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ABSTRACT: To validate a method of accurately confirming the orientation of the Contura multilumen balloon catheter before each fraction and to determine if any residual device rotation remains after adjustment.
Sixteen patients underwent CT scans before each treatment with accelerated partial breast irradiation. Before acquisition of CT scans for planning, each patient had a skin mark drawn to align with Lumen #1 (the Contura [SenoRx, Inc., Irvine, CA] has a black line on the shaft of the applicator to identify this lumen). In addition, a CT spot marker was used as a fixed reference point on the patient's skin. CT markers (used for lumen identification and reconstruction) were also used as additional reference points for distance measurements. The distances measured from the CT spot marker to the three reproducible points on the CT markers were used for balloon rotation verification. These measurements were performed for each daily fraction on reproducible CT axial views.
Three hundred eighteen measurements were obtained. Median residual rotation for all cases was 0.2mm (standard deviation=0.797). Later fractions and skin spacing changes over time were associated with slightly greater residual rotation (Fraction #1 vs. Fraction #10, 0.1 vs. 0.3mm, p=0.05; and skin spacing change ≤2 vs. >2mm, 0.2 vs. 0.5mm, p=0.0019, respectively).
These results confirm external alignment of a skin mark with Lumen #1 (on the Contura catheter) is an accurate and reliable method to align the balloon before treatment and that no significant internal device rotation (0.2mm) is likely to occur.
Brachytherapy 01/2011; 10(4):325-30. · 1.47 Impact Factor
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ABSTRACT: The radiobiology of prostate cancer appears to favor large fractions. Accelerated hypofractionation treatments may therefore be used to improve the therapeutic ratio, particularly when the doses to rectum and bladder are kept below the prostate dose. The 5-year experience at William Beaumont Hospital (WBH) and the California Endocurietherapy Center (CET) with accelerated-hypofractionated high-dose-rate (HDR) monotherapy in favorable prostate cancer is presented.
Between 1993 and 2004, 454 patients were treated with brachytherapy of which 248 treated with HDR and 206 patients treated with low-dose-rate Palladium (LDR-Pd¹⁰³). The WBH-HDR dose was 38 Gy, in 4 fractions, twice a day. The CET-HDR dose was 42 Gy in 6 fractions in 2 separate implants 1 week apart. The WBH-LDR dose was 120 Gy.
Median follow-up was 4.8 years. The 5-year Phoenix biochemical control (BC) was 89%, 91%, and 88% for WBH-LDR, WBH- HDR, and CET-HDR, respectively. The majority of complications were grade 1. HDR was associated with less acute grade 1 to 3 dysuria 60% versus 39%, (P < 0.001), urinary frequency/urgency 90% to58% (P < 0.001), and rectal pain 17% to 6.5% (P < 0.001). Long-term urinary frequency/urgency 54% versus 43%, (P = 0.03) and dysuria 22% versus 15% were less with HDR. The 5-year actuarial impotence rate was 30% for LDR and 20% for HDR (P = 0.23).
Although the same 5-year BC rates were achieved with HDR (248 patients) and LDR (206 patients) monotherapy, HDR brachytherapy was associated with less acute and chronic genitourinary and gastrointestinal toxicities. As another accepted standard of care, accelerated hypofractionated HDR monotherapy is target specific and efficient radiobiologically than EBRT which has many smaller doses per fraction. It could be considered today as the best option in accelerated hypofractionated prostate cancer treatment.
American journal of clinical oncology 11/2009; 33(5):481-8. · 2.21 Impact Factor
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ABSTRACT: The purpose of this study is to establish the in vivo verification of proton beam path by using proton-activated positron emission distributions.
A total of 50 PET/CT imaging studies were performed on ten prostate cancer patients immediately after daily proton therapy treatment through a single lateral portal. The PET/CT and planning CT were registered by matching the pelvic bones, and the beam path of delivered protons was defined in vivo by the positron emission distribution seen only within the pelvic bones, referred to as the PET-defined beam path. Because of the patient position correction at each fraction, the marker-defined beam path, determined by the centroid of implanted markers seen in the posttreatment (post-Tx) CT, is used for the planned beam path. The angular variation and discordance between the PET- and marker-defined paths were derived to investigate the intrafraction prostate motion. For studies with large discordance, the relative location between the centroid and pelvic bones seen in the post-Tx CT was examined. The PET/CT studies are categorized for distinguishing the prostate motion that occurred before or after beam delivery. The post-PET CT was acquired after PET imaging to investigate prostate motion due to physiological changes during the extended PET acquisition.
