Prostatic Neoplasms: Kuban DA

Montie JE, Clark PE, Eisenberger MA, El-Galley R, Greenberg RE, Herr HW, Hudes GR, Kuban DA, Kuzel TM, Lange PH, Lele SM, Michalski J, Patterson A, Pohar KS, Richie JP, Sexton WJ, Shipley WU, Small EJ, Trump DL, Walther PJ, Wilson TG, Anonymous00046. · University of Michigan Comprehensive Cancer Center. · J Natl Compr Canc Netw. · Pubmed #19176203 No free full text.

This publication has no abstract.

Kuban DA, Dong L, Cheung R, Strom E, De Crevoisier R. · Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. · Semin Radiat Oncol. · Pubmed #15983943 No free full text.

Abstract: Ultrasound is a noninvasive, relatively easy, rapid, and real-time imaging technique for organ targeting for radiotherapy. Its application has been developed to a greater extent in prostate cancer than in other sites in which it has been shown to improve the accuracy of daily treatment delivery. With the move toward dose escalation and the need to maximally spare the adjacent critical structures through more conformal therapy and smaller field margins, an innovative technique for accurate and reproducible tumor targeting is mandatory. Basic ultrasound principles and organ location lend themselves well to the application of this modality in prostate cancer. Promising results using daily ultrasound-guided B-mode acquisition and targeting for patients with upper abdominal tumors suggest an area for additional trials and study. For breast cancer radiotherapy, ultrasound serves to define involved primary and nodal sites, especially in patients in whom surgical evaluation will not be the first therapeutic step.

Kuban DA, Thames HD, Shipley WU. · Department of Radiation Oncology and Biostatistics, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA. · J Urol. · Pubmed #15879766 No free full text.

Abstract: PURPOSE: We reviewed prostate specific antigen (PSA) definitions of recurrence after external beam radiation for prostatic cancer and related them to the definitions used for other treatment modalities. MATERIALS AND METHODS: The literature on defining recurrence after external beam radiation, brachytherapy and prostatectomy for prostate cancer was reviewed through a MEDLINE search to ensure completeness and the inclusion of all pertinent information. RESULTS: Although the definition, which is the current standard for estimating recurrence after external beam radiation, has proved to be a reasonable measure, alternative options that are more sensitive and specific have now been defined. Similar statistical testing and comparison must also be done for other treatment modalities since the choice of failure definitions has not been evaluated nearly as thoroughly for these therapies. As much as possible, outcome reporting should be done according to the same method to ensure fairness when comparisons are made. However, inherent differences between treatment modalities and their effect on PSA production must also be considered. CONCLUSIONS: With the latest available information from patients with long-term followup PSA definitions of tumor recurrence after external beam radiation for prostatic cancer must again be reviewed in a consensus conference format. The application of a universal PSA definition of tumor recurrence across multiple treatment modalities should also be explored.

Kuban DA, Thames HD, Levy LB. · Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77007, USA. · Oncology (Williston Park). · Pubmed #15209188 No free full text.

Abstract: The introduction of prostate-specific antigen (PSA) as a reliable tumor marker for prostate cancer brought significant changes in the end points used for outcome reporting after therapy. With regard to a definition of failure after radiation, a consensus was reached in 1996 that took into account the particular issues of an intact prostate after therapy. Over the next several years, the consensus definition issued by the American Society for Therapeutic Radiology and Oncology (ASTRO) was used and studied. Concerns and criticisms were raised. The sensitivity and specificity of this definition vs other proposals has been investigated, and differences in outcome analyzed and compared. Although the ASTRO definition came from analysis of datasets on external-beam radiation and most of the work on this topic has been with this modality, failure definitions for brachytherapy must be explored as well. The concept of a universal definition of failure that might be applied to multiple modalities, including surgery, should also be investigated, at least for comparative study and research purposes.

Kuban DA, Dong L. · Department of Radiation Oncology, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 97, Houston, TX 77007, USA. · Curr Urol Rep. · Pubmed #15161568 No free full text.

Abstract: The trend in prostate cancer radiation over the past several years has been to increase the dose to the gland while minimizing the dose to normal tissues. Intensity modulated radiation therapy is a computer-driven treatment planning and delivery system that has shown promise in improving disease-free outcome while decreasing the associated gastrointestinal and urinary complication rates. This technique continues to evolve, working toward image-guided radiation therapy, which is adjusted daily for positional and architectural changes of the gland.

Thames HD, D'Souza W, Kuban DA. · Department of Biomathematics, University of Maryland, Baltimore, USA. · Int J Radiat Biol. · Pubmed #14530158 No free full text.

