Nathan Bittner

American Society for Radiation Oncology (ASTRO) and American College of Radiology (ACR) practice guideline for the transperineal permanent brachytherapy of prostate cancer.

Transperineal permanent prostate brachytherapy is a safe and efficacious treatment option for patients with organ-confined prostate cancer. Careful adherence to established brachytherapy standards has been shown to improve the likelihood of procedural success and reduce the incidence of treatment-related morbidity. A collaborative effort of the American College of Radiology (ACR) and American Society for Therapeutic Radiation Oncology (ASTRO) has produced a practice guideline for permanent prostate brachytherapy. The guideline defines the qualifications and responsibilities of all the involved personnel, including the radiation oncologist, physicist and dosimetrist. Factors with respect to patient selection and appropriate use of supplemental treatment modalities such as external beam radiation and androgen suppression therapy are discussed. Logistics with respect to the brachytherapy implant procedure, the importance of dosimetric parameters, and attention to radiation safety procedures and documentation are presented. Adherence to these practice guidelines can be part of ensuring quality and safety in a successful prostate brachytherapy program.

Incidence and Pathological Features of Prostate Cancer Detected on Transperineal Template Guided Mapping Biopsy After Negative Transrectal Ultrasound Guided Biopsy

PURPOSE We determined the incidence of cancer detection by transperineal template guided mapping biopsy of the prostate in patients with at least 1 previously negative transrectal ultrasound guided biopsy. MATERIALS AND METHODS From January 2005 to January 2012 at least 1 negative transrectal ultrasound guided biopsy was done in 485 patients in our clinical database before proceeding with transperineal template guided mapping biopsy. No study patient had a previous prostate cancer diagnosis. The incidence of patients with 1, 2, or 3 or greater previous transrectal ultrasound guided biopsies was 55.3%, 25.9% and 18.8%, respectively. Transperineal template guided mapping biopsy was done in 74.8% of patients for increasing or occasionally persistently increased prostate specific antigen, in 19.4% for atypical small acinar proliferation and in 5.8% for high grade prostatic intraepithelial neoplasia. RESULTS For the entire study population a median of 59 cores was submitted at transperineal template guided mapping biopsy. Cancer was ultimately detected in 226 patients (46.6%) using the transperineal template guided method, including 196 (86.7%) with clinically significant disease according to the Epstein criteria. The most common cancer detection site on transperineal template guided mapping biopsy was the anterior apex. CONCLUSIONS Transperineal template guided mapping biopsy detected clinically significant prostate cancer in a substantial proportion of patients with negative transrectal ultrasound guided biopsy. This technique should be strongly considered in the context of increasing prostate specific antigen with failed confirmation of the tissue diagnosis.

Transperineal template-guided mapping biopsy as a staging procedure to select patients best suited for active surveillance.

Objectives:Patients with clinically insignificant prostate cancer are candidates for active surveillance. However, uncertainty regarding the true extent of disease limits enthusiasm. In this study, we report our initial findings in patients with transrectal ultrasound (TRUS)-detected clinically insignificant prostate cancer undergoing transperineal template-guided mapping biopsy (TTMB) as a staging procedure. Methods:Sixty-four patients who met the Epstein criteria for clinically insignificant prostate cancer underwent TTMB. Each biopsy core position was recorded in 3 dimensions with documentation of location of each positive biopsy core, Gleason score, percentage of involvement of each core, and presence/absence of perineural invasion. Results:Mean pre-TRUS prostate specific antigen was 4.7 ng/mL with a Gleason score of 6 involving a median of 5% of 1 TRUS core. The mean number of TTMB biopsy cores was 58.5, with 6.6 cores positive for malignancy. Ten patients had clinically insignificant prostate cancer (15.7%), 8 had no TTMB-detected cancer (12.5%), and 46 (71.9%) had clinically significant cancer. Of patients with cancer, 37 (66.1%) had bilobar involvement and 25 (44.6%) harbored a Gleason score of ≥7. In a multivariate analysis, tobacco consumption was found to be most closely related to clinically significant disease on TTMB. Conclusions:TRUS biopsy underestimates disease extent and Gleason score in some patients. TTMB provides a more accurate assessment of the presence of aggressive histology.

