Mark K Buyyounouski

Stanford University, Palo Alto, California, United States

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Publications (194)746.2 Total impact

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    ABSTRACT: Purpose: To compare patterns of prostate-specific antigen (PSA) response following stereotactic body radiation therapy (SBRT), high-dose-rate (HDR) brachytherapy, and conventionally fractionated intensity modulated radiation therapy (IMRT) in patients with low- or intermediate-risk prostate cancer (CaP). Methods and materials: Eligible study patients included 439 patients with low- or intermediate-risk prostate cancer who were treated with radiation therapy (RT) alone between 2003 and 2013, remained free of biochemical recurrence, and had at least 2 PSA values within the first year following RT. Of these, 130 were treated with SBRT, 220 with HDR brachytherapy, and 89 with IMRT. Multivariate regression analysis was used to compare PSA nadirs (nPSA), time to nPSA, and PSA bounce parameters among the 3 modalities. Indicator variable analysis was used to develop empirical models of PSA decay using the treatment modalities as indicator variables. Results: Significantly more patients treated with SBRT or HDR brachytherapy achieved raw nPSAs of <0.5 ng/mL compared with patients treated with IMRT (76.2% and 75.9% vs 44.9%, respectively; P < .0001 for SBRT or HDR brachytherapy vs IMRT). On multivariate analysis, nPSA was significantly lower with SBRT and HDR compared with IMRT (P < .0001). Time to nPSA and bounce parameters was not significantly different among IMRT, SBRT, and HDR. Overall, SBRT and HDR brachytherapy caused significantly larger PSA decay rates (P < .001). When truncating follow-up at 1000 days, the corresponding decay rates were larger for all 3 modalities, with no significant differences between them. Conclusions: Stereotactic body radiation therapy and HDR brachytherapy produce lower nPSAs than IMRT. Within 1000 days of follow-up, the modalities produce similar rates of PSA decay; subsequently, decay continues (albeit at a slower pace) after SBRT and HDR brachytherapy but plateaus with IMRT. Because nPSA is a validated predictor of long-term outcome, these data not only suggest a distinct radiobiological effect with SBRT and HDR brachytherapy, but also predict for clinical outcomes that might equal or surpass those of IMRT.
    No preview · Article · Nov 2015 · Practical Radiation Oncology

  • No preview · Article · Nov 2015 · International journal of radiation oncology, biology, physics

