Torsional force microscopy of van der Waals moirés and atomic lattices.

In a stack of atomically thin van der Waals layers, introducing interlayer twist creates a moiré superlattice whose period is a function of twist angle. Changes in that twist angle of even hundredths of a degree can dramatically transform the system's electronic properties. Setting a precise and uniform twist angle for a stack remains difficult; hence, determining that twist angle and mapping its spatial variation is very important. Techniques have emerged to do this by imaging the moiré, but most of these require sophisticated infrastructure, time-consuming sample preparation beyond stack synthesis, or both. In this work, we show that torsional force microscopy (TFM), a scanning probe technique sensitive to dynamic friction, can reveal surface and shallow subsurface structure of van der Waals stacks on multiple length scales: the moirés formed between bi-layers of graphene and between graphene and hexagonal boron nitride (hBN) and also the atomic crystal lattices of graphene and hBN. In TFM, torsional motion of an Atomic Force Microscope (AFM) cantilever is monitored as it is actively driven at a torsional resonance while a feedback loop maintains contact at a set force with the sample surface. TFM works at room temperature in air, with no need for an electrical bias between the tip and the sample, making it applicable to a wide array of samples. It should enable determination of precise structural information including twist angles and strain in moiré superlattices and crystallographic orientation of van der Waals flakes to support predictable moiré heterostructure fabrication.

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.

Erectile dysfunction is predictive of all-cause mortality in patients with prostate cancer treated with permanent interstitial brachytherapy.

OBJECTIVE: To evaluate the relationship between pre-treatment erectile function and all-cause mortality in patients with prostate cancer treated with brachytherapy. PATIENTS AND METHODS: In all, 1279 consecutive patients with clinically localized prostate cancer and pre-implant erectile function assessed by the International Index of Erectile Function-6 (IIEF-6) underwent brachytherapy. Potency was defined as an IIEF-6 score of ≥13 without pharmacological or mechanical support. Patients were stratified into IIEF-6-score cohorts (≤12, 13-23 and 24-30). The median follow-up was 5.0 years. RESULTS: The 8-year overall survival (OS) of the study population was 85.1%. The 8-year OS for IIEF-6scores ≤12, 13-23 and 24-30 were 78.0%, 92.8% and 91.4%, respectively (P < 0.001). Cardiovascular events accounted for a significant portion of deaths in each IIEF-6 group. When combined with other risk factors for cardiovascular disease, an IIEF-6 score of ≤12 had an additive effect on all-cause mortality (IIEF-6 score of ≤12 and less than two comorbidities vs two or more comorbidities were 18.2% and 32.1%). CONCLUSIONS: A pre-implant IIEF-6score of ≤12 was associated with a higher incidence of all-cause mortality. Pre-treatment erectile dysfunction is a surrogate for underlying vascular pathology, probably explaining the lower OS in this subset of patients. Aggressive treatment of medical co-morbidity is warranted to impactOS.

ACR-ABS-ASTRO Practice Parameter for Transperineal Permanent Brachytherapy of Prostate Cancer.

AIM/OBJECTIVES/BACKGROUND: The American College of Radiology (ACR), American Brachytherapy Society (ABS), and American Society for Radiation Oncology (ASTRO) have jointly developed the following practice parameter for transperineal permanent brachytherapy of prostate cancer. Transperineal permanent brachytherapy of prostate cancer is the interstitial implantation of low-dose rate radioactive seeds into the prostate gland for the purpose of treating localized prostate cancer. METHODS: This practice parameter was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters-Radiation Oncology of the Commission on Radiation Oncology, in collaboration with ABS and ASTRO. RESULTS: This practice parameter provides a framework for the appropriate use of low-dose rate brachytherapy in the treatment of prostate cancer either as monotherapy or as part of a treatment regimen combined with external-beam radiation therapy. The practice parameter defines the qualifications and responsibilities of all involved radiation oncology personnel, including the radiation oncologist, medical physicist, dosimetrist, radiation therapist, and nursing staff. Patient selection criteria and the utilization of supplemental therapies such as external-beam radiation therapy and androgen deprivation therapy are discussed. The logistics of the implant procedure, postimplant dosimetry assessment, and best practices with regard to safety and quality control are presented. CONCLUSIONS: Adherence to established standards can help to ensure that permanent prostate brachytherapy is delivered in a safe and efficacious manner.