The less than 2 degrees of angular variation indicates that the patient roll was minimal within the immobilization device. Thirty of the 50 studies with small discordance, referred as good cases, show a consistent alignment between the field edges and the positron emission distributions from the entrance to the distal edge. For those good cases, average displacements are 0.6 and 1.3 mm along the anterior-posterior (D(AP)) and superior-inferior (D(SI)) directions, respectively, with 1.6 mm standard deviations in both directions. For the remaining 20 studies demonstrating a large discordance (more than 6 mm in either D(AP) or D(SI)), 13 studies, referred as motion-after-Tx cases, also show large misalignment between the field edge and the positron emission distribution in lipomatous tissues around the prostate. These motion-after-Tx cases correspond to patients with large changes in volume of rectal gas between the post-Tx and the post-PET CTs. The standard deviations for D(AP) and D(SI) are 5.0 and 3.0 mm, respectively, for these motion-after-Tx cases. The final seven studies, referred to as position-error cases, which had a large discordance but no misalignment, were found to have deviations of 4.6 and 3.6 mm in D(AP) and D(SI), respectively. The position-error cases correspond to a large discrepancy on the relative location between the centroid and pelvic bones seen in post-Tx CT and recorded x-ray radiographs.
Systematic analyses of proton-activated positron emission distributions provide patient-specific information on prostate motion (sigmaM) and patient position variability (sigmap) during daily proton beam delivery. The less than 2 mm of displacement variations in the good cases indicates that population-based values of sigmap and sigmaM, used in margin algorithms for treatment planning at the authors' institution are valid for the majority of cases. However, a small fraction of PET/CT studies (approximately 14%) with -4 mm displacement variations may require different margins. Such data are useful in establishing patient-specific planning target volume margins.
Medical Physics 09/2009; 36(9):4136-46. · 2.83 Impact Factor
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ABSTRACT: To compare dose distributions in targeted tissues (prostate, seminal vesicles, pelvic regional nodes) and nontargeted tissues in the pelvis with intensity-modulated radiotherapy (IMRT) and forward-planned, double-scattered, three-dimensional proton radiotherapy (3D-PRT).
IMRT, IMRT followed by a prostate 3D-PRT boost (IMRT/3D-PRT), and 3D-PRT plans were created for 5 high-risk prostate cancer patients (n = 15 plans). A 78-CGE/Gy dose was prescribed to the prostate and proximal seminal vesicles and a 46-CGE/Gy was prescribed to the pelvic nodes. Various dosimetric endpoints were compared.
Target coverage of the prostate and nodal planning target volumes was adequate for all three plans. Compared with the IMRT and IMRT/3D-PRT plans, the 3D-PRT plans reduced the mean dose to the rectum, rectal wall, bladder, bladder wall, small bowel, and pelvis. The relative benefit of 3D-PRT (vs IMRT) at reducing the rectum and rectal wall V5-V40 was 53% to 71% (p < 0.05). For the bladder and bladder wall, the relative benefit for V5 to V40 CGE/Gy was 40% to 63% (p < 0.05). The relative benefit for reducing the volume of small bowel irradiated from 5 to 30 CGE/Gy in the 3D-PRT ranged from 62% to 69% (p < 0.05). Use of 3D-PRT did not produce the typical low-dose "bath" of radiation to the pelvis seen with IMRT. Femoral head doses were higher for the 3D-PRT.
Use of 3D-PRT significantly reduced the dose to normal tissues in the pelvis while maintaining adequate target coverage compared with IMRT or IMRT/3D-PRT. When treating the prostate, seminal vesicles, and pelvic lymph nodes in prostate cancer, proton therapy may improve the therapeutic ratio beyond what is possible with IMRT.
International journal of radiation oncology, biology, physics 08/2009; 75(4):994-1002. · 4.59 Impact Factor
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ABSTRACT: Determine prostate intrafraction motion with Cine-magnetic resonance imaging (MRI) and deformable registration.
A total of 68 cine-MRI studies were done in 17 different series with 4 scans per series in 7 patients. In without rectal balloon (WORB) scans, 100 mL of water was infused in the rectum. Each series consisted of supine and prone, with a rectal balloon (WRB) and WORB. Each scan was performed over 4 minutes. Automatic deformable registration software developed by View Ray, Inc., Cleveland, Ohio was employed to segment the prostate for each cine-MRI image. A time-based analysis was done for the different positions and the use of the rectal balloon.
The variation/standard deviation of the prostate position during 240 seconds was: supine WRB: 0.55 mm, WORB: 1.2 mm, and prone WRB: 1.48 mm, WORB: 2.15 mm (P < 0.001). A strong relationship was observed between time and prostate motion. For the initial 120 s the standard deviation was smaller than for the second 120 s supine WRB 0.54 mm versus 1.37 mm; supine WORB 0.61 mm versus 1.70 mm; prone WRB 0.85 mm versus 1.85 mm; and prone WORB 1.60 mm versus 2.56 mm. The probabilities for prostate staying within +/-2 mm to its initial position are: 94.8% supine WRB; 91.5% supine WORB; 92.3% prone WRB; 79.2% prone WORB.
Intrafraction prostate motion was found dependent on time, patient position, and the use of a rectal balloon. Relatively stable positions can be obtained for 4 minutes or less especially in the supine position with a rectal balloon.