Abstract: Dual interpretations are different radiobiological mechanisms that explain theoretically the same observed results. Radiobiological interpretations of the time factor are most frequently based on changes in total dose that produce a given effect. If this dose is increased by different mechanisms (e.g. increasing overall time and decreasing dose per fraction) at the same time, proposals for altered fractionation schemes based on the choice of one or the other mechanism, in principle, can lead to erroneous predictions of outcome. This is especially the case when the analyses are based on retrospective clinical data, where the influence of patient selection is unknown. Examples of dual interpretations taken from the literature on head and neck, melanoma and prostate cancer are discussed.

Kuban DA, Thames HD, Levy LB. · Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Box 97, TX 77030, Houston, USA. · World J Urol. · Pubmed #12923658 No free full text.

Abstract: The introduction of prostate-specific antigen (PSA) as a reliable tumor marker for prostate cancer brought significant changes in endpoints after therapy and in outcome reporting. Over the last 15 years we have collected follow-up information in this new era and struggled with failure definitions using this new tool. Parameters for failure after radiation were especially controversial due to the fact that, unlike surgery, a variable amount of normal prostate function and PSA production remained. In 1996, the ASTRO Consensus Conference established a PSA failure definition based on the available information at the time. It was commonly used for outcome reporting subsequently although criticisms have been voiced and alternate definitions proposed. A recently assembled multi-institutional database was used both for long-term outcome reporting with external beam radiation and to test various other failure definitions. A summary of these results and the associated issues are presented here.

Pollack A, Kuban DA, Zagars GK. · Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. · Urology. · Pubmed #12231041 No free full text.

Abstract: A number of retrospective and randomized trials have studied the effect of external-beam radiation therapy (EBRT) plus androgen deprivation therapy (ADT) on locally advanced/high-risk prostate cancer. Of 6 published randomized trials that have compared EBRT plus ADT with EBRT alone, 2 have shown a highly significant overall survival benefit for EBRT plus ADT, and 2 have demonstrated an advantage for the combination in patient subsets based on Gleason score. The results from the positive trials of EBRT plus ADT versus EBRT alone, as well as a recent report of a comparison of short-term (6 months) ADT plus EBRT versus long-term (>6 months) ADT plus EBRT, suggest that short-term ADT plus EBRT preferentially lengthens the survival of patients with Gleason score 2 to 6 disease, whereas for Gleason score 8 to 10 disease, prolongation of survival requires long-term ADT plus EBRT. These data are far from clear-cut because there are factors that confound interpretation of the subgroup analyses. Retrospective data on patients with positive lymph node status support the assertion that EBRT plus ADT prolongs survival to a greater degree than either treatment given individually. The weight of the available investigations on the survival effect of EBRT plus ADT supports its use on a routine basis for patients with high-risk prostate cancer. The results with long-term ADT are much more convincing than short-term ADT, and, as a consequence, 2 to 3 years are recommended.

Vance W, Tucker SL, de Crevoisier R, Kuban DA, Cheung MR. · Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #17161554 No free full text.

Abstract: PURPOSE: To determine the value of a 2-year post-radiotherapy (RT) prostate biopsy for predicting eventual biochemical failure in patients who were treated for localized prostate cancer. METHODS AND MATERIALS: This study comprised 164 patients who underwent a planned 2-year post-RT prostate biopsy. The independent prognostic value of the biopsy results for forecasting eventual biochemical outcome and overall survival was tested with other factors (the Gleason score, 1992 American Joint Committee on Cancer tumor stage, pretreatment prostate-specific antigen level, risk group, and RT dose) in a multivariate analysis. The current nadir + 2 (CN + 2) definition of biochemical failure was used. Patients with rising prostate-specific antigen (PSA) or suspicious digital rectal examination before the biopsy were excluded. RESULTS: The biopsy results were normal in 78 patients, scant atypical and malignant cells in 30, carcinoma with treatment effect in 43, and carcinoma without treatment effect in 13. Using the CN + 2 definition, we found a significant association between biopsy results and eventual biochemical failure. We also found that the biopsy status provides predictive information independent of the PSA status at the time of biopsy. CONCLUSION: A 2-year post-RT prostate biopsy may be useful for forecasting CN + 2 biochemical failure. Posttreatment prostate biopsy may be useful for identifying patients for aggressive salvage therapy.

Little DJ, Kuban DA, Levy LB, Zagars GK, Pollack A. · Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA. · Urology. · Pubmed #14550448 No free full text.

