Rajat J. Kudchadker

Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

OBJECTIVE To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. METHODS AND MATERIALS Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. RESULTS 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). CONCLUSIONS Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this hypofractionation regimen.

A Comprehensive Comparison of IMRT and VMAT Plan Quality for Prostate Cancer Treatment

PURPOSE We performed a comprehensive comparative study of the plan quality between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) for the treatment of prostate cancer. METHODS AND MATERIALS Eleven patients with prostate cancer treated at our institution were randomly selected for this study. For each patient, a VMAT plan and a series of IMRT plans using an increasing number of beams (8, 12, 16, 20, and 24 beams) were examined. All plans were generated using our in-house-developed automatic inverse planning (AIP) algorithm. An existing eight-beam clinical IMRT plan, which was used to treat the patient, was used as the reference plan. For each patient, all AIP-generated plans were optimized to achieve the same level of planning target volume (PTV) coverage as the reference plan. Plan quality was evaluated by measuring mean dose to and dose-volume statistics of the organs at risk, especially the rectum, from each type of plan. RESULTS For the same PTV coverage, the AIP-generated VMAT plans had significantly better plan quality in terms of rectum sparing than the eight-beam clinical and AIP-generated IMRT plans (p < 0.0001). However, the differences between the IMRT and VMAT plans in all the dosimetric indices decreased as the number of beams used in IMRT increased. IMRT plan quality was similar or superior to that of VMAT when the number of beams in IMRT was increased to a certain number, which ranged from 12 to 24 for the set of patients studied. The superior VMAT plan quality resulted in approximately 30% more monitor units than the eight-beam IMRT plans, but the delivery time was still less than 3 min. CONCLUSIONS Considering the superior plan quality as well as the delivery efficiency of VMAT compared with that of IMRT, VMAT may be the preferred modality for treating prostate cancer.

Late rectal complications after prostate brachytherapy for localized prostate cancer

This review of the literature on late rectal complications after prostate brachytherapy indicated that it is a highly effective treatment modality for patients with clinically localized prostate cancer but can cause chronic radiation proctitis. The most common manifestation of chronic radiation proctitis was anterior rectal wall bleeding, which often occurred within the first 2 years after brachytherapy. It is interesting to note that the rates of late rectal morbidity appear to have declined over time, which may reflect improvements in implantation techniques and imaging. Rectal biopsy as part of the workup to evaluate rectal bleeding can lead to rectal fistula and the need for colostomy, a rare but major complication. The authors recommend 1) screening colonoscopy before brachytherapy for patients who have not had a screening colonoscopy within the preceding 3 years to rule out colorectal malignancies and, thus, facilitate conservative management should rectal bleeding occur; 2) lifestyle modifications during treatment to limit exposure of the rectum to radiation; and 3) conservative management for rectal bleeding that occurs within 2 years after brachytherapy. Cancer 2009.

QUANTIFICATION OF PROSTATE AND SEMINAL VESICLE INTERFRACTION VARIATION DURING IMRT

PURPOSE To quantify the interfraction variability in prostate and seminal vesicle (SV) positions during a course of intensity-modulated radiotherapy (IMRT) using an integrated computed tomography (CT)-linear accelerator system and to assess the impact of rectal and bladder volume changes. METHODS AND MATERIALS We studied 15 patients who had undergone IMRT for prostate carcinoma. Patients had one pretreatment planning CT scan followed by three in-room CT scans per week using a CT-on-rails system. The prostate, bladder, rectum, and pelvic bony anatomy were contoured in 369 CT scans. Using the planning CT scan as a reference, the volumetric and positional changes were analyzed in the subsequent CT scans. RESULTS For all 15 patients, the mean systematic internal prostate and SV variation was 0.1 +/- 4.1 mm and 1.2 +/- 7.3 mm in the anteroposterior axis, -0.5 +/- 2.9 mm and -0.7 +/- 4.5 mm in the superoinferior axis, and 0.2 +/- 0.9 mm and -0.9 +/- 1.9 mm in the lateral axis, respectively. The mean magnitude of the three-dimensional displacement vector was 4.6 +/- 3.5 mm for the prostate and 7.6 +/- 4.7 mm for the SVs. The rectal and bladder volume changes during treatment correlated with the anterior and superior displacement of the prostate and SVs. CONCLUSION The dominant prostate and SV variations occurred in the anteroposterior and superoinferior directions. The systematic prostate and SV variation between the treatment planning CT and daily therapy as a result of the rectal and bladder volume changes emphasizes the need for daily directed target localization and/or immobilization techniques.