  • No preview · Article · Nov 2015 · International journal of radiation oncology, biology, physics
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    ABSTRACT: Purpose We assessed the prognostic value of the interval to biochemical failure (IBF) after salvage radiation therapy (SRT) following radical prostatectomy (RP) for prostate cancer to identify patients at high risk for distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall mortality (OM). Methods From 1991 and 2007, 222 men with T2a-4a, N0/X, M0 prostate cancer received SRT for a rising PSA after RP. Of these, 48 experienced BF. Univariate and multivariate analyses (UVA, MVA, respectively) included initial PSA; T-stage; RT dose; nadir PSA; risk group; IBF; time from surgery to SRT; seminal vesicle invasion; Gleason score; and PSA doubling time. Results Median follow-up from SRT was 67 months. The median IBF was 33 months (range, 4–96). On UVA, IBF < 12 or <18 months and risk group predicted for DM, PCSM, and OM (p < 0.05). On MVA, IBF < 12 or <18 months predicted for DM (HRs 36.1, 15.3, respectively, p = 0.02). The 5-year DM, PCSM, and OM rates for an IBF of < vs. ≥18 months were 50 vs. 17 %, 45 vs. 0 %, 53 vs. 0 %, respectively (all p < 0.01). Conclusions Patients with IBF < 18 months are at significantly higher risk of DM and death from prostate cancer. The IBF may be used to guide patients and physicians considering the initiation of salvage ADT. Furthermore, an IBF < 18 months could be used to select “high-risk” patients for clinical trials investigating novel salvage systemic therapy.
    Full-text · Article · Jul 2015
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    ABSTRACT: Objectives The objective of the study is to determine if aspirin use is associated with decreased risk of biochemical failure, distant metastasis, and prostate cancer specific mortality in prostate cancer patients after adjuvant or salvage radiation therapy following radical prostatectomy. Methods We identified 189 men with pathologic T2a-4a, N0/X, M0 prostate adenocarcinoma who received adjuvant or salvage radiation therapy following prostatectomy. Aspirin use (defined as use at time of radiation therapy or during follow-up) was present in 60 men (32 %). Cox multivariate analysis was performed using Kaplan-Meier estimation and log-rank test with the following covariates: pre-radiation therapy prostate-specific antigen, Gleason score, prostate-specific antigen doubling time, warfarin or clopidogrel use, aspirin use, surgical margin status, radiation dose, time interval from prostatectomy to radiation therapy, and radiation technique. Results The median follow-up time was 50 months. Aspirin use was associated with improved 5-year rates of prostate-specific antigen nadir + 2 ng/mL biochemical failure (15 vs. 42 %, p = 0.002), distant metastases (0 vs. 8 %, p = 0.02), and prostate cancer-specific mortality (0 vs. 5 %, p = 0.14). On multivariate analysis, aspirin nonuse (hazard ratio = 2.9, 95 % confidence interval = 1.3-6.6) was the only predictor for prostate-specific antigen nadir + 2 ng/mL biochemical failure. Conclusion In patients who received adjuvant and salvage radiation therapy after primary radical prostatectomy, aspirin use was associated with a decreased risk of biochemical failure.
    Full-text · Article · Jun 2015
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    ABSTRACT: Prostate biopsy positivity after radiotherapy (RT) is a significant determinant of eventual biochemical failure. We mapped pre- and post-treatment tumor locations to determine if residual disease is location-dependent. There were 303 patients treated on a randomized hypofractionation trial. Of these, 125 underwent prostate biopsy 2-years post-RT. Biopsy cores were mapped to a sextant template, and 86 patients with both pre-/post-treatment systematic sextant biopsies were analyzed. The pretreatment distribution of positive biopsy cores was not significantly related to prostate region (base, mid, apex; p=0.723). Whereas all regions post-RT had reduced positive biopsies, the base was reduced to the greatest degree and the apex the least (p=0.045). In 38 patients who had a positive post-treatment biopsy, there was change in the rate of apical positivity before and after treatment (76 vs. 71%; p=0.774), while significant reductions were seen in the mid and base. In our experience, persistence of prostate tumor cells after RT increases going from the base to apex. MRI was used in planning and image guidance was performed daily during treatment, so geographic miss of the apex is unlikely. Nonetheless, the pattern observed suggests that attention to apex dosimetry is a priority. Copyright © 2015. Published by Elsevier Ireland Ltd.
    No preview · Article · May 2015 · Radiotherapy and Oncology
  • Mark K. Buyyounouski

    No preview · Article · Apr 2015 · International journal of radiation oncology, biology, physics
  • Ben Y. Durkee · Mark K. Buyyounouski

