Pin-Chieh Wang

Health-Related Quality of Life After Stereotactic Body Radiation Therapy for Localized Prostate Cancer: Results From a Multi-institutional Consortium of Prospective Trials

PURPOSE To evaluate the early and late health-related quality of life (QOL) outcomes among prostate cancer patients following stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS Patient self-reported QOL was prospectively measured among 864 patients from phase 2 clinical trials of SBRT for localized prostate cancer. Data from the Expanded Prostate Cancer Index Composite (EPIC) instrument were obtained at baseline and at regular intervals up to 6 years. SBRT delivered a median dose of 36.25 Gy in 4 or 5 fractions. A short course of androgen deprivation therapy was given to 14% of patients. RESULTS Median follow-up was 3 years and 194 patients remained evaluable at 5 years. A transient decline in the urinary and bowel domains was observed within the first 3 months after SBRT which returned to baseline status or better within 6 months and remained so beyond 5 years. The same pattern was observed among patients with good versus poor baseline function and was independent of the degree of early toxicities. Sexual QOL decline was predominantly observed within the first 9 months, a pattern not altered by the use of androgen deprivation therapy or patient age. CONCLUSION Long-term outcome demonstrates that prostate SBRT is well tolerated and has little lasting impact on health-related QOL. A transient and modest decline in urinary and bowel QOL during the first few months after SBRT quickly recovers to baseline levels. With a large number of patients evaluable up to 5 years following SBRT, it is unlikely that unexpected late adverse effects will manifest themselves.

Evaluation of high ipsilateral subventricular zone radiation therapy dose in glioblastoma: a pooled analysis.

PURPOSE Cancer stem cells (CSCs) may play a role in the recurrence of glioblastoma. They are believed to originate from neural stem cells in the subventricular zone (SVZ). Because of their radioresistance, we hypothesized that high doses of radiation (>59.4 Gy) to the SVZ are necessary to control CSCs and improve progression-free survival (PFS) or overall survival (OS) in glioblastoma. METHODS AND MATERIALS 173 patients with glioblastoma pooled from 2 academic centers were treated with resection followed by chemoradiation therapy. The SVZ was segmented on computed tomography to calculate radiation doses delivered to the presumptive CSC niches. The relationships between high SVZ doses and PFS and OS were examined using Cox proportional hazards models. Five covariates were included to estimate their impact on PFS or OS: ipsilateral and contralateral SVZ doses, clinical target volume dose, age, and extent of resection. RESULTS Median PFS and OS were 10.4 and 19.6 months for the cohort. The mean ipsilateral SVZ, contralateral SVZ, and clinical target volume doses were 49.2, 35.2, and 60.1 Gy, respectively. Twenty-one patients who received high ipsilateral SVZ dose (>59.4 Gy) had significantly longer median PFS (12.6 vs 9.9 months, P=.042) and longer OS (25.8 vs 19.2 months, P=.173). On multivariate analysis, high radiation therapy doses to ipsilateral SVZ remained a statistically significant independent predictor of improved PFS but not of OS. The extent of surgery affected both PFS and OS on multivariate analysis. CONCLUSION High radiation therapy doses to ipsilateral CSC niches are associated with improved PFS in glioblastoma.

Clinical Outcomes for Patients with Gleason Score 9–10 Prostate Adenocarcinoma Treated With Radiotherapy or Radical Prostatectomy: A Multi-institutional Comparative Analysis

