation of antimuscarinics for overactive bladder (OAB) in older patients and how dose escalation affects treatment efficacy. A post hoc analysis of data from the 12-week randomized, placebo controlled phase of the SOFIA study investigating treatment with fesoterodine in older people with OAB. Predictors and outcomes in patients aged ≥65 years with OAB who did or did not choose to escalate from fesoterodine 4 to 8 mg before the first dose-escalation choice point (week 4) and at the end of the study (week 12) were assessed. Variables which significantly increased likelihood of dose escalation were, at baseline, body mass index (OR: 1.06, 95% CI 1.01, 1.12; P = 0.0222), and male gender (OR: 2.06, 95% CI 1.28, 3.32; P = 0.0028) and at week 4, change from baseline in urgency episodes (OR: 1.12, 95% CI 1.05, 1.20; P = 0.0008), patient perception of bladder control (PPBC) (OR: 1.44, 95% CI 1.12, 1.84; P = 0.004). At week 12, dose escalation was associated with slightly reduced treatment outcomes compared to week 4 non-escalators. No baseline disease related factor associated with dose escalation was identified. Magnitude of change in urgency episodes and reduction in PPBC at 4 weeks were associated with dose escalation. These data may be of use to healthcare providers as they allow judgement to be made in individual patients, allowing treatment decisions to be made. At end of treatment, improvements in efficacy and quality of life were achieved in both escalators and non-escalators. © 2014 Wiley Periodicals, Inc.

  3. Optimizing Collimator Margins for Isotoxically Dose-Escalated Conformal Radiation Therapy of Non-Small Cell Lung Cancer

    SciTech Connect

    Warren, Samantha; Panettieri, Vanessa; Panakis, Niki; Bates, Nicholas; Lester, Jason F.; Jain, Pooja; Landau, David B.; Nahum, Alan E.; Mayles, W. Philip M.; Fenwick, John D.

    2014-04-01

    Purpose: Isotoxic dose escalation schedules such as IDEAL-CRT [isotoxic dose escalation and acceleration in lung cancer chemoradiation therapy] (ISRCTN12155469) individualize doses prescribed to lung tumors, generating a fixed modeled risk of radiation pneumonitis. Because the beam penumbra is broadened in lung, the choice of collimator margin is an important element of the optimization of isotoxic conformal radiation therapy for lung cancer. Methods and Materials: Twelve patients with stage I-III non-small cell lung cancer (NSCLC) were replanned retrospectively using a range of collimator margins. For each plan, the prescribed dose was calculated according to the IDEAL-CRT isotoxic prescription method, and the absolute dose (D{sub 99}) delivered to 99% of the planning target volume (PTV) was determined. Results: Reducing the multileaf collimator margin from the widely used 7 mm to a value of 2 mm produced gains of 2.1 to 15.6 Gy in absolute PTV D{sub 99}, with a mean gain ± 1 standard error of the mean of 6.2 ± 1.1 Gy (2-sided P<.001). Conclusions: For NSCLC patients treated with conformal radiation therapy and an isotoxic dose prescription, absolute doses in the PTV may be increased by using smaller collimator margins, reductions in relative coverage being offset by increases in prescribed dose.

  4. Phase I dose-escalation studies of roniciclib, a pan-cyclin-dependent kinase inhibitor, in advanced malignancies.

    PubMed

    Bahleda, Rastislav; Grilley-Olson, Juneko E; Govindan, Ramaswamy; Barlesi, Fabrice; Greillier, Laurent; Perol, Maurice; Ray-Coquard, Isabelle; Strumberg, Dirk; Schultheis, Beate; Dy, Grace K; Zalcman, Gérard; Weiss, Glen J; Walter, Annette O; Kornacker, Martin; Rajagopalan, Prabhu; Henderson, David; Nogai, Hendrik; Ocker, Matthias; Soria, Jean-Charles

    2017-06-06

    To evaluate safety, pharmacokinetics, and maximum tolerated dose of roniciclib in patients with advanced malignancies, with dose expansion to evaluate clinical benefit at the recommended phase II dose (RP2D). Two phase I dose-escalation studies evaluated two roniciclib dosing schedules: 3 days on/4 days off or 4 weeks on/2 weeks off. The expansion phase included patients with small-cell lung cancer (SCLC), ovarian cancer, or tumour mutations involving the CDK signalling pathway. Ten patients were evaluable in the 4 weeks on/2 weeks off schedule (terminated following limited tolerability) and 47 in the 3 days on/4 days off schedule dose-escalation cohorts. On the 3 days on/4 days off schedule, RP2D was 5 mg twice daily in solid tumours (n=40); undetermined in lymphoid malignancies (n=7). Common roniciclib-related adverse events included nausea (76.6%), fatigue (65.8%), diarrhoea (63.1%), and vomiting (57.7%). Roniciclib demonstrated rapid absorption and dose-proportional increase in exposure. One partial response (1.0%) was observed. In RP2D expansion cohorts, the disease control rate (DCR) was 40.9% for patients with ovarian cancer (n=25), 17.4% for patients with SCLC (n=33), and 33.3% for patients with CDK-related tumour mutations (n=6). Roniciclib demonstrated an acceptable safety profile and moderate DCR in 3 days on/4 days off schedule.

  5. Radiotherapy Dosing for Locally Advanced Non-Small Cell Lung Carcinoma: “MTD” or “ALARA”?

    PubMed Central

    Ohri, Nitin

    2017-01-01

    Locally advanced non-small cell lung cancer (LA-NSCLC) is typically treated with thoracic radiotherapy, often in combination with cytotoxic chemotherapy. Despite tremendous advances in the evaluation, treatment techniques, and supportive care measures provided to LA-NSCLC patients, local disease progression and distant metastases frequently develop following definitive therapy. A recent landmark randomized trial demonstrated that radiotherapy dose escalation may reduce survival rates, highlighting our poor understanding of the effects of thoracic radiotherapy for LA-NSCLC. Here, we present rationale for further studies of radiotherapy dose escalation as well as arguments for exploring relatively low radiotherapy doses for LA-NSCLC.

  6. [Image guided dental implantology].

    PubMed

    Shohat, M; Tal, C

    2005-01-01

    Dental implants insertion is a predictable surgical procedure with very high success rates. An optimal implants placement requires excellent surgical skills and good prosthetic perception. Performing an inaccurate implantation can lead to irreversible surgical damage on the one hand or a prosthetic failure on the other hand. Planning software provide the surgeon with good planning tool; existing navigation systems allow for translating them into performance by semi-active or passive guidance. The later allows for flexibility in the implant location during the operation and real-time tracking of drill position. All of these tools are helpful in avoiding damage to anatomical structures by performing the implantation in close relation to the CT scan. But the solutions that provide most possible advantages requires CT with special markers, long and expansive preoperative preparations and most of all a very high initial cost. These, in addition to a very long learning curve are the reason for these systems not to become a popular working tool. The most important challenges of the next generation systems in dental implants navigation are lower price, smaller size, good performance and reliability and ease of use. This kind of image guided system should allow for preplanning of implants locations, and guided insertion by minimal invasive procedure.

  7. A randomised controlled trial of the efficacy and safety of allopurinol dose escalation to achieve target serum urate in people with gout.

    PubMed

    Stamp, Lisa K; Chapman, Peter T; Barclay, Murray L; Horne, Anne; Frampton, Christopher; Tan, Paul; Drake, Jill; Dalbeth, Nicola

    2017-09-01

    To determine the efficacy and safety of allopurinol dose escalation using a treat-to-target serum urate (SU) approach. A randomised, controlled, parallel-group, comparative clinical trial was undertaken. People with gout receiving at least creatinine clearance (CrCL)-based allopurinol dose for ≥1 month and SU ≥6 mg/dL were recruited. Participants were randomised to continue current dose (control) or allopurinol dose escalation for 12 months. In the dose escalation group, allopurinol was increased monthly until SU was <6 mg/dL. The primary endpoints were reduction in SU and adverse events (AEs). 183 participants (93 control, 90 dose escalation) were recruited. At baseline, mean (SD) urate was 7.15 (1.6) mg/dL and allopurinol dose 269 mg/day. 52% had CrCL<60 mL/min. Mean changes in SU at the final visit were -0.34 mg/dL in the control group and -1.5 mg/dL in the dose escalation group (p<0.001) with a mean difference of 1.2 mg/dL (95% CI 0.67 to 1.5, p<0.001). At month 12, 32% of controls and 69% in the dose escalation had SU <6 mg/dL. There were 43 serious AEs in 25 controls and 35 events in 22 dose escalation participants. Only one was considered probably related to allopurinol. Five control and five dose escalation participants died; none was considered allopurinol related. Mild elevations in LFTs were common in both groups, a few moderate increases in gamma glutamyl transferase (GGT) were noted. There was no difference in renal function changes between randomised groups. Higher than CrCL-based doses of allopurinol can effectively lower SU to treatment target in most people with gout. Allopurinol dose escalation is well tolerated. ANZCTR12611000845932; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  8. Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

    SciTech Connect

    Wong, Jeffrey Y.C.; Forman, Stephen; Somlo, George; Liu An; Schultheiss, Timothy; Radany, Eric; Palmer, Joycelynne; Stein, Anthony

    2013-01-01

    Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days -10 to -6, etoposide (VP16) on Day -5 (60 mg/kg), and cyclophosphamide (CY) on Day -3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days -12 to -8 (800 {mu}M min), TMI on Days -8 to -4, and VP16 on Day -3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible with BU/VP16 due to

  9. A collaborative analysis of stereotactic lung radiotherapy outcomes for early-stage non-small-cell lung cancer using daily online cone-beam computed tomography image-guided radiotherapy.

    PubMed

    Grills, Inga Siiner; Hope, Andrew J; Guckenberger, Matthias; Kestin, Larry L; Werner-Wasik, Maria; Yan, Di; Sonke, Jan-Jakob; Bissonnette, Jean-Pierre; Wilbert, Juergen; Xiao, Ying; Belderbos, Jose

    2012-09-01

    We report lung stereotactic-body radiotherapy (SBRT) outcomes for a large pooled cohort treated using daily online cone-beam computed tomography. Five hundred and five stage I-IIB (T1-3N0M0) non-small-cell lung cancer (NSCLC) cases underwent SBRT using cone-beam computed tomography image guidance at five international institutions from 1998 to 2010. Median age was 74 years (range, 42-92) whereas median forced expiratory volume in 1 second/diffusing lung capacity for carbon monoxide were 1.4 liter (65%) and 10.8 ml/min/mmHg (53%). Of the 505 cases, 64% were biopsy proven and 87% medically inoperable. Staging was: IA 63%, IB 33%, IIA 2%, and recurrent 1%. Median max tumor dimension was 2.6 cm (range, 0.9-8.5). Median heterogeneously calculated volumetric prescription dose (PD) was 54 Gy (range, 20-64 Gy) in three fractions (range, 1-15) over 8 days (range, 1-27). Median biologically equivalent PD biological equivalent doses (BED10) was 132 Gy (range, 60-180). With a median follow-up of 1.6 years (range, 0.1-7.3), the 2-year Kaplan-Meier local control (LC), regional control, and distant metastasis (DM) rates were 94%, 89%, and 20%, respectively, whereas cause-specific and overall survival were 87% and 60% (78% operable, 58% inoperable, p = 0.01), respectively. Stage, gross-tumor volume size (≥ 2.7 cm) and PD(BED10) predicted local relapse (LR) and DM. LR was 15% for BED10 less than 105 Gy versus 4% for BED10 of 105 Gy or more (p < 0.001); DM was 31% versus 18% for BED10 less than 105 versus 105 Gy or more (p = 0.01). On multivariate analysis, PD(BED10) and elapsed days during radiotherapy predicted LR; gross-tumor volume size predicted DM. Grade 2 or higher pneumonitis, rib fracture, myositis, and dermatitis were 7%, 3%, 1%, and 2%, respectively. In the largest early-stage NSCLC SBRT data set to date, a high rate of local control was achieved, which was correlated with a PD(BED10) of 105 Gy or more. Failures were primarily distant, severe toxicities were rare, and

  10. A dosimetric analysis of dose escalation using two intensity-modulated radiation therapy techniques in locally advanced pancreatic carcinoma

    SciTech Connect

    Brown, Michael W.; Ning, Holly; Arora, Barbara; Albert, Paul S.; Poggi, Matthew; Camphausen, Kevin; Citrin, Deborah . E-mail: citrind@mail.nih.gov

    2006-05-01

    Purpose: To perform an analysis of three-dimensional conformal radiation therapy (3D-CRT), sequential boost intensity-modulated radiation therapy (IMRTs), and integrated boost IMRT (IMRTi) for dose escalation in unresectable pancreatic carcinoma. Methods and Materials: Computed tomography images from 15 patients were used. Treatment plans were generated using 3D-CRT, IMRTs, and IMRTi for dose levels of 54, 59.4, and 64.8 Gy. Plans were analyzed for target coverage, doses to liver, kidneys, small bowel, and spinal cord. Results: Three-dimensional-CRT exceeded tolerance to small bowel in 1 of 15 (6.67%) patients at 54 Gy, and 4 of 15 (26.7%) patients at 59.4 and 64.8 Gy. 3D-CRT exceeded spinal cord tolerance in 1 of 15 patients (6.67%) at 59.4 Gy and liver constraints in 1 of 15 patients (6.67%) at 64.8 Gy; no IMRT plans exceeded tissue tolerance. Both IMRT techniques reduced the percentage of total kidney volume receiving 20 Gy (V20), the percentage of small bowel receiving 45 Gy (V45), and the percentage of liver receiving 35 Gy (V35). IMRTi appeared superior to IMRTs in reducing the total kidney V20 (p < 0.0001), right kidney V20 (p < 0.0001), and small bowel V45 (p = 0.02). Conclusions: Sequential boost IMRT and IMRTi improved the ability to achieve normal tissue dose goals compared with 3D-CRT. IMRTi allowed dose escalation to 64.8 Gy with acceptable normal tissue doses and superior dosimetry compared with 3D-CRT and IMRTs.