    No preview · Article · Mar 2015 · International journal of radiation oncology, biology, physics
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    ABSTRACT: This formative research study describes the development and preliminary evaluation of a theory-guided, online multimedia psycho-educational program (PROGRESS) designed to facilitate adaptive coping among prostate cancer patients transitioning from treatment into long-term survivorship. Guided by the Cognitive-Social Health Information Processing Model (C-SHIP) and using health communications best practices, we conducted a two-phase, qualitative formative research study with early stage prostate cancer patients (n = 29) to inform the Web program development. Phase 1 included individual (n = 5) and group (n = 12) interviews to help determine intervention content and interface. Phase 2 employed iterative user/usability testing (n = 12) to finalize the intervention. Interview data were independently coded and collectively analyzed to achieve consensus. Survivors expressed interest in action-oriented content on (1) managing treatment side effects, (2) handling body image and comorbidities related to overweight/obesity, (3) coping with emotional and communication issues, (4) tips to reduce disruptions of daily living activities, and (5) health skills training tools. Patients also desired the use of realistic and diverse survivor images. Incorporation of an established theoretical framework, application of multimedia intervention development best practices, and an evidence-based approach to content and format resulted in a psycho-educational tool that comprehensively addresses survivors' needs in a tailored fashion. The results suggest that an interactive Web-based multimedia program is useful for survivors if it covers the key topics of symptom control, emotional well-being, and coping skills training; this tool has the potential to be disseminated and implemented as an adjunct to routine clinical care.
    Full-text · Article · Feb 2015 · Journal of Cancer Survivorship
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    ABSTRACT: Inflammatory bowel disease (IBD) is considered a contraindication to abdominopelvic radiation therapy (RT). We examined our experience in men with IBD who were treated with definitive RT for prostate cancer.Methods and materialsWe queried our institutional database for patients with a diagnosis of ulcerative colitis, Crohn disease, or IBD not otherwise specified. Endpoints were: acute and late ≥ grade 2 (G2) GI toxicity and IBD flare after RT. Outcomes were compared with controls using propensity scoring matched 3 to 1. We matched controls to the IBD cohort according to: RT technique, RT dose, risk group, hormone use, treatment year, and age. We determined predictors of acute outcomes using the Fisher exact test and time to outcomes using the log-rank test.ResultsBetween 1990 and 2010, 84 men were included. Sixty-three men served as matched controls and 21 with IBD: 13 ulcerative colitis, 7 Crohn disease, and 1 IBD not otherwise specified. For men with IBD, median age was 69 years, and median follow-up was 49 months. Median flare-free interval before RT was 10 years. Seven were taking IBD medications during RT. There was no difference in acute or late gastrointestinal (GI) toxicity in the IBD group versus controls. Among IBD patients, IBD medication use was the only predictor of acute ≥ G2 GI toxicity: 57.1% with medication versus7.7% without (49.4% absolute difference, 95% confidence interval [CI] 10.0%-88.9%, P = .03). The 5-year risk of late GI toxicity in men with IBD versus controls was not statistically significant (hazard ratio = 1.19, 95%CI 0.28-5.01, P = .83). The crude incidence of late ≥ G2 GI toxicity was 10%.Conclusions Acute GI toxicity appears to be exacerbated in patients on concomitant medical therapy for IBD. Overall, late GI toxicity was relatively low and not significantly different between patients with IBD versus no IBD. However, the small sample size limits the interpretation of our estimates and the wide confidence intervals indicate these patients warrant careful selection.
    No preview · Article · Oct 2014 · Practical Radiation Oncology
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    Lynn Chang · Mark K Buyyounouski
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    ABSTRACT: Purpose To report outcomes on 5 patients treated with salvage partial low-dose-rate (LDR) 125-iodine (125I) permanent prostate seed brachytherapy (BT) for biopsy-proven locally persistent prostate cancer, following failure of dose-escalated external beam radiotherapy (EBRT). Material and methods A retrospective review of the Fox Chase Cancer Center prostate cancer database identified five patients treated with salvage partial LDR 125I seed implant for locally persistent disease following dose-escalated EBRT to 76-84 Gy in 2 Gy per fraction equivalent. All patients had post-EBRT biopsies confirming unilateral locally persistent prostate cancer. Pre-treatment, EBRT and BT details, as well as post-treatment characteristics were documented and assessed. Results The median follow-up post-implant was 41 months. All five patients exhibited low acute genitourinary and gastrointestinal toxicities. Increased erectile dysfunction was noted in three patients. There were no biochemical failures following salvage LDR 125I seed BT to date, with a median post-salvage PSA of 0.4 ng/mL. Conclusions In carefully selected patients with local persistence of disease, partial LDR 125I permanent prostate seed implant appears to be a feasible option for salvage local therapy with an acceptable toxicity profile. Further study is needed to determine long-term results of this approach.
    Preview · Article · Oct 2014 · Journal of Contemporary Brachytherapy
  • Mark K Buyyounouski