BACKGROUND The long natural history of prostate cancer (CaP) limits comparisons of efficacy between radical prostatectomy (RP) and external beam radiotherapy (EBRT), since patients treated years ago received treatments considered suboptimal by modern standards (particularly with regards to androgen deprivation therapy [ADT] and radiotherapy dose-escalation]. Gleason score (GS) 9-10 CaP is particularly aggressive, and clinically-relevant endpoints occur early, facilitating meaningful comparisons. OBJECTIVE To compare outcomes of patients with GS 9-10 CaP following EBRT, extremely-dose escalated radiotherapy (as exemplified by EBRT+brachytherapy [EBRT+BT]), and RP. DESIGN, SETTING, PARTICIPANTS Retrospective analysis of 487 patients with biopsy GS 9-10 CaP treated between 2000 and 2013 (230 with EBRT, 87 with EBRT+BT, and 170 with RP). Most radiotherapy patients received ADT and dose-escalated radiotherapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Kaplan-Meier analysis and multivariate Cox regression estimated and compared 5-yr and 10-yr rates of distant metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS). RESULTS AND LIMITATIONS The median follow-up was 4.6 yr. Local salvage and systemic salvage were performed more frequently in RP patients (49.0% and 30.1%) when compared with either EBRT patients (0.9% and 19.7%) or EBRT+BT patients (1.2% and 16.1%, p<0.0001). Five-yr and 10-yr distant metastasis-free survival rates were significantly higher with EBRT+BT (94.6% and 89.8%) than with EBRT (78.7% and 66.7%, p=0.0005) or RP (79.1% and 61.5%, p<0.0001). The 5-yr and 10-yr CSS and OS rates were similar across all three cohorts. CONCLUSIONS Radiotherapy and RP provide equivalent CSS and OS. Extremely dose-escalated radiotherapy with ADT in particular offers improved systemic control when compared with either EBRT or RP. These data suggest that extremely dose-escalated radiotherapy with ADT might be the optimal upfront treatment for patients with biopsy GS 9-10 CaP. PATIENT SUMMARY While some prostate cancers are slow-growing requiring many years, sometimes decades, of follow-up in order to compare between radiation and surgery, high-risk and very aggressive cancers follow a much shorter time course allowing such comparisons to be made and updated as treatments, especially radiation, rapidly evolve. We showed that radiation-based treatments and surgery, with contemporary standards, offer equivalent survival for patients with very aggressive cancers (defined as Gleason score 9-10). Extremely-dose escalated radiotherapy with short-course androgen deprivation therapy offered the least risk of developing metastases, and equivalent long term survival.

Prostate-Specific Antigen Bounce After High-Dose-Rate Monotherapy for Prostate Cancer.

PURPOSE To characterize the magnitude and kinetics of prostate-specific antigen (PSA) bounces after high-dose-rate (HDR) monotherapy and determine relationships between certain clinical factors and PSA bounce. METHODS AND MATERIALS Longitudinal PSA data and various clinical parameters were examined in 157 consecutive patients treated with HDR monotherapy between 1996 and 2005. We used the following definition for PSA bounce: rise in PSA ≥threshold, after which it returns to the prior level or lower. Prostate-specific antigen failure was defined per the Phoenix definition (nadir +2 ng/mL). RESULTS A PSA bounce was noted in 67 patients (43%). The number of bounces per patient was 1 in 45 cases (67%), 2 in 19 (28%), 3 in 2 (3%), 4 in 0, and 5 in 1 (1%). The median time to maximum PSA bounce was 1.3 years, its median magnitude was 0.7, and its median duration was 0.75 years. Three patients (2%) were noted to have PSA failure. None of the 3 patients who experienced biochemical failure exhibited PSA bounce. In the fully adjusted model for predicting each bounce, patients aged <55 years had a statistically significant higher likelihood of experiencing a bounce (odds ratio 2.22, 95% confidence interval 1.38-3.57, P=.001). There was also a statistically significant higher probability of experiencing a bounce for every unit decrease in Gleason score (odds ratio 1.52, 95% confidence interval 1.01-2.04, P=.045). CONCLUSIONS A PSA bounce occurs in a significant percentage of patients treated with HDR monotherapy, with magnitudes varying from <1 in 28% of cases to ≥1 in 15%. The median duration of bounce is <1 year. More bounces were identified in patients with lower Gleason score and age <55 years. Further investigation using a model to correlate magnitude and frequency of bounces with clinical variables are under way.

