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Biomedical subjects

Ronald D Ennis

Publications and source records attributed to Ronald D Ennis.

13 recordsLinked to original sources
PubMed2007

Phase II study of neoadjuvant androgen deprivation followed by external-beam radiotherapy with 9 months of androgen deprivation for intermediate- to high-risk localized prostate cancer.

PURPOSE: To evaluate the toxicity and efficacy of individualized neoadjuvant androgen deprivation (AD) to maximal response followed by external beam radiotherapy (RT) with continued AD for a total of 9 months in a prospective phase II trial. PATIENTS AND METHODS: One hundred twenty-three patients received a total of 9 months of flutamide and luprolide combined with RT. RT initiation was individualized to begin after maximum response to AD as assessed by monthly digital rectal examination and prostate-specific antigen (PSA). The neoadjuvant phase was restricted to no more than 6 months. RESULTS: Median time to initiation of RT was 4.7 months. Indications to begin RT (and their rates) were undetectable PSA (28%), PSA unchanged from one month to the next (46%), PSA rising from one month to the next (10%), 6 months of AD (14%), and other (2%). Five-year outcomes were biochemical disease-free survival, (DFS) 63% +/- 7%; clinical DFS, 75% +/- 5%; cancer-specific survival, 99% +/- 1%; and overall survival, 89% +/- 3%. Patients initiating RT after 6 months of AD had significantly lower biochemical and clinical DFS. Those patients whose testosterone recovered to normal after completion of AD had a significantly superior survival rate. Of those patients potent before treatment, 65% remained so at last follow-up. CONCLUSION: The combination of 9 months of AD and RT, with initiation of RT individualized on the basis of maximum response to AD, achieves disease control rates comparable with past studies, while preserving potency in many patients. Further studies are warranted to determine the optimal combination of AD and RT in this patient population.

Adenocarcinoma↗
PubMed2006

The role of perioperative chemotherapy in the treatment of urothelial cancer.

Cancer of the urothelium is the fourth most common malignancy in men in the U.S. and the ninth most common in women. More than 63,000 Americans will be diagnosed with bladder cancer this year (47,010 men and 16,200 women), and more than 13,000 (8,970 men and 4,210 women) can expect to die of their disease. The approximate 5:1 ratio of incidence to mortality roughly parallels the frequency of superficial to invasive disease. Efforts to improve this ratio have generated a potential paradigm shift in the treatment of urothelial cancer, incorporating increasingly active chemotherapy into treatment regimens for high-risk tumors in both the pre-and postoperative settings. This review summarizes the evolution of chemotherapeutic treatment of urothelial cancer and the rationale for its perioperative administration and addresses the future directions of clinical research in this field.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Rectal toxicity profile after transperineal interstitial permanent prostate brachytherapy: use of a comprehensive toxicity scoring system and identification of rectal dosimetric toxicity predictors.

PURPOSE: To better understand rectal toxicity after prostate brachytherapy, we employed the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 3.0), a comprehensive system with distinct and separately reported gastrointestinal adverse event items (unlike Radiation Therapy Oncology Group morbidity scoring), to evaluate item-specific postimplant rectal toxicities. METHODS AND MATERIALS: We analyzed 135 patients treated with brachytherapy +/- hormonal therapy, using CTCAE v3.0 to score acute/late rectal toxicities (median follow-up, 41 months). Dosimetric parameters were evaluated for ability to predict toxicities. RESULTS: Use of CTCAE yielded a novel rectal toxicity profile consisting of diarrhea, incontinence, urgency, proctitis, pain, spasms, and hemorrhage event rates. No item had a < 5% Grade 1-2 acute toxicity rate (except spasms). Rectal dosimetry predicted late toxicities: for diarrhea, 5% Grade 1 toxicity rate for %V25 (percent of rectal volume receiving 25% of prescribed prostate dose) < or = 25% vs. 60% for %V25 > 25% (p < 0.001); for maximum toxicity, 10% Grade 1 toxicity rate for %V10 < or = 40% vs. 44% for %V10 > 40% (p = 0.007). CONCLUSIONS: A comprehensive understanding of item-specific postimplant rectal toxicities was obtained using CTCAE. Rectal %V25 > 25% and %V10 > 40% predicted worse late diarrhea and maximum toxicity, respectively.

Aged↗
PubMed2004

Localization of neurovascular bundles on pelvic CT and evaluation of radiation dose to structures putatively involved in erectile dysfunction after prostate brachytherapy.

