Faculty Bibliography

PURPOSE/OBJECTIVE:Robust detection of implanted fiducials is essential for monitoring intrafractional motion during hypofractionated treatment. The authors developed a plan optimization strategy to ensure clear visibility of implanted fiducials and facilitate 3D localization during volumetric modulated arc therapy (VMAT). METHODS:Periodic kilovoltage (kV) images were acquired at 20° gantry intervals and paired with simultaneously acquired 4.4° short arc megavoltage digital tomosynthesis (MV-DTS) to localize three fiducials during VMAT delivery for hypofractionated prostate cancer treatment. Beginning with the original optimized plan, control point segments where fiducials were consistently blocked by multileaf collimator (MLC) within each 4.4° MV-DTS interval were first identified. For each segment, MLC apertures were edited to expose the fiducial that led to the least increase in the cost function. Subsequently, MLC apertures of all control points not involved with fiducial visualization were reoptimized to compensate for plan quality losses and match the original dose-volume histogram. MV dose for each MV-DTS was also kept above 0.4 MU to ensure acceptable image quality. Different imaging (gantry) intervals and visibility margins around fiducials were also evaluated. RESULTS:Fiducials were consistently blocked by the MLC for, on average, 36% of the imaging control points for five hypofractionated prostate VMAT plans but properly exposed after reoptimization. Reoptimization resulted in negligible dosimetric differences compared with original plans and outperformed simple aperture editing: on average, PTV D98 recovered from 87% to 94% of prescription, and PTV dose homogeneity improved from 9% to 7%. Without violating plan objectives and compromising delivery efficiency, the highest imaging frequency and largest margin that can be achieved are a 10° gantry interval, and 15 mm, respectively. CONCLUSIONS:VMAT plans can be made to accommodate MV-kV imaging of fiducials. Fiducial visualization rate and workflow efficiency are significantly improved with an automatic modification and reoptimization approach.

BACKGROUND:The purpose of this study was to examine patterns of failure and the relationship to radiation doses in patients with head and neck carcinoma of unknown primary (HNCUP). METHODS:We reviewed 85 patients with HNCUP treated with curative-intent radiation therapy (RT) during 1995 to 2012. RESULTS:There have been no failures in the pharyngeal axis. Relapse at initial neck sites of disease developed in 7 patients (8.2%). The median dose to these sites was 70 Gy (range, 63-70 Gy). Failure at neck sites without initial disease occurred in 4 patients (4.7%). The median dose was 54 Gy (range, 50-58.8 Gy). There were no contralateral failures in a small cohort of patients receiving unilateral treatment (n = 6). Percutaneous endoscopic gastrostomy (PEG) tube dependence at 12 months was 7.4%, and 2.5% at 3 years. Esophageal stricture developed in 5 patients (5.9%). CONCLUSION:RT for HNCUP produces excellent locoregional control rates with acceptably low levels of late toxicity. Doses prescribed to sites of eventual failure did not vary significantly from those sites that were treated and remain in control. © 2015 Wiley Periodicals, Inc. Head Neck 38: E426-E431, 2016.

The purpose of this study was to evaluate the accuracy and clinical feasibility of a motion monitoring method employing simultaneously acquired MV and kV images during volumetric-modulated arc therapy (VMAT). Short-arc digital tomosynthesis (SA-DTS) is used to improve the quality of the MV images that are then combined with orthogonally acquired kV images to assess 3D motion. An anthropomorphic phantom with implanted gold seeds was used to assess accuracy of the method under static, typical prostatic, and respiratory motion scenarios. Automatic registra-tion of kV images and single MV frames or MV SA-DTS reconstructed with arc lengths from 2° to 7° with the appropriate reference fiducial template images was performed using special purpose-built software. Clinical feasibility was evaluated by retrospectively analyzing images acquired over four or five sessions for each of three patients undergoing hypofractionated prostate radiotherapy. The standard deviation of the registration error in phantom using MV SA-DTS was similar to single MV images for the static and prostate motion scenarios (σ = 0.25 mm). Under respiratory motion conditions, the standard deviation of the registration error increased to 0.7mm and 1.7 mm for single MV and MV SA-DTS, respectively. Registration failures were observed with the respiratory scenario only and were due to motion-induced fiducial blurring. For the three patients studied, the mean and standard deviation of the difference between automatic registration using 4° MV SA-DTS and manual registration using single MV images results was 0.07±0.52mm. The MV SA-DTS results in patients were, on average, superior to single-frame MV by nearly 1 mm - significantly more than what was observed in phantom. The best MV SA-DTS results were observed with arc lengths of 3° to 4°. Registration failures in patients using MV SA-DTS were primarily due to blockage of the gold seeds by the MLC. The failure rate varied from 2% to 16%. Combined MV SA-DTS and kV imaging is feasible for intratreatment motion monitoring during VMAT of anatomic sites where limited motion is expected, and improves registration accuracy compared to single MV/kV frames. To create a clinically robust technique, further improvements to ensure visualization of fiducials at the desired control points without degradation of the treatment plan are needed.