  11. Phase I, multicenter, open-label, dose-escalation study of sonidegib in Asian patients with advanced solid tumors.

    PubMed

    Minami, Hironobu; Ando, Yuichi; Ma, Brigette Buig Yue; Hsiang Lee, Jih-; Momota, Hiroyuki; Fujiwara, Yutaka; Li, Leung; Fukino, Koichi; Ito, Koji; Tajima, Takeshi; Mori, Asuka; Lin, Chia-Chi

    2016-10-01

    Sonidegib is a selective inhibitor of Smoothened receptor, which is a key regulator of the Hedgehog signaling pathway. The purpose of this study was to determine the maximum tolerated dose based on dose-limiting toxicity (DLT) and the recommended dose (RD) of sonidegib in Asian patients with advanced solid tumors. This was an open-label, single-arm, multicenter, two-group, parallel, dose-escalation, phase I study undertaken in Asian patients; group 1 included patients from Japan and group 2 included patients from Hong Kong and Taiwan. Dose escalation was guided by a Bayesian logistic regression model dependent on DLTs in cycle 1 and other safety findings. A total of 45 adult Asian patients with confirmed advanced solid tumors were enrolled. Group 1 included 21 patients (12 treated with 400 mg q.d. [once daily] and 9 treated with 600 mg q.d.) and group 2 included 24 patients (12 treated with 400 mg q.d., 8 treated with 600 mg q.d., and 4 treated with 800 mg q.d.). Elevation in creatine kinase was the DLT in both groups. The most common adverse events suspected to be related to sonidegib in both patient groups were increase in creatine kinase levels, myalgia, fatigue, and abnormal hepatic function. The RD of 400 mg q.d. was defined in both groups. Difference in tolerability was noted between the East Asian patients and Western population. The RD in East Asian patients (400 mg q.d.) was lower than in patients from Europe and the USA (800 mg q.d. and 250 mg twice daily). (Registered with Clinicaltrials.gov: NCT01208831.).

  12. Perineural Invasion Predicts Increased Recurrence, Metastasis, and Death From Prostate Cancer Following Treatment With Dose-Escalated Radiation Therapy

    SciTech Connect

    Feng, Felix Y.; Qian Yushen; Stenmark, Matthew H.; Halverson, Schuyler; Blas, Kevin; Vance, Sean; Sandler, Howard M.; Hamstra, Daniel A.

    2011-11-15

    Purpose: To assess the prognostic value of perineural invasion (PNI) for patients treated with dose-escalated external-beam radiation therapy for prostate cancer. Methods and Materials: Outcomes were analyzed for 651 men treated for prostate cancer with EBRT to a minimum dose {>=}75 Gy. We assessed the impact of PNI as well as pretreatment and treatment-related factors on freedom from biochemical failure (FFBF), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival. Results: PNI was present in 34% of specimens at biopsy and was significantly associated with higher Gleason score (GS), T stage, and prostate-specific antigen level. On univariate and multivariate analysis, the presence of PNI was associated with worse FFBF (hazard ratio = 1.7, p <0.006), FFM (hazard ratio = 1.8, p <0.03), and CSS (HR = 1.4, p <0.05) compared with absence of PNI; there was no difference in overall survival. Seven-year rates of FFBF, FFM, and CCS were 64% vs. 80%, 84% vs. 92%, and 91% vs. 95% for those patients with and without PNI, respectively. On recursive partitioning analysis, PNI predicted for worse FFM and CSS in patients with GS 8-10, with FFM of 67% vs. 89% (p <0.02), and CSS of 69% vs. 91%, (p <0.04) at 7 years for those with and without PNI, respectively. Conclusions: The presence of PNI in the prostate biopsy predicts worse clinical outcome for patients treated with dose-escalated external-beam radiation therapy. Particularly in patients with GS 8-10 disease, the presence of PNI suggests an increased risk of metastasis and prostate cancer death.

  13. Safety and immunogenicity of the PRAME cancer immunotherapeutic in metastatic melanoma: results of a phase I dose escalation study

    PubMed Central

    Gutzmer, R; Rivoltini, L; Levchenko, E; Testori, A; Utikal, J; Ascierto, P A; Demidov, L; Grob, J J; Ridolfi, R; Schadendorf, D; Queirolo, P; Santoro, A; Loquai, C; Dreno, B; Hauschild, A; Schultz, E; Lesimple, T P; Vanhoutte, N; Salaun, B; Gillet, M; Jarnjak, S; De Sousa Alves, P M; Louahed, J; Brichard, V G; Lehmann, F F

    2016-01-01

    Purpose The PRAME tumour antigen is expressed in several tumour types but in few normal adult tissues. A dose-escalation phase I/II study (NCT01149343) assessed the safety, immunogenicity and clinical activity of the PRAME immunotherapeutic (recombinant PRAME protein (recPRAME) with the AS15 immunostimulant) in patients with advanced melanoma. Here, we report the phase I dose-escalation study segment. Patients and methods Patients with stage IV PRAME-positive melanoma were enrolled to 3 consecutive cohorts to receive up to 24 intramuscular injections of the PRAME immunotherapeutic. The RecPRAME dose was 20, 100 or 500 µg in cohorts 1, 2 and 3, respectively, with a fixed dose of AS15. Adverse events (AEs), including predefined dose-limiting toxicity (DLT) and the anti-PRAME humoral response (ELISA), were coprimary end points. Cellular immune responses were evaluated using in vitro assays. Results 66 patients were treated (20, 24 and 22 in the respective cohorts). AEs considered by the investigator to be causally related were mostly grade 1 or 2 injection site symptoms, fatigue, chills, fever and headache. Two DLTs (grade 3 brain oedema and proteinuria) were recorded in two patients in two cohorts (cohorts 2 and 3). All patients had detectable anti-PRAME antibodies after four immunisations. Percentages of patients with predefined PRAME-specific-CD4+T-cell responses after four immunisations were similar in each cohort. No CD8+ T-cell responses were detected. Conclusions The PRAME immunotherapeutic had an acceptable safety profile and induced similar anti-PRAME-specific humoral and cellular immune responses in all cohorts. As per protocol, the phase II study segment was initiated to further evaluate the 500 µg PRAME immunotherapeutic dose. Trial registration number NCT01149343, Results. PMID:27843625

  14. Phase 1 Study of Dose Escalation in Hypofractionated Proton Beam Therapy for Non-Small Cell Lung Cancer

    SciTech Connect

    Gomez, Daniel R.; Gillin, Michael; Liao, Zhongxing; Wei, Caimiao; Lin, Steven H.; Swanick, Cameron; Alvarado, Tina; Komaki, Ritsuko; Cox, James D.; Chang, Joe Y.

    2013-07-15

    Background: Many patients with locally advanced non-small cell lung cancer (NSCLC) cannot undergo concurrent chemotherapy because of comorbidities or poor performance status. Hypofractionated radiation regimens, if tolerable, may provide an option to these patients for effective local control. Methods and Materials: Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy (PBT) from September 2010 through July 2012. Eligible patients had histologically documented lung cancer, thymic tumors, carcinoid tumors, or metastatic thyroid tumors. Concurrent chemotherapy was not allowed, but concurrent treatment with biologic agents was. The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectiveness [RBE])/fraction, 3.5 Gy(RBE)/fraction, or 4 Gy(RBE)/fraction. Dose constraints were derived from biologically equivalent doses of standard fractionated treatment. Results: The median follow-up time for patients alive at the time of analysis was 13 months (range, 8-28 months). Fifteen patients received treatment to hilar or mediastinal lymph nodes. Two patients experienced dose-limiting toxicity possibly related to treatment; 1 received 3.5-Gy(RBE) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab. The other patient received 4-Gy(RBE) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT. Conclusion: Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures. Phase 2/3 trials are needed to compare the efficacy of this technique with standard treatment for locally advanced NSCLC.

  15. Protocol for a phase III randomised trial of image-guided intensity modulated radiotherapy (IG-IMRT) and conventional radiotherapy for late small bowel toxicity reduction after postoperative adjuvant radiation in Ca cervix

    PubMed Central

    Chopra, Supriya; Engineer, Reena; Mahantshetty, Umesh; Misra, Shagun; Phurailatpam, Reena; Paul, Siji N; Kannan, Sadhna; Kerkar, Rajendra; Maheshwari, Amita; Shylasree, TS; Ghosh, Jaya; Gupta, Sudeep; Thomas, Biji; Singh, Shalini; Sharma, Sanjiv; Chilikuri, Srinivas; Shrivastava, Shyam Kishore

    2012-01-01

    Introduction External beam radiation followed by vaginal brachytherapy (±chemotherapy) leads to reduction in the risk of local recurrence and improves progression-free survival in patients with adverse risk factors following Wertheim's hysterectomy albeit at the risk of late bowel toxicity. Intensity Modulated Radiotherapy (IMRT) results in reduction in bowel doses and has potential to reduce late morbidity, however, needs to be confirmed prospectively in a randomised trial. The present randomised trial tests reduction if any in late small bowel toxicity with the use of IMRT in postoperative setting. Methods and analysis Patients more than 18 years of age who need adjuvant (chemo) radiation will be eligible. Patients with residual pelvic or para-aortic nodal disease, history of multiple abdominal surgeries or any other medical bowel condition will be excluded. The trial will randomise patients into standard radiation or IMRT. The primary aim is to compare differences in late grades II–IV bowel toxicity between the two arms. The secondary aims of the study focus on evaluating correlation of dose–volume parameters and late toxicity and quality of life. The trial is planned as a multicentre randomised study. The trial is designed to detect a 13% difference in late grades II–IV bowel toxicity with an α of 0.05 and β of 0.80. A total of 240 patients will be required to demonstrate the aforesaid difference. Ethics and dissemination The trial is approved by institutional ethics review board and will be routinely monitored as per standard guidelines. The study results will be disseminated via peer reviewed scientific journals, conference presentations and submission to regulatory authorities. Registration The trial is registered with clinicaltrials.gov (NCT 01279135). PMID:23242243

  16. PMH 9907: Long-term outcomes of a randomized phase 3 study of short-term bicalutamide hormone therapy and dose-escalated external-beam radiation therapy for localized prostate cancer.

    PubMed

    McPartlin, Andrew J; Glicksman, Rachel; Pintilie, Melania; Tsuji, Debbie; Mok, Gary; Bayley, Andrew; Chung, Peter; Bristow, Robert G; Gospodarowicz, Mary K; Catton, Charles N; Milosevic, Michael; Warde, Padraig R

    2016-08-15

    The role of hormone therapy (HT) with dose-escalated external-beam radiotherapy (DE-EBRT) in the treatment of intermediate-risk prostate cancer (IRPC) remains controversial. The authors report the long-term outcome of a phase 3 study of DE-EBRT with or without HT for patients with localized prostate cancer (LPC). From 1999 to 2006, 252 of an intended 338 patients with LPC were randomized to receive DE-EBRT with or without 5 months of neoadjuvant and concurrent bicalutamide 150 mg once daily. The study was closed early because of contemporary concerns surrounding bicalutamide. The primary outcome was biochemical failure (BF) incidence, and the secondary endpoints were overall survival (OS), local control (LC), and quality of life. The BF and OS rates were estimated using the cumulative incidence function and Kaplan-Meier methods and were compared using the Gray test and the log-rank test. Eleven patients were excluded from analysis. Characteristics were well balanced in each treatment arm. Ninety-five percent of patients had IRPC. The prescribed dose increased from 75.6 grays (Gy) in 42 fractions to 78 Gy in 39 fractions over the period. At a median follow-up of 9.1 years, 98 BFs occurred, with no significant effect of HT versus no HT on the BF rate (40% vs 47%; P = .32), the OS rate (82% vs 86%; P = .37), the LC rate (52% vs 48 %; P = .32) or quality of life, in the patients who completed the questionnaires. Dose escalation to 75.6 Gy versus >75.6 Gy reduced the BF rate by 26% (P = .004). For patients who predominantly have IRPC, the addition of HT to DE-EBRT did not significantly affect BF, OS, or LC. Bicalutamide appeared to be well tolerated. The conclusions from the study are limited by incomplete recruitment. Cancer 2016;122:2595-603. © 2016 American Cancer Society. © 2016 American Cancer Society.

  17. Dosimetric and radiobiological comparison of helical tomotherapy, forward-planned intensity-modulated radiotherapy and two-phase conformal plans for radical radiotherapy treatment of head and neck squamous cell carcinomas.

    PubMed

    Chatterjee, S; Willis, N; Locks, S M; Mott, J H; Kelly, C G

    2011-12-01

    The usual radical radiotherapy treatment prescribed for head and neck squamous cell carcinoma (HNSCC) is 70 Gy (in 2 Gy per fraction equivalent) administered to the high-risk target volume (TV). This can be planned using either a forward-planned photon-electron junction technique (2P) or a single-phase (1P) forward-planned technique developed in-house. Alternatively, intensity-modulated radiotherapy (IMRT) techniques, including helical tomotherapy (HT), allow image-guided inversely planned treatments. This study was designed to compare these three planning techniques with regards to TV coverage and the dose received by organs at risk. We compared the dose-volume histograms and conformity indices (CI) of the three planning processes in five patients with HNSCC. The tumour control probability (TCP), normal tissue complication probability (NTCP) and uncomplicated tumour control probability (UCP) were calculated for each of the 15 plans. In addition, we explored the radiobiological rationality of a dose-escalation strategy. The CI for the high-risk clinical TV (CTV1) in the 5 patients were 0.78, 0.76, 0.82, 0.72 and 0.81 when HT was used; 0.58, 0.56, 0.47, 0.35 and 0.60 for the single-phase forward-planned technique and 0.46, 0.36, 0.29, 0.22 and 0.49 for the two-phase technique. The TCP for CTV1 with HT were 79.2%, 85.2%, 81.1%, 83.0% and 53.0%; for single-phase forward-planned technique, 76.5%, 86.9%, 73.4%, 81.8% and 31.8% and for the two-phase technique, 38.2%, 86.2%, 42.7%, 0.0% and 3.4%. Dose escalation using HT confirmed the radiobiological advantage in terms of TCP. TCP for the single-phase plans was comparable to that of HT plans, whereas that for the two-phase technique was lower. Centres that cannot provide IMRT for the radical treatment of all patients could implement the single-phase technique as standard to attain comparable TCP. However, IMRT produced better UCP, thereby enabling the exploration of dose escalation.

