Daily patient setup error in prostate image guided radiation therapy with fiducial-based kilovoltage onboard imaging and conebeam computed tomography.

BACKGROUND: This study examined the interfraction setup error in patients undergoing prostate radiotherapy using fiducial markers and on-board imaging. METHODS: Patients (n=53) were aligned to the treatment isocenter by laser followed by orthogonal kilovoltage (kV) radiographs to visualize bony anatomy and implanted fiducial markers. The magnitude and direction of couch shifts for isocenter correction required was determined by image registration for bony anatomy and fiducial markers. Twice weekly, 25 of the 53 patients also underwent conebeam computed tomography (CBCT) to measure any residual error in patient positioning. Based on individual coordinate shifts from CBCT, a net three-dimensional (3D) residual shift magnitude vector R was calculated. RESULTS: The average couch shifts were 0.26 and 0.40 cm in inferior direction and 0.25 and 0.33 cm in superior direction for alignments made with bony anatomy and fiducial markers, respectively (P<0.0001). There were no significant differences noted in the vertical or lateral planes between the two image registration methods. In subset of 25 patients, no residual shift from fiducial plain film set up was required with CBCT matching in 66.5%, 52.4% and 57.9% of fractions for longitudinal, vertical and lateral planes, respectively, with majority (79%) of patients having a net residual 3D shifts of <0.3 cm. The use of CBCT increased average treatment time by approximately 6 min compared to kV radiographs alone. CONCLUSIONS: The residual setup errors following daily kV image guided localization, as determined by CBCT, were small, which demonstrates high accuracy of kV localization when fiducial markers are present.

Acute gastrointestinal toxicity and tumor response with preoperative intensity modulated radiation therapy for rectal cancer.

BACKGROUND: Preoperative chemoradiotherapy (preopCRT) for locally advanced rectal cancer is associated with grade 3 or higher acute gastrointestinal (GI) toxicity. This study was conducted to determine whether intensity-modulated radiation therapy (IMRT) significantly reduces acute GI toxicity, compared to 3-dimensional conformal RT (3D-CRT) in preopCRT for rectal cancer. METHODS: A retrospective analysis was conducted of 48 patients treated between January 2002 and August 2010 with preopCRT for rectal cancer. 3D-CRT or IMRT was administered at a planned dose of 45-50.4 Gy to patients positioned prone on a bowel-displacement device. Data regarding patient and tumor characteristics, treatment, acute toxicity, and tumor response were collected. Comparisons of acute toxicity and treatment response between 3D-CRT and IMRT were performed with the Chi-square or Fisher's exact test. RESULTS: There were no significant differences in radiation dose, median age, race, gender, stage, type of concurrent chemotherapy, pathologic complete response (pCR), or type of surgery (lower anterior or abdominal perineal resection) between 3D-CRT and IMRT. There was a significant reduction in grade 2 or higher GI toxicity (3D-CRT, 60.7%; IMRT, 30%; P = .036) and grade 2 or higher diarrhea (3D-CRT, 42.8%; IMRT, 10%; P = .014). Two patients who underwent 3D-CRT required a treatment break (grade 3 diarrhea and grade 3 dehydration). Radiation duration was significantly less (IMRT, 35 days; 3D-CRT, 39 days; P ≤ .0001). pCR rates were 16.7% for 3D-CRT and 21.4% for IMRT (nonsignificant [NS]); pCR+microscopic residual rates were 57.1% for IMRT and 27.8% for 3D-CRT (P = .093). CONCLUSION: Maximal bowel displacement with IMRT yields favorable acute GI toxicity and pathologic downstaging profiles, as compared to 3D-CRT in preoperative CRT for rectal cancer and warrants further prospective investigation.

Cone-beam computed tomography image guided therapy to evaluate lumpectomy cavity variation before and during breast radiotherapy.

