Mark K Buyyounouski

Stanford University, Palo Alto, California, United States

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Publications (160)574.6 Total impact

  • [Show abstract] [Hide abstract]
    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.
    Practical Radiation Oncology. 10/2014;
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    Lynn Chang, Mark K Buyyounouski
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    ABSTRACT: To report outcomes on 5 patients treated with salvage partial low-dose-rate (LDR) 125-iodine ((125)I) permanent prostate seed brachytherapy (BT) for biopsy-proven locally persistent prostate cancer, following failure of dose-escalated external beam radiotherapy (EBRT).
    Journal of Contemporary Brachytherapy 10/2014; 6(3):304-10.
  • Mark K Buyyounouski
    European Urology 08/2014; · 12.48 Impact Factor
  • Journal of Clinical Oncology 04/2014; · 17.88 Impact Factor
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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. Identifier: NCT00931528.
    JAMA The Journal of the American Medical Association 04/2014; 311(13):1300-7. · 29.98 Impact Factor
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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.
    Radiotherapy and Oncology 02/2014; · 4.86 Impact Factor
  • 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.
    Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
  • 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.
    Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
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    ABSTRACT: Purpose/Objective(s):A small decrease in testosterone has been documented after prostate irradiation. One theory is that this may be due to incidental dose delivered to the testes. We calculated the testicular dose from prostate external beam radiation plans with either IMRT or VMAT to investigate any difference between the two modalities.Materials/Methods:We prospectively selected 16 patients being treated for localized prostate cancer and contoured the testicles of each patient in addition to the other normal tissue structures typically contoured. Two plans were created for each patient using the Eclipse® treatment planning system, one plan with IMRT and the other with VMAT. No specific attempt was made to reduce testicular dose in either plan. Minimum, maximum and mean dose to the testicles was recorded for each plan. Paired Wilcoxon rank sum test was used to assess the significance of a difference in dose between the two treatment modalities.Results:Of the 16 patients, 4 were treated to a total dose of 7800cGy to the prostate alone, 7 were treated to 8000cGy to the prostate alone, 5 were treated to 8000cGy to the prostate and pelvic lymph nodes. The median (range) of the mean testicular dose with an IMRT plan was 56.3cGy (21.1-91.9) and 54.7cGy (25.1-93.4) with a VMAT plan (p=0.016). The minimum dose with IMRT was 22.0cGy (0-34.7) and 20.9(0.1-38.6) with a VMAT plan (p=0.022). The maximum dose with IMRT was 158cGy (55.6-367.5) and 130.1cGy (57.5-395.8) with a VMAT plan (p=0.562). The difference in mean testicular dose remained significant when considering only the 11 patients who were treated to the prostate alone, IMRT dose was 55.4cGy and VMAT dose was 55cGy (p=0.003). There was no difference in testicular dose based upon prescription dose of 8000cGy vs. 7800cGy (p>0.05).Conclusion:There was a small but statistically significant increase in incidental mean testicular dose delivered by an IMRT prostate plan when compared with a VMAT plan. Although the dose to the testes is low for both cases, prior studies have shown that doses in this range have been associated with subtle changes in Leydig cell function. Further investigation is warranted to determine the clinical significance of this difference.
    Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
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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.
    Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
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    ABSTRACT: To determine if escalated radiation dose using hypofractionation significantly reduces biochemical and/or clinical disease failure (BCDF) in men treated primarily for prostate cancer. Between June 2002 and May 2006, men with favorable- to high-risk prostate cancer were randomly allocated to receive 76 Gy in 38 fractions at 2.0 Gy per fraction (conventional fractionation intensity-modulated radiation therapy [CIMRT]) versus 70.2 Gy in 26 fractions at 2.7 Gy per fraction (hypofractionated IMRT [HIMRT]