American journal of clinical oncology 08/2009; 33(1):11-6. · 2.21 Impact Factor
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ABSTRACT: To investigate axillary 2-dimensional treatment planning accuracy.
Computed tomography (CT) simulation data for 16 breast cancer cases taken after level I-II axillary dissection were analyzed. An additional 6 patients underwent CT simulation using the historical 90-degree position (HP), and the standard-bore CT position (CT-P). Two physicians identified the lateral and medial borders of the coracoid process (CCP) on digitally reconstructed radiography (DRR). The DRR-identified x coordinates were compared with the CT-measured x coordinates. x coordinates differences between the most medial surgical clip and the borders of the CCP as identified on CT were analyzed. Fields were designed to cover various amounts of the axilla, and treatment plans were generated to compare doses to the most medial surgical clip.
In 11 and 6 cases for each physician, respectively (lateral border), and in all cases for both physicians (medial border), the DRR identification of the CCP was medial to that on CT. In 9 and 8 cases, the most medial surgical clip was lateral to the medial and lateral borders of the CCP, respectively. In all data sets, the average difference was larger in the HP compared with CT position. The number of patients who received more than 90% of the prescribed dose when using the plans with the mid humeral head border, lateral border of the CCP, and medial border of the CCP were as follows: 6, 1, and 0, respectively.
When using 2-dimensional treatment planning, the dose to the undissected axilla can vary depending on the anatomic landmark used to define the lateral border of the axillary field. This may account for outcome differences found in older radiotherapy studies.
American journal of clinical oncology 07/2009; 32(4):387-95. · 2.21 Impact Factor
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ABSTRACT: To identify differences in regional node irradiation using historical treatment planning techniques between 2 arm positions.
Sixteen breast cancer patients were scanned using a wide-bore computed tomography (CT) scanner. The patients were scanned in 2 arm positions: historical position (HP), in which the ipsilateral arm is at 90 degrees to the body axis; and standard-bore position (CT-P), in which the arms are above the head. The locations of the axillary lymph nodes were compared between the 2 positions. The dose distribution to the axillary lymph nodes was compared between the HP and the CT-P using fields designed based on bony landmarks.
When the arm position changed from the HP to the CT-P, level I lymph nodes moved anteriorly and medially. Level II and III axillary nodes moved posteriorly and medially. If historical treatment planning techniques are used to treat the axillary lymph nodes with the patient in the CT-P, level I nodes could receive a higher dose of radiation and levels II and III could be significantly underdosed as compared with treatment in the HP. The dose distribution for the CT-P was more homogeneous compared with that of the HP.
Coverage of the axillary lymph nodes varies significantly with arm position when using historical treatment planning techniques. Physicians should accurately contour the lymph node levels on the treatment planning CT and not rely on bony landmarks to design the axillary fields. CT-based treatment planning should be used to ensure adequate coverage of these nodes.
American journal of clinical oncology 06/2009; 32(4):381-6. · 2.21 Impact Factor
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ABSTRACT: The ability to determine the accuracy of the final prostate position within a determined action level threshold for image-guided proton therapy is unclear.
Three thousand one hundred ten images for 20 consecutive patients treated in 1 of our 3 proton prostate protocols from February to May of 2007 were analyzed. Daily kV images and patient repositioning were performed employing an action-level threshold (ALT) of > or = 2.5 mm for each beam. Isocentric orthogonal x-rays were obtained, and prostate position was defined via 3 gold markers for each patient in the 3 axes.
To achieve and confirm our action level threshold, an average of 2 x-rays sets (median 2; range, 0-4) was taken daily for each patient. Based on our ALT, we made no corrections in 8.7% (range, 0%-54%), 1 correction in 82% (41%-98%), and 2 to 3 corrections in 9% (0-27%). No patient needed 4 or more corrections. All patients were treated with a confirmed error of < 2.5 mm for every beam delivered. After all corrections, the mean and standard deviations were: anterior-posterior (z): 0.003 +/- 0.094 cm; superior-inferior (y): 0.028 +/- 0.073 cm; and right-left (x) -0.013 +/- 0.08 cm.
It is feasible to limit all final prostate positions to less than 2.5 mm employing an action level image-guided radiation therapy (IGRT) process. The residual errors after corrections were very small.
American journal of clinical oncology 03/2009; 32(2):180-6. · 2.21 Impact Factor
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ABSTRACT: The authors we evaluate the uncertainty in proton therapy dose distribution for prostate cancer due to organ displacement, varying penumbra width of proton beams, and the amount of rectal gas inside the rectum.
Proton beam treatment plans were generated for ten prostate patients with a minimum dose of 74.1 cobalt gray equivalent (CGE) to the planning target volume (PTV) while 95% of the PTV received 78 CGE. Two lateral or lateral oblique proton beams were used for each plan. The authors we investigated the uncertainty in dose to the rectal wall (RW) and the bladder wall (BW) due to organ displacement by comparing the dose-volume histograms (DVH) calculated with the original or shifted contours. The variation between DVHs was also evaluated for patients with and without rectal gas in the rectum for five patients who had 16 to 47 cc of visible rectal gas in their planning computed tomography (CT) imaging set. The uncertainty due to the varying penumbra width of the delivered protons for different beam setting options on the proton delivery system was also evaluated.