BACKGROUND:Despite revisions in 2005 and 2014, the Gleason prostate cancer (PCa) grading system still has major deficiencies. Combining of Gleason scores into a three-tiered grouping (6, 7, 8-10) is used most frequently for prognostic and therapeutic purposes. The lowest score, assigned 6, may be misunderstood as a cancer in the middle of the grading scale, and 3+4=7 and 4+3=7 are often considered the same prognostic group. OBJECTIVE:To verify that a new grading system accurately produces a smaller number of grades with the most significant prognostic differences, using multi-institutional and multimodal therapy data. DESIGN, SETTING, AND PARTICIPANTS/METHODS:Between 2005 and 2014, 20,845 consecutive men were treated by radical prostatectomy at five academic institutions; 5501 men were treated with radiotherapy at two academic institutions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/METHODS:Outcome was based on biochemical recurrence (BCR). The log-rank test assessed univariable differences in BCR by Gleason score. Separate univariable and multivariable Cox proportional hazards used four possible categorizations of Gleason scores. RESULTS AND LIMITATIONS/CONCLUSIONS:In the surgery cohort, we found large differences in recurrence rates between both Gleason 3+4 versus 4+3 and Gleason 8 versus 9. The hazard ratios relative to Gleason score 6 were 1.9, 5.1, 8.0, and 11.7 for Gleason scores 3+4, 4+3, 8, and 9-10, respectively. These differences were attenuated in the radiotherapy cohort as a whole due to increased adjuvant or neoadjuvant hormones for patients with high-grade disease but were clearly seen in patients undergoing radiotherapy only. A five-grade group system had the highest prognostic discrimination for all cohorts on both univariable and multivariable analysis. The major limitation was the unavoidable use of prostate-specific antigen BCR as an end point as opposed to cancer-related death. CONCLUSIONS:The new PCa grading system has these benefits: more accurate grade stratification than current systems, simplified grading system of five grades, and lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa. PATIENT SUMMARY/RESULTS:We looked at outcomes for prostate cancer (PCa) treated with radical prostatectomy or radiation therapy and validated a new grading system with more accurate grade stratification than current systems, including a simplified grading system of five grades and a lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa.

PURPOSE/OBJECTIVE:We evaluated quality-of-life changes (QoL) in 907 patients treated with either radical prostatectomy (open or laparoscopic), real-time planned conformal brachytherapy, or high-dose intensity-modulated radiotherapy (IMRT) on a prospective IRB-approved longitudinal study. METHODS:Validated questionnaires given pretreatment (baseline) and at 3, 6, 9, 12, 15, 18, 24, 36, and 48 months addressed urinary function, urinary bother, bowel function, bowel bother, sexual function, and sexual bother. RESULTS:At 48 months, surgery had significantly higher urinary incontinence than others (both P<.001), but fewer urinary irritation/obstruction symptoms (all P<.001). Very low levels of bowel dysfunction were observed and only small subsets in each group showed rectal bleeding. Brachytherapy and IMRT showed better sexual function than surgery accounting for baseline function and other factors (delta 14.29 of 100, 95% CI, 8.57-20.01; and delta 10.5, 95% CI, 3.78-17.88). Sexual bother was similar. Four-year outcomes showed persistent urinary incontinence for surgery with more obstructive urinary symptoms for radiotherapy. Using modern radiotherapy delivery, bowel function deterioration is less-often observed. Sexual function was strongly affected in all groups yet significantly less for radiotherapy. CONCLUSIONS:Treatment selection should include patient preferences and balance predicted disease-free survival over a projected time vs potential impairment of QoL important for the patient.