Safety and Efficacy of Stereotactic Body Radiation Therapy in the Treatment of Pulmonary Metastases from High Grade Sarcoma

Introduction. Patients with high-grade sarcoma (HGS) frequently develop metastatic disease thus limiting their long-term survival. Lung metastases (LM) have historically been treated with surgical resection (metastasectomy). A potential alternative for controlling LM could be stereotactic body radiation therapy (SBRT). We evaluated the outcomes from our institutional experience utilizing SBRT. Methods. Sixteen consecutive patients with LM from HGS were treated with SBRT between 2009 and 2011. Routine radiographic and clinical follow-up was performed. Local failure was defined as CT progression on 2 consecutive scans or growth after initial shrinkage. Radiation pneumonitis and radiation esophagitis were scored using Common Toxicity Criteria (CTC) version 3.0. Results. All 16 patients received chemotherapy, and a subset (38%) also underwent prior pulmonary metastasectomy. Median patient age was 56 (12–85), and median follow-up time was 20 months (range 3–43). A total of 25 lesions were treated and evaluable for this analysis. Most common histologies were leiomyosarcoma (28%), synovial sarcoma (20%), and osteosarcoma (16%). Median SBRT prescription dose was 54 Gy (36–54) in 3-4 fractions. At 43 months, local control was 94%. No patient experienced G2-4 radiation pneumonitis, and no patient experienced radiation esophagitis. Conclusions. Our retrospective experience suggests that SBRT for LM from HGS provides excellent local control and minimal toxicity.

High-Dose-Rate Prostate Brachytherapy Consistently Results in High Quality Dosimetry

PURPOSE We performed a dosimetry analysis to determine how well the goals for clinical target volume coverage, dose homogeneity, and normal tissue dose constraints were achieved with high-dose-rate (HDR) prostate brachytherapy. METHODS AND MATERIALS Cumulative dose-volume histograms for 208 consecutively treated HDR prostate brachytherapy implants were analyzed. Planning was based on ultrasound-guided catheter insertion and postoperative CT imaging; the contoured clinical target volume (CTV) was the prostate, a small margin, and the proximal seminal vesicles. Dosimetric parameters analyzed for the CTV were D90, V90, V100, V150, and V200. Dose to the urethra, bladder, bladder balloon, and rectum were evaluated by the dose to 0.1 cm(3), 1 cm(3), and 2 cm(3) of each organ, expressed as a percentage of the prescribed dose. Analysis was stratified according to prostate size. RESULTS The mean prostate ultrasound volume was 38.7 ± 13.4 cm(3) (range: 11.7-108.6 cm(3)). The mean CTV was 75.1 ± 20.6 cm(3) (range: 33.4-156.5 cm(3)). The mean D90 was 109.2% ± 2.6% (range: 102.3%-118.4%). Ninety-three percent of observed D90 values were between 105 and 115%. The mean V90, V100, V150, and V200 were 99.9% ± 0.05%, 99.5% ± 0.8%, 25.4% ± 4.2%, and 7.8% ± 1.4%. The mean dose to 0.1 cm(3), 1 cm(3), and 2 cm(3) for organs at risk were: Urethra: 107.3% ± 3.0%, 101.1% ± 14.6%, and 47.9% ± 34.8%; bladder wall: 79.5% ± 5.1%, 69.8% ± 4.9%, and 64.3% ± 5.0%; bladder balloon: 70.3% ± 6.8%, 59.1% ± 6.6%, and 52.3% ± 6.2%; rectum: 76.3% ± 2.5%, 70.2% ± 3.3%, and 66.3% ± 3.8%. There was no significant difference between D90 and V100 when stratified by prostate size. CONCLUSIONS HDR brachytherapy allows the physician to consistently achieve complete prostate target coverage and maintain normal tissue dose constraints for organs at risk over a wide range of target volumes.