  18. Parameters Favorable to Intraprostatic Radiation Dose Escalation in Men With Localized Prostate Cancer

    SciTech Connect

    Housri, Nadine; Ning, Holly; Ondos, John; Choyke, Peter; Camphausen, Kevin; Citrin, Deborah; Arora, Barbara; Shankavaram, Uma; Kaushal, Aradhana

    2011-06-01

    Purpose: To identify , within the framework of a current Phase I trial, whether factors related to intraprostatic cancer lesions (IPLs) or individual patients predict the feasibility of high-dose intraprostatic irradiation. Methods and Materials: Endorectal coil MRI scans of the prostate from 42 men were evaluated for dominant IPLs. The IPLs, prostate, and critical normal tissues were contoured. Intensity-modulated radiotherapy plans were generated with the goal of delivering 75.6 Gy in 1.8-Gy fractions to the prostate, with IPLs receiving a simultaneous integrated boost of 3.6 Gy per fraction to a total dose of 151.2 Gy, 200% of the prescribed dose and the highest dose cohort in our trial. Rectal and bladder dose constraints were consistent with those outlined in current Radiation Therapy Oncology Group protocols. Results: Dominant IPLs were identified in 24 patients (57.1%). Simultaneous integrated boosts (SIB) to 200% of the prescribed dose were achieved in 12 of the 24 patients without violating dose constraints. Both the distance between the IPL and rectum and the hip-to-hip patient width on planning CT scans were associated with the feasibility to plan an SIB (p = 0.002 and p = 0.0137, respectively). Conclusions: On the basis of this small cohort, the distance between an intraprostatic lesion and the rectum most strongly predicted the ability to plan high-dose radiation to a dominant intraprostatic lesion. High-dose SIB planning seems possible for select intraprostatic lesions.

  19. Review of image-guided radiation therapy.

    PubMed

    Jaffray, David; Kupelian, Patrick; Djemil, Toufik; Macklis, Roger M

    2007-01-01

    Image-guided radiation therapy represents a new paradigm in the field of high-precision radiation medicine. A synthesis of recent technological advances in medical imaging and conformal radiation therapy, image-guided radiation therapy represents a further expansion in the recent push for maximizing targeting capabilities with high-intensity radiation dose deposition limited to the true target structures, while minimizing radiation dose deposited in collateral normal tissues. By improving this targeting discrimination, the therapeutic ratio may be enhanced significantly. The principle behind image-guided radiation therapy relies heavily on the acquisition of serial image datasets using a variety of medical imaging platforms, including computed tomography, ultrasound and magnetic resonance imaging. These anatomic and volumetric image datasets are now being augmented through the addition of functional imaging. The current interest in positron-emitted tomography represents a good example of this sort of functional information now being correlated with anatomic localization. As the sophistication of imaging datasets grows, the precise 3D and 4D positions of the target and normal structures become of great relevance, leading to a recent exploration of real- or near-real-time positional replanning of the radiation treatment localization coordinates. This 'adaptive' radiotherapy explicitly recognizes that both tumors and normal tissues change position in time and space during a multiweek course of treatment, and even within a single treatment fraction. As targets and normal tissues change, the attenuation of radiation beams passing through these structures will also change, thus adding an additional level of imprecision in targeting unless these changes are taken into account. All in all, image-guided radiation therapy can be seen as further progress in the development of minimally invasive highly targeted cytotoxic therapies with the goal of substituting remote

  20. Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

    SciTech Connect

    Vainshtein, Jeffrey M.; Schipper, Matthew; Zalupski, Mark M.; Lawrence, Theodore S.; Abrams, Ross; Francis, Isaac R.; Khan, Gazala; Leslie, William; Ben-Josef, Edgar

    2013-05-01

    Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

  1. Safety and efficacy of flexible-dose fesoterodine in British subjects with overactive bladder: insights into factors associated with dose escalation.

    PubMed

    Cardozo, Linda; Hall, Timothy; Ryan, John; Ebel Bitoun, Caty; Kausar, Imran; Darekar, Amanda; Wagg, Adrian

    2012-11-01

    This study evaluated the efficacy and safety of flexible-dose fesoterodine and factors associated with dose escalation in subjects with overactive bladder (OAB). In this 12-week, open-label study, 331 adults with OAB symptoms for ≥3 months, ≥8 micturitions and ≥3 urgency episodes per 24 h and who reported at least "some moderate" bladder-related problems were treated with fesoterodine 4 mg once daily for 4 weeks, with the option to escalate to 8 mg for the remaining 8 weeks based on discussion of efficacy and tolerability with the investigator. Factors influencing dose escalation were identified using stepwise logistic regression. Efficacy was assessed via 3-day bladder diaries and patient-reported outcomes. Of the subjects, 59 % dose escalated at week 4; 93 % of escalators cited insufficient clinical response. The decision to escalate was most often made by the subject (alone or with the investigator). Improvements from baseline were observed in diary and patient-reported outcomes at weeks 4 and 12. Smaller improvements in micturition frequency and worse bladder-related problems at week 4 were significantly associated with increased likelihood of dose escalation; baseline micturition frequency, age, sex, body mass index, antimuscarinic-associated adverse events and OAB symptom duration were not. Non-escalators had greater improvement from baseline to week 4 than escalators; by week 12, improvement was similar among escalators and non-escalators. Fesoterodine was well tolerated. Treatment with flexible-dose fesoterodine improved bladder diary and patient-reported outcomes. Lower clinical response was related to dose escalation; after escalation, response in escalators approached that of non-escalators.

  2. Phase I Three-Dimensional Conformal Radiation Dose Escalation Study in Newly Diagnosed Glioblastoma: Radiation Therapy Oncology Group Trial 98-03

    SciTech Connect

    Tsien, Christina Moughan, Jennifer; Michalski, Jeff M.; Gilbert, Mark R.; Purdy, James; Simpson, Joseph; Kresel, John J.; Curran, Walter J.; Diaz, Aidnag; Mehta, Minesh P.

    2009-03-01

    Purpose: To evaluate in a Phase I trial the feasibility and toxicity of dose-escalated three-dimensional conformal radiotherapy (3D-CRT) concurrent with chemotherapy in patients with primary supratentorial glioblastoma (GBM). Methods and Materials: A total of 209 patients were enrolled. All received 46 Gy in 2-Gy fractions to the first planning target volume (PTV{sub 1}), defined as the gross tumor volume (GTV) plus 1.8 cm. A subsequent boost was given to PTV{sub 2}, defined as GTV plus 0.3 cm. Patients were stratified into two groups (Group 1: PTV{sub 2} <75 cm{sup 3}; Group 2: PTV{sub 2} {>=}75 cm{sup 3}). Four RT dose levels were evaluated: 66, 72, 78, and 84 Gy. Carmustine 80 mg/m{sup 2} was given during RT, then every 8 weeks for 6 cycles. Pretreatment characteristics were well balanced. Results: Acute and late Grade 3/4 RT-related toxicities were no more frequent at higher RT dose or with larger tumors. There were no dose-limiting toxicities (acute Grade {>=}3 irreversible central nervous system toxicities) observed on any dose level in either group. On the basis of the absence of dose-limiting toxicities, dose was escalated to 84 Gy in both groups. Late RT necrosis was noted at 66 Gy (1 patient), 72 Gy (2 patients), 78 Gy (2 patients), and 84 Gy (3 patients) in Group 1. In Group 2, late RT necrosis was noted at 78 Gy (1 patient) and 84 Gy (2 patients). Median time to RT necrosis was 8.8 months (range, 5.1-12.5 months). Median survival in Group 1 was 11.6-19.3 months. Median survival in Group 2 was 8.2-13.9 months. Conclusions: Our study shows the feasibility of delivering higher than standard (60 Gy) RT dose with concurrent chemotherapy for primary GBM, with an acceptable risk of late central nervous system toxicity.

  3. Treatment of early non-response in patients with schizophrenia: assessing the efficacy of antipsychotic dose escalation.

    PubMed

    Loebel, Antony; Citrome, Leslie; Correll, Christoph U; Xu, Jane; Cucchiaro, Josephine; Kane, John M

    2015-10-31

    Early non-response to antipsychotic treatment in patients with schizophrenia has been shown in multiple studies to predict poor response at short-term trial endpoint. Therefore, strategies to address the challenge of non-improvement early in the course of treatment are needed. A novel trial design was developed to assess the potential utility of antipsychotic dose escalation in patients with an inadequate initial treatment response. This design was embedded in a study intended to assess the efficacy of low dose lurasidone in patients with schizophrenia. The purpose of this report is to describe the background, rationale and design of this study that included a novel method for the assessment of the potential for dose-response in early non-responding patients with schizophrenia. In this 6-week, international, multicenter, double-blind trial, eligible adults with acute schizophrenia were randomized to receive fixed doses of lurasidone 20 mg/day, 80 mg/day (active control), or placebo in a 1:2:1 ratio. Patients initially randomized to lurasidone 80 mg/day who did not have a Positive and Negative Syndrome Scale total score improvement ≥ 20% at Week 2 were re-randomized on a 1:1 basis to receive either lurasidone 80 mg/day or lurasidone 160 mg/day for the remainder of the trial. All other groups remained on their initially assigned treatment. The formal primary objective of the study was to evaluate the efficacy of low-dose lurasidone (20 mg/day) compared to placebo; secondary objectives included evaluating the efficacy of lurasidone 80 mg/day versus 160 mg/day in early non-responders, and evaluating the efficacy of lurasidone in all subjects initially randomized to 80 mg/day versus placebo. Since a lack of early improvement predicts poor response to short-term antipsychotic treatment in patients with schizophrenia, several treatment strategies have been proposed to enhance treatment outcome in early non-responders. A novel clinical trial design involving a placebo

  4. Trigeminal Neuralgia Treated With Stereotactic Radiosurgery: The Effect of Dose Escalation on Pain Control and Treatment Outcomes.

    PubMed

    Kotecha, Rupesh; Kotecha, Ritesh; Modugula, Sujith; Murphy, Erin S; Jones, Mark; Kotecha, Rajesh; Reddy, Chandana A; Suh, John H; Barnett, Gene H; Neyman, Gennady; Machado, Andre; Nagel, Sean; Chao, Samuel T

    2016-09-01

    To analyze the effect of dose escalation on treatment outcome in patients undergoing stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). A retrospective review was performed of 870 patients who underwent SRS for a diagnosis of TN from 2 institutions. Patients were typically treated using a single 4-mm isocenter placed at the trigeminal nerve dorsal root entry zone. Patients were divided into groups based on treatment doses: ≤82 Gy (352 patients), 83 to 86 Gy (85 patients), and ≥90 Gy (433 patients). Pain response was classified using a categorical scoring system, with fair or poor pain control representing treatment failure. Treatment-related facial numbness was classified using the Barrow Neurological Institute scale. Log-rank tests were performed to test differences in time to pain failure or development of facial numbness for patients treated with different doses. Median age at first pain onset was 63 years, median age at time of SRS was 71 years, and median follow-up was 36.5 months from the time of SRS. A majority of patients (827, 95%) were clinically diagnosed with typical TN. The 4-year rate of excellent to good pain relief was 87% (95% confidence interval 84%-90%). The 4-year rate of pain response was 79%, 82%, and 92% in patients treated to ≤82 Gy, 83 to 86 Gy, and ≥90 Gy, respectively. Patients treated to doses ≤82 Gy had an increased risk of pain failure after SRS, compared with patients treated to ≥90 Gy (hazard ratio 2.0, P=.0007). Rates of treatment-related facial numbness were similar among patients treated to doses ≥83 Gy. Nine patients (1%) were diagnosed with anesthesia dolorosa. Dose escalation for TN to doses >82 Gy is associated with an improvement in response to treatment and duration of pain relief. Patients treated at these doses, however, should be counseled about the increased risk of treatment-related facial numbness. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. SU-C-BRB-02: Automatic Planning as a Potential Strategy for Dose Escalation for Pancreas SBRT?