Evaluation of the Role of Radiation Therapy in the Management of Malignant Thymoma

PURPOSE The management of patients diagnosed with thymoma remains unclear. This report attempts to identify the impact of adjuvant radiotherapy on overall survival (OS) and cause-specific survival (CSS) in patients diagnosed with thymoma. METHODS AND MATERIALS Patients diagnosed with thymic malignancy between 1973 and 2003 were retrospectively identified from centers participating in the Surveillance, Epidemiology, and End Results (SEER) program. Those patients classified as having thymic carcinoma were excluded from this analysis. OS and CSS were estimated by the Kaplan-Meier method. Outcomes for patients treated with and without radiation therapy were compared using the log-rank test. Multivariate analysis was performed with the Cox proportional hazards model to analyze factors predictive of OS and CSS. RESULTS A total of 1,464 patients were identified as having thymic malignancy, and of these, 1,254 patients were identified as having malignant thymoma. The median follow-up time was 41 months (range, 4-337 months). Among patients who did not receive radiotherapy (RT), the 10-year rate of OS was 41% compared to 42% for those who did receive RT (p = 0.06). The median OS for the patients who did not receive RT was 80 months compared to 97 months for those who did receive RT. In patients with Masaoka stage II-III malignancy, OS was significantly improved with RT (p = 0.002), and a trend in improved CSS was observed (p = 0.1). Patients were also analyzed based on resection status. For those patients who had an incomplete excision, the 10-year OS was 63% with RT and 46% without RT (p = 0.38). On multivariate analysis, factors predictive of OS included age, extent of surgery, stage, and number of lymph nodes examined. CONCLUSIONS This study reports treatment results of a large cohort of patients who were diagnosed with malignant thymoma. This study demonstrates that the use of RT following resection for thymoma significantly improves OS for those with regional disease and marginally improves CSS.

Electromagnetic Tracking of Intrafraction Prostate Displacement in Patients Externally Immobilized in the Prone Position

PURPOSE To evaluate intrafraction prostate displacement among patients immobilized in the prone position using real-time monitoring of implanted radiofrequency transponders. METHODS AND MATERIALS The Calypso localization system was used to track prostate motion in patients receiving external beam radiation therapy (XRT) for prostate cancer. All patients were treated in the prone position and immobilized with a thermoplastic immobilization device. Real-time measurement of prostate displacement was recorded for each treatment fraction. These measurements were used to determine the duration and magnitude of displacement along the three directional axes. RESULTS The calculated centroid of the implanted transponders was offset from the treatment isocenter by >or=2 mm, >or=3 mm, and >or=4 mm for 38.0%, 13.9%, and 4.5% of the time. In the lateral dimension, the centroid was offset from the treatment isocenter by >or=2 mm, >or=3 mm, and >or=4 mm for 2.7%, 0.4%, and 0.06% of the time. In the superior-inferior dimension, the centroid was offset from the treatment isocenter by >or=2 mm, >or=3 mm, and >or=4 mm for 16.1%, 4.7%, and 1.5% of the time, respectively. In the anterior-posterior dimension, the centroid was offset from the treatment isocenter by >or=2 mm, >or=3 mm, and >or=4 mm for 13.4%, 3.0%, and 0.5% of the time. CONCLUSIONS Intrafraction prostate displacement in the prone position is comparable to that in the supine position. For patients with large girth, in whom the supine position may preclude accurate detection of implanted radiofrequency transponders, treatment in the prone position is a suitable alternative.