For a 5 mm anterior shift, the relative change in the RW volume receiving 70 CGE dose (V70) was 37.9% (5.0% absolute change in 13.2% of a mean V70). The relative change in the BW volume receiving 70 CGE dose (V70) was 20.9% (4.3% absolute change in 20.6% of a mean V70) with a 5 mm inferior shift. A 2 mm penumbra difference in beam setting options on the proton delivery system resulted in the relative variations of 6.1% (0.8% absolute change) and 4.4% (0.9% absolute change) in V70 of RW and BW, respectively. The data show that the organ displacements produce absolute DVH changes that generally shift the entire isodose line while maintaining the same shape. The overall shape of the DVH curve for each organ is determined by the penumbra and the distance of the target in beam's eye view (BEV) from the block edge. The beam setting option producing a 2 mm sharper penumbra at the isocenter can reduce the magnitude of maximal doses to the RW by 2% compared to the alternate option utilizing the same block margin of 7 mm. The dose to 0.1 cc of the femoral head on the distal side of the lateral-posterior oblique beam is increased by 25 CGE for a patient with 25 cc of rectal gas.
Variation in the rectal and bladder wall DVHs due to uncertainty in the position of the organs relative to the location of sharp dose falloff gradients should be accounted for when evaluating treatment plans. The proton beam delivery option producing a sharper penumbra reduces maximal doses to the rectal wall. Lateral-posterior oblique beams should be avoided in patients prone to develop a large amount of rectal gas.
Medical Physics 12/2008; 35(11):4800-7. · 2.83 Impact Factor
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Carlos Vargas,
Marcus Wagner,
Daniel Indelicato,
Amber Fryer,
David Horne,
Angela Chellini,
Craig McKenzie,
Paula Lawlor,
Chaitali Mahajan,
Zuofeng Li,
Liyong Lin,
Sameer Keole
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ABSTRACT: To determine the target coverage for proton therapy with and without image guidance and daily prebeam reorientation.
A total of 207 prostate positions were analyzed for 9 prostate cancer patients treated using our low-risk prostate proton therapy protocol (University of Florida Proton Therapy Institute 001). The planning target volume was defined as the prostate plus a 5-mm axial and 8-mm superoinferior extension. The prostate was repositioned using 5- and 10-mm shifts (anteriorly, inferiorly, posteriorly, and superiorly) and for Points A-D using a combination of 10-mm multidimensional movements (anteriorly or inferiorly; posteriorly or superiorly; and left or right). The beams were then realigned using the new prostate position. The prescription dose was 78 Gray equivalent (GE) to 95% of the planning target volume.
For small movements in the anterior, inferior, and posterior directions within the planning target volume (< or =5 mm), treatment realignment demonstrated small, but significant, improvements in the clinical target volume (CTV) coverage to the prescribed dose (78 GE). The anterior and posterior shifts also significantly increased the minimal CTV dose (Delta +1.59 GE). For prostate 10-mm movements in the inferior, posterior, and superior directions, the beam realignment produced larger and significant improvements for both the CTV V(78) (Delta +6.4%) and the CTV minimal dose (Delta +8.22 GE). For the compounded 10-mm multidimensional shifts, realignment significantly improved the CTV V(78) (Delta +11.8%) and CTV minimal dose (Delta +23.6 GE). After realignment, the CTV minimal dose was >76.6 GE (>98%) for all points (A-D).
Proton beam realignment after target shift will enhance CTV coverage for different prostate positions.
International Journal of Radiation OncologyBiologyPhysics 09/2008; 71(5):1322-8. · 4.11 Impact Factor
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Carlos Vargas,
Marcus Wagner,
Chaitali Mahajan,
Daniel Indelicato,
Amber Fryer,
Aaron Falchook,
David Horne,
Angela Chellini,
Craig McKenzie,
Paula Lawlor,
Zuofeng Li,
Liyong Lin,
Sameer Keole
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ABSTRACT: To determine the impact of prostate motion on dose coverage in proton therapy.
A total of 120 prostate positions were analyzed on 10 treatment plans for 10 prostate patients treated using our low-risk proton therapy prostate protocol (University of Florida Proton Therapy Institute 001). Computed tomography and magnetic resonance imaging T(2)-weighted turbo spin-echo scans were registered for all cases. The planning target volume included the prostate with a 5-mm axial and 8-mm superoinferior expansion. The prostate was repositioned using 5- and 10-mm one-dimensional vectors and 10-mm multidimensional vectors (Points A-D). The beam was realigned for the 5- and 10-mm displacements. The prescription dose was 78 Gy equivalent (GE).