The purpose of this study was to evaluate the rate of change (RoC) in the size of the lumpectomy cavity (LC) before and during breast radiotherapy (RT) using cone-beam computed tomography (CBCT), relative to the initial LC volume at CT simulation (CTVLC) and timing from surgery. A prospective institutional review board-approved study included 26 patients undergoing breast RT: 20 whole breast irradiation (WBI) patients and six partial breast irradiation (PBI) patients, with surgical clips outlining the LC. The patients underwent CT simulation (CTsim) followed by five CBCTs during RT, once daily for PBI and once weekly for WBI. The distance between surgical clips and their centroid (D) acted as a surrogate for LC size. The RoC of the LC size, defined as the percentage change of D between two scans divided by the time interval in days between the scans, was calculated before (CTsim to CBCT1) and during RT (CBCT1 to CBCT5). The mean RoC of D for all patients before starting RT was -0.25%/day (range, -1.3 to 1.4) and for WBI patients during RT was -0.15%/day (range, -0.45 to 0.40). Stratified by median CTVLC, the RoC before RT for large CTVLC group (≥ 25.7 cc) was 15 times higher (-0.47%/day) than for small CTVLC group (< 25.7 cc) (-0.03%/day), p = 0.06. For patients undergoing CTsim < 42 days from surgery, the RoC before RT was -0.43%/day compared to -0.07%/day for patients undergoing CTsim ≥ 42 days from surgery, p = 0.12. For breast cancer RT, the rate of change of the LC is affected by the initial cavity size and the timing from surgery. Resimulation closer to the time of boost treatment should be considered in patients who are initially simulated within six weeks of surgery and/or with large CTVLC.

RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal.

PURPOSE: A multi-institutional phase 2 trial assessed the utility of dose-painted intensity modulated radiation therapy (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% compared with the conventional radiation/5FU/MMC arm from RTOG 9811. METHODS AND MATERIALS: T2-4N0-3M0 anal cancer patients received 5FU and MMC on days 1 and 29 of DP-IMRT, prescribed per stage: T2N0, 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3, 45 Gy elective nodal, 50.4 Gy ≤ 3 cm or 54 Gy >3 cm metastatic nodal and 54 Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator's ability to perform DP-IMRT. RESULTS: Of 63 accrued patients, 52 were evaluable. Tumor stage included 54% II, 25% IIIA, and 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=.032), grade 3+ gastrointestinal, 21% (9811 36%, P=.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81% required DP-IMRT replanning, and final review revealed only 3 cases with normal tissue major deviations. CONCLUSIONS: Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic and grade 3+ dermatologic and gastrointestinal toxicity. Although DP-IMRT proved feasible, the high pretreatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials.

Daily orthogonal kilovoltage imaging using a gantry-mounted on-board imaging system results in a reduction in radiation therapy delivery errors.

PURPOSE: To determine whether the use of routine image guided radiation therapy (IGRT) using pretreatment on-board imaging (OBI) with orthogonal kilovoltage X-rays reduces treatment delivery errors. METHODS AND MATERIALS: A retrospective review of documented treatment delivery errors from 2003 to 2009 was performed. Following implementation of IGRT in 2007, patients received daily OBI with orthogonal kV X-rays prior to treatment. The frequency of errors in the pre- and post-IGRT time frames was compared. Treatment errors (TEs) were classified as IGRT-preventable or non-IGRT-preventable. RESULTS: A total of 71,260 treatment fractions were delivered to 2764 patients. A total of 135 (0.19%) TEs occurred in 39 (1.4%) patients (3.2% in 2003, 1.1% in 2004, 2.5% in 2005, 2% in 2006, 0.86% in 2007, 0.24% in 2008, and 0.22% in 2009). In 2007, the TE rate decreased by >50% and has remained low (P = .00007, compared to before 2007). Errors were classified as being potentially preventable with IGRT (e.g., incorrect site, patient, or isocenter) vs. not. No patients had any IGRT-preventable TEs from 2007 to 2009, whereas there were 9 from 2003 to 2006 (1 in 2003, 2 in 2004, 2 in 2005, and 4 in 2006; P = .0058) before the implementation of IGRT. CONCLUSIONS: IGRT implementation has a patient safety benefit with a significant reduction in treatment delivery errors. As such, we recommend the use of IGRT in routine practice to complement existing quality assurance measures.

Radiation dose to the brachial plexus in head-and-neck intensity-modulated radiation therapy and its relationship to tumor and nodal stage.