The Incidence of Transition Zone Prostate Cancer Diagnosed by Transperineal Template-guided Mapping Biopsy: Implications for Treatment Planning

OBJECTIVES To report the incidence of transition zone (TZ) cancer in patients undergoing transperineal template-guided mapping biopsy (TTMB) of the prostate gland. METHODS Five hundred thirty-nine consecutive patients underwent TTMB by means of an anatomic technique with sampling of 24 defined prostate regions. The position of each biopsy core was recorded in 3 dimensions. For every patient, the location of each positive biopsy core, the number of positive cores, the Gleason score, the percentage involvement of each core, and the presence/absence of perineural invasion was documented. RESULTS The median volumetric prostate volume was 56.0 cm(3) with an ellipsoid TZ volume of 20.1 cm(3). The median number of TTMB cores was 58 with a median of 11 TZ cores. Two hundred eighty-seven (53.2%) were diagnosed with prostate cancer. TZ cancer was detected in 130 (45.3%) of patients with prostate cancer but only 6 (4.6%) were confined to the TZ. Overall, 38.9% of TZ cores were positive for malignancy. Of the TZ cancers, 37 (28.5%), 64 (49.2%), and 29 (22.3%) were assigned Gleason scores 6, 7, and 8-10. Compared with a standard 12-core biopsy approach, the results of the TZ biopsy upgraded the Gleason score in 24.6% of patients. Only 4 cancers (3.1%) involving the TZ were classified as clinically insignificant. CONCLUSIONS Although only 4.6% of cancers were confined to the TZ, 45.3% of all prostate cancer patients had TZ involvement.

Treatment of locally advanced adenoid cystic carcinoma of the trachea with neutron radiotherapy.

PURPOSE To examine the efficacy of fast neutron radiotherapy in the treatment of locally advanced adenoid cystic carcinoma (ACC) of the trachea and to compare outcomes with and without high-dose-rate (HDR) endobronchial brachytherapy boost. METHODS AND MATERIALS Between 1989 and 2005, a total of 20 patients with ACC of the trachea were treated with fast neutron radiotherapy at the University of Washington. Of these 20 patients, 19 were treated with curative intent. Neutron doses ranged from 10.7 to 19.95 Gy (median, 19.2 Gy). Six of these patients received an endobronchial brachytherapy boost using an HDR (192)Ir source (3.5 Gy x 2 fractions). Median duration of follow-up was 46 months (range, 10-121 months). RESULTS The 5-year actuarial overall survival rate and median overall survival for the entire cohort were 89.4%, and 97 months, respectively. Overall survival was not statistically different among those patients receiving an endobronchial boost compared with those receiving neutron radiotherapy alone (100% vs. 68%, p = 0.36). The 5-year actuarial locoregional control rate for the entire cohort was 54.1%. The locoregional control rate was not statistically different among patients who received an endobronchial boost compared with those who received neutron radiotherapy alone (40% vs. 58%, p = 0.94). There were no cases of Grade > or =3 acute toxicity. There were 2 cases of Grade 3/4 chronic toxicity. CONCLUSIONS Fast neutron radiotherapy is an effective treatment for locally advanced adenoid cystic carcinoma of the trachea, with acceptable treatment-related toxicity.

WHOLE-PELVIS RADIOTHERAPY IN COMBINATION WITH INTERSTITIAL BRACHYTHERAPY: DOES COVERAGE OF THE PELVIC LYMPH NODES IMPROVE TREATMENT OUTCOME IN HIGH-RISK PROSTATE CANCER?

PURPOSE To compare biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) rates among high-risk prostate cancer patients treated with brachytherapy and supplemental external beam radiation (EBRT) using either a mini-pelvis (MP) or a whole-pelvis (WP) field. METHODS AND MATERIALS From May 1995 to October 2005, 186 high-risk prostate cancer patients were treated with brachytherapy and EBRT with or without androgen-deprivation therapy (ADT). High-risk prostate cancer was defined as a Gleason score of > or =8 and/or a prostate-specific antigen (PSA) concentration of > or =20 ng/ml. RESULTS With a median follow-up of 6.7 years, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 91.7% vs. 84.4% (p = 0.126), 95.5% vs. 92.6% (p = 0.515), and 79.5% vs. 67.1% (p = 0.721), respectively. Among those patients who received ADT, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 93.6% vs. 90.1% (p = 0.413), 94.2% vs. 96.0% (p = 0.927), and 73.7% vs. 70.2% (p = 0.030), respectively. Among those patients who did not receive ADT, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 82.4% vs. 75.0% (p = 0.639), 100% vs. 88% (p = 0.198), and 87.5% vs. 58.8% (p = 0.030), respectively. Based on multivariate analysis, none of the evaluated parameters predicted for CSS, while bPFS was best predicted by ADT and percent positive biopsy results. OS was best predicted by age and percent positive biopsy results. CONCLUSIONS For high-risk prostate cancer patients receiving brachytherapy, there is a nonsignificant trend toward improved bPFS, CSS, and OS rates when brachytherapy is given with WPRT. This trend is most apparent among ADT-naïve patients, for whom a significant improvement in OS was observed.