Urinary Side Effects and Complications After Permanent Prostate Brachytherapy: The MD Anderson Cancer Center Experience

OBJECTIVES To evaluate acute and long-term urinary morbidity after permanent prostate brachytherapy at a single tertiary care center. To minimize the risk of long-term urinary morbidity, it is important for clinicians to be able to distinguish acute urinary side effects after prostate brachytherapy from longer-term treatment-related urinary complications. METHODS The medical records of 351 consecutive patients who underwent prostate brachytherapy at the MD Anderson Cancer Center between 1998 and 2006 were analyzed. To evaluate the short-term urinary side effects, the Expanded Prostate Cancer Index Composite questionnaire was administered at baseline and at 1, 4, 8, and 12 months. Long-term urinary complications were scored using a modified Radiation Therapy Oncology Group scale. RESULTS All 4 urinary subdomain scores evaluating acute urinary side effects after treatment (bother, function, incontinence, and irritation or obstruction) had returned to baseline levels by 8 months after implantation. At 5 years, the cumulative risks of late urinary complications by grade were 8.6% for grade 1 complications, 6.5% for grade 2, 1.7% for grade 3%, and 0.5% for grade 4. The most common grade 2 late urinary complications were urethral stricture (4 patients), incontinence requiring daily pads (3 patients), and intermittent hematuria (3 patients). Grade 3 complications were urinary retention requiring self-catheterization (2 patients) and severe frequency with dysuria (2 patients). The only grade 4 event was severe hemorrhagic cystitis. CONCLUSIONS Short-term urinary side effects after prostate brachytherapy are common, follow a predictable course, and typically resolve within 1 year. Conservative management of short-term urinary side effects is recommended to minimize the risk of long-term urinary complications.

Utilization of custom electron bolus in head and neck radiotherapy

Conventional methods of treating superficial head and neck tumors, such as the wedge pair technique or the use of multiple electron fields of varying energies, can result in excellent tumor control. However, in some cases, these techniques irradiate healthy tissue unnecessarily and/or create hot and cold spots injunction regions, particularly in patients with complex surface contour modification or varying planning target volume (PTV) thickness. The objective of this work is to demonstrate how bolus electron conformal therapy can be used for these patients. Two patients treated using this technique are presented. The first patient was diagnosed with malignant fibrous histiocytoma involving the right ear concha and was treated with 12‐MeV electrons. The second patient was diagnosed with acinic cell carcinoma of the left parotid gland and was treated with 20‐MeV electrons after having undergone a complete parotidectomy. Each patients bolus was designed using bolus design tools implemented in an in‐house treatment‐planning system (TPS). The bolus was fabricated using a computer‐controlled milling machine. As part of the quality assurance process to ensure proper fabrication and placement of the bolus, the patients underwent a second computed tomography (CT) scan with the bolus in place. Using that data, the final dose distribution was computed using the Philips Pinnacle 3 TPS (Philips Medical Systems, Andover, MA). Results showed that the 90% isodose surface conformed well to the PTV and that the dose to critical structures such as cord, brain, and lung was well below tolerance limits. Both patients showed no evidence of disease six months post‐radiotherapy. In conclusion, electron bolus conformal therapy is a viable option for treating head and neck tumors, particularly patients having a variable thickness PTV or surface anatomy with surgical defects. PACS number(s): 87.53.Kn

Electron conformal radiotherapy using bolus and intensity modulation

PURPOSE Conformal electron beam therapy can be delivered using shaped bolus, which varies the penetration of the electrons across the incident beam so that the 90% isodose surface conforms to the distal surface of the planning target volume (PTV). Previous use of this modality has shown that the irregular proximal surface of the bolus causes the dose heterogeneity in the PTV to increase from 10%, the typical dose spread of a flat-water surface to approximately 20%. The present work evaluates the ability to restore dose homogeneity by varying the incident electron intensity. METHODS AND MATERIALS Three patients, one each with chest wall, thorax, and head-and-neck cancer, were planned using electron conformal therapy with bolus, with and without intensity modulation. Resulting dose distributions and dose-volume histograms were compared with non-intensity-modulated bolus plans. RESULTS In all cases, the DeltaD(90%-10%) for the PTV was reduced; for example, for the head-and-neck case, the DeltaD(90%-10%) for the PTV was reduced from 14.9% to 9.2%. This reduction in dose spread is a direct result of intensity modulation. CONCLUSIONS The results showed that intensity-modulated electron beams could significantly improve the dose homogeneity in the PTV for patients treated with electron conformal therapy using shaped bolus.