    SciTech Connect

    Wang, S; Zheng, D; Ma, R; Lin, C; Zhu, X; Lei, Y; Enke, C; Zhou, S

    2016-06-15

    Purpose: Stereotactic body radiation therapy (SBRT) has been suggested to provide high rates of local control for locally advanced pancreatic cancer. However, the close proximity of highly radiosensitive normal tissues usually causes the labor-intensive planning process, and may impede further escalation of the prescription dose. The present study evaluates the potential of an automatic planning system as a dose escalation strategy. Methods: Ten pancreatic cancer patients treated with SBRT were studied retrospectively. SBRT was delivered over 5 consecutive fractions with 6 ∼ 8Gy/fraction. Two plans were generated by Pinnacle Auto-Planning with the original prescription and escalated prescription, respectively. Escalated prescription adds 1 Gy/fraction to the original prescription. Manually-created planning volumes were excluded in the optimization goals in order to assess the planning efficiency and quality simultaneously. Critical organs with closest proximity were used to determine the plan normalization to ensure the OAR sparing. Dosimetric parameters including D100, and conformity index (CI) were assessed. Results: Auto-plans directly generate acceptable plans for 70% of the cases without necessity of further improvement, and two more iterations at most are necessary for the rest of the cases. For the pancreas SBRT plans with the original prescription, autoplans resulted in favorable target coverage and PTV conformity (D100 = 96.3% ± 1.48%; CI = 0.88 ± 0.06). For the plans with the escalated prescriptions, no significant target under-dosage was observed, and PTV conformity remains reasonable (D100 = 93.3% ± 3.8%, and CI = 0.84 ± 0.05). Conclusion: Automatic planning, without substantial human-intervention process, results in reasonable PTV coverage and PTV conformity on the premise of adequate OAR sparing for the pancreas SBRT plans with escalated prescription. The results highlight the potential of autoplanning as a dose escalation strategy for pancreas

  6. Acute Toxicity in High-Risk Prostate Cancer Patients Treated With Androgen Suppression and Hypofractionated Intensity-Modulated Radiotherapy

    SciTech Connect

    Pervez, Nadeem; Small, Cormac; MacKenzie, Marc; Yee, Don; Parliament, Matthew; Ghosh, Sunita; Mihai, Alina; Amanie, John; Murtha, Albert; Field, Colin; Murray, David; Fallone, Gino; Pearcey, Robert

    2010-01-15

    Purpose: To report acute toxicity resulting from radiotherapy (RT) dose escalation and hypofractionation using intensity-modulated RT (IMRT) treatment combined with androgen suppression in high-risk prostate cancer patients. Methods and Materials: Sixty patients with a histological diagnosis of high-risk prostatic adenocarcinoma (having either a clinical Stage of >=T3a or an initial prostate-specific antigen [PSA] level of >=20 ng/ml or a Gleason score of 8 to 10 or a combination of a PSA concentration of >15 ng/ml and a Gleason score of 7) were enrolled. RT prescription was 68 Gy in 25 fractions (2.72 Gy/fraction) over 5 weeks to the prostate and proximal seminal vesicles. The pelvic lymph nodes and distal seminal vesicles concurrently received 45 Gy in 25 fractions. The patients were treated with helical TomoTherapy-based IMRT and underwent daily megavoltage CT image-guided verification prior to each treatment. Acute toxicity scores were recorded weekly during RT and at 3 months post-RT, using Radiation Therapy Oncology Group acute toxicity scales. Results: All patients completed RT and follow up for 3 months. The maximum acute toxicity scores were as follows: 21 (35%) patients had Grade 2 gastrointestinal (GI) toxicity; 4 (6.67%) patients had Grade 3 genitourinary (GU) toxicity; and 30 (33.33%) patients had Grade 2 GU toxicity. These toxicity scores were reduced after RT; there were only 8 (13.6%) patients with Grade 1 GI toxicity, 11 (18.97%) with Grade 1 GU toxicity, and 5 (8.62%) with Grade 2 GU toxicity at 3 months follow up. Only the V60 to the rectum correlated with the GI toxicity. Conclusion: Dose escalation using a hypofractionated schedule to the prostate with concurrent pelvic lymph node RT and long-term androgen suppression therapy is well tolerated acutely. Longer follow up for outcome and late toxicity is required.

  7. [Prostate cancer external beam radiotherapy].

    PubMed

    de Crevoisier, R; Pommier, P; Latorzeff, I; Chapet, O; Chauvet, B; Hennequin, C

    2016-09-01

    The prostate external beam radiotherapy techniques are described, when irradiating the prostate or after prostatectomy, with and without pelvic lymph nodes. The following parts are presented: indications of radiotherapy, total dose and fractionation, planning CT image acquisition, volume of interest delineation (target volumes and organs at risk) and margins, Intensity modulated radiotherapy planning and corresponding dose-volume constraints, and finally Image guided radiotherapy.

  8. Image guided percutaneous splenic interventions.

    PubMed

    Kang, Mandeep; Kalra, Naveen; Gulati, Madhu; Lal, Anupam; Kochhar, Rohit; Rajwanshi, Arvind

    2007-10-01

    The objective of this study is to evaluate the efficacy and safety of image-guided percutaneous splenic interventions as diagnostic or therapeutic procedures. We performed a retrospective review of our interventional records from July 2001 to June 2006. Ninety-five image-guided percutaneous splenic interventions were performed after informed consent in 89 patients: 64 men and 25 women who ranged in age from 5 months to 71 years (mean, 38.4 years) under ultrasound (n=93) or CT (n=2) guidance. The procedures performed were fine needle aspiration biopsy of focal splenic lesions (n=78) and aspiration (n=10) or percutaneous catheter drainage of a splenic abscess (n=7). Splenic fine needle aspiration biopsy was successful in 62 (83.78%) of 74 patients with benign lesions diagnosed in 43 (58.1%) and malignancy in 19 (25.67%) patients. The most common pathologies included tuberculosis (26 patients, 35.13%) and lymphoma (14 patients, 18.91%). Therapeutic aspiration or pigtail catheter drainage was successful in all (100%) patients. There were no major complications. Image-guided splenic fine needle aspiration biopsy is a safe and accurate technique that can provide a definitive diagnosis in most patients with focal lesions in the spleen. This study also suggests that image-guided percutaneous aspiration or catheter drainage of splenic abscesses is a safe and effective alternative to surgery.

  9. A Phase I dose-escalation study of the VEGFR inhibitor tivozanib hydrochloride with weekly paclitaxel in metastatic breast cancer.

    PubMed

    Mayer, Erica L; Scheulen, M E; Beckman, J; Richly, H; Duarte, A; Cotreau, M M; Strahs, A L; Agarwal, S; Steelman, L; Winer, E P; Dickler, M N

    2013-07-01

    Tivozanib is a potent selective tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3. This Phase Ib study investigated the safety/tolerability, pharmacokinetics (PK), and activity of tivozanib with weekly paclitaxel in metastatic breast cancer (MBC). MBC patients with no prior VEGFR TKI treatment received daily oral tivozanib (3 weeks on, 1 week off) with weekly paclitaxel 90 mg/m(2). Standard 3 + 3 dose escalation was used; tivozanib cohorts (C) included C1 0.5 mg, C2 1.0 mg, and C3 1.5 mg. Assessments included Response Evaluation Criteria in Solid Tumors response, PK, and vascular function. Eighteen patients enrolled. Toxicities in >20 % of patients included fatigue, alopecia, nausea, diarrhea, peripheral sensory neuropathy, and hypertension. Grade 3/4 toxicities in >15 % of patients included fatigue and neutropenia. Maximum tolerated dose was tivozanib 1.5 mg with paclitaxel 90 mg/m(2). Four patients withdrew because of toxicity and one due to progressive disease. Thirteen patients were evaluable for response: four (30.8 %) had confirmed partial response; four had stable disease ≥6 months (30.8 %). PK data suggest no influence of paclitaxel on tivozanib concentrations. Tivozanib plus weekly paclitaxel was tolerable at all dose levels, supporting their combination at full dose. Activity in this small population was encouraging.

  10. Imatinib dose escalation versus sunitinib as a second line treatment in KIT exon 11 mutated GIST: a retrospective analysis.

    PubMed

    Vincenzi, Bruno; Nannini, Margherita; Fumagalli, Elena; Bronte, Giuseppe; Frezza, Anna Maria; De Lisi, Delia; Spalato Ceruso, Mariella; Santini, Daniele; Badalamenti, Giuseppe; Pantaleo, Maria Abbondanza; Russo, Antonio; Dei Tos, Angelo Paolo; Casali, Paolo; Tonini, Giuseppe

    2016-10-25

    We retrospectively reviewed data from 123 patients (KIT exon 11 mutated) who received sunitinib or dose-escalated imatinib as second line.All patients progressed on imatinib (400 mg/die) and received a second line treatment with imatinib (800 mg/die) or sunitinib (50 mg/die 4 weeks on/2 off or 37.5 mg/day). Deletion versus other KIT 11 mutation was recorded, correlated with clinical benefits.64% received imatinib, 36% sunitinib. KIT exon 11 mutation was available in 94 patients. With a median follow-up of 61 months, median time to progression (TTP) in patients receiving sunitinib and imatinib was 10 (95% CI 9.7-10.9) and 5 months (95% CI 3.6-6.7) respectively (P = 0.012). No difference was found in overall survival (OS) (P = 0.883). In imatinib arm, KIT exon 11 deletions was associated with a shorter TTP (7 vs 17 months; P = 0.02), with a trend in OS (54 vs 71 months P = 0.063). No difference was found in patients treated with sunitinib (P = 0.370).A second line with sunitinib was associated with an improved TTP in KIT exon 11 mutated patients progressing on imatinib 400 mg/die. Deletions in exon 11 seemed to be correlated with worse outcome in patients receiving imatinib-based second line.

  11. The Missing Pieces in Reporting of Randomized Controlled Trials of External Beam Radiation Therapy Dose Escalation for Prostate Cancer.

    PubMed

    Zaorsky, Nicholas G; Egleston, Brian L; Horwitz, Eric M; Dicker, Adam P; Nguyen, Paul L; Showalter, Timothy N; Den, Robert B

    2016-08-01

    Randomized controlled trials (RCTs) are the most rigorous way of determining whether a cause-effect relation exists between treatment and outcome and for assessing the cost-effectiveness of a treatment. For many patients, cancer is a chronic illness; RCTs evaluating treatments for indolent cancers must evolve to facilitate medical decision-making, as "concrete" patient outcomes (eg, survival) will likely be excellent independent of the intervention, and detecting a difference between trial arms may be impossible. In this commentary, we articulate 9 recommendations that we hope future clinical trialists and funding agencies (including those under the National Cancer Institute) will take into consideration when planning RCTs to help guide subsequent interpretation of results and clinical decision making, based on RCTs of external beam radiation therapy dose escalation for the most common indolent cancer in men, that is, prostate cancer. We recommend routinely reporting: (1) race; (2) medical comorbidities; (3) psychiatric comorbidities; (4) insurance status; (5) education; (6) marital status; (7) income; (8) sexual orientation; and (9) facility-related characteristics (eg, number of centers involved, type of facilities, yearly hospital volumes). We discuss how these factors independently affect patient outcomes and toxicities; future clinicians and governing organizations should consider this information to plan RCTs accordingly (to maximize patient accrual and total n), select appropriate endpoints (eg, toxicity, quality of life, sexual function), actively monitor RCTs, and report results so as to identify the optimal treatment among subpopulations.

  12. Gut hormone release and appetite regulation in healthy non-obese participants following oligofructose intake. A dose-escalation study.

    PubMed

    Pedersen, Camilla; Lefevre, Solenne; Peters, Véronique; Patterson, Michael; Ghatei, Mohammad A; Morgan, Linda M; Frost, Gary S

    2013-07-01

    Prevention of weight gain in adults is a major public health target. Animal experiments have consistently demonstrated a relationship between fermentable carbohydrate intake, such as oligofructose, anorectic gut hormones, and appetite suppression and body weight control. This study was designed to determine the dose of oligofructose which would augment the release of anorectic gut hormones and reduce appetite consistently in non-obese humans. Twelve non-obese participants were recruited for a 5-week dose-escalation study. Following a 9-14-day run-in, participants increased their daily oligofructose intake every week from 15, 25, 35, 45, to 55 g daily. Subjective appetite and side effects were monitored daily. Three-day food diaries were completed every week. Appetite study sessions explored the acute effects of 0, 15, 35, and 55 g oligofructose on appetite-related hormones, glycaemia, subjective appetite, and energy intake. In the home environment, oligofructose suppressed hunger, but did not affect energy intake. Oligofructose dose-dependently increased peptide YY, decreased pancreatic polypeptide and tended to decrease ghrelin, but did not significantly affect appetite profile, energy intake, glucose, insulin, or glucagon-like peptide 1 concentrations during appetite study sessions. In conclusion, oligofructose supplementation at ≥ 35 g/day increased peptide YY and suppressed pancreatic polypeptide and hunger; however, energy intake did not change significantly.

  13. Study protocol: a dose-escalating, phase-2 study of oral lisdexamfetamine in adults with methamphetamine dependence.

    PubMed

    Ezard, Nadine; Dunlop, Adrian; Clifford, Brendan; Bruno, Raimondo; Carr, Andrew; Bissaker, Alexandra; Lintzeris, Nicholas

    2016-12-01

    The treatment of methamphetamine dependence is a continuing global health problem. Agonist type pharmacotherapies have been used successfully to treat opioid and nicotine dependence and are being studied for the treatment of methamphetamine dependence. One potential candidate is lisdexamfetamine, a pro-drug for dexamphetamine, which has a longer lasting therapeutic action with a lowered abuse potential. The purpose of this study is to determine the safety of lisdexamfetamine in this population at doses higher than those currently approved for attention deficit hyperactivity disorder or binge eating disorder. This is a phase 2 dose escalation study of lisdexamfetamine for the treatment of methamphetamine dependence. Twenty individuals seeking treatment for methamphetamine dependence will be recruited at two Australian drug and alcohol services. All participants will undergo a single-blinded ascending-descending dose regime of 100 to 250 mg lisdexamfetamine, dispensed daily on site, over an 8-week period. Participants will be offered counselling as standard care. For the primary objectives the outcome variables will be adverse events monitoring, drug tolerability and regimen completion. Secondary outcomes will be changes in methamphetamine use, craving, withdrawal, severity of dependence, risk behaviour and other substance use. Medication acceptability, potential for non-prescription use, adherence and changes in neurocognition will also be measured. Determining the safety of lisdexamfetamine will enable further research to develop pharmacotherapies for the treatment of methamphetamine dependence. Australian and New Zealand Clinical Trials Registry ACTRN12615000391572 Registered 28(th) April 2015.