The mean percentage of rectum receiving 70 Gy (V(70)) was 7.9%, the bladder V(70) was 14.0%, and the femoral head/neck V(50) was 0.1%, and the mean pelvic dose was 4.6 GE. The percentage of prostate receiving 78 Gy (V(78)) with the 5-mm movements changed by -0.2% (range, 0.006-0.5%, p > 0.7). However, the prostate V(78) after a 10-mm displacement changed significantly (p < 0.003) with different movements: 3.4% (superior), -5.6% (inferior), and -10.2% (posterior). The corresponding minimal doses were also reduced: 4.5 GE, -4.7 GE, and -11.7 GE (p < or = 0.003). For displacement points A-D, the clinical target volume V(78) coverage had a large and significant reduction of 17.4% (range, 13.5-17.4%, p < 0.001) in V(78) coverage of the clinical target volume. The minimal prostate dose was reduced 33% (25.8 GE), on average, for Points A-D. The prostate minimal dose improved from 69.3 GE to 78.2 GE (p < 0.001) with realignment for 10-mm movements.
The good dose coverage and low normal doses achieved for the initial plan was maintained with movements of < or = 5 mm. Beam realignment improved coverage for 10-mm displacements.
International Journal of Radiation OncologyBiologyPhysics 05/2008; 70(5):1492-501. · 4.11 Impact Factor
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Carlos Vargas,
Amber Fryer,
Chaitali Mahajan,
Daniel Indelicato,
David Horne,
Angela Chellini,
Craig McKenzie,
Paula Lawlor,
Randal Henderson,
Zuofeng Li,
Liyong Lin,
Kenneth Olivier,
Sameer Keole
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ABSTRACT: The contrast in dose distribution between proton radiotherapy (RT) and intensity-modulated RT (IMRT) is unclear, particularly in regard to critical structures such as the rectum and bladder.
Between August and November 2006, the first 10 consecutive patients treated in our Phase II low-risk prostate proton protocol (University of Florida Proton Therapy Institute protocol 0001) were reviewed. The double-scatter proton beam plans used in treatment were analyzed for various dosimetric endpoints. For all plans, each beam dose distribution, angle, smearing, and aperture margin were optimized. IMRT plans were created for all patients and simultaneously analyzed. The IMRT plans were optimized through multiple volume objectives, beam weighting, and individual leaf movement. The patients were treated to 78 Gray-equivalents (GE) in 2-GE fractions with a biologically equivalent dose of 1.1.
All rectal and rectal wall volumes treated to 10-80 GE (percentage of volume receiving 10-80 GE [V(10)-V(80)]) were significantly lower with proton therapy (p < 0.05). The rectal V(50) was reduced from 31.3% +/- 4.1% with IMRT to 14.6% +/- 3.0% with proton therapy for a relative improvement of 53.4% and an absolute benefit of 16.7% (p < 0.001). The mean rectal dose decreased 59% with proton therapy (p < 0.001). For the bladder and bladder wall, proton therapy produced significantly smaller volumes treated to doses of 10-35 GE (p < 0.05) with a nonsignificant advantage demonstrated for the volume receiving < or =60 GE. The bladder V(30) was reduced with proton therapy for a relative improvement of 35.3% and an absolute benefit of 15.1% (p = 0.02). The mean bladder dose decreased 35% with proton therapy (p = 0.002).
Compared with IMRT, proton therapy reduced the dose to the dose-limiting normal structures while maintaining excellent planning target volume coverage.
International Journal of Radiation OncologyBiologyPhysics 04/2008; 70(3):744-51. · 4.11 Impact Factor
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Carlos Vargas,
Chaitali Mahajan,
Amber Fryer,
Daniel Indelicato,
Randal H Henderson,
Craig McKenzie,
David Horne,
Angela Chellini,
Paula Lawlor,
Zuofeng Li,
Kenneth Oliver,
Sameer Keole
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ABSTRACT: To describe dose-volume values with the use of water alone vs. a rectal balloon (RB) for the treatment of prostate cancer with proton therapy.
We analyzed 30 proton plans for 15 patients who underwent CT and MRI scans with an RB or water alone. Simulation was performed with a modified MRI endorectal coil and an RB with 100 mL of water or water alone. Doses of 78-82 gray equivalents were prescribed to the planning target volume. The two groups were compared for three structures: rectum, rectal wall (RW), and rectal wall 7 cm (RW7) at the level of the planning target volume.
Rectum and RW volumes radiated to low, intermediate, and high doses were small: rectum V10, 33.7%; V50, 17.3%; and V70, 10.2%; RW V10, 32.4%; V50, 20.4%; and V70, 14.6%. The RB effectively increased the rectal volume for all cases (139.8 +/- 44.9 mL vs. 217.7 +/- 32.2 mL (p < 0.001). The RB also decreased the volume of the rectum radiated to doses V10-V65 (p < or = 0.05); RW for V10-V50; and RW7 for V10-V35. An absolute rectum V50 improvement >5% was seen for the RB in 5 of 15 cases, for a benefit of 9.2% +/- 2.3% compared with 2.4% +/- 1.3% for the remaining 10 cases (p < 0.001). Similar benefit was seen for the rectal wall. No benefit was seen for doses > or =70 gray equivalents for the rectum, RW, or RW7. No benefit of < or =1% was seen with an RB in 46% for the rectum V70 and in 40% for the rectal wall V70.