Abstract: OBJECTIVES: To assess patient-reported prostate cancer-specific quality of life 2 and 3 years after radiotherapy to the prostate in a randomized dose-escalation trial of 70 versus 78 Gy conducted from 1993 to 1998. METHODS: Two years after completing radiotherapy, a questionnaire that assessed bladder, rectal, and sexual function was sent to 301 patients in the study. Three years after treatment, a second questionnaire was sent to the 175 patients with adequate follow-up. RESULTS: Three years after radiotherapy, urinary incontinence was reported by 35% of patients, but only 6% required the use of a pad or other protective device. Patients reported increased leakage with a full bladder (urge incontinence) between the 2 and 3-year questionnaires (42% versus 50%; P = 0.03). At 3 years, 33% of patients reported rectal bleeding compared with 47% at 2 years (P = 0.006). Patients in the 78-Gy arm reported more frequent bowel movements at 3 years and less change in bowel function at 2 years than patients in the 70-Gy arm. Before radiotherapy, 84% of patients reported erections adequate for intercourse at least a few times during the previous year. After 2 and 3 years, this had decreased to 49% and 41%, respectively (P <0.02). CONCLUSIONS: By patient-reported questionnaire, 78 Gy produced an increase in bowel movement frequency and no increase in bladder or sexual side effects at 3 years compared with 70 Gy. Comparing the results 2 and 3 years after radiotherapy, the symptoms of rectal bleeding had improved, erectile function had decreased, and urinary urge incontinence had increased.

Pollack A, Zagars GK, Antolak JA, Kuban DA, Rosen II. · Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #12377318 No free full text.

Abstract: PURPOSE: A positive biopsy after external beam radiotherapy in patients free of any evidence of treatment failure is not synonymous with eventual recurrence. Although biopsy positivity is a predictor of outcome, the utility of biopsy status as a surrogate end point, the effect of radiation dose on biopsy status, and the interrelationships of these associations to prostate-specific antigen (PSA) nadir level are not well-defined. These issues were investigated in a cohort of men with Stage T1-T3 prostate cancer who were randomized to receive between 70 Gy and 78 Gy and were prospectively biopsied at about 2 years after the completion of radiotherapy (RT). METHODS AND MATERIALS: Of the 301 assessable patients in the trial, 168 underwent planned sextant or greater prostate post-RT biopsies in the absence of biochemical or clinical failure; this group constituted the study cohort. Of the 168 patients, 87 were in the 70-Gy arm and 81 in the 78-Gy arm. Biopsies were classified into four groups: negative (no tumor), atypical/suspicious cells (not diagnostic of carcinoma), carcinoma with treatment effect (CaTxEffect), and carcinoma without treatment effect (CaNoTxEffect). Any diagnosis of carcinoma in the specimen was classified as biopsy positive. Freedom from failure (FFF) included biochemical failure and/or clinical failure. Kaplan-Meier curves were calculated from the completion of RT. For those alive in the study cohort, the median follow-up was 65 months. RESULTS: The rate of biopsy without tumor was 42%; with atypical cells, it was 28%, with CaTxEffect 21%, and with CaNoTxEffect 9%. The overall biopsy positivity rate (CaTxEffect + CaNoTxEffect) was 30%; 28% in the 70-Gy group and 32% in the 78-Gy group (p = 0.52). The distribution of PSA nadir levels was 73% <or=0.5, 20% >0.5-1.0, 5% >1.0-2.0, and 1% >2.0 ng/mL. Significantly more patients randomized to 78 Gy had a PSA nadir of <or=0.5 ng/mL (80% vs. 67%; p = 0.02). No relationship was found between PSA nadir level and prostate biopsy status. The 5-year FFF rate for those classified as biopsy negative was 84% and for those biopsy positive was 60% (p = 0.0002). Radiation dose did not significantly alter FFF rates by prostate biopsy status. Nadir PSA level correlated with FFF, although this was dependent on the inclusion of the 2 patients with a PSA nadir >2.0 ng/mL. CONCLUSION: For patients free of treatment failure at the time of prostate biopsy 2 years after RT, the prognosis of no tumor cells was the same as that of atypical/suspicious cells and CaTxEffect was the same as CaNoTxEffect. The biopsy positivity rate was not altered by dose, suggesting that most of the outcome differences between the 70-Gy and 78-Gy groups were due to events occurring before prostate biopsy at 2 years and/or were not entirely dependent on biopsy status. Biopsy status is a strong prognostic factor, but, as an early end point, it may be misleading. PSA nadir appears to have little clinical value in patients treated to doses of >/=70 Gy who are failure free 2 years after RT.

Pollack A, Zagars GK, Starkschall G, Antolak JA, Lee JJ, Huang E, von Eschenbach AC, Kuban DA, Rosen I. · Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #12128107 No free full text.