PURPOSE: To (a) locate neurovascular bundles (NVB) on pelvic CT and (b) retrospectively evaluate relationships between radiation dose to structures putatively involved in prostate brachytherapy-induced erectile dysfunction (ED) and incidence of postbrachytherapy ED. METHODS AND MATERIALS: (a) Right/left NVB were identified on nine prostate MRIs. Structures visible on MRI and CT were cross-referenced. Cross-sectional area of each NVB was measured. (b) All patients treated with implant alone and whose treatment was planned on Variseed (Varian Medical Systems, Palo Alto, CA), with follow-up of >12 months were included; n = 41. Median follow-up was 20 months. All patients were potent (+/- sildenafil) before implant (erection sufficient for intercourse). The right/left NVB (using results from part "a"), penile bulb, and right/left crus were outlined on postimplant CT. Volumes and doses to these structures were calculated. RESULTS: (a) On prostate MRI, NVB was consistently located where the prostate border bends away from the levator ani, at the gland's smallest radius of curvature. Average area of the circle best encompassing the NVB = 0.27 cm(2); diameter was 0.58 cm. (b) 11 of 41 (27%) patients had ED; 30 of 41 were potent (15 with sildenafil). There was no significant difference between potent/impotent patients in isotope, age, diabetes, hypertension, follow-up, or volume of prostate, bulb, right/left NVB, or right/left crus. There was a relationship between smoking and ED (p = 0.05). There was a relationship between bulb %D90 and ED: >10% 67% (4 of 6) vs. <10% 20% (7 of 35) (p = 0.03), which remained when controlling for smoking. There was no relationship between dose to left NVB and potency. There was paradoxical decreased risk of ED with right NVB %V100 >60% (p = 0.019), and right NVB %D60 >100% (p = 0.003). There was no relationship between dose to right/left crus and ED. CONCLUSIONS: A reliable method for localizing NVB on CT is demonstrated. There is no increased risk of prostate brachytherapy-induced ED with increasing dose to crus or NVB at the doses given in this study. There is a possible dose-response relationship between dose to the bulb and risk of ED.

Brachytherapy↗
PubMed2004

Combined chemotherapy and external beam radiotherapy for transitional cell carcinoma of the bladder.

A growing body of evidence supports the treatment of invasive transitional cell carcinoma of the bladder with transurethral resection, chemotherapy, and external beam radiotherapy. Randomized trials have demonstrated the superiority of chemotherapy plus radiotherapy to radiotherapy alone. Several series with 10 years of follow-up demonstrate that the success of this approach can be maintained. Preservation of the urothelium, however, results in continued risk of de novo bladder cancer development in addition to the possibility of recurrence. Thus, continued close surveillance and treatment of subsequent superficial or invasive bladder cancer is an essential component of this bladder preservation approach. Concomitant cisplatin chemotherapy and radiotherapy or initial (neoadjuvant) combination cisplatin-based chemotherapy followed by radiotherapy are the two options best supported by the literature. How these regimens compare with each other and with cystectomy-based treatment remains to be defined.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Prostate localization using transabdominal ultrasound imaging.

PURPOSE: Adding margin around a target is done in an attempt to ensure complete coverage of the target. The B-mode acquisition and targeting (BAT) system allows ultrasound imaging of the prostate in patients with a full bladder. This provides a setup tool for patients with localized prostate cancer that takes into account real-time prostate position and may make it possible to decrease tumor margins. Prostate localization using the conventional setup verification method and daily isocenter shifts recommended by the ultrasound imaging system (BAT) were compared and analyzed. METHODS AND MATERIALS: Daily treatment isocenter shifts for patients with localized adenocarcinoma of the prostate, obtained from two different imaging modalities, electronic portal imaging (EPI) and BAT, were calculated. We studied the difference in patient setup error calculated using BAT contour alignment and measured from EPI; the reproducibility of BAT contour alignment; intrafraction prostate motion; and how the BAT imaging procedure itself affected the prostate position. Prostate motion relative to its position during simulation was calculated by subtracting the EPI-measured isocenter shifts from the corresponding BAT-defined isocenter shifts. BAT reproducibility was measured by taking a verification BAT image after the patient was moved according to the initial BAT-defined isocenter shifts. Intrafraction prostate motion was measured by repeating BAT imaging at the end of a treatment fraction. The BAT imaging effect on prostate position was studied by examining the effect of suprapubic pressure on seed position in patients after a seed implant. RESULTS: The mean BAT isocenter shifts for prostate motion were 0.32 +/- 0.46 cm in the lateral, 0.31 +/- 0.73 cm in the superoinferior, and 0.32 +/- 0.56 cm in the AP directions. Isocenter shifts obtained from EPI measurements were significantly smaller, with a mean of 0.05 +/- 0.24 cm in the lateral, 0.01 +/- 0.11 cm in the superoinferior and -0.11 +/- 0.29 cm in the AP directions. This larger shift seen by BAT was due to prostate motion. For BAT reproducibility, the results showed that for BAT verification images, 90% of the lateral shifts were <0.2 cm, 93% of the superoinferior shifts were <0.3 cm, and 83% of the AP shifts were <0.2 cm. The mean isocenter shift (intrafraction localization error) during patient treatment fraction was 0.02 +/- 0.28 cm in the lateral, 0.04 +/- 0.48 cm in the superoinferior, and 0.0 +/- 0.32 cm in the AP direction. The BAT procedure itself induced an average motion of 1 mm in the AP and superoinferior directions. CONCLUSIONS: Prostate patient setup verification on the basis of bony anatomy position does not reflect the actual prostate position. BAT ultrasound target alignment provides a real-time prostate localization system that may make it possible to measure prostate position variations and reduce margins.