Rectum and rectal wall doses with proton radiation were low whether using water or an RB. Selected patients will have a small but significant advantage with an RB; however, water alone was well tolerated and will be an alternative for most patients.
International Journal of Radiation OncologyBiologyPhysics 12/2007; 69(4):1110-6. · 4.11 Impact Factor
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ABSTRACT: To identify factors predictive for chronic urinary toxicity secondary to high-dose adaptive three-dimensional conformal radiation.
From 1999 to 2002, 331 consecutive patients with clinical Stage II-III prostate cancer were prospectively treated (median dose, 75.6 Gy). The bladder was contoured, and the bladder wall was defined as the outer 3 mm of the bladder solid volume. Toxicity was quantified according to the National Cancer Institute Common Toxicity Criteria 2.0. Median follow-up was 1.6 years.
The 3-year rates of Grade > or =2 and Grade 3 chronic urinary toxicity were 17.0% and 3.6%, respectively. Prostate volume, confidence-limited patient-specific planning target volume, bladder wall volume, and acute urinary toxicity were all found to be accurate predictors for chronic urinary toxicity. The volume of bladder wall receiving > or =30 Gy (V30) and > or =82 Gy (V82), along with prostate volume, were all clinically useful predictors of Grade > or =2 and Grade 3 chronic urinary toxicity and chronic urinary retention. Both Grade > or =2 (p = 0.001) and Grade 3 (p = 0.03) acute urinary toxicity were predictive for the development of Grade > or =2 (p = 0.001, p = 0.03) and Grade 3 (p = 0.05, p < 0.001) chronic urinary toxicity. On Cox multivariate analysis the development of acute toxicity was independently predictive for the development of both Grade > or =2 and Grade 3 chronic urinary toxicity.
Acute urinary toxicity and bladder wall dose-volume endpoints are strong predictors for the development of subsequent chronic urinary toxicity. Our recommendation is to attempt to limit the bladder wall V30 to <30 cm(3) and the V82 to <7 cm(3) when possible. If bladder wall information is not available, bladder solid V30 and V82 may be used.
International Journal of Radiation OncologyBiologyPhysics 12/2007; 69(4):1100-9. · 4.11 Impact Factor
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ABSTRACT: The Berg muscle-based categorization of axillary lymph node location (commonly referred to as levels I, II, and III) was used extensively by pathologists and surgeons to describe the extent of axillary node dissection in breast cancer patients. However, its reproducibility with different arm positions and utility in 3-dimensional radiation treatment planning hasn't been tested.
Computed tomography scans were observed in 16 patients in 2 positions: historical position (HP), ipsilateral arm abducted 90 degrees to the body axis; standard position (SP), arms above head. The volume, contents, and location of Berg lymph node levels (LNL) and the location of lymph nodes, surgical clips, pectoral muscles, and vascular structures relative to reference points were compared.
From HP to SP there was no difference in LNL volumes. However, if measured from an anatomic landmark, the third thoracic vertebra (T3), LNL position varied: level I, an average of 23.1 mm anteriorly, P < 0.01; level II, 7.5 mm medially, P = 0.04; level III, 18.8 mm medially, P = 0.05. Using T3 as a reference: pectoralis major and minor muscles displaced medially (23.9 mm, P < 0.01 and 7.5 mm, P = 0.09) and anteriorly (18.2 mm, P < 0.01 and 11.2 mm, P < 0.01); axillary (18.0 mm, P < 0.01), subscapular (25.4 mm, P < 0.01), and lateral thoracic (8.4 mm, P < 0.01) vessels displaced anteriorly; axillary vessels displaced also medially (15.1 mm, P = 0.03). Disagreements in LN coverage with changes in arm position were observed in 60% (LNs) and 66% (clips) for level II.
Surgeons, radiologists, and radiation oncologists should be aware that LNL coverage based on muscle boundaries varies significantly with arm position changes, making objective comparisons of information collected in different arm positions unreliable.
American journal of clinical oncology 03/2007; 30(1):69-77. · 2.21 Impact Factor
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ABSTRACT: Accurate modeling of rectal complications based on dose-volume histogram (DVH) data are necessary to allow safe dose escalation in radiotherapy of prostate cancer. We applied different equivalent uniform dose (EUD)-based and dose-volume-based normal tissue complication probability (NTCP) models to rectal wall DVHs and follow-up data for 319 prostate cancer patients to identify the dosimetric factors most predictive for Grade > or = 2 rectal bleeding.