Abstract: PURPOSE: A randomized radiotherapy dose escalation trial was undertaken between 1993 and 1998 to compare the efficacy of 70 vs. 78 Gy in controlling prostate cancer. METHODS AND MATERIALS: A total of 305 Stage T1-T3 patients were entered into the trial and, of these, 301 with a median follow-up of 60 months, were assessable. Of the 301 patients, 150 were in the 70 Gy arm and 151 were in the 78 Gy arm. The primary end point was freedom from failure (FFF), including biochemical failure, which was defined as 3 rises in the prostate-specific antigen (PSA) level. Kaplan-Meier survival analyses were calculated from the completion of radiotherapy. The log-rank test was used to compare the groups. Cox proportional hazard regression analysis was used to examine the independence of study randomization in multivariate analysis. RESULTS: There was an even distribution of patients by randomization arm and stage, Gleason score, and pretreatment PSA level. The FFF rates for the 70- and 78 Gy arms at 6 years were 64% and 70%, respectively (p = 0.03). Dose escalation to 78 Gy preferentially benefited those with a pretreatment PSA >10 ng/mL; the FFF rate was 62% for the 78 Gy arm vs. 43% for those who received 70 Gy (p = 0.01). For patients with a pretreatment PSA <or=10 ng/mL, no significant dose response was found, with an average 6-year FFF rate of about 75%. Although no difference occurred in overall survival, the freedom from distant metastasis rate was higher for those with PSA levels >10 ng/mL who were treated to 78 Gy (98% vs. 88% at 6 years, p = 0.056). Rectal side effects were also significantly greater in the 78 Gy group. Grade 2 or higher toxicity rates at 6 years were 12% and 26% for the 70 Gy and 78 Gy arms, respectively (p = 0.001). Grade 2 or higher bladder complications were similar at 10%. For patients in the 78 Gy arm, Grade 2 or higher rectal toxicity correlated highly with the proportion of the rectum treated to >70 Gy. CONCLUSION: An increase of 8 Gy resulted in a highly significant improvement in FFF for patients at intermediate-to-high risk, although the rectal reactions were also increased. Dose escalation techniques that limit the rectal volume that receives >or=70 Gy to <25% should be used.

Lawton CA, Grignon D, Newhouse JH, Schellhammer PF, Kuban DA. · Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee 53226, USA. · Radiographics. · Pubmed #9925399 links to  free full text

This publication has no abstract.

Tu SM, Lopez A, Leibovici D, Bilen MA, Evliyaoglu F, Aparicio A, Guo CC, Kuban DA, Johnson MM, Pisters LL. · Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. · Cancer. · Pubmed #19402048 No free full text.

Abstract: BACKGROUND: Ductal or endometrioid adenocarcinoma of the prostate may be a subtype of prostate cancer that is amenable to aggressive local therapeutic strategies. The authors of this report investigated the clinical outcome of patients who had prostate ductal adenocarcinoma after primary radical prostatectomy or radiotherapy. METHODS: The clinical features of 108 patients with locally confined or advanced prostate ductal adenocarcinoma who had undergone primary radical prostatectomy (surgical group, n = 76 men) or no surgery (nonsurgical group, n = 32 men) were evaluated retrospectively. Clinical records were reviewed, and Gleason scores, clinical/pathologic stages, and preoperative prostate-specific antigen levels were examined. The clinical features that were assessed included local recurrence, distant metastasis, and progression-free and overall survival after primary therapy. RESULTS: In the surgical group, patients who had pure ductal prostate cancer survived longer (median, 13.8 years; 95% confidence interval [CI], from 13.8 years to not attained) than patients who had mixed ductal prostate cancer (median, 8.9 years; 95% CI, from 7.1 years to not attained; P = .05). In addition, the median time to local progression was shorter (2.8 years vs 4.9 years) and the median time to distant metastasis was longer (3.9 years vs 2.0 years) for patients who had pure ductal adenocarcinoma than for patients who had mixed ductal adenocarcinoma of the prostate after surgery, respectively. CONCLUSIONS: The results of this preliminary study suggested that pure ductal prostate adenocarcinoma tends to pursue an indolent clinical course and poses an increased risk for local recurrence. Local control (particularly prostatectomy) may improve the clinical outcome of patients with pure prostate ductal adenocarcinoma. These results need to be confirmed in prospective studies.

Frank SJ, Levy LB, Kuban DA, Lee AK, Kudchadker RJ, Bruno TL, van Vulpen M, Swanson DA. · Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA. · J Urol. · Pubmed #19233434 No free full text.