Prostate cancer death is unlikely in high-risk patients following quality permanent interstitial brachytherapy.

OBJECTIVE: To evaluate cause-specific survival (CSS), biochemical progression-free survival (bPFS) and overall survival (OS) in high-risk prostate cancer brachytherapy patients. PATIENTS AND METHODS: From April 1995 to June 2005, 284 patients with high-risk prostate cancer (Gleason score ≥ 8 or prostate-specific antigen > 20 ng/mL or clinical stage ≥ T2 c) underwent brachytherapy. Supplemental external beam radiation therapy was given to 257 (90.5%) patients and 179 (63.0%) received androgen deprivation therapy (ADT). Median follow up was 7.8 years. The median post-implant day 0 D90 was 118.9% of prescription dose. Patients with metastatic prostate cancer or castrate-resistant disease without obvious metastases who died of any cause were classified as dead from prostate cancer. Multiple parameters were evaluated for impact on survival. RESULTS: Twelve-year CSS, bPFS and OS were 94.2%, 89.0% and 69.7%. On multivariate analysis, bPFS was best predicted by percent positive biopsies and ADT. The analysis failed to identify any predictors for CSS, while OS was highly correlated with patient age, percent positive biopsies and diabetes. Fourteen percent of patients died from diseases of the heart, while 8%, 8% and 6% of patients died from non-prostate cancer, other causes and prostate cancer, respectively. When OS was stratified by patients with 0-3 vs ≥ 4 comorbidities, the 12-year OS was 73.0% and 52.7% (P = 0.036). CONCLUSIONS: High-quality brachytherapy results in favourable bPFS and CSS for high-risk patients. Death from diseases of the heart is more than twice as likely as death from prostate cancer. Strategies to improve cardiovascular health may positively impact OS.

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.

Primary causes of death after permanent prostate brachytherapy.

PURPOSE: To evaluate the primary causes of death in low-risk (low-risk), intermediate-risk (intermediate-risk), and high-risk (high-risk) patients undergoing permanent prostate brachytherapy with or without supplemental therapies. METHODS AND MATERIALS: From April 1995 through November 2004, a total of 1,354 consecutive patients underwent prostate brachytherapy. All patients underwent brachytherapy >3 years before analysis. Of the patients, 532 (39.3%) received androgen deprivation therapy and 703 (51.9%) received supplemental radiation therapy. The median follow-up was 5.4 years. Multiple parameters were evaluated as predictors of cause-specific, biochemical progression-free, and overall survival. RESULTS: The 10-year cause-specific survival was 97.0% (99.7%, 99.0%, and 90.1% for low-risk, intermediate-risk, and high-risk patients). Overall survival was 76.7% (82.5%, 78.3%, and 67.6% for low-, intermediate-, and high-risk patients, respectively). The cumulative death rate for cardiovascular disease was 11.5% (8.7%, 9.3%, and 19.8% for low-, intermediate-, and high-risk patients). The death rate from second malignancies (nonprostate cancer) was 7.2% and was not substantially different when stratified by risk group. Death from all other causes was 6.5% for the entire cohort but 1.3%, 5.0%, and 10.8% for low-, intermediate-, and high-risk patients. In multivariate analysis, death from prostate cancer was best predicted by Gleason score and risk group, whereas death from cardiovascular disease, nonprostate cancer, and all other causes were most closely related to patient age and tobacco use. CONCLUSIONS: Although cardiovascular mortality was the predominant cause of death, prostate cancer was responsible for approximately 10% of all deaths. In particular, overall survival was poorest in the high-risk group. Although high-risk patients were most likely to die of prostate cancer, the divergence in overall survival between high-risk and lower-risk patients primarily resulted from an excess of cardiovascular deaths. Changes in lifestyle to improve cardiovascular health may improve overall survival in patients with clinically localized prostate cancer.