  14. A Dosimetric Comparison between Conventional Fractionated and Hypofractionated Image-guided Radiation Therapies for Localized Prostate Cancer

    PubMed Central

    Li, Ming; Li, Gao-Feng; Hou, Xiu-Yu; Gao, Hong; Xu, Yong-Gang; Zhao, Ting

    2016-01-01

    Background: Image-guided radiation therapy (IGRT) is the preferred method for curative treatment of localized prostate cancer, which could improve disease outcome and reduce normal tissue toxicity reaction. IGRT using cone-beam computed tomography (CBCT) in combination with volumetric-modulated arc therapy (VMAT) potentially allows smaller treatment margins and dose escalation to the prostate. The aim of this study was to compare the difference of dosimetric diffusion in conventional IGRT using 7-field, step-and-shoot intensity-modulated radiation therapy (IMRT) and hypofractionated IGRT using VMAT for patients with localized prostate cancer. Methods: We studied 24 patients who received 78 Gy in 39 daily fractions or 70 Gy in 28 daily fractions to their prostate with/without the seminal vesicles using IMRT (n = 12) or VMAT (n = 12) for prostate cancer between November 2013 and October 2015. Image guidance was performed using kilovoltage CBCT scans equipped on the linear accelerator. Offline planning was performed using the daily treatment images registered with simulation computed tomography (CT) images. A total of 212 IMRT plans in conventional cohort and 292 VMAT plans in hypofractionated cohort were enrolled in the study. Dose distributions were recalculated on CBCT images registered with the planning CT scanner. Results: Compared with 7-field, step-and-shoot IMRT, VMAT plans resulted in improved planning target volume (PTV) D95% (7663.17 ± 69.57 cGy vs. 7789.17 ± 131.76 cGy, P < 0.001). VMAT reduced the rectal D25 (P < 0.001), D35 (P < 0.001), and D50 (P < 0.001), bladder V50 (P < 0.001), D25 (P = 0.002), D35 (P = 0.028), and D50 (P = 0.029). However, VMAT did not statistically significantly reduce the rectal V50, compared with 7-field, step-and-shoot IMRT (25.02 ± 5.54% vs. 27.43 ± 8.79%, P = 0.087). Conclusions: To deliver the hypofractionated radiotherapy in prostate cancer, VMAT significantly increased PTV D95% dose and decreased the dose of radiation

  15. Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study.

    PubMed

    Elliott, Julian H; McMahon, James H; Chang, Christina C; Lee, Sulggi A; Hartogensis, Wendy; Bumpus, Namandje; Savic, Rada; Roney, Janine; Hoh, Rebecca; Solomon, Ajantha; Piatak, Michael; Gorelick, Robert J; Lifson, Jeff; Bacchetti, Peter; Deeks, Steven G; Lewin, Sharon R

    2015-12-01

    In vitro, disulfiram activated HIV transcription in a primary T-cell model of HIV latency and in a pilot clinical study increased plasma HIV RNA in individuals with adequate drug exposure. We assessed the effect of disulfiram on HIV transcription in a dose-escalation study. In this prospective dose-escalation study, to optimise disulfiram exposure we included adults with HIV on suppressive antiretroviral therapy, with plasma HIV RNA of less than 50 copies per mL and a CD4 cell count greater than 350 cells per μL. Participants were allocated sequentially to one of three dosing groups (500 mg, 1000 mg, and 2000 mg) and received disulfiram daily for 3 days. Only the staff who did laboratory assays were masked to group assignment. The primary endpoint was change in cell-associated unspliced HIV RNA in CD4 cells. The primary analysis method was a negative binomial regression, with the number of copies as the outcome variable and the input total RNA or plasma volume as an exposure variable, which is equivalent to modelling copies or input. We used these models to estimate changes from before disulfiram to timepoints during and after disulfiram administration. This study is registered with ClinicalTrials.gov, number NCT01944371. Of 34 participants screened for eligibility at The Alfred Hospital (Melbourne, VIC, Australia), and San Francisco General Hospital (San Francisco, CA, USA), 30 people were enrolled between Sept 24, 2013, and March 31, 2014. The estimated fold increases in cell-associated unspliced HIV RNA from baseline were 1·7 (95% CI 1·3-2·2; p<0·0001) to the timepoint during disulfiram treatment and 2·1 (1·5-2·9; p<0·0001) to the timepoint after disulfiram in the 500 mg group; 1·9 (1·6-2·4; p<0·0001) and 2·5 (1·9-3·3; p<0·0001) in the 1000 mg group; and 1·6 (1·2-2·1; p=0·0026) and 2·1 (1·5-3·1; p=0·0001) in the 2000 mg group. No deaths occurred, and no serious adverse events were noted. Disulfiram was well tolerated at all doses. Short

  16. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial.

    PubMed

    El-Khoueiry, Anthony B; Sangro, Bruno; Yau, Thomas; Crocenzi, Todd S; Kudo, Masatoshi; Hsu, Chiun; Kim, Tae-You; Choo, Su-Pin; Trojan, Jörg; Welling, Theodore H; Meyer, Tim; Kang, Yoon-Koo; Yeo, Winnie; Chopra, Akhil; Anderson, Jeffrey; Dela Cruz, Christine; Lang, Lixin; Neely, Jaclyn; Tang, Hao; Dastani, Homa B; Melero, Ignacio

    2017-06-24

    For patients with advanced hepatocellular carcinoma, sorafenib is the only approved drug worldwide, and outcomes remain poor. We aimed to assess the safety and efficacy of nivolumab, a programmed cell death protein-1 (PD-1) immune checkpoint inhibitor, in patients with advanced hepatocellular carcinoma with or without chronic viral hepatitis. We did a phase 1/2, open-label, non-comparative, dose escalation and expansion trial (CheckMate 040) of nivolumab in adults (≥18 years) with histologically confirmed advanced hepatocellular carcinoma with or without hepatitis C or B (HCV or HBV) infection. Previous sorafenib treatment was allowed. A dose-escalation phase was conducted at seven hospitals or academic centres in four countries or territories (USA, Spain, Hong Kong, and Singapore) and a dose-expansion phase was conducted at an additional 39 sites in 11 countries (Canada, UK, Germany, Italy, Japan, South Korea, Taiwan). At screening, eligible patients had Child-Pugh scores of 7 or less (Child-Pugh A or B7) for the dose-escalation phase and 6 or less (Child-Pugh A) for the dose-expansion phase, and an Eastern Cooperative Oncology Group performance status of 1 or less. Patients with HBV infection had to be receiving effective antiviral therapy (viral load <100 IU/mL); antiviral therapy was not required for patients with HCV infection. We excluded patients previously treated with an agent targeting T-cell costimulation or checkpoint pathways. Patients received intravenous nivolumab 0·1-10 mg/kg every 2 weeks in the dose-escalation phase (3+3 design). Nivolumab 3 mg/kg was given every 2 weeks in the dose-expansion phase to patients in four cohorts: sorafenib untreated or intolerant without viral hepatitis, sorafenib progressor without viral hepatitis, HCV infected, and HBV infected. Primary endpoints were safety and tolerability for the escalation phase and objective response rate (Response Evaluation Criteria In Solid Tumors version 1.1) for the expansion phase

  17. TU-AB-201-07: Image Guided Endorectal HDR Brachytherapy Using a Compliant Balloon Applicator

    SciTech Connect

    Cohen, G; Goodman, K

    2015-06-15

    Purpose: High dose rate endorectal brachytherapy is an option to deliver a focal, high-dose radiotherapy to rectal tumors for patients undergoing non-operative management. We investigate a new multichannel, MR compatible applicator with a novel balloon-based design to provide improved treatment geometry. We report on the initial clinical experience using this applicator. Methods: Patients were enrolled on an IRB-approved, dose-escalation protocol evaluating the use of the anorectal (AR-1) applicator (Ancer Medical, Hialeah, FL), a multichannel applicator with two concentric balloons. The inner balloon supports 8 source lumens; the compliant outer balloon expands to separate the normal rectal wall and the source lumens, yet deforms around a firm, exophytic rectal mass, leading to dose escalation to tumor while sparing normal rectum. Under general anesthesia, gold fiducial markers were inserted above and below the tumor, and the AR applicator was placed in the rectum. MRI-based treatment plans were prepared to deliver 15 Gy in 3 weekly fractions to the target volume while sparing healthy rectal tissue, bladder, bowel and anal muscles. Prior to each treatment, CBCT/Fluoroscopy were used to place the applicator in the treatment position and confirm the treatment geometry using rigid registration of the CBCT and planning MRI. After registration of the applicator images, positioning was evaluated based on the match of the gold markers. Results: Highly conformal treatment plans were achieved. MR compatibility of the applicator enabled good tumor visualization. In spite of the non-rigid nature of the applicators and the fact that a new applicator was used at each treatment session, treatment geometry was reproducible to within 2.5 mm. Conclusions: This is the first report on using the AR applicator in patients. Highly conformal plans, confidence in MRI target delineation, in combination with reproducible treatment geometry provide encouraging feedback for continuation with

  18. Sex Differences in Dose Escalation and Overdose Death during Chronic Opioid Therapy: A Population-Based Cohort Study

    PubMed Central

    Kaplovitch, Eric; Gomes, Tara; Camacho, Ximena; Dhalla, Irfan A.; Mamdani, Muhammad M.; Juurlink, David N.

    2015-01-01

    Background The use of opioids for noncancer pain is widespread, and more than 16,000 die of opioid-related causes in the United States annually. The patients at greatest risk of death are those receiving high doses of opioids. Whether sex influences the risk of dose escalation or opioid-related mortality is unknown. Methods and Findings We conducted a cohort study using healthcare records of 32,499 individuals aged 15 to 64 who commenced chronic opioid therapy for noncancer pain between April 1, 1997 and December 31, 2010 in Ontario, Canada. Patients were followed from their first opioid prescription until discontinuation of therapy, death from any cause or the end of the study period. Among patients receiving chronic opioid therapy, 589 (1.8%) escalated to high dose therapy and n = 59 (0.2%) died of opioid-related causes while on treatment. After multivariable adjustment, men were more likely than women to escalate to high-dose opioid therapy (adjusted hazard ratio 1.44; 95% confidence interval 1.21 to 1.70) and twice as likely to die of opioid-related causes (adjusted hazard ratio 2.04; 95% confidence interval 1.18 to 3.53). These associations were maintained in a secondary analysis of 285,520 individuals receiving any opioid regardless of the duration of therapy. Conclusions Men are at higher risk than women for escalation to high-dose opioid therapy and death from opioid-related causes. Both outcomes were more common than anticipated. PMID:26291716

  19. Phase I dose-escalation and pharmacokinetic study of oral gefitinib and irinotecan in children with refractory solid tumors

    PubMed Central

    Brennan, R. C.; Furman, W.; Mao, S.; Wu, J.; Turner, D. C.; Stewart, C. F.; Santana, V.; McGregor, L. M.

    2015-01-01

    Purpose This phase I study endeavored to estimate the maximum tolerated dose (MTD) and describe the dose-limiting toxicities (DLTs) of oral irinotecan with gefitinib in children with refractory solid tumors. Methods Oral irinotecan was administered on days 1-5 and 8-12 with oral gefitinib (fixed dose, 150mg/m2/day) on days 1-12 of a 21-day course. The Escalation with Overdose Control (EWOC) method guided irinotecan dose escalation (7 dose levels, range 5mg/m2/day to 40mg/m2/day). Results Sixteen of 19 patients were evaluable, with serial pharmacokinetic studies in 10 patients. Diagnoses included osteosarcoma (N=5), neuroblastoma (N=3), sarcoma (N=3), and others (N=5). Patients received a median of two courses (range 1-20), with at least two patients treated on dose levels 2-7. Three patients had five DLTs; the most common being metabolic (hypokalemia, N=2 and hypophosphatemia, N=1) at dose levels two (10mg/m2) and four (20mg/m2). One patient experienced grade 3 diarrhea (40mg/m2). Irinotecan bioavailability was 2.5-fold higher when co-administered with gefitinib while the conversion rate of irinotecan to SN-38 lactone was unaffected. The study closed due to poor accrual before evaluation of the next recommended irinotecan dose level (35mg/m2). Of eleven patients receiving at least two courses of therapy, three had stable disease (SD) lasting two to four courses and one patient maintained a complete response through 18 courses. Conclusions The combination of oral gefitinib and irinotecan has acceptable toxicity and anti-tumor activity in pediatric patients with refractory solid tumors. Pharmacokinetic analysis confirms that co-administration of gefitinib increases irinotecan bioavailability leading to an increased SN-38 lactone systemic exposure. PMID:25257509

  20. Safety of intravenously applied mistletoe extract - results from a phase I dose escalation study in patients with advanced cancer.

    PubMed

    Huber, Roman; Schlodder, Dietrich; Effertz, Carola; Rieger, Sabine; Tröger, Wilfried

    2017-09-18

    Mistletoe extracts have anti-tumor properties and are approved for subcutaneous use in cancer patients. Data on Intravenous application are limited. An aqueous extract from pine-mistletoe was used to investigate maximum tolerable dose (MTD) and safety of intravenous application. It was infused once weekly for 3 weeks in patients with advanced cancer. Any type of cancer was included; relevant exclusion criteria were concurrent chemo- or radiation therapy. The classical phase I 3 + 3 dose escalation scheme was followed. Predefined dose groups were 200, 400, 700, 1200 and 2000 mg. Maximum planned dose was 2000 mg. With the MTD three more patients should be treated for 9 weeks in order to evaluate intermediate term tolerability. Weekly during the treatment and 1 week later tolerability, clinical status, safety laboratory parameters and adverse events were documented. Twenty-one patients (3 in the dose groups 200, 400, 700 and 1200 mg, respectively, 9 in the dose group 2000 mg) were included. MTD was not reached. Because one dose-limiting toxicity (DLT), an allergic reaction, occurred during infusion of 2000 mg, three more patients had to be included in this dose group and tolerated it, as well as the three patients who received 2000 mg for 9 weeks. Occasionally in the dose group 2000 mg mild to moderate fever occurred. Weekly infusions of 2000 mg of the pine-mistletoe extract were tolerated and can be used in further studies but had a risk for allergic reactions and fever. German Clinical Trials Register (Trial registration number DRKS00005028).