    No preview · Article · Aug 2014 · European Urology
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    Preview · Article · Apr 2014 · Journal of Clinical Oncology
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    ABSTRACT: Tadalafil is used to treat erectile dysfunction after prostate cancer treatment, but its role as a preventive agent is undefined. To determine primarily whether tadalafil preserved erectile function in men treated with radiotherapy for prostate cancer, and secondarily to determine whether participant- or partner-reported overall sexual function and sexual and marital satisfaction were affected. Stratified, placebo-controlled, double-blind, parallel-group study with 1:1 randomization at 76 community-based and tertiary medical sites in the United States and Canada. Two hundred forty-two participants with intact erectile function scheduled to receive radiotherapy for prostate cancer were recruited between November 2009 and February 2012 with follow-up through March 2013. One hundred twenty-one participants were assigned 5 mg of tadalafil daily and 121 were assigned placebo for 24 weeks starting with external radiotherapy (63%) or brachytherapy (37%). Participant-reported International Index of Erectile Function response before radiotherapy and at weeks 2 and 4, between weeks 20 and 24, between weeks 28 and 30, and 1 year thereafter. Participants and partners could respond also to the Sexual Adjustment Questionnaire and to the Locke Marital Adjustment Test before radiotherapy, between weeks 20 and 24 and weeks 28 and 30, and at 1 year. Primary outcome was off-drug spontaneous erectile function 28 to 30 weeks after radiotherapy started. Secondary end points were spontaneous erection at 1 year; overall sexual function and satisfaction; marital adjustment; and partner-reported satisfaction and marital adjustment at 28 to 30 weeks and 1 year, predictors of tadalafil response; and adverse events. Among 221 evaluable participants, 80 (79%; 95% CI, 70%-88%) assigned to receive tadalafil retained erectile function between weeks 28 and 30 compared with 61 (74%; 95% CI, 63%-85%) assigned to receive placebo (P = .49); an absolute difference of 5% (95% CI, -9% to 19%). A significant difference was also not observed at 1 year (72%; 95% CI, 60%-84% vs 71%; 95% CI, 59%-84%; P = .93). Tadalafil was not associated with significantly improved overall sexual function or satisfaction; a significant difference was not observed in any domain subscale. Partners of men assigned tadalafil noted no significant effect on sexual satisfaction, and marital adjustment was not significantly improved in participants or partners. Among men undergoing radiotherapy for prostate cancer, daily use of tadalafil compared with placebo did not result in improved erectile function. These findings do not support daily use of tadalafil to prevent erectile dysfunction in these patients. clinicaltrials.gov Identifier: NCT00931528.
    No preview · Article · Apr 2014 · JAMA The Journal of the American Medical Association
  • Hilary Bagshaw · Karen Ruth · Eric M. Horwitz · David Y.T. Chen · Mark K. Buyyounouski
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    ABSTRACT: Objective To examine family history (FH) as a prognostic factor following radiotherapy (RT). Materials and methods Between 1989 and 2007, 1711 men with clinically localized prostate cancer and complete family history who had received RT (median RT dose = 74 Gy) without androgen deprivation therapy were analyzed. FH was defined as any prostate cancer in a first degree relative. For the biochemical failure (BF) outcome, this sample size has 85% power to detect a hazard ratio of 1.56 for positive versus negative FH. Results With a median follow-up of 71 months, there was no significant difference in the distribution of Gleason score (GS) or prostate specific antigen (PSA) based on FH. A positive FH was not an independent predictor of BF, distant metastasis (DM), prostate cancer specific mortality (PCSM), or overall mortality (OM) in Cox proportional multivariable analysis. On further analysis in a Cox proportional multivariable analysis, men with two or more first degree relatives with prostate cancer had a significantly higher likelihood of BF and DM than those with no FH, although there was no difference in PCSM or OM. Men with a positive FH (23%) were more likely to be younger, have a lower PSA, and non-palpable disease. There was no interaction between a positive FH and neither race nor treatment era (pre-PSA vs. PSA era). Conclusions A positive FH is not a prognostic factor following RT and should not alter standard treatment recommendations. Patients with two or more first degree relatives with prostate cancer had a higher likelihood of BF and DM, but there was no effect on survival. There was no interaction between a positive FH and African American race or treatment era. A positive FH was however, associated with more favorable PSA values and T-stage that may be the result of earlier screening.
    No preview · Article · Feb 2014 · Radiotherapy and Oncology