Abstract: PURPOSE: Many clinicians use Prostogram data to advise patients selecting prostate cancer therapy. We examined whether the Prostogram accurately predicted recurrence at 5 years in patients treated with (125)I brachytherapy at 1 tertiary cancer center. MATERIALS AND METHODS: We retrospectively reviewed the records of 208 consecutive patients with prostate cancer treated with a permanent (125)I implant without neoadjuvant androgen deprivation therapy at 1 tertiary cancer center during 1998 to 2006. In each patient the Prostogram brachytherapy formula was used to calculate 5-year biochemical recurrence-free survival probability based on clinical stage, Gleason sum score, prostate specific antigen and the receipt or not of external beam radiotherapy. Recurrence was defined as clinical relapse, death from disease, posttreatment androgen deprivation therapy, secondary treatments administered before prostate specific antigen failure or biochemical recurrence based on the Kattan modification of the American Society for Therapeutic Radiology and Oncology definition of biochemical recurrence after external beam radiation therapy. Patients were divided into quartiles based on Prostogram predicted 5-year recurrence-free survival probability and mean probability was compared to the actual 5-year recurrence-free survival rate in each quartile. Harrell's concordance statistic was used to assess the predictive accuracy of the nomogram. RESULTS: Actual 5-year biochemical recurrence-free survival rates were superior to Prostogram predicted probabilities, including 89% vs 80%, 87% vs 86%, 100% vs 89% and 100% vs 94% in quartiles 1 to 4, respectively. Harrell's concordance value was 0.487 (95% CI 0.369-0.605), indicating that the predictive accuracy of the nomogram in our patients was less than 50%. CONCLUSIONS: The Prostogram did not predict recurrence after permanent prostate brachytherapy in this series. Institutional variability requires that clinicians be cautious when using the Prostogram to counsel patients about the probability of success after permanent prostate brachytherapy.

Wang H, Garden AS, Zhang L, Wei X, Ahamad A, Kuban DA, Komaki R, O'Daniel J, Zhang Y, Mohan R, Dong L. · Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #18722272 No free full text.

Abstract: PURPOSE: Auto-propagation of anatomic regions of interest from the planning computed tomography (CT) scan to the daily CT is an essential step in image-guided adaptive radiotherapy. The goal of this study was to quantitatively evaluate the performance of the algorithm in typical clinical applications. METHODS AND MATERIALS: We had previously adopted an image intensity-based deformable registration algorithm to find the correspondence between two images. In the present study, the regions of interest delineated on the planning CT image were mapped onto daily CT or four-dimensional CT images using the same transformation. Postprocessing methods, such as boundary smoothing and modification, were used to enhance the robustness of the algorithm. Auto-propagated contours for 8 head-and-neck cancer patients with a total of 100 repeat CT scans, 1 prostate patient with 24 repeat CT scans, and 9 lung cancer patients with a total of 90 four-dimensional CT images were evaluated against physician-drawn contours and physician-modified deformed contours using the volume overlap index and mean absolute surface-to-surface distance. RESULTS: The deformed contours were reasonably well matched with the daily anatomy on the repeat CT images. The volume overlap index and mean absolute surface-to-surface distance was 83% and 1.3 mm, respectively, compared with the independently drawn contours. Better agreement (>97% and <0.4 mm) was achieved if the physician was only asked to correct the deformed contours. The algorithm was also robust in the presence of random noise in the image. CONCLUSION: The deformable algorithm might be an effective method to propagate the planning regions of interest to subsequent CT images of changed anatomy, although a final review by physicians is highly recommended.

Trabulsi EJ, Valicenti RK, Hanlon AL, Pisansky TM, Sandler HM, Kuban DA, Catton CN, Michalski JM, Zelefsky MJ, Kupelian PA, Lin DW, Anscher MS, Slawin KM, Roehrborn CG, Forman JD, Liauw SL, Kestin LL, DeWeese TL, Scardino PT, Stephenson AJ, Pollack A. · Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. · Urology. · Pubmed #18672274 No free full text.

Abstract: OBJECTIVES: It is unclear whether postoperative salvage radiation therapy (SRT) and early adjuvant radiotherapy (ART) after radical prostatectomy lead to equivalent long-term tumor control. We studied a group of patients undergoing ART by comparing them with a matched control group undergoing SRT after biochemical failure. METHODS: Using a multi-institutional database of 2299 patients, 449 patients with pT3-4N0 disease were eligible for inclusion, including 211 patients receiving ART and 238 patients receiving SRT. Patients were matched in a 1:1 ratio according to preoperative prostate-specific antigen Gleason score, seminal vesicle invasion, surgical margin status, and follow-up from date of surgery. RESULTS: A total of 192 patients were matched (96:96). The median follow-up was 94 months from surgery and 73 months from RT completion. There was a significant reduction in biochemical failure with ART compared with SRT. The 5-year freedom from biochemical failure (FFBF) from surgery was 75% after ART, compared with 66% for SRT (hazard ratio [HR] = 1.6, P = .049). The 5-year FFBF from the end of RT was 73% after ART, compared with 50% after SRT (HR = 2.3, log rank [LR] P = .0007). From the end of RT, SRT and Gleason score >or=8 were independent predictors of diminished FFBF. From the date of surgery, Gleason score >or=8 was a significant predictor of FFBF. CONCLUSIONS: Early ART for pT3-4N0 prostate cancer significantly reduces the risk of long-term biochemical progression after radical prostatectomy compared with SRT. Gleason score >or=8 was the only factor on multivariate analysis associated with metastasic progression.