Data for 319 patients treated at the William Beaumont Hospital with three-dimensional conformal radiotherapy (3D-CRT) under an adaptive radiotherapy protocol were used for this study. The following models were considered: (1) Lyman model and (2) logit-formula with DVH reduced to generalized EUD, (3) serial reconstruction unit (RU) model, (4) Poisson-EUD model, and (5) mean dose- and (6) cutoff dose-logistic regression model. The parameters and their confidence intervals were determined using maximum likelihood estimation.
Of the patients, 51 (16.0%) showed Grade 2 or higher bleeding. As assessed qualitatively and quantitatively, the Lyman- and Logit-EUD, serial RU, and Poisson-EUD model fitted the data very well. Rectal wall mean dose did not correlate to Grade 2 or higher bleeding. For the cutoff dose model, the volume receiving > 73.7 Gy showed most significant correlation to bleeding. However, this model fitted the data more poorly than the EUD-based models.
Our study clearly confirms a volume effect for late rectal bleeding. This can be described very well by the EUD-like models, of which the serial RU- and Poisson-EUD model can describe the data with only two parameters. Dose-volume-based cutoff-dose models performed worse.
International Journal of Radiation OncologyBiologyPhysics 03/2007; 67(4):1066-73. · 4.11 Impact Factor
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ABSTRACT: To quantify changes in patients' diaphragm motion pattern over the course of radiotherapy and to evaluate the implications of these changes for 4D radiotherapy.
From January 2004 to October 2004, 10 patients with lung malignancies treated at our department underwent weekly respiratory motion verification during the course of external beam radiation. An onboard kilovoltage imaging system was used to acquire fluoroscopy weekly for patients with lung neoplasms. The diaphragm position as a function of time was extracted automatically from the fluoroscopy and used to calculate the daily mean and daily SD of motion. The diaphragm position was related to both a bony reference point and machine isocenter. Changes in the daily mean and daily SD in relation to the reference (first day) daily mean and reference daily SD were measured.
The mean change in the daily mean was 0.32 mm+/-6.11 mm in relation to the bony reference point and 0.38 mm+/-6.28 mm in relation to isocenter. The mean change in the daily SD was 0.91 mm+/-1.81 mm. The mean systematic change in the daily mean was 4.97 mm, and the mean random change in the daily mean was 3.61 mm.
Daily verification of 4D radiotherapy techniques to assess the necessity of online set-up correction may be required due to the large change in the mean diaphragm position observed for these patients. However, the variation of the daily SD was small for most patients. Adaptive adjustment of the margin may be necessary for those patients with larger variation of the daily SD.
Radiotherapy and Oncology 04/2006; 78(3):326-31. · 5.58 Impact Factor
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ABSTRACT: We reviewed our institution's experience treating patients with ductal carcinoma in situ (DCIS) of the breast to determine risk factors for ipsilateral breast tumor recurrence (IBTR) and cause-specific survival (CSS) after breast-conserving therapy (BCT) or mastectomy.
Between 1981 and 1999, 410 cases of DCIS (405 patients) were treated at our institution; 367 were managed with breast-conserving surgery (54 with lumpectomy alone and 313 with adjuvant radiation therapy (RT) [median dose, 45 Gy]). Of these 313 patients, 298 received also a supplemental boost of RT to the lumpectomy cavity (median dose, 16 Gy). Forty-three patients underwent mastectomy; 2 (5%) received adjuvant RT to the chest wall. A true recurrence/marginal miss (TR/MM) IBTR was defined as failure within or adjacent to the tumor bed in patients undergoing BCT. Median follow-up for all patients was 7 years (mean: 6.1 years).
Thirty patients (8.2%) experienced an IBTR after BCT (25 [8%] after RT, 5 [9.3%] after no RT), and 2 patients (4.7%) developed a chest wall recurrence after mastectomy. Of the 32 local failures, 20 (63%) were invasive (18/30 [60%] after BCT and 2/2 [100%] after mastectomy), and 37% were DCIS alone. Twenty-four (80%) of the IBTRs were classified as TR/MM. The 10-year freedom from local failure, CSS, and overall survival after BCT or mastectomy were 89% vs. 90% (p = 0.4), 98% vs. 100% (p = 0.7), and 89% vs. 100% (p = 0.3), respectively. Factors associated with IBTR on Cox multivariate analysis were younger age (p = 0.02, hazard ratio [HR] 1.06 per year), electron boost energy < or = 9 MeV (p = 0.03, HR 1.41), final margins < or = 2 mm (p = 0.007; HR, 3.65), and no breast radiation (p = 0.002, HR 5.56). On Cox univariate analysis for BCT patients, IBTR, TR/MM failures, and predominant nuclear Grade 3 were associated with an increased risk of distant metastases and a reduced CSS.