Dose perturbations and image artifacts caused by carbon-coated ceramic and stainless steel fiducials used in proton therapy for prostate cancer

Image-guided radiation therapy using implanted fiducial markers is a common solution for prostate localization to improve targeting accuracy. However, fiducials that are typically used for conventional photon radiotherapy cause large dose perturbations in patients who receive proton radiotherapy. A proposed solution has been to use fiducials of lower atomic number (Z) materials to minimize this effect in tissue, but the effects of these fiducials on dose distributions have not been quantified. The objective of this study was to analyze the magnitude of the dose perturbations caused by select lower-Z fiducials (a carbon-coated zirconium dioxide fiducial and a plastic-coated stainless steel fiducial) and compare them to perturbations caused by conventional gold fiducials. Sets of phantoms were used to assess select components of the effects on dose. First, the fiducials were assessed for radiographic visibility using both conventional computed tomography (CT) and an on-board kilovoltage imaging device at our proton therapy center. CT streak artifacts from the fiducials were also measured in a separate phantom. Second, dose perturbations were measured downstream of the fiducials using radiochromic film. The magnitude of dose perturbation was characterized as a function of marker material, implantation depth and orientation with respect to the beam axis. The radiographic visibility of the markers was deemed to be acceptable for clinical use. The dose measurements showed that the perpendicularly oriented zirconium dioxide and stainless steel fiducials located near the center of modulation of the proton beam perturbed the dose by less than 10%, but that the same fiducials in a parallel orientation near the end of the range of the beam could perturb the dose by as much as 38%. This suggests that carbon-coated and stainless steel fiducials could be used in proton therapy if they are located far from the end of the range of the beam and if they are oriented perpendicular to the beam axis.

A Novel MRI Marker for Prostate Brachytherapy

PURPOSE Magnetic resonance imaging (MRI) is the optimal imaging modality for the prostate and surrounding critical organ structures. However, on MRI, the titanium radioactive seeds used for brachytherapy appear as black holes (negative contrast) and cannot be accurately localized. We sought to develop an encapsulated contrast agent marker (ECAM) with high-signal intensity on MRI to permit accurate localization of radioactive seeds with MRI during and after prostate brachytherapy. METHODS AND MATERIALS We investigated several agents with paramagnetic and superparamagnetic properties. The agents were injected into titanium, acrylic, and glass seeds, which were linked together in various combinations and imaged with MRI. The agent with the greatest T1-weighted signal was tested further in a canine prostate and agarose phantom. Studies were performed on a 1.5-T clinical MRI scanner. RESULTS The cobalt-chloride complex contrast (C4) agent with stoichiometry (CoCl(2))(0.8)(C(2)H(5)NO(2))(0.2) had the greatest T1-weighted signal (positive contrast) with a relaxivity ratio >1 (r(2)/r(1) = 1.21 +/- 0.29). Acrylic-titanium and glass-titanium seed strands were clearly visualized with the encapsulated contrast agent marker. CONCLUSION We have developed a novel ECAM that permits positive identification of the radioactive seeds used for prostate brachytherapy on MRI. Preclinical in vitro phantom studies and in vivo canine studies are needed to further optimize MRI sequencing techniques to facilitate MRI-based dosimetry.

Effectiveness of Using Fewer Implanted Fiducial Markers for Prostate Target Alignment

PURPOSE To evaluate the impact of the number and location of intraprostatic fiducial markers on the accuracy and reproducibility of daily prostate target alignment and to evaluate the migration of such markers. METHODS AND MATERIALS Three gold fiducial markers were implanted transrectally under ultrasound guidance near the apex, middle, and base of the prostate in 10 prostate cancer patients. The patients had pretreatment in-room computed tomography (CT) scans three times a week, for approximately 25 CT scans per patient during the 8-week treatment course. A total of 1280 alignments were performed using different alignment scenarios: whole-prostate soft tissue alignment (the gold standard), bone alignment, and seven permutations of alignments using one, two, or three fiducial markers. The results of bone alignment and fiducial alignment were compared with the results of whole-prostate alignment. Fiducial migration was also evaluated. RESULTS Single-fiducial-marker alignment was more accurate and reproducible than bone alignment. However, due to organ deformation, single fiducial markers did not always reliably represent the position of the entire prostate. The use of two-fiducial combinations was more accurate and reproducible than single-fiducial alignment, and use of all three fiducials was the best. Use of an apex fiducial together with a base fiducial rivaled the use of all three fiducials markers together. Fiducial migration was minimal. CONCLUSIONS The number and the location of implanted fiducial markers affect the accuracy and reliability of daily prostate target alignment. The use of two or more fiducial markers is recommended.