Feasibility of magnetic resonance imaging–guided liver stereotactic body radiation therapy: A comparison between modulated tri-cobalt-60 teletherapy and linear accelerator–based intensity modulated radiation therapy

PURPOSE The purpose of this study was to investigate the dosimetric feasibility of liver stereotactic body radiation therapy (SBRT) using a teletherapy system equipped with 3 rotating (60)Co sources (tri-(60)Co system) and a built-in magnetic resonance imager (MRI). We hypothesized tumor size and location would be predictive of favorable dosimetry with tri-(60)Co SBRT. METHODS AND MATERIALS The primary study population consisted of 11 patients treated with SBRT for malignant hepatic lesions whose linear accelerator (LINAC)-based SBRT plans met all mandatory Radiation Therapy Oncology Group (RTOG) 1112 organ-at-risk (OAR) constraints. The secondary study population included 5 additional patients whose plans did not meet the mandatory constraints. Patients received 36 to 60 Gy in 3 to 5 fractions. Tri-(60)Co system SBRT plans were planned with ViewRay system software. RESULTS All patients in the primary study population had tri-(60)Co SBRT plans that passed all RTOG constraints, with similar planning target volume coverage and OAR doses to LINAC plans. Mean liver doses and V10Gy to the liver, although easily meeting RTOG 1112 guidelines, were significantly higher with tri-(60)Co plans. When the 5 additional patients were included in a univariate analysis, the tri-(60)Co SBRT plans were still equally able to pass RTOG constraints, although they did have inferior ability to pass more stringent liver and kidney constraints (P < .05). A multivariate analysis found the ability of a tri-(60)Co SBRT plan to meet these constraints depended on lesion location and size. Patients with smaller or more peripheral lesions (as defined by distance from the aorta, chest wall, liver dome, and relative lesion volume) were significantly more likely to have tri-(60)Co plans that spared the liver and kidney as well as LINAC plans did (P < .05). CONCLUSIONS It is dosimetrically feasible to perform liver SBRT with a tri-(60)Co system with a built-in MRI. Patients with smaller or more peripheral lesions are more likely to have optimal liver and kidney sparing, with the added benefit of MRI guidance, when receiving tri-(60)Co-based SBRT.

Image guidance during head-and-neck cancer radiation therapy: analysis of alignment trends with in-room cone-beam computed tomography scans.

PURPOSE On-board cone-beam computed tomography (CBCT) is currently available for alignment of patients with head-and-neck cancer before radiotherapy. However, daily CBCT is time intensive and increases the overall radiation dose. We assessed the feasibility of using the average couch shifts from the first several CBCTs to estimate and correct for the presumed systematic setup error. METHODS AND MATERIALS 56 patients with head-and-neck cancer who received daily CBCT before intensity-modulated radiation therapy had recorded shift values in the medial-lateral, superior-inferior, and anterior-posterior dimensions. The average displacements in each direction were calculated for each patient based on the first five or 10 CBCT shifts and were presumed to represent the systematic setup error. The residual error after this correction was determined by subtracting the calculated shifts from the shifts obtained using daily CBCT. RESULTS The magnitude of the average daily residual three-dimensional (3D) error was 4.8 ± 1.4 mm, 3.9 ± 1.3 mm, and 3.7 ± 1.1 mm for uncorrected, five CBCT corrected, and 10 CBCT corrected protocols, respectively. With no image guidance, 40.8% of fractions would have been >5 mm off target. Using the first five CBCT shifts to correct subsequent fractions, this percentage decreased to 19.0% of all fractions delivered and decreased the percentage of patients with average daily 3D errors >5 mm from 35.7% to 14.3% vs. no image guidance. Using an average of the first 10 CBCT shifts did not significantly improve this outcome. CONCLUSIONS Using the first five CBCT shift measurements as an estimation of the systematic setup error improves daily setup accuracy for a subset of patients with head-and-neck cancer receiving intensity-modulated radiation therapy and primarily benefited those with large 3D correction vectors (>5 mm). Daily CBCT is still necessary until methods are developed that more accurately determine which patients may benefit from alternative imaging strategies.