Kudchadker RJ, Swanson DA, Kuban DA, Lee AK, Bruno TL, Frank SJ. · Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #18410998 No free full text.

Abstract: PURPOSE: To characterize the amount of activity required to treat the prostate with stranded (125)I radioactive seeds and compare our stranded data with the amount of activity recommended when individual seeds are implanted using a Mick applicator. METHODS AND MATERIALS: Data from two groups of patients at The University of Texas M. D. Anderson Cancer Center who were treated with prostate brachytherapy as monotherapy were analyzed. The first group included 100 patients implanted with individual seeds in 2000 and 2001. The second group comprised 81 patients for whom stranded seeds were implanted in 2006 and 2007. Seeds in both groups were (125)I seeds with an air kerma strength of 0.497 U per seed (0.391 mCi per seed). The prescribed dose to planning target volume was 145 Gy. RESULTS: The total implanted activity and the number of seeds used were significantly lower in the second group (p < 0.0001) than in the first group. The reduction in activity in the stranded-seed group was approximately 23% for a 20-cm(3) prostate and approximately 15% for a 60-cm(3) prostate. With equivalent activity between the two groups, the stranded-seed treatment covered a larger treatment volume with the prescribed dose. CONCLUSIONS: The amount of activity required to effectively treat a prostate of a given volume was lower with stranded seeds than with loose seeds. Our experience suggests that prostate brachytherapy that uses stranded seeds leads to a more efficient implant with fewer seeds and lower overall activity, resulting in improved homogeneity.

O'Daniel JC, Dong L, Zhang L, Wang H, Tucker SL, Kudchadker RJ, Lee AK, Cheung R, Cox JD, Kuban DA, Mohan R. · Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #18406891 No free full text.

Abstract: PURPOSE: To compare the effectiveness of daily ultrasound (US)- and computed tomography (CT)-guided alignments with an off-line correction protocol using daily bone alignment plus a correction factor for systematic internal prostate displacement (CF(ID)). METHODS AND MATERIALS: Ten prostate cancer patients underwent CT scans three times weekly using an integrated CT-linear accelerator system, followed by alignment using US for daily radiotherapy. Intensity-modulated radiotherapy plans were designed with our current clinical margins. The treatment plan was copied onto the repeat CT images and aligned using several methods: (1) bone alignment plus CF(ID) after three off-line CT scans (bone+3CT), (2) bone alignment plus CF(ID) after six off-line CT scans (bone+6CT), (3) US alignment, and (4) CT alignment. The accuracy of the repeated US and CT measurements to determine the CF(ID) was compared. The target dosimetric effect was quantified. RESULTS: The CF(ID) for internal systematic prostate displacements was more accurately measured with limited repeat CT scans than with US (residual error, 0.0 +/- 0.7 mm vs. 2.0 +/- 3.2 mm). Bone+3CT, bone+6CT, and US provided equivalent prostate and seminal vesicle dose coverage, but bone+3CT and bone+6CT produced more precise daily alignments. Daily CT alignment provided the greatest target dose coverage. CONCLUSION: Daily bone alignment plus CF(ID) for internal systematic prostate displacement provided better daily alignment precision and equivalent dose coverage compared with daily US alignment. The CF(ID) should be based on at least three repeat CT scans, which could be collected before the start of treatment or during the first 3 treatment days. Daily bone alignment plus CF(ID) provides another option for accurate prostate cancer patient positioning.

Frank SJ, Dong L, Kudchadker RJ, De Crevoisier R, Lee AK, Cheung R, Choi S, O'Daniel J, Tucker SL, Wang H, Kuban DA. · Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #18207664 No free full text.