OBJECTIVE:To characterize the impact of androgen-deprivation therapy (ADT) on the incidence of cardiovascular events (CE) in prostate cancer patients treated with radiotherapy (RT). MATERIALS AND METHODS/METHODS:There were 2211 patients with localized prostate cancer treated with RT from 1988 to 2008 at our institution. There were 991 patients (44.8%) who received ADT at the time of RT for a median of 6.1 months. Salvage ADT was initiated prior to CE in 365 men (16.5%) at a median of 5.5 years (range: 0.6 to 18.4 years) after RT and continued for a median of 4.3 years. A nomogram was constructed to predict the 10-year risk of CE "post-RT" (i.e., after RT). RESULTS:Patients receiving ADT at the time of RT exhibited significantly higher 10-year incidence of CE (19.6%, 95% CI 17.0%-22.6%) than those not receiving ADT (14.3%, 95% CI 12.2%-16.7%, P = .005). On multivariate analysis, both ADT at the time of RT (P = .007) and the time of salvage (P = .0004) were associated with increased CE risk, as were advanced age (P  =  .02), smoking (P  =  .0007), history of diabetes (P  =  .0007), and history of CE before RT (P  <  .0001). A nomogram using patient age, smoking status, history of pre-RT CE, history of diabetes, and ADT use at the time of RT predicted the rate of 10-year CE with a C-index of 0.81 (95% CI, 0.72-0.88). CONCLUSION/CONCLUSIONS:While ADT is often an essential part of prostate cancer treatment, patients should be counseled regarding increased risks of CE and prophylactic efforts should be considered to mitigate that risk.

PURPOSE/OBJECTIVE:Local recurrence is a significant problem after surgical resection of thoracic tumors. As intraoperative radiotherapy (IORT) can deliver radiation directly to the threatened margin, we have used this therapy in an attempt to reduce local recurrence, using high-dose-rate (HDR) as well as low-dose-rate (LDR) techniques. METHODS AND MATERIALS/METHODS:We performed a retrospective review of patients undergoing LDR ((125)I) mesh placement or HDR ((192)Ir) afterloading therapy during lung tumor resection between 2001 and 2013 at our institution. Competing risks methods were used to estimate the cumulative incidence of local failure. We also assessed possible predictive factors of local failure. RESULTS:Fifty-nine procedures (41 LDR and 18 HDR) were performed on 58 patients. Median follow-up was 55.1 months. Cumulative incidence of local failure at 1, 2, and 3 years was 28.5%, 34.2%, and 34.2%, respectively. Median overall survival was 39.9 months. There was no significant difference in local failure according to margin status, HDR vs. LDR, use of adjuvant external beam radiotherapy, or metastatic vs. primary tumor. Two patients (3.4%) experienced Grade 3+ toxicities likely related to brachytherapy. Additionally, 7 patients experienced Grade 3+ postsurgical complications unlikely related to brachytherapy. CONCLUSIONS:IORT is associated with good local control after resection of thoracic tumors otherwise at very high risk for local recurrence. There is a low incidence of severe toxicity attributable to brachytherapy. HDR-IORT appears to have equivalent outcomes to LDR-IORT. HDR or LDR-IORT can, therefore, be considered in situations where the oncologic completeness of thoracic tumor resection is in doubt.

PURPOSE:To report the long-term control and toxicity outcomes of patients with clinically localized prostate cancer, who underwent low-dose-rate prostate brachytherapy with magnetic resonance spectroscopic image (MRSI)-directed dose escalation to intraprostatic regions. METHODS AND MATERIALS:Forty-seven consecutive patients between May 2000 and December 2003 were analyzed retrospectively. Each patient underwent a preprocedural MRSI, and MRS-positive voxels suspicious for malignancy were identified. Intraoperative planning was used to determine the optimal seed distribution to deliver a standard prescription dose to the entire prostate, while escalating the dose to MRS-positive voxels to 150% of prescription. Each patient underwent transperineal implantation of radioactive seeds followed by same-day CT for postimplant dosimetry. RESULTS:The median prostate D90 (minimum dose received by 90% of the prostate) was 125.7% (interquartile range [IQR], 110.3-136.5%) of prescription. The median value for the MRS-positive mean dose was 229.9% (IQR, 200.0-251.9%). Median urethra D30 and rectal D30 values were 142.2% (137.5-168.2%) and 56.1% (40.1-63.4%), respectively. Median followup was 86.4 months (IQR, 49.8-117.6). The 10-year actuarial prostate-specific antigen relapse-free survival was 98% (95% confidence interval, 93-100%). Five patients (11%) experienced late Grade 3 urinary toxicity (e.g., urethral stricture), which improved after operative intervention. Four of these patients had dose-escalated voxels less than 1.0 cm from the urethra. CONCLUSIONS:Low-dose-rate brachytherapy with MRSI-directed dose escalation to suspicious intraprostatic regions exhibits excellent long-term biochemical control. Patients with dose-escalated voxels close to the urethra were at higher risk of late urinary stricture.