Humans↗
PubMed2003

RT-PCR for PSA as a prognostic factor for patients with clinically localized prostate cancer treated with radiotherapy.

OBJECTIVES: To study prospectively the prognostic significance of the reverse transcriptase-polymerase chain reaction (RT-PCR) assay for patients with prostate cancer treated definitively with external beam radiotherapy. The RT-PCR assay for prostate-specific antigen (PSA) has been used to detect circulating prostate cancer cells in the serum of patients with prostate cancer. METHODS: In prospective fashion, serum RT-PCR testing was performed before and/or after definitive therapy, with the results scored as positive or negative. The results were analyzed for 161 patients, and the RT-PCR result was correlated with the treatment outcome. RESULTS: The median follow-up was 29 months. The pretreatment RT-PCR result was not predictive of biochemical relapse-free survival (bRFS) or clinical disease-free survival (DFS). Of 25 patients with T3-T4 tumors, those with a negative pretreatment RT-PCR result had better bRFS and a trend was noted toward better DFS compared with those with a positive result. Among patients with Gleason score 8 to 10 tumor who underwent pretreatment testing (n = 19), those with a negative RT-PCR result had better bRFS and DFS compared with those with a positive result. A trend toward better bRFS was seen for patients with negative versus positive post-treatment RT-PCR results. The DFS was better for patients with negative versus positive post-treatment RT-PCR results. CONCLUSIONS: RT-PCR, when obtained before radiotherapy, may be predictive of outcome for patients with more advanced stages or higher Gleason scores. Post-treatment testing predicted for clinical relapse. Additional study is needed before RT-PCR is used regularly in clinical practice.

Androgen Antagonists↗
PubMed2002

Hyperbaric oxygen for the treatment of radiation cystitis and proctitis.

Chronic radiation cystitis and radiation proctitis are known complications of the use of radiotherapy in the treatment of pelvic malignancies. These complications are, in part, due to endothelial damage and decreased vascularity and oxygenation to pelvic tissues. Hyperbaric oxygen therapy may be able to improve oxygenation and induce angiogenesis in damaged organs, resulting in recovery from radiation injury. Several studies have shown significant rates of response to hyperbaric oxygen treatment, however, no randomized trial exists to definitively demonstrate its effectiveness for cystitis and proctitis. In addition, concerns exist regarding the durability of the beneficial effect.

Cystitis↗
PubMed2002

Ultrasonic spectrum-analysis and neural-network classification as a basis for ultrasonic imaging to target brachytherapy of prostate cancer.

Conventional B-mode ultrasound is the standard means of imaging the prostate for guiding prostate biopsies and planning brachytherapy of prostate cancer. Yet B-mode images do not allow adequate visualization of cancerous lesions of the prostate. Ultrasonic tissue-typing imaging based on spectrum analysis of radiofrequency echo signals has shown promise for overcoming the limitations of B-mode imaging for visualizing prostate tumors. Tissue typing based on radiofrequency spectrum analysis uses nonlinear methods, such as neural networks, to classify tissue by using spectral-parameter and clinical-variable values. Two- and three-dimensional images based on these methods show potential for improving the guidance of prostate biopsies and the targeting of radiotherapy of prostate cancer. Two-dimensional images have been imported into instrumentation for real-time biopsy guidance and into commercial dose-planning software for brachytherapy planning. Three-dimensional renderings seem to be capable of depicting locations and volumes of cancer foci.