Abstract: PURPOSE: To quantify the interfraction variability in prostate and seminal vesicle (SV) positions during a course of intensity-modulated radiotherapy (IMRT) using an integrated computed tomography (CT)-linear accelerator system and to assess the impact of rectal and bladder volume changes. METHODS AND MATERIALS: We studied 15 patients who had undergone IMRT for prostate carcinoma. Patients had one pretreatment planning CT scan followed by three in-room CT scans per week using a CT-on-rails system. The prostate, bladder, rectum, and pelvic bony anatomy were contoured in 369 CT scans. Using the planning CT scan as a reference, the volumetric and positional changes were analyzed in the subsequent CT scans. RESULTS: For all 15 patients, the mean systematic internal prostate and SV variation was 0.1 +/- 4.1 mm and 1.2 +/- 7.3 mm in the anteroposterior axis, -0.5 +/- 2.9 mm and -0.7 +/- 4.5 mm in the superoinferior axis, and 0.2 +/- 0.9 mm and -0.9 +/- 1.9 mm in the lateral axis, respectively. The mean magnitude of the three-dimensional displacement vector was 4.6 +/- 3.5 mm for the prostate and 7.6 +/- 4.7 mm for the SVs. The rectal and bladder volume changes during treatment correlated with the anterior and superior displacement of the prostate and SVs. CONCLUSION: The dominant prostate and SV variations occurred in the anteroposterior and superoinferior directions. The systematic prostate and SV variation between the treatment planning CT and daily therapy as a result of the rectal and bladder volume changes emphasizes the need for daily directed target localization and/or immobilization techniques.

Melancon AD, O'Daniel JC, Zhang L, Kudchadker RJ, Kuban DA, Lee AK, Cheung RM, de Crevoisier R, Tucker SL, Newhauser WD, Mohan R, Dong L. · Department of Radiation Physics, The University of Texas M.D. Anderson Cancer Center, USA. · Radiother Oncol. · Pubmed #17892900 No free full text.

Abstract: PURPOSE: To determine whether a 3-mm isotropic target margin adequately covers the prostate and seminal vesicles (SVs) during administration of an intensity-modulated radiation therapy (IMRT) treatment fraction, assuming that daily image-guided setup is performed just before each fraction. MATERIALS AND METHODS: In-room computed tomographic (CT) scans were acquired immediately before and after a daily treatment fraction in 46 patients with prostate cancer. An eight-field IMRT plan was designed using the pre-fraction CT with a 3-mm margin and subsequently recalculated on the post-fraction CT. For convenience of comparison, dose plans were scaled to full course of treatment (75.6 Gy). Dose coverage was assessed on the post-treatment CT image set. RESULTS: During one treatment fraction (21.4+/-5.5 min), there were reductions in the volumes of the prostate and SVs receiving the prescribed dose (median reduction 0.1% and 1.0%, respectively, p<0.001) and in the minimum dose to 0.1 cm(3) of their volumes (median reduction 0.5 and 1.5 Gy, p<0.001). Of the 46 patients, three patients' prostates and eight patients' SVs did not maintain dose coverage above 70 Gy. Rectal filling correlated with decreased percentage-volume of SV receiving 75.6, 70, and 60 Gy (p<0.02). CONCLUSIONS: The 3-mm intrafractional margin was adequate for prostate dose coverage. However, a significant subset of patients lost SV dose coverage. The rectal volume change significantly affected SV dose coverage. For advanced-stage prostate cancers, we recommend to use larger margins or improve organ immobilization (such as with a rectal balloon) to ensure SV coverage.

Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, Cheung MR, Lee AK, Pollack A. · Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #17765406 No free full text.

Abstract: PURPOSE: To report the long-term results of a randomized radiotherapy dose escalation trial for prostate cancer. METHODS AND MATERIALS: From 1993 to 1998, a total of 301 patients with stage T1b to T3 prostate cancer were accrued to a randomized external beam dose escalation trial using 70 Gy versus 78 Gy. The median follow-up is now 8.7 years. Kaplan-Meier analysis was used to compute rates of prostate-specific antigen (PSA) failure (nadir + 2), clinical failure, distant metastasis, disease-specific, and overall survival as well as complication rates at 8 years post-treatment. RESULTS: For all patients, freedom from biochemical or clinical failure (FFF) was superior for the 78-Gy arm, 78%, as compared with 59% for the 70-Gy arm (p = 0.004, and an even greater benefit was seen in patients with initial PSA >10 ng/ml (78% vs. 39%, p = 0.001). The clinical failure rate was significantly reduced in the 78-Gy arm as well (7% vs. 15%, p = 0.014). Twice as many patients either died of prostate cancer or are currently alive with cancer in the 70-Gy arm. Gastrointestinal toxicity of grade 2 or greater occurred twice as often in the high dose patients (26% vs. 13%), although genitourinary toxicity of grade 2 or greater was less (13% vs. 8%) and not statistically significantly different. Dose-volume histogram analysis showed that the complication rate could be significantly decreased by reducing the amount of treated rectum. CONCLUSIONS: Modest escalation in radiotherapy dose improved freedom from biochemical and clinical progression with the largest benefit in prostate cancer patients with PSA >10 ng/ml.

Kry SF, Followill D, White RA, Stovall M, Kuban DA, Salehpour M. · Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #17637398 No free full text.