Interstitial brachytherapy should be standard of care for treatment of high-risk prostate cancer.

High-risk prostate cancer represents a therapeutic challenge for both the urologist and radiation oncologist. Biochemical outcomes with radical prostatectomy and external-beam radiation therapy are poor in this subset of patients. These unfavorable results have led some to believe that high-risk prostate cancer is not curable with conventional treatment approaches, which has been an impetus for many of the current trials using neoadjuvant chemotherapy and prostatectomy. With the established efficacy of interstitial brachytherapy, these efforts are likely excessive. Most modern trials indicate excellent biochemical control rates among high-risk patients treated with an aggressive locoregional approach that includes brachytherapy. A thoughtful review of the literature would suggest that interstitial brachytherapy offers a therapeutic advantage over other local treatment modalities and should be considered standard treatment for aggressive organ-confined prostate cancer.

Location and Grade of Prostate Cancer Diagnosed by Transperineal Template-guided Mapping Biopsy After Negative Transrectal Ultrasound-guided Biopsy.

OBJECTIVES: To determine the location and grade of prostate cancer diagnosed by transperineal template-guided mapping (TTMB) after negative transrectal ultrasound-guided (TRUS) biopsy. MATERIALS AND METHODS: This analysis consisted of 1118 consecutive patients who underwent TTMB from January 2005 to August 2015. Eight hundred thirty-five underwent TTMB after at least 1 negative TRUS biopsy and 283 underwent TTMB as the first biopsy procedure. The study population was divided into cohorts based on the number of prior TRUS biopsy sessions (0, 1, 2, and ≥3). No patient underwent multiparametric magnetic resonance imaging. Differences in location and cancer grade detected on TTMB were evaluated as a function of the number of prior TRUS biopsies. RESULTS: Of the 1118 patients, 679 were diagnosed with prostate cancer. This included 208, 325, 104, and 42 patients who underwent 0, 1, 2, and ≥3 prior TRUS biopsies. The incidence of cancer detection on TTMB decreased as the number of prior TRUS biopsies increased (73.5% vs. 62.4% vs. 51.7% vs. 37.2%, P<0.001); however, it became increasingly likely that TTMB would detect anterior prostate only as the number of prior TRUS biopsies increased (P=0.007). Moreover, the incidence of high grade cancer (Gleason score ≥7) in the anterior gland increased with the number of previous TRUS biopsies. CONCLUSIONS: TTMB detected prostate cancer in over half of the patients with one or more negative TRUS biopsies. The majority of TTMB detected cancers were Gleason score ≥7. As the number of prior TRUS biopsies increased, there was a commensurate increase in the proportion of high-grade, anterior only disease.

The impact of acute urinary morbidity on late urinary function after permanent prostate brachytherapy.

PURPOSE: Acute prostate brachytherapy-related morbidity is dominated by urinary symptomatology. In this study, we evaluated the effect of severe early brachytherapy-related urinary morbidity on late urinary function. METHODS AND MATERIALS: From January 1998 to September 2003, 1029 patients were implanted for clinical stage T1b-T3a (2002 American Joint Committee on Cancer [AJCC] criteria) prostate cancer. Five hundred sixteen (50.1%) received supplemental external beam radiation therapy and 440 (42.8%) received androgen deprivation therapy. Severe acute urinary morbidity (SAUM) was defined as a dysuria frequency score of at least 4 (of 5), a dysuria severity score of at least 8 (of 10), an internation prostate symptom score (IPSS) elevated to at least 30 or 15 above preimplant value for 4 weeks, and/or requirement of a urinary catheter for at least 5 days. Dysuria severity and frequency resolution were defined as a return to within one point of baseline. IPSS resolution was defined as a return to within two points of baseline. RESULTS: Of the 1029 patients, 175 met at least one of the criteria for inclusion. Dysuria frequency resolved in 5.0 vs. 1.3 weeks and dysuria severity in 5.7 vs. 1.4 weeks, for patients with and without SAUM. The mean time for IPSS resolution was 13.8 vs. 6.6 weeks, for patients with and without SAUM. The incidence of transurethral resection (2.3% [4/173] vs. 1.5% [13/841]) and bulbomembranous urethral strictures (2.2% [4/175] vs. 1.8% [15/854]) were comparable among patients with and without SAUM. CONCLUSIONS: Patients experiencing brachytherapy-related SAUM have long-term urinary function and complications comparable to patients who did not develop SAUM.