  • No preview · Conference Paper · Feb 2014
  • Jelle O. Barentsz · Mark Kenneth Buyyounouski
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    ABSTRACT: LEARNING OBJECTIVES 1) Introduce imaging anatomy relevant to prostate cancer and review imaging issues for contouring primary tumors, nodal regions, and adjacent critical structures. 2) Review how the integration of different imaging modalities can affect tumor delineation. 3) How to choose appropriate imaging methods for specific purposes and to discuss the significance of certain imaging findings.
    No preview · Conference Paper · Dec 2013
  • Mark Kenneth Buyyounouski · Jelle O. Barentsz
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    ABSTRACT: LEARNING OBJECTIVES 1) To use MRI in contouring local prostate cancer as well as pelvic lymph nodes.
    No preview · Conference Paper · Dec 2013
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    ABSTRACT: A small decrease in testosterone level has been documented after prostate irradiation, possibly owing to the incidental dose to the testes. Testicular doses from prostate external beam radiation plans with either intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) were calculated to investigate any difference. Testicles were contoured for 16 patients being treated for localized prostate cancer. For each patient, 2 plans were created: 1 with IMRT and 1 with VMAT. No specific attempt was made to reduce testicular dose. Minimum, maximum, and mean doses to the testicles were recorded for each plan. Of the 16 patients, 4 received a total dose of 7800cGy to the prostate alone, 7 received 8000cGy to the prostate alone, and 5 received 8000cGy to the prostate and pelvic lymph nodes. The mean (range) of testicular dose with an IMRT plan was 54.7cGy (21.1 to 91.9) and 59.0cGy (25.1 to 93.4) with a VMAT plan. In 12 cases, the mean VMAT dose was higher than the mean IMRT dose, with a mean difference of 4.3cGy (p = 0.019). There was a small but statistically significant increase in mean testicular dose delivered by VMAT compared with IMRT. Despite this, it unlikely that there is a clinically meaningful difference in testicular doses from either modality.
    No preview · Conference Paper · Dec 2013
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    ABSTRACT: Purpose/Objective(s): To compare clinical outcomes following intensity modulated radiotherapy (IMRT) to the prostate bed (PB) based on the image-guided radiotherapy (IGRT) technique. Materials/Methods: We identified 289 men treated to the PB with IGRT in our prospective database: 135 with B-mode acquisition and targeting system (BAT) stereotactic ultrasound, 134 with cone beam CT (CBCT), and 20 with electromagnetic transponders (Calypso®). IGRT modality was determined by physician and patient preference, except for patients with extreme abdominal girth or hip prosthesis who were not eligible for Calypso. All patients underwent both CT and MRI simulation. Unless otherwise specified by a clinical trial, the planning target volume (PTV) = clinical target volume + 8 mm, except 6mm posteriorly. All IMRT plans were evaluated using identical rectal and bladder dose-volume histogram constraints with priority given to bowel constraints. Grade 2 and higher gastrointestinal (GI) and genitourinary (GU) toxicity were scored according to a modified version of the CTCAE v3.0. Statistical analysis was performed via Chi-square test, Kaplan-Meier estimation, and Cox proportional hazards model.Results: The three groups did not vary in regard to age, race, Gleason score, T-stage, N-stage, or interval between surgery and radiation. The mean PB PTV was larger in the Calypso (mean 313cc) and CBCT (mean 300cc) groups compared to the mean BAT volume of 237cc (p<0.001), although the difference in mean volume between Calypso and CBCT groups was not significant (p=0.32). The median dose prescribed was 68 Gy for all three groups.With a median follow-up of 40 months, there was no significant difference between the three groups for late GI toxicity, which occurred in 3.7% of the BAT group, 1.5% of the CBCT group, and 0% of the Calypso group (p=0.38). Late GU toxicity was seen most frequently in the CBCT group, 25.4%, compared to 16.3% of the BAT group (p=0.081) and 10% of the Calypso group (p=0.015). Acute GI toxicity was seen significantly more in the CBCT group, 12.7% compared to 1.5% in the BAT group (p<0.001) and 0% in the Calypso group (p=0.037). Acute GU toxicity was seen most frequently in the CBCT group, occurring in 35.8% of patients, compared to 19.2% for the BAT group (<0.001) and 15% for the Calypso group (p=0.004). There were no significant toxicity differences when BAT and Calypso groups were compared.Conclusion: Calypso was associated with less acute GI, acute GU, and late GU toxicity in patients treated with IMRT to the PB when compared to CBCT. BAT was associated with less acute GI and GU toxicity in patients treated with IMRT to the PB when compared to CBCT, although CBCT patients were treated to a larger mean PTV. There was no difference in toxicity between Calypso and BAT groups, despite larger PB PTV in the Calypso group.
    No preview · Conference Paper · Dec 2013

Publication Stats

2k Citations
746.20 Total Impact Points

Institutions

  • 2013-2015
    • Stanford University
      • Department of Radiation Oncology
      Palo Alto, California, United States
  • 2002-2014
    • Fox Chase Cancer Center
      • Department of Radiation Oncology
      Filadelfia, Pennsylvania, United States
  • 2011
    • Treatment Research Institute, Philadelphia PA
      Filadelfia, Pennsylvania, United States