Abstract: PURPOSE: The significance of risk estimates for fatal secondary malignancies caused by out-of-field radiation exposure remains unresolved because the uncertainty in calculated risk estimates has not been established. This work examines the uncertainty in absolute risk estimates and in the ratio of risk estimates between different treatment modalities. METHODS AND MATERIALS: Clinically reasonable out-of-field doses and calculated risk estimates were taken from the literature for several prostate treatment modalities, including intensity-modulated radiotherapy (IMRT), and were recalculated using the most recent risk model. The uncertainties in this risk model and uncertainties in the linearity of the dose-response model were considered in generating 90% confidence intervals for the uncertainty in the absolute risk estimates and in the ratio of the risk estimates. RESULTS: The absolute risk estimates of fatal secondary malignancy were associated with very large uncertainties, which precluded distinctions between the risks associated with the different treatment modalities considered. However, a much smaller confidence interval exists for the ratio of risk estimates, and this ratio between different treatment modalities may be statistically significant when there is an effective dose equivalent difference of at least 50%. Such a difference may exist between clinically reasonable treatment options, including 6-MV IMRT versus 18-MV IMRT for prostate therapy. CONCLUSION: The ratio of the risk between different treatment modalities may be significantly different. Consequently risk models and associated risk estimates may be useful and meaningful for evaluating different treatment options. The calculated risk of secondary malignancy should be considered in the selection of an optimal treatment plan.

Vassiliev ON, Kry SF, Kuban DA, Salehpour M, Mohan R, Titt U. · Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030-4009, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #17544596 No free full text.

Abstract: PURPOSE: To assess the feasibility of intensity-modulated radiotherapy for prostate cancer using photon beams from an accelerator operated without a flattening filter; and to determine potential benefits and drawbacks of using unflattened beams for this type of treatment. METHODS AND MATERIALS: Intensity-modulated radiotherapy plans were generated for 10 patients with early-stage prostate cancer. For each patient, four plans were generated: with and without the flattening filter, at 6 and 18 MV. The prescription dose was 75.6 Gy to 98% of the planning target volume. The number of beams, their orientations, and optimization constraints were the same for all plans. Plans were generated with Eclipse 8.0 (Varian Medical Systems). RESULTS: All the plans developed with unflattened beams were clinically acceptable. In terms of patient dose distributions, plans with unflattened beams were similar to the corresponding plans with flattened beams. Plans with unflattened beams required fewer monitor units (MUs) per plan: on average, by a factor of 2.0 at 6 MV and 2.6 at 18 MV, assuming that removal of the flattening filter was not followed by recalibration of MUs. CONCLUSIONS: Clinically acceptable intensity-modulated radiotherapy plans for prostate cancer can be developed with unflattened beams at both 6 and 18 MV. Dosimetrically, flattened and unflattened beams generated similar treatment plans. The plans with unflattened beams required substantially fewer MUs. The reduction in the number of MUs indicates corresponding reduction in beam-on time and in the amount of radiation outside the target.

de Crevoisier R, Melancon AD, Kuban DA, Lee AK, Cheung RM, Tucker SL, Kudchadker RJ, Newhauser WD, Zhang L, Mohan R, Dong L. · Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #17544595 No free full text.

Abstract: PURPOSE: To quantify the three-dimensional variations of pelvic anatomy after a single treatment fraction. METHODS AND MATERIALS: Forty-six prostate cancer patients underwent computed tomography (CT) scanning with an in-room CT-on-rail system, before and immediately after one intensity-modulated radiotherapy (IMRT) session. To study the soft-tissue anatomy changes, the pre- and post-treatment CT images were registered using the bony structure with an in-house image registration software system. The center of volume for both the prostate and seminal vesicles was used to assess the relative displacement of the same structure after the treatment fraction. RESULTS: During one treatment fraction (21 +/- 4 min), both the prostate and seminal vesicles showed statistically significant systematic trends in the superior and anterior directions of the patient's anatomy. The net increase in bladder volume was huge (127 +/- 79 cm(3)), yet this change did not translate into large target displacements. Although the population mean displacements in either direction were 1.3 +/- 2.9 mm for the prostate and 1.2 +/- 4.1 mm for the seminal vesicles in the anterior direction, a few patients had displacements as large as 8.4 mm and 15.6 mm, respectively. These large displacements correlated strongly (p < 0.001) with large rectal volume increases caused by gaseous build-up in the rectum. CONCLUSION: The observed intrafraction variations in anatomy during prostate IMRT sessions suggest that, for any given fraction, the organ motion and volume changes can potentially lead to compromised target coverage in about 15% of patients in whom the prostate position shifted >4 mm.