  1. Whole Brain Irradiation With Hippocampal Sparing and Dose Escalation on Multiple Brain Metastases: A Planning Study on Treatment Concepts

    SciTech Connect

    Prokic, Vesna; Wiedenmann, Nicole; Fels, Franziska; Schmucker, Marianne; Nieder, Carsten; Grosu, Anca-Ligia

    2013-01-01

    Purpose: To develop a new treatment planning strategy in patients with multiple brain metastases. The goal was to perform whole brain irradiation (WBI) with hippocampal sparing and dose escalation on multiple brain metastases. Two treatment concepts were investigated: simultaneously integrated boost (SIB) and WBI followed by stereotactic fractionated radiation therapy sequential concept (SC). Methods and Materials: Treatment plans for both concepts were calculated for 10 patients with 2-8 brain metastases using volumetric modulated arc therapy. In the SIB concept, the prescribed dose was 30 Gy in 12 fractions to the whole brain and 51 Gy in 12 fractions to individual brain metastases. In the SC concept, the prescription was 30 Gy in 12 fractions to the whole brain followed by 18 Gy in 2 fractions to brain metastases. All plans were optimized for dose coverage of whole brain and lesions, simultaneously minimizing dose to the hippocampus. The treatment plans were evaluated on target coverage, homogeneity, and minimal dose to the hippocampus and organs at risk. Results: The SIB concept enabled more successful sparing of the hippocampus; the mean dose to the hippocampus was 7.55 {+-} 0.62 Gy and 6.29 {+-} 0.62 Gy, respectively, when 5-mm and 10-mm avoidance regions around the hippocampus were used, normalized to 2-Gy fractions. In the SC concept, the mean dose to hippocampus was 9.8 {+-} 1.75 Gy. The mean dose to the whole brain (excluding metastases) was 33.2 {+-} 0.7 Gy and 32.7 {+-} 0.96 Gy, respectively, in the SIB concept, for 5-mm and 10-mm hippocampus avoidance regions, and 37.23 {+-} 1.42 Gy in SC. Conclusions: Both concepts, SIB and SC, were able to achieve adequate whole brain coverage and radiosurgery-equivalent dose distributions to individual brain metastases. The SIB technique achieved better sparing of the hippocampus, especially when a10-mm hippocampal avoidance region was used.

  2. Randomized Double-Blinded Dose Escalation Trial of Triptorelin for Ovary Protection in Childhood-Onset Systemic Lupus Erythematosus

    PubMed Central

    Brunner, Hermine I.; Silva, Clovis A; Reiff, Andreas; Higgins, Gloria C.; Imundo, Lisa; Williams, Calvin B.; Wallace, Carol A; Aikawa, Nadia E.; Nelson, Shannen; Klein-Gitelman, Marisa S.; Rose, Susan R.

    2015-01-01

    Objectives To determine for females with childhood-onset systemic lupus erythematosus (cSLE) who require cyclophosphamide the dose of triptorelin that suffices to maintain complete ovarian suppression (COS); measure the time needed to achieve ovarian suppression after triptorelin initiation, and explore the safety of triptorelin. Methods In this randomized double-blind placebo-controlled dose-escalation study females (< 21 years) were randomized 4:1 to receive triptorelin or placebo (25 triptorelin, 6 placebo). Starting doses of triptorelin between 25 and 100 microgram/kg/dose were used. Triptorelin dosage was escalated until COS was maintained. The primary outcome was the weight-adjusted dose of triptorelin that for at least 90% of the patients provides COS based on Gonadotropin-releasing-hormone Agonist Stimulation Testing. Secondary outcomes were time to ovarian suppression measured by unstimulated FSH and LH levels after study drug initiation. Results Triptorelin dosed at 120 microgram/kg bodyweight led to sustained COS in 90% of the patients. After the initial dose of triptorelin 22 days were needed for achieve COS. Rates of adverse events (AE) and serious adverse events (SAE) per 100 patient-month of follow-up were not higher in the triptorelin group as compared to the placebo group (triptorelin vs. placebo; AE: 189 vs. 362; SAE: 2.05 vs. 8.48). Conclusions For achieving and maintaining COS high doses of triptorelin are needed but appear to be well tolerated in adolescent females with cSLE. Our data suggest that a lag time of 22 days after triptorelin initiation is required before starting or continuing cyclophosphamide-therapy. Trial Registration Number clinicaltrials.gov identifier: NCT00124514 PMID:25676588

  3. Randomized, double-blind, dose-escalation trial of triptorelin for ovary protection in childhood-onset systemic lupus erythematosus.

    PubMed

    Brunner, Hermine I; Silva, Clovis A; Reiff, Andreas; Higgins, Gloria C; Imundo, Lisa; Williams, Calvin B; Wallace, Carol A; Aikawa, Nadia E; Nelson, Shannen; Klein-Gitelman, Marisa S; Rose, Susan R

    2015-05-01

    To determine the dose of triptorelin that is sufficient to maintain complete ovarian suppression in female patients with childhood-onset systemic lupus erythematosus (SLE) who require cyclophosphamide therapy, to determine the length of time needed to achieve ovarian suppression after initiation of triptorelin treatment, and to investigate the safety of triptorelin. In this randomized, double-blind, placebo-controlled, dose-escalation study, female patients ages <21 years were randomized 4:1 to receive triptorelin (n = 25) or placebo (n = 6). The starting doses of triptorelin were 25, 50, 75, and 100 μg/kg, and the dose was escalated until complete ovarian suppression was maintained. The primary outcome was the weight-adjusted dose of triptorelin that provided complete ovarian suppression in at least 90% of the patients, as determined by gonadotropin-releasing hormone agonist stimulation testing. The secondary outcome was the period of time required to achieve ovarian suppression, as measured by unstimulated follicle-stimulating hormone and luteinizing hormone levels after the initiation of triptorelin treatment. Treatment with triptorelin at a weight-adjusted dose of 120 μg/kg body weight provided sustained complete ovarian suppression in 90% of the patients. After administration of the initial dose of triptorelin, 22 days were required to achieve complete ovarian suppression. The rates of adverse events (AEs) and serious adverse events (SAEs) per 100 patient-months of followup were not higher in the triptorelin group compared with the placebo group (for AEs, 189 versus 362; for SAEs, 2.1 versus 8.5). High doses of triptorelin are needed to achieve and maintain complete ovarian suppression, but such doses appear to be well tolerated in adolescent female patients with childhood-onset SLE. Our data suggest that a lag time of 22 days after initiation of triptorelin treatment is required before cyclophosphamide therapy is started or continued. © 2015

  4. Influence of Ethanol on Oxycodone-induced Respiratory Depression: A Dose-escalating Study in Young and Elderly Individuals.

    PubMed

    van der Schrier, Rutger; Roozekrans, Margot; Olofsen, Erik; Aarts, Leon; van Velzen, Monique; de Jong, Merijn; Dahan, Albert; Niesters, Marieke

    2017-03-01

    Respiratory depression is a potentially fatal complication of opioid use, which may be exacerbated by simultaneous ethanol intake. In this three-way sequential crossover dose-escalating study, the influence of coadministration of oral oxycodone and intravenous ethanol was assessed on resting ventilation, apneic events and the hypercapnic ventilatory response in healthy young and older volunteers. Twelve young (21 to 28 yr) and 12 elderly (66 to 77 yr) opioid-naive participants ingested one 20 mg oxycodone tablet combined with an intravenous infusion of 0, 0.5, or 1 g/l ethanol. Resting respiratory variables and the primary outcome, minute ventilation at isohypercapnia (end-tidal partial pressure of carbon dioxide of 55 mmHg or VE55), were obtained at regular intervals during treatment. Oxycodone reduced baseline minute ventilation by 28% (P < 0.001 vs. control). Ethanol caused a further decrease of oxycodone-induced respiratory depression by another 19% at 1 g/l ethanol plus oxycodone (P < 0.01 vs. oxycodone). Ethanol combined with oxycodone caused a significant increase in the number of apneic events measured in a 6-min window with a median (range) increase from 1 (0 to 3) at 0 g/l ethanol to 1 (0 to 11) at 1 g/l ethanol (P < 0.01). Mean (95% CI) VE55 decreased from 33.4 (27.9 to 39.0) l/min (control) to 18.6 (15.6 to 21.6) l/min (oxycodone, P < 0.01 vs. control) and to 15.7 (12.7 to 18.6) l/min (oxycodone combined with ethanol, 1 g/l; P < 0.01 vs. oxycodone). Ethanol together with oxycodone causes greater ventilatory depression than either alone, the magnitude of which is clinically relevant. Elderly participants were more affected than younger volunteers.

  5. Design of a prospective, dose-escalation study evaluating the Safety of Pioglitazone for Hematoma Resolution in Intracerebral Hemorrhage (SHRINC).

    PubMed

    Gonzales, Nicole R; Shah, Jharna; Sangha, Navdeep; Sosa, Lenis; Martinez, Rebecca; Shen, Loren; Kasam, Mallikarjunarao; Morales, Miriam M; Hossain, M Monir; Barreto, Andrew D; Savitz, Sean I; Lopez, George; Misra, Vivek; Wu, Tzu-Ching; El Khoury, Ramy; Sarraj, Amrou; Sahota, Preeti; Hicks, William; Acosta, Indrani; Sline, M Rick; Rahbar, Mohammad H; Zhao, Xiurong; Aronowski, Jaroslaw; Grotta, James C

    2013-07-01

    RATIONALE : Preclinical work demonstrates that the transcription factor peroxisome proliferator-activated receptor gamma plays an important role in augmenting phagocytosis while modulating oxidative stress and inflammation. We propose that targeted stimulation of phagocytosis to promote efficient removal of the hematoma without harming surrounding brain cells may be a therapeutic option for intracerebral hemorrhage. AIMS : The primary objective is to assess the safety of the peroxisome proliferator-activated receptor gamma agonist, pioglitazone, in increasing doses for three-days followed by a maintenance dose, when administered to patients with spontaneous intracerebral hemorrhage within 24 h of symptom onset compared with standard care. We will determine the maximum tolerated dose of pioglitazone. STUDY DESIGN : This is a prospective, randomized, blinded, placebo-controlled, dose-escalation safety trial in which patients with spontaneous intracerebral hemorrhage are randomly allocated to placebo or treatment. The Continual Reassessment Method for dose finding is used to determine the maximum tolerated dose of pioglitazone. Hematoma and edema resolution is evaluated with serial magnetic resonance imaging (MRI) at specified time points. Functional outcome will be evaluated at three- and six-months. OUTCOMES : The primary safety outcome is mortality at discharge. Secondary safety outcomes include mortality at three-months and six-months, symptomatic cerebral edema, clinically significant congestive heart failure, edema, hypoglycemia, anemia, and hepatotoxicity. Radiographic outcomes will explore the time frame for resolution of 25%, 50%, and 75% of the hematoma. Clinical outcomes are measured by the National Institutes of Health Stroke Scale (NIHSS), the Barthel Index, modified Rankin Scale, Stroke Impact Scale-16, and EuroQol at three- and six-months.

  6. Continual reassessment method for dose escalation clinical trials in oncology: a comparison of prior skeleton approaches using AZD3514 data.

    PubMed

    James, Gareth D; Symeonides, Stefan N; Marshall, Jayne; Young, Julia; Clack, Glen

    2016-08-31

    The continual reassessment method (CRM) requires an underlying model of the dose-toxicity relationship ("prior skeleton") and there is limited guidance of what this should be when little is known about this association. In this manuscript the impact of applying the CRM with different prior skeleton approaches and the 3 + 3 method are compared in terms of ability to determine the true maximum tolerated dose (MTD) and number of patients allocated to sub-optimal and toxic doses. Post-hoc dose-escalation analyses on real-life clinical trial data on an early oncology compound (AZD3514), using the 3 + 3 method and CRM using six different prior skeleton approaches. All methods correctly identified the true MTD. The 3 + 3 method allocated six patients to both sub-optimal and toxic doses. All CRM approaches allocated four patients to sub-optimal doses. No patients were allocated to toxic doses from sigmoidal, two from conservative and five from other approaches. Prior skeletons for the CRM for phase 1 clinical trials are proposed in this manuscript and applied to a real clinical trial dataset. Highly accurate initial skeleton estimates may not be essential to determine the true MTD, and, as expected, all CRM methods out-performed the 3 + 3 method. There were differences in performance between skeletons. The choice of skeleton should depend on whether minimizing the number of patients allocated to suboptimal or toxic doses is more important. NCT01162395 , Trial date of first registration: July 13, 2010.