PURPOSE: The purpose of this retrospective study was to determine tumor factors contributing to brachial plexus (BP) dose in head-and-neck cancer (HNC) patients treated with intensity-modulated radiotherapy (IMRT) when the BP is routinely contoured as an organ at risk (OAR) for IMRT optimization. METHODS AND MATERIALS: From 2004 to 2011, a total of 114 HNC patients underwent IMRT to a total dose of 69.96 Gy in 33 fractions, with the right and left BP prospectively contoured as separate OARs in 111 patients and the ipsilateral BP contoured in 3 patients (total, 225 BP). Staging category T4 and N2/3 disease were present in 34 (29.8%) and 74 (64.9%) patients, respectively. During IMRT optimization, the intent was to keep the maximum BP dose to ≤60 Gy, but prioritizing tumor coverage over achieving the BP constraints. BP dose parameters were compared with tumor and nodal stage. RESULTS: With a median follow-up of 16.2 months, 43 (37.7%) patients had ≥24 months of follow-up with no brachial plexopathy reported. Mean BP volume was 8.2 ± 4.5 cm(3). Mean BP maximum dose was 58.1 ± 12.2 Gy, and BP mean dose was 42.2 ± 11.3 Gy. The BP maximum dose was ≤60, ≤66, and ≤70 Gy in 122 (54.2%), 185 (82.2%), and 203 (90.2%) BP, respectively. For oropharynx, hypopharynx, and larynx sites, the mean BP maximum dose was 58.4 Gy and 63.4 Gy in T0-3 and T4 disease, respectively (p = 0.002). Mean BP maximum dose with N0/1 and N2/3 disease was 52.8 Gy and 60.9 Gy, respectively (p < 0.0001). CONCLUSIONS: In head-and-neck IMRT, dose constraints for the BP are difficult to achieve to ≤60 to 66 Gy with T4 disease of the larynx, hypopharynx, and oropharynx or N2/3 disease. The risk of brachial plexopathy is likely very small in HNC patients undergoing IMRT, although longer follow-up is required.

Dose-painted intensity-modulated radiation therapy for anal cancer: a multi-institutional report of acute toxicity and response to therapy.

PURPOSE: Chemoradiation for anal cancer yields effective tumor control, but is associated with significant acute toxicity. We report our multi-institutional experience using dose-painted IMRT (DP-IMRT). PATIENTS AND METHODS: Between August 2005 and May 2009, 43 patients were treated with DP-IMRT and concurrent chemotherapy for biopsy-proven, squamous cell carcinoma of the anal canal at two academic medical centers. DP-IMRT was prescribed as follows: T2N0: 42 Gy, 1.5 Gy/fraction (fx) to elective nodal planning target volume (PTV) and 50.4 Gy, 1.8 Gy/fx to anal tumor PTV; T3-4N0-3: 45 Gy, 1.5 Gy/fx to elective nodal PTV, and 54 Gy, 1.8 Gy/fx to the anal tumor and metastatic nodal PTV >3 cm with 50.4 Gy, 1.68 Gy/fx to nodal PTVs ≤ 3 cm in size. Acute and late toxicity was reported by the treating physician. Actuarial analysis was performed using the Kaplan-Meier method. RESULTS: Median age was 58 years; 67% female; 16% Stage I, 37% II; 42% III; 5% IV. Fourteen patients were immunocompromised: 21% HIV-positive and 12% on chronic immunosuppression. Median follow-up was 24 months (range, 0.6-43.5 months). Sixty percent completed chemoradiation without treatment interruption; median duration of treatment interruption was 2 days (range, 2-24 days). Acute Grade 3+ toxicity included: hematologic 51%, dermatologic 10%, gastrointestinal 7%, and genitourinary 7%. Two-year local control, overall survival, colostomy-free survival, and metastasis-free survival were 95%, 94%, 90%, and 92%, respectively. CONCLUSIONS: Dose-painted IMRT appears effective and well-tolerated as part of a chemoradiation therapy regimen for the treatment of anal canal cancer.

Induced radioactive potential for a medical accelerator.

Medical accelerators operating over 10 MV can induce short-lived radionuclides in components near the beam and in the air (McGinley 1992). We evaluated a Clinac 2100 C/D at 18 MV photon mode for radionuclidic exposure, contamination, and airborne potential to the accelerator staff entering the room after patient radiation treatment. The gantry, patient couch, wedges, floor, and air were activated. Most activated components appear to decay with a half-life of 2.5 min, except the gantry and port with half-lives approaching 10 min. The highest exposure was from the port at <2 mR h(-1). No removable contamination on any activated component was detected including coolant water in the machine. Airborne radionuclides were measured in the room and at the roof exhaust. The airborne potential is short lived because of ventilation and decay with the highest exposure of 0.3 mR h(-1) lasting for 1 s. Our measurements support the insignificant exposures received by accelerator staff wearing whole body personnel monitors. Accelerator roof effluents to unrestricted areas during patient treatments indicate that regulatory limits are not exceeded.