The American College of Radiology and the American Brachytherapy Society practice parameter for the performance of radionuclide-based high-dose-rate brachytherapy.

Brachytherapy is a radiation therapy method in which radionuclide sources are used to deliver a radiation dose at a distance of up to a few centimeters by surface, intracavitary, intraluminal, or interstitial application. This practice parameter refers only to the use of radionuclides for brachytherapy. Brachytherapy alone or combined with external beam therapy plays an important role in the management and treatment of patients with cancer. High-dose-rate (HDR) brachytherapy uses radionuclides such as iridium-192 at dose rates of 20 cGy per minute (12 Gy per hour) or more to a designated target point or volume. High-dose-rate (HDR) brachytherapy is indicated for treating malignant or benign tumors where the treatment volume or targeted points are defined and accessible.

The American College of Radiology and the American Brachytherapy Society practice parameter for transperineal permanent brachytherapy of prostate cancer.

Transperineal permanent brachytherapy is a safe and effective 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 the American Brachytherapy Society (ABS) has produced practice parameters for LDR prostate brachytherapy. These practice parameters define 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 guidelines, and attention to radiation safety procedures and documentation are presented. Adherence to these parameters can be part of ensuring quality and safety in a successful prostate brachytherapy program.

Effect of metal hip prosthesis on the accuracy of electromagnetic localization tracking.

PURPOSE: To quantify the effect of metal hip prosthesis on the ability to track and localize electromagnetic transponders. METHODS AND MATERIALS: Three Calypso Beacon (Varian Medical Systems, Palo Alto, CA) transponders were implanted into 2 prostate phantoms. The geometric center of the transponders were identified on computed tomography and set as the isocenter. With the phantom stationary on the treatment table and the tracking array 14-cm above the isocenter, data were acquired by the Calypso system at 10 Hz to establish the uncertainty in measurements. Transponder positional data were acquired with unilateral hip prostheses of different metallic compositions and then with bilateral hips placed at variable separation from the phantom. RESULTS: Regardless of hip prosthesis composition, the average vector displacement in the presence of a unilateral prosthesis was <0.5 mm. The greatest contribution to overall vector displacement occurred in the lateral dimension. With bilateral hip prosthesis, the average vector displacement was 0.3 mm. The displacement in the lateral dimension was markedly reduced compared with a unilateral hip, suggesting that there was a countervailing effect with bilateral hip prosthesis. The greatest average vector displacement was 0.6 mm and occurred when bilateral hip prostheses were placed within 4 cm of the detector array. CONCLUSIONS: Unilateral and bilateral hip prostheses did not have any meaningful effect on the ability to accurately track electromagnetic transponders implanted in a prostate phantom. At clinically realistic distances between the hip and detection array, the average tracking error is negligible.

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.

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.

Gleason score 7 prostate cancer treated with interstitial brachytherapy with or without supplemental external beam radiation and androgen deprivation therapy: is the primary pattern on needle biopsy prognostic?