  7. A phase I dose-escalation study of Tivantinib (ARQ 197) in adult patients with metastatic solid tumors.

    PubMed

    Rosen, Lee S; Senzer, Neil; Mekhail, Tarek; Ganapathi, Ram; Chai, Feng; Savage, Ronald E; Waghorne, Carol; Abbadessa, Giovanni; Schwartz, Brian; Dreicer, Robert

    2011-12-15

    Tivantinib, an oral, non-ATP competitive, selective c-MET inhibitor, exhibited antitumor activity in preclinical models. This open-label, phase I, dose-escalation study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of tivantinib in patients with advanced or metastatic solid tumors refractory to standard therapy. Thirteen dose levels of tivantinib ranging from 10 to 360 mg twice a day were administered to patient cohorts in 21-day cycles (14 days on/7 days off); three active pharmaceutical ingredient forms of tivantinib (amorphous, crystalline A, and crystalline B) were also investigated. Treatment was continued until the occurrence of unacceptable toxicity, tumor progression, patient withdrawal, or death. A total of 79 patients with advanced solid tumors were enrolled. A maximum tolerated dose was not determined. Tivantinib was well tolerated, with mild to moderate toxicities. Two patients discontinued the study drug due to treatment-emergent adverse events. Dose-limiting grade of 3 or more toxicities including leukopenia, neutropenia, thrombocytopenia, vomiting, and dehydration, were observed in 2 patients treated with tivantinib 360 mg twice a day. The rate of absorption of tivantinib peaked approximately 2 to 4 hours after initial dosing, followed by a linear decrease in plasma concentrations. Increases in tivantinib exposure were not dose proportional. There was significant interpatient pharmacokinetic variability; however the clinical safety of tivantinib seemed unaffected. Three patients (3.8%) achieved a partial response and 40 patients (50.6%) maintained stable disease for a median of 19.9 weeks. Tivantinib 360 mg twice a day was well tolerated in patients with refractory advanced solid tumors. The results of this trial warrant further clinical investigation. Clin Cancer Res; 17(24); 7754-64. ©2011 AACR. ©2011 AACR.

  8. Phase I trial of dose-escalating metronomic temozolomide plus bevacizumab and bortezomib for patients with recurrent glioblastoma.

    PubMed

    McCracken, D Jay; Celano, Emma C; Voloschin, Alfredo D; Read, William L; Olson, Jeffrey J

    2016-10-01

    The average survival time for patients with recurrent glioblastoma is between 5 and 9 months. Phase I and II trials have shown a modest survival benefit with combination temozolomide and other chemotherapeutics. We conducted a phase I trial of dose-escalating temozolomide with bevacizumab and the proteasome inhibitor bortezomib for patients with recurrent disease. Three groups of three patients were scheduled to receive daily doses of temozolomide at 25, 50, and 75 mg/m(2). Fixed doses of bortezomib and bevacizumab were given at standard intervals. Patients were monitored for dose-limiting toxicities (DLT) to determine the maximum-tolerated dose (MTD) of temozolomide with this regimen. No DLT were seen in the first two groups (25 and 50 mg/m(2) temozolomide). One patient in the 75 mg/m(2) group experienced a grade 4 elevation of ALT and three more patients were accrued for a total of six patients at that dose level. No other DLT occurred, thus making 75 mg/m(2) the MTD. Progression-free survival was 3.27 months for all patients and mean overall survival was 20.75 months. The MTD of temozolomide was 75 mg/m(2) in combination with bevacizumab and bortezomib for recurrent glioblastoma. Only one patient experienced a severe (Grade 4) elevation of ALT. This study will provide the framework for further studies to elicit effectiveness and better determine a safety profile for this drug combination.

  9. ISIS-DME: a prospective, randomized, dose-escalation intravitreal steroid injection study for refractory diabetic macular edema.

    PubMed

    Kim, Judy E; Pollack, John S; Miller, David G; Mittra, Robert A; Spaide, Richard F

    2008-05-01

    : To determine safety and efficacy of intravitreal triamcinolone acetonide (IVTA) for refractory clinically significant diabetic macular edema (DME). : Prospective, randomized, dose-escalation pilot study comparing single injection of 2 mg versus 4 mg doses of IVTA. : Inclusion criteria included clinically significant DME persisting >/=3 months after maximal laser treatment and visual acuity 15 letters at 3 months in 23% (3/13) of 2 mg group and in 33% (5/15) of 4 mg group (P = 0.69), and 0% (0/11) and 21% (3/14) at 6 months, respectively (P = 0.23). Visual improvement was more likely in cystoid-type DME than diffuse DME. Intraocular pressure rise of >/=10 mmHg occurred in 19% (3/16) of 2 mg group and 41% (7/17) of 4 mg group. : Both doses of IVTA were well tolerated and had significant positive effects on refractory DME for short term. There were consistent trends throughout the study that suggest that a 4 mg IVTA may be more effective than a 2 mg dose. The benefit of IVTA was greater for cystoid-type DME.

  10. A 12-week dose-escalating study of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, for secondary hyperparathyroidism in Japanese hemodialysis patients
.

    PubMed

    Yokoyama, Keitaro; Fukagawa, Masafumi; Shigematsu, Takashi; Akiba, Takashi; Fujii, Akifumi; Odani, Motoi; Akizawa, Tadao

    2017-08-01

    To evaluate dose-escalation of etelcalcetide (ONO-5163/AMG 416), a novel, intravenous (IV), long-acting calcium-sensing receptor agonist, for treatment of secondary hyperparathyroidism (SHPT) in Japanese hemodialysis patients. In this multicenter study, IV injections of etelcalcetide (3 times a week for 12 weeks) were administered, with dose escalation every 4 weeks depending on changes in serum intact parathyroid hormone (iPTH) and corrected calcium (cCa). A total of 24 patients participated in this study. Serum iPTH was reduced in a time- and dose-dependent manner, with reductions (in pg/mL) at 12 weeks of -226.1 ± 125.3, -362.5 ± 161.5, and -412.4 ± 130.2, respectively, for maximum doses of 5, 10, and 15 mg. At the end of the treatment, 50% of patients had serum iPTH levels within the target range (60 - 240 pg/mL). Serum cCa and phosphorus were reduced in parallel with iPTH. Adverse events (AEs) occurred in 20 patients (83.3%). The most frequently observed AEs (> 10%) were either mild or moderate nasopharyngitis (29.2%), decreased serum calcium (16.7%), and vomiting (12.5%). Dose-escalated triweekly etelcalcetide was effective for SHPT in Japanese hemodialysis patients and was satisfactorily tolerated.
.

  11. Sorafenib dose escalation in treatment-naïve patients with metastatic renal cell carcinoma: a non-randomised, open-label, Phase 2b study.

    PubMed

    Gore, Martin E; Jones, Robert J; Ravaud, Alain; Kuczyk, Markus; Demkow, Tomasz; Bearz, Alessandra; Shapiro, JoAnn; Strauss, Uwe Phillip; Porta, Camillo

    2017-06-01

    To assess the efficacy and safety of sorafenib dose escalation in metastatic renal cell carcinoma (mRCC). Intra-patient dose escalation may enhance the clinical benefit of targeted anticancer agents in metastatic disease. In this non-randomised, open-label, Phase 2b study, treatment-naïve patients with mRCC were initially treated with the standard oral sorafenib dose [400 mg twice daily (BID)]. Two dose escalations were planned, each 200 mg BID after 28 days at the prior level. Dose reductions, interruptions, or delayed escalations were used to manage adverse events (AEs). The primary endpoint was objective response rate (ORR) in the modified intent-to-treat (mITT) population, which comprised patients with ≥6 months of treatment including ≥4 months of therapy at their highest tolerated dose. Secondary endpoints included progression-free survival (PFS) and safety. In all, 83 patients received sorafenib. The dose received for the longest duration was 400, 600, and 800 mg BID in 48.2%, 15.7%, and 24.1% of patients, respectively. The ORR was 44.4% [n = 8/18; 95% confidence interval (CI) 21.5-69.2] and 17.9% (n = 12/67; 95% CI 9.6-29.2) in the mITT and ITT populations, respectively. The median (95% CI) PFS was 7.4 (6.0-11.7) months (ITT). The most common AEs of any grade were hand-foot skin reaction (66.3%) and diarrhoea (63.9%). Sorafenib demonstrated clinical benefit in treatment-naïve patients with mRCC. However, relatively few patients could sustain doses of >400 mg BID. There was evidence that, where tolerated, escalation from the standard sorafenib dose may have enhanced clinical benefit. However, this study does not support dose escalation for most patients with treatment-naïve mRCC. Alternative protocols for sorafenib dose escalation could be explored. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

  12. Interactive image-guided neurosurgery.

    PubMed

    Galloway, R L; Maciunas, R J; Edwards, C A

    1992-12-01

    Interactive image-guided (IIG) surgery involves the synchronal display of the tip of a surgical device on preoperative scans. This display allows the surgeon to locate the present surgical position relative to the final site of surgical interest. We have developed a technique for IIG surgery device based on a six-degree-of-freedom articulated arm. Design accuracy for the arm is less than 0.1 mm and the present implementation has a submillimetric accuracy. The display can show the surgical position on any tomographic image set with simultaneous display on up to three image sets. Laboratory results and clinical applications are discussed.

  13. Vorinostat and Concurrent Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases: A Phase 1 Dose Escalation Trial.

    PubMed

    Choi, Clara Y H; Wakelee, Heather A; Neal, Joel W; Pinder-Schenck, Mary C; Yu, Hsiang-Hsuan Michael; Chang, Steven D; Adler, John R; Modlin, Leslie A; Harsh, Griffith R; Soltys, Scott G

    2017-09-01

    To determine the maximum tolerated dose (MTD) of vorinostat, a histone deacetylase inhibitor, given concurrently with stereotactic radiosurgery (SRS) to treat non-small cell lung cancer (NSCLC) brain metastases. Secondary objectives were to determine toxicity, local failure, distant intracranial failure, and overall survival rates. In this multicenter study, patients with 1 to 4 NSCLC brain metastases, each ≤2 cm, were enrolled in a phase 1, 3 + 3 dose escalation trial. Vorinostat dose levels were 200, 300, and 400 mg orally once daily for 14 days. Single-fraction SRS was delivered on day 3. A dose-limiting toxicity (DLT) was defined as any Common Terminology Criteria for Adverse Events version 3.0 grade 3 to 5 acute nonhematologic adverse event related to vorinostat or SRS occurring within 30 days. From 2009 to 2014, 17 patients were enrolled and 12 patients completed study treatment. Because no DLTs were observed, the MTD was established as 400 mg. Acute adverse events were reported by 10 patients (59%). Five patients discontinued vorinostat early and withdrew from the study. The most common reasons for withdrawal were dyspnea (n=2), nausea (n=1), and fatigue (n=2). With a median follow-up of 12 months (range, 1-64 months), Kaplan-Meier overall survival was 13 months. There were no local failures. One patient (8%) at the 400-mg dose level with a 2.0-cm metastasis developed histologically confirmed grade 4 radiation necrosis 2 months after SRS. The MTD of vorinostat with concurrent SRS was established as 400 mg. Although no DLTs were observed, 5 patients withdrew before completing the treatment course, a result that emphasizes the need for supportive care during vorinostat administration. There were no local failures. A larger, randomized trial may evaluate both the tolerability and potential local control benefit of vorinostat concurrent with SRS for brain metastases. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Safety and effectiveness of oral misoprostol for induction of labour in a resource-limited setting: a dose escalation study.

    PubMed

    Morris, Marilyn; Bolnga, John W; Verave, Ovoi; Aipit, Jimmy; Rero, Allanie; Laman, Moses

    2017-09-08

    Oral misoprostol as an induction of labour (IOL) agent is rapidly gaining popularity in resource-limited settings because it is cheap, stable at ambient temperatures, and logistically easier to administer compared to dinoprostone and oxytocin. We aim to investigate the safety and effectiveness of a regimen of oral misoprostol in Papua New Guinean women undergoing IOL. As part of a prospective dose escalation study conducted at Modilon Hospital in Papua New Guinea, women with a singleton pregnancy in cephalic presentation and an unfavourable cervix who gave written informed consent were administered oral misoprostol, commencing at 25mcg once every 2 h for 4 doses and increased to 50mcg once every 2 h for 8 doses within 24 h. The primary outcomes studied were i) the proportion of women delivering within 24 h of oral misoprostol administration, and ii) rates of maternal and perinatal severe adverse events. Of 6167 labour ward screened admissions, 209 women (3%) fulfilled the study inclusion criteria and underwent IOL. Overall, 74% (155/209 [95% confidence interval 67.6-79.9]) delivered within 24 h. Most women (90%; 188/209; 95% CI [84.9-93.5]) delivered vaginally with 86% (180/209) having a good outcome for both the mother and baby. Of the 10% (21/209) who failed IOL and underwent caesarean section, a significant proportion of their babies were admitted to special-care nursery compared to babies delivered vaginally (20/21 [95%] versus 8/188 [4%]; Fisher Exact test P < 0.001), but their perinatal mortality rate was not significantly higher (1/21 [5%] versus 2/188 [1%]; P = 0.30). The only maternal death was not study related and occurred in a patient with post-partum haemorrhage, 15 h post-delivery. The oral misoprostol regimen for IOL described in the present study is safe, effective and logistically feasible to administer in a resource-limited setting.

  15. Overview of image-guided radiation therapy

    SciTech Connect

    Xing Lei . E-mail: lei@reyes.stanford.edu; Thorndyke, Brian; Schreibmann, Eduard; Yang Yong; Li, T.-F.; Kim, Gwe-Ya; Luxton, Gary; Koong, Albert

    2006-07-01

    Radiation therapy has gone through a series of revolutions in the last few decades and it is now possible to produce highly conformal radiation dose distribution by using techniques such as intensity-modulated radiation therapy (IMRT). The improved dose conformity and steep dose gradients have necessitated enhanced patient localization and beam targeting techniques for radiotherapy treatments. Components affecting the reproducibility of target position during and between subsequent fractions of radiation therapy include the displacement of internal organs between fractions and internal organ motion within a fraction. Image-guided radiation therapy (IGRT) uses advanced imaging technology to better define the tumor target and is the key to reducing and ultimately eliminating the uncertainties. The purpose of this article is to summarize recent advancements in IGRT and discussed various practical issues related to the implementation of the new imaging techniques available to radiation oncology community. We introduce various new IGRT concepts and approaches, and hope to provide the reader with a comprehensive understanding of the emerging clinical IGRT technologies. Some important research topics will also be addressed.