A treatment planning comparison between modulated tri-cobalt-60 teletherapy and linear accelerator–based stereotactic body radiotherapy for central early-stage non−small cell lung cancer

We evaluated the feasibility of planning stereotactic body radiotherapy (SBRT) for large central early-stage non-small cell lung cancer with a tri-cobalt-60 (tri-(60)Co) system equipped with real-time magnetic resonance imaging (MRI) guidance, as compared to linear accelerator (LINAC)-based SBRT. In all, 20 patients with large central early-stage non-small cell lung cancer who were treated between 2010 and 2015 with LINAC-based SBRT were replanned using a tri-(60)Co system for a prescription dose of 50Gy in 4 fractions. Doses to organs at risk were evaluated based on established MD Anderson constraints for central lung SBRT. R100 values were calculated as the total tissue volume receiving 100% of the dose (V100) divided by the planning target volume and compared to assess dose conformity. Dosimetric comparisons between LINAC-based and tri-(60)Co SBRT plans were performed using Student׳s t-test and Wilcoxon Ranks test. Blinded reviews by radiation oncologists were performed to assess the suitability of both plans for clinical delivery. The mean planning target volume was 48.3cc (range: 12.1 to 139.4cc). Of the tri-(60)Co SBRT plans, a mean 97.4% of dosimetric parameters per patient met MD Anderson dose constraints, whereas a mean 98.8% of dosimetric parameters per patient were met with LINAC-based SBRT planning (p = 0.056). R100 values were similar between both plans (1.20 vs 1.21, p = 0.79). Upon blinded review by 4 radiation oncologists, an average of 90% of the tri-(60)Co SBRT plans were considered acceptable for clinical delivery compared with 100% of the corresponding LINAC-based SBRT plans (p = 0.17). SBRT planning using the tri-(60)Co system with built-in MRI is feasible and achieves clinically acceptable plans for most central lung patients, with similar target dose conformity and organ at risk dosimetry. The added benefit of real-time MRI-guided therapy may further optimize tumor targeting while improving normal tissue sparing, which warrants further investigation in a prospective feasibility clinical trial.

Dosimetric parameters predict short-term quality-of-life outcomes for patients receiving stereotactic body radiation therapy for prostate cancer

PURPOSE Stereotactic body radiation therapy (SBRT) is a treatment option for patients with localized prostate cancer, with reported clinical and health-related quality-of-life (QOL) outcomes comparable to standard fractionation radiation therapy. The goal of this study was to evaluate correlations between short-term QOL outcomes and dosimetric parameters to guide future prostate SBRT planning. METHODS AND MATERIALS From 2010 to 2013, QOL data were prospectively collected from 75 patients enrolled in a prostate SBRT clinical trial. A comparison was made between Expanded Prostate Cancer Index Composite scores for patients with the top 25th percentile versus the bottom 75th percentile of the following dose-volume histogram parameters: planning target volume V100; bladder V50 and V100; and rectum V50, V80, V90, and V100. A linear mixed-effect model was used to estimate the difference between the 2 strata for each parameter. RESULTS Median follow-up was 12 months. Patients with planning target volume V100 volumes >120 cm(3) had the worst reduction in urinary QOL. Urinary QOL was also decreased significantly in patients with bladder V100 volumes >5.5 cm(3). Bowel QOL was decreased significantly in patients with rectal V90 and V100 volumes >4.2 and >1.5 cm(3), respectively. CONCLUSIONS Patients with large prostate size or large volumes of rectum and bladder that receive ≥90% of the prescribed radiation dose are more susceptible to short-term QOL decrements after prostate SBRT. These volumes should be minimized to maximize recovery to baseline QOL after prostate SBRT.