Brachytherapy↗
PubMedDate not supplied

Postprostatectomy salvage radiation therapy for prostate cancer: impact of pathological and biochemical variables and prostate fossa biopsy.

PURPOSE: A subgroup of prostate cancer patients who have experienced biochemical relapse after radical retropubic prostatectomy (RRP) can benefit from radiation therapy to the prostate fossa. These patients demonstrate biochemical relapse secondary to local failure in the absence of distant failure. In order to define this subgroup, we investigated the impact of pathological and biochemical variables and pre-radiation therapy biopsy of the prostate fossa on biochemical disease-free survival (bNED) and initial prostate-specific antigen response. METHODS: Sixty-two patients with localized prostate cancer who had biochemical relapse after RRP were treated with post-RRP radiation therapy localized to the prostate fossa (median dose, 6120 cGy) and were subsequently followed up for a median time of 47 months. Cox regression analyses and Kaplan-Meier estimates for bNED were used to identify prognostic variables. The Fisher's exact test was used to test the interaction of initial prostate-specific antigen response with identified prognostic variables. RESULTS: Cox regression analysis of bNED as a function of pathological and biochemical parameters showed that only Gleason's score was a significant predictor of bNED. On univariate analysis, seminal vesicle involvement was also found to be a significant predictor. Prostate fossa biopsy result was not significantly related to bNED. Because of the overall high rates of biochemical failure, we wished to identify a high-risk subgroup that did not have local relapse as a component of biochemical relapse after RRP. We assessed initial biochemical response following radiation therapy as a surrogate for local relapse. A complete biochemical response was observed in 50% of patients, and a partial biochemical response was observed in an additional 34%, yielding an overall biochemical response rate of 84%. When stratified by Gleason's score, seminal vesicle, pre-radiation therapy prostate-specific antigen, and biopsy result, response rates greater than 50% were seen for all subgroups. CONCLUSIONS: Gleason's score and seminal vesicle involvement predicted bNED after post-RRP radiation therapy in our cohort. Overall biochemical response rates were high in all subgroups, suggesting that all subgroups demonstrated a high likelihood of residual local disease as a component of failure. Pre-radiation therapy biopsy was predictive of neither bNED nor overall biochemical response.

Adenocarcinoma↗
PubMedDate not supplied

Improved biochemical control and clinical disease-free survival with intraoperative versus preoperative preplanning for transperineal interstitial permanent prostate brachytherapy.

PURPOSE: We hypothesized that intraoperative preplanning for transperineal interstitial permanent prostate brachytherapy may yield better prostate cancer control than preoperative preplanning. We tested this hypothesis by comparing treatment outcomes of patients who underwent implantation using these two preplanning methods. PATIENTS AND METHODS: We analyzed the data of 135 consecutive patients with localized prostate cancer treated from 1996 to 2001 with transperineal interstitial permanent prostate brachytherapy+/-preimplantation hormonal therapy: 42 received preoperative preplanning (group 1), and 93 underwent intraoperative preplanning (group 2). Biochemical status was assessed using two failure definitions: American Society for Therapeutic Radiology and Oncology (ASTRO) (three consecutive rises in prostate-specific antigen level) and Houston (prostate-specific antigen level>or=current nadir+2 ng/mL). Clinical disease-free survival and postimplantation dosimetry were also examined. RESULTS: All disease control outcomes were superior for group 2. The 4-year ASTRO biochemical no evidence of disease rate was 80% for group 1 versus 94% for group 2. The 4-year Houston biochemical no evidence of disease rate was 82% for group 1 versus 96% for group 2. The 4-year clinical disease-free survival rate was 87% for group 1 versus 99% for group 2. Preplanning method (preoperative versus intraoperative) remained predictive of disease control outcomes in multivariate analyses with the covariates of pretreatment prostate-specific antigen level, Gleason score, clinical stage, and case sequence number (proxy for brachytherapist experience and "stage migration"). Dosimetric prostate coverage was superior for group 2. The mean percentage of the prescription dose delivered to 90% of the prostate volume (%D90) was 75% for group 1 versus 90% for group 2. A %D90>or=70% predicted for improved disease control; fewer group 1 than 2 patients met this dosimetric criterion (55% versus 87%). DISCUSSION: Intraoperative preplanning yielded superior disease control outcomes in this analysis, likely due at least in part to improved dosimetric prostate coverage with this method. Although not mandatory for obtaining high prostate brachytherapy efficacy, intraoperative preplanning nevertheless may offer an excellent means of improving dosimetric prostate coverage and therefore disease control outcomes.

Adenocarcinoma↗