After treatment for DCIS, 10-year rates of local control, CSS, and overall survival were similar after mastectomy and BCT. Young age (<45 years), close/positive margins (< or = 2 mm), no breast radiation, and lower electron boost energies (< or = 9 MeV) were associated with IBTR. Local failure and predominant nuclear Grade 3 were found to have a small (4%-12%) but statistically significantly negative impact on the rates of distant metastasis and CSS. These results suggest that optimizing local therapy (surgery and radiation) is crucial to improve local control and CSS in patients treated with DCIS.
International Journal of Radiation OncologyBiologyPhysics 01/2006; 63(5):1514-21. · 4.11 Impact Factor
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ABSTRACT: In our Phase II prostate cancer Adaptive Radiation Therapy (ART) study, the highest possible dose was selected on the basis of normal tissue tolerance constraints. We analyzed rectal toxicity rates in different dose levels and treatment groups to determine whether equivalent toxicity rates were achieved as hypothesized when the protocol was started.
From 1999 to 2002, 331 patients with clinical stage T1 to T3, node-negative prostate cancer were prospectively treated with three-dimensional conformal adaptive RT. A patient-specific confidence-limited planning target volume was constructed on the basis of 5 CT scans and 4 sets of electronic portal images after the first 4 days of treatment. For each case, the rectum (rectal solid) was contoured in its entirety. The rectal wall was defined by use of a 3-mm wall thickness (median volume: 29.8 cc). The prescribed dose level was chosen using the following rectal wall dose constraints: (1) Less than 30% of the rectal wall volume can receive more than 75.6 Gy. (2) Less than 5% of the rectal wall can receive more than 82 Gy. Low-risk patients (PSA < 10, Stage < or = T2a, Gleason score < 7) were treated to the prostate alone (Group 1). All other patients, intermediate and high risk, where treated to the prostate and seminal vesicles (Group 2). The risk of chronic toxicity (NCI Common Toxicity Criteria 2.0) was assessed for the different dose levels prescribed. HIC approval was acquired for all patients. Median follow-up was 1.6 years.
Grade 2 chronic rectal toxicity was experienced by 34 patients (10%) (9% experienced rectal bleeding, 6% experienced proctitis, 3% experienced diarrhea, and 1% experienced rectal pain) at a median interval of 1.1 year. Nine patients (3%) experienced grade 3 or higher chronic rectal toxicity (1 Grade 4) at a median interval of 1.2 years. The 2-year rates of Grade 2 or higher and Grade 3 or higher chronic rectal toxicity were 17% and 3%, respectively. No 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).
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.
International Journal of Radiation OncologyBiologyPhysics 09/2005; 63(1):141-9. · 4.11 Impact Factor
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ABSTRACT: Prostate brachytherapy is an established treatment modality in early stage prostate cancer. We retrospectively reviewed our experience with low dose rate (LDR) and high dose rate (HDR) brachytherapy as a single treatment modality for early prostate cancer with emphasis on chronic toxicity.
From June 1996 to August 2003, 253 patients with stage II prostate cancer, prostate specific antigen less than 12 and Gleason score less than 7 were treated with brachytherapy alone at our institution. A total of 92 patients underwent HDR brachytherapy with 192Ir, while 161 underwent LDR brachytherapy with 103Pd. HDR minimum prostate dose was 38 Gy, delivered in 4 fractions with a single implant during 36 hours. For HDR we used real-time dynamic 3-dimensional ultrasound base dosimetry. For 103Pd seed implants the dose was 120 Gy using selective peripheral weighted dose distribution. Treatment was given based on patient preference after pretreatment transrectal ultrasound. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria 2.0. Median followup in all 253 cases was 2.9 years.
In all patients the rate of 3-year urinary toxicity grade 2 or greater and grade 3 or greater was 26% and 6.9%, which was not significantly different between HDR and LDR (p = 0.3 and 0.4, respectively). However, grade 1 urogenital toxicity was lower for HDR (p = 0.002). The 3-year grade 2 rectal toxicity rate was 0.8% with no grade 3 or greater events, which was and similar in the HDR and LDR groups (1% and 0.6%, respectively). No cancer related deaths occurred and 4-year overall survival was 99% for HDR and 96.4% for LDR (p = 0.4). The 3-year American Society for Therapeutic Radiology and Oncology biochemical control rate was 90% for LDR and 93% for HDR. Cox multivariate analysis for grade 2 or greater urinary toxicity was significant for the use of 14 or greater needles (HR 6.1, p = 0.02) and hormonal therapy (HR 2.2, p = 0.02). In the absence of risk factors the 4-year grade 2 or greater urinary toxicity rate was 7% vs 65% if the 2 risk factors were present (p <0.001). Impotence crude rates were 18.3% for HDR and 41.3% for LDR (p = 0.002).
HDR and LDR chronic urinary toxicity grade 2 or greater rates were equivalent. However, grade 1 was lower for HDR. The impotence rate was decrease by half with HDR. Neoadjuvant hormonal therapy and 14 or greater needles were significantly associated with increased chronic urinary toxicity on multivariate analysis.
The Journal of Urology 09/2005; 174(3):882-7. · 3.75 Impact Factor