PURPOSE: To evaluate the effect of primary Gleason pattern on biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) in Gleason 7 prostate cancer patients treated with low-dose-rate (LDR) interstitial brachytherapy with or without supplemental external beam radiation therapy and androgen deprivation therapy. METHODS AND MATERIALS: We retrospectively reviewed the medical records of 932 consecutive patients with biopsy-confirmed Gleason 7 prostate cancer who received LDR interstitial brachytherapy as a component of their definitive treatment regimen. Treatment outcomes were compared between patients with primary Gleason pattern 3 and 4. RESULTS: With a median followup of 7.4 years, the 10- and 14-year bPFS, CSS, and OS for the entire Gleason 7 study group were 95.7/95.7%, 98.6/98.6% and 77.2/64.3%, respectively. When biochemical control was evaluated as a function of primary Gleason pattern, the primary pattern 3 had a statistically higher 10- and 14-year bPFS (97.8/97.8% vs. 93.1/93.1%, p=0.006). The Gleason pattern 3 patients also trended toward a higher 10- and 14-year CSS (99.3/99.3% vs. 96.9/96.9%, p=0.058). OS was not statistically different between the two Gleason 7 cohorts. CONCLUSIONS: Gleason 7 prostate cancer patients treated with LDR interstitial brachytherapy have an excellent long-term outcome. There was a small but statistically significant advantage in bPFS and a trend toward improved CSS in patients with a primary Gleason pattern of 3.

American College of Radiology (ACR) and American Society for Radiation Oncology (ASTRO) practice guideline for the performance of total body irradiation (TBI).

Total body irradiation (TBI) is a specialized radiotherapy technique. It is frequently used as a component of treatment plans involving hematopoietic stem cell transplant for a variety of disorders, most commonly hematologic malignancies. A variety of treatment delivery techniques, doses, and fractionation schemes can be utilized. A collaborative effort of the American College of Radiology and American Society for Radiation Oncology has produced a practice guideline for delivery of TBI. The guideline defines the qualifications and responsibilities of the involved personnel, including the radiation oncologist, physicist, dosimetrist, and radiation therapist. Review of the typical indications for TBI is presented, and the importance of integrating TBI into the multimodality treatment plan is discussed. Procedures and special considerations related to the simulation, treatment planning, treatment delivery, and quality assurance for patients treated with TBI are reviewed. This practice guideline can be part of ensuring quality and safety in a successful TBI program.

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.

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.

Higher percentage of positive biopsy cores and Gleason score are associated with a greater degree of prostate gland shrinkage after neoadjuvant cytoreductive therapy.

PURPOSE: To determine whether adverse pathologic features, including tumor grade and percent positive biopsy (PPB) cores, predict for prostate size reduction after neoadjuvant cytoreductive therapy. METHODS AND MATERIALS: Eighty-two consecutive patients who were diagnosed with prostate cancer by transperineal template-guided mapping biopsy (TTMB) received neoadjuvant cytoreductive therapy. The median number of biopsy cores was 59. Thirty patients received a leutinizing hormone-releasing hormone agonist and bicalutamide, whereas 52 patients received bicalutamide (50mg daily) and dutasteride (0.5mg daily). A transrectal ultrasound volumetric study of the prostate gland and ellipsoid volume determinations of the prostate gland and transition zone (TZ) were obtained immediately before TTMB and at 90 days (±7 days) after the initiation of neoadjuvant medical therapy. Univariate and multivariate regression analyses were performed to identify predictors of prostate gland and TZ volume reduction. RESULTS: At TTMB, the mean prostate volumetric and ellipsoid volumes were 55.4 cm(3) and 49.0 cm(3), respectively. After neoadjuvant medical therapy, the mean volumetric and ellipsoid prostate volumes were 30.8 cm(3) and 28.5 cm(3), respectively. On average, the prostate volume decreased by 43.9% and 41.0% on volumetric and ellipsoid measurements, respectively. The TZ volume decreased from 19.8 cm(3) to 10.1 cm(3) (mean volume reduction of 47.7%). In multivariate analysis, prostate volume cytoreduction was most closely associated with PPB (p=0.014), TTMB prostate volume (p=0.01), and drug regimen (p=0.001). CONCLUSIONS: The degree of prostate volume cytoreduction was positively associated with higher Gleason score and PPBs. Greater reductions in prostate volume may be an indicator of more aggressive cancer.