  16. Personalized estimation of dose to red bone marrow and the associated leukaemia risk attributable to pelvic kilo-voltage cone beam computed tomography scans in image-guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Zhang, Yibao; Yan, Yulong; Nath, Ravinder; Bao, Shanglian; Deng, Jun

    2012-07-01

    The aim of this study is to investigate the imaging dose to red bone marrow (RBM) and the associated leukaemia risks attributable to pelvic kilo-voltage cone beam computed tomography (kVCBCT) scans in image-guided radiation therapy (IGRT). The RBM doses of 42 patients (age 2.7-86.4 years) were calculated using Monte Carlo simulations. The trabecular spongiosa was segmented to substitute RBM rather than the whole bone. Quantitative correlations between anthropometric variables such as age, physical bone density (PBD) and RBM dose were established. Personalized leukaemia risk was evaluated using an improved Boice model which included the age-associated RBM involvement. An incremental leukaemia risk of 29%-82% (mean = 45%) was found to be associated with 40 pelvic kVCBCT scans in the subject group used in a typical external beam radiation therapy course. Higher risks were observed in children. Due to the enhanced photoelectric effect in high atomic number materials, PBD was observed to strongly affect the RBM dose. Considerable overestimations (9%-42%, mean = 28%) were observed if the whole bone doses were used as surrogates of RBM doses. The personalized estimation of RBM dose and associated leukaemia risk caused by pelvic kVCBCT scans is clinically feasible with the proposed empirical models. Higher radiogenic cancer risks are associated with repeated kVCBCT scans in IGRT of cancer patients, especially children.

  17. Image-guided tissue engineering

    PubMed Central

    Ballyns, Jeffrey J; Bonassar, Lawrence J

    2009-01-01

    Replication of anatomic shape is a significant challenge in developing implants for regenerative medicine. This has lead to significant interest in using medical imaging techniques such as magnetic resonance imaging and computed tomography to design tissue engineered constructs. Implementation of medical imaging and computer aided design in combination with technologies for rapid prototyping of living implants enables the generation of highly reproducible constructs with spatial resolution up to 25 μm. In this paper, we review the medical imaging modalities available and a paradigm for choosing a particular imaging technique. We also present fabrication techniques and methodologies for producing cellular engineered constructs. Finally, we comment on future challenges involved with image guided tissue engineering and efforts to generate engineered constructs ready for implantation. PMID:19583811

  18. PSA Response to Neoadjuvant Androgen Deprivation Therapy Is a Strong Independent Predictor of Survival in High-Risk Prostate Cancer in the Dose-Escalated Radiation Therapy Era

    SciTech Connect

    McGuire, Sean E.; Lee, Andrew K.; Cerne, Jasmina Z.; Munsell, Mark F.; Levy, Lawrence B.; Kudchadker, Rajat J.; Choi, Seungtaek L.; Nguyen, Quynh N.; Hoffman, Karen E.; Pugh, Thomas J.; Frank, Steven J.; Corn, Paul G.; Logothetis, Christopher J.; Kuban, Deborah A.

    2013-01-01

    Purpose: The aim of the study was to evaluate the prognostic value of prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) prior to dose-escalated radiation therapy (RT) and long-term ADT in high-risk prostate cancer. Methods and Materials: We reviewed the charts of all patients diagnosed with high-risk prostate cancer and treated with a combination of long-term ADT (median, 24 months) and dose-escalated (median, 75.6 Gy) RT between 1990 and 2007. The associations among patient, tumor, and treatment characteristics with biochemical response to neoadjuvant ADT and their effects on failure-free survival (FFS), time to distant metastasis (TDM), prostate cancer-specific mortality (PCSM) and overall survival (OS) were examined. Results: A total of 196 patients met criteria for inclusion. Median follow-up time for patients alive at last contact was 7.0 years (range, 0.5-18.1 years). Multivariate analysis identified the pre-RT PSA concentration (<0.5 vs {>=}0.5 ng/mL) as a significant independent predictor of FFS (P=.021), TDM (P=.009), PCSM (P=.039), and OS (P=.037). On multivariate analysis, pretreatment PSA (iPSA) and African-American race were significantly associated with failure to achieve a pre-RT PSA of <0.5 ng/mL. Conclusions: For high-risk prostate cancer patients treated with long-term ADT and dose-escalated RT, a pre-RT PSA level {>=}0.5 ng/mL after neoadjuvant ADT predicts for worse survival measures. Both elevated iPSA and African-American race are associated with increased risk of having a pre-RT PSA level {>=}0.5 ng/mL. These patients should be considered for clinical trials that test newer, more potent androgen-depleting therapies such as abiraterone and MDV3100 in combination with radiation.

  19. A test-based strategy is more cost effective than empiric dose escalation for patients with Crohn's disease who lose responsiveness to infliximab.

    PubMed

    Velayos, Fernando S; Kahn, James G; Sandborn, William J; Feagan, Brian G

    2013-06-01

    Patients with Crohn's disease who become unresponsive to therapy with tumor necrosis factor antagonists are managed initially with either empiric dose escalation or testing-based strategies. The comparative cost effectiveness of these 2 strategies is unknown. We investigated whether a testing-based strategy is more cost effective than an empiric dose-escalation strategy. A decision analytic model that simulated 2 cohorts of patients with Crohn's disease compared outcomes for the 2 strategies over a 1-year time period. The incremental cost-effectiveness ratio of the empiric strategy was expressed as cost per quality-adjusted life-year (QALY) gained, compared with the testing-based strategy. We performed 1-way, probabilistic, and prespecified secondary analyses. The testing strategy yielded similar QALYs compared with the empiric strategy (0.801 vs 0.800, respectively) but was less expensive ($31,870 vs $37,266, respectively). In sensitivity analyses, the incremental cost-effectiveness ratio of the empiric strategy ranged from $500,000 to more than $5 million per QALY gained. Similar rates of remission (63% vs 66%) and response (28% vs 26%) were achieved through differential use of available interventions. The testing-based strategy resulted in a higher percentage of surgeries (48% vs 34%) and lower percentage use of high-dose biological therapy (41% vs 54%). A testing-based strategy is a cost-effective alternative to the current strategy of empiric dose escalation for managing patients with Crohn's disease who have lost responsiveness to infliximab. The basis for this difference is lower cost at similar outcomes. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  20. What to expect from immediate salvage hysterectomy following concomitant chemoradiation and image-guided adaptive brachytherapy in locally advanced cervical cancer.

    PubMed

    Castelnau-Marchand, P; Chargari, C; Bouaita, R; Dumas, I; Farha, G; Kamsu-Kom, L; Rivin Del Campo, E; Martinetti, F; Morice, P; Haie-Meder, C; Mazeron, R

    2015-12-01

    Concomitant chemoradiation followed by brachytherapy is the standard treatment for locally advanced cervical cancers. The place of adjuvant hysterectomy remains unclear but tends to be limited to incomplete responses to radiotherapy or local relapse. The aim was to analyse the benefit from immediate salvage surgery following radiation therapy in incomplete responders. Among the patients with locally advanced cervical cancer treated with concomitant chemoradiation followed by 3D image-guided adaptive brachytherapy and hysterectomy, cases with genuine macroscopic remnant, defined as at least 1cm in width, were identified. Their clinical data and outcomes were retrospectively reviewed and compared to the patients treated with the same modalities. Fifty-eight patients were included, with a median follow-up of 4.2 years. After hysterectomy, 9 patients had macroscopic residual disease, 10 microscopic and the remaining 39 patients were considered in complete histological response. The 4-year overall survival and disease-free survival rates were significantly decreased in patients with macroscopic residual disease: 50 and 51% versus 92% and 93%, respectively. Intestinal grades 3-4 toxicities were reported in 10.4% and urinary grades 3-4 in 8.6% in the whole population without distinctive histological features. Planning aims were reached in only one patient with macroscopic residuum (11.1%). In univariate analysis, overall treatment time (>55 days) and histological subtype (adenocarcinomas or adenosquamous carcinomas) appeared to be significant predictive factors for macroscopic remnant after treatment completion (P=0.021 and P=0.017, respectively). In multivariate analysis, treatment time was the only independent factor (P=0.046, odds ratio=7.0). Although immediate salvage hysterectomy in incomplete responders provided a 4-year disease-free survival of 51%, its impact on late morbidity is significant. Efforts should focus on respect of treatment time and dose escalation

  1. A comparison of HDR brachytherapy and IMRT techniques for dose escalation in prostate cancer: A radiobiological modeling study

    SciTech Connect

    Fatyga, M.; Williamson, J. F.; Dogan, N.; Todor, D.; Siebers, J. V.; George, R.; Barani, I.; Hagan, M.

    2009-09-15

    A course of one to three large fractions of high dose rate (HDR) interstitial brachytherapy is an attractive alternative to intensity modulated radiation therapy (IMRT) for delivering boost doses to the prostate in combination with additional external beam irradiation for intermediate risk disease. The purpose of this work is to quantitatively compare single-fraction HDR boosts to biologically equivalent fractionated IMRT boosts, assuming idealized image guided delivery (igIMRT) and conventional delivery (cIMRT). For nine prostate patients, both seven-field IMRT and HDR boosts were planned. The linear-quadratic model was used to compute biologically equivalent dose prescriptions. The cIMRT plan was evaluated as a static plan and with simulated random and setup errors. The authors conclude that HDR delivery produces a therapeutic ratio which is significantly better than the conventional IMRT and comparable to or better than the igIMRT delivery. For the HDR, the rectal gBEUD analysis is strongly influenced by high dose DVH tails. A saturation BED, beyond which no further injury can occur, must be assumed. Modeling of organ motion uncertainties yields mean outcomes similar to static plan outcomes.

  2. Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: a multicentre, randomised, dose-escalation phase 1 study.

    PubMed

    Issa, Jean-Pierre J; Roboz, Gail; Rizzieri, David; Jabbour, Elias; Stock, Wendy; O'Connell, Casey; Yee, Karen; Tibes, Raoul; Griffiths, Elizabeth A; Walsh, Katherine; Daver, Naval; Chung, Woonbok; Naim, Sue; Taverna, Pietro; Oganesian, Aram; Hao, Yong; Lowder, James N; Azab, Mohammad; Kantarjian, Hagop

    2015-09-01

    Hypomethylating agents are used to treat cancers driven by aberrant DNA methylation, but their short half-life might limit their activity, particularly in patients with less proliferative diseases. Guadecitabine (SGI-110) is a novel hypomethylating dinucleotide of decitabine and deoxyguanosine resistant to degradation by cytidine deaminase. We aimed to assess the safety and clinical activity of subcutaneously given guadecitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome. In this multicentre, open-label, phase 1 study, patients from nine North American medical centres with myelodysplastic syndrome or acute myeloid leukaemia that was refractory to or had relapsed after standard treatment were randomly assigned (1:1) to receive subcutaneous guadecitabine, either once-daily for 5 consecutive days (daily × 5), or once-weekly for 3 weeks, in a 28-day treatment cycle. Patients were stratified by disease. A 3 + 3 dose-escalation design was used in which we treated patients with guadecitabine doses of 3-125 mg/m(2) in separate dose-escalation cohorts. A twice-weekly treatment schedule was added to the study after a protocol amendment. The primary objective was to assess safety and tolerability of guadecitabine, determine the maximum tolerated and biologically effective dose, and identify the recommended phase 2 dose of guadecitabine. Safety analyses included all patients who received at least one dose of guadecitabine. Pharmacokinetic and pharmacodynamic analyses to determine the biologically effective dose included all patients for whom samples were available. This study is registered with ClinicalTrials.gov, number NCT01261312. Between Jan 4, 2011, and April 11, 2014, we enrolled and treated 93 patients: 35 patients with acute myeloid leukaemia and nine patients with myelodysplastic syndrome in the daily × 5 dose-escalation cohorts, 28 patients with acute myeloid leukaemia and six patients with myelodysplastic syndrome in the once-weekly dose-escalation

  3. Image-guided endobronchial ultrasound

    NASA Astrophysics Data System (ADS)

    Higgins, William E.; Zang, Xiaonan; Cheirsilp, Ronnarit; Byrnes, Patrick; Kuhlengel, Trevor; Bascom, Rebecca; Toth, Jennifer

    2016-03-01

    Endobronchial ultrasound (EBUS) is now recommended as a standard procedure for in vivo verification of extraluminal diagnostic sites during cancer-staging bronchoscopy. Yet, physicians vary considerably in their skills at using EBUS effectively. Regarding existing bronchoscopy guidance systems, studies have shown their effectiveness in the lung-cancer management process. With such a system, a patient's X-ray computed tomography (CT) scan is used to plan a procedure to regions of interest (ROIs). This plan is then used during follow-on guided bronchoscopy. Recent clinical guidelines for lung cancer, however, also dictate using positron emission tomography (PET) imaging for identifying suspicious ROIs and aiding in the cancer-staging process. While researchers have attempted to use guided bronchoscopy systems in tandem with PET imaging and EBUS, no true EBUS-centric guidance system exists. We now propose a full multimodal image-based methodology for guiding EBUS. The complete methodology involves two components: 1) a procedure planning protocol that gives bronchoscope movements appropriate for live EBUS positioning; and 2) a guidance strategy and associated system graphical user interface (GUI) designed for image-guided EBUS. We present results demonstrating the operation of the system.

  4. From clinical imaging and computational models to personalised medicine and image guided interventions.