Long-term outcome for very high-risk prostate cancer treated primarily with a triple modality approach to include permanent interstitial brachytherapy

PURPOSE To evaluate outcome in the most unfavorable subset of high-risk prostate cancer patients treated with a combination of supplemental external beam radiation therapy (EBRT) and brachytherapy. METHODS AND MATERIALS Very high-risk prostate cancer was defined as follows: any Gleason score 10, Gleason score 8-9 with >50% of the biopsy cores positive for malignancy, Gleason score 8-9 with a prostate-specific antigen (PSA) >20ng/mL, any clinical stage T3, or any PSA >40ng/mL. One hundred thirty-one patients were identified who met the aforementioned criteria. The median followup was 6.6 years. One hundred twenty (91.6%) patients received supplemental EBRT and 100 (76.4%) received androgen deprivation therapy (median duration, 19.5 months; range, 4-36 months). The median postimplant day 0 D(90) (i.e., the minimum percentage of the prescription dose that covers the planning target volume) was 121.9% of prescription dose. Multiple clinical treatment and dosimetric parameters were evaluated for impact on the evaluated survival parameters. RESULTS The median pretreatment PSA and Gleason score were 11.0ng/mL and 8. One hundred ten (84%) patients had a Gleason score ≥8. At 9 and 12 years, the cause-specific survival, biochemical progression-free survival, and overall survival were 91.0% and 86.5%, 87.3% and 87.3%, and 70.5% and 60.5%, respectively. The most common cause of death was heart disease (22.2%) with deaths from nonprostate cancer (12.7%) and prostate cancer (8.3%) being less likely. CONCLUSIONS Permanent interstitial brachytherapy usually with supplemental EBRT and androgen deprivation therapy results in excellent biochemical control and cause-specific survival in the most unfavorable subset of high-risk prostate cancer patients. Death from diseases of the heart was more than twice as likely as death from prostate cancer.

Diagnostic Performance of Initial Transperineal Template-guided Mapping Biopsy of the Prostate Gland.

Objectives:To evaluate the utility of transperineal template-guided mapping biopsy (TTMB) of the prostate as an initial means of establishing tissue diagnosis. Materials and Methods:A total of 191 consecutive patients underwent TTMB of the prostate using an anatomic-based technique with sampling of 24 regions. All patients had elevated prostate-specific antigen on routine screening which was followed by a confirmatory prostate-specific antigen and none had undergone previous biopsy of the prostate. The locations of cancer involvement were recorded for each patient in an effort to approximate the percentage of men whose cancer would have been missed or Gleason score underestimated on a standard 12-core biopsy. The median number of submitted biopsy cores was 54.0. Results:Of the 191 study patients, 140 (73.3%) were diagnosed with cancer on TTMB. Among these biopsy-positive patients, 124 (88.6%) had clinically significant cancer. Eighty-nine of the biopsy-positive patients (64.6%) had a Gleason score of ≥7. A total of 34 of the 140 diagnosed cancers were identified exclusively in regions that fell outside of the theoretical 12-core biopsy scheme, suggesting that 24.3% of these cancers would have gone undiagnosed in the absence of TTMB. Among the 107 cancers that would have been diagnosed using a 12-core biopsy approach, 18 (16.8%) were upgraded to a Gleason score of ≥7 with mapping biopsy. Conclusions:TTMB appears to provide more detailed information about prostate cancer grade and location compared with standard 12-core biopsy scheme. This information may serve as a baseline reference for image-guided biopsy (ie, magnetic resonance imaging) regimens, may facilitate clinical decision making and aid in the appropriate selection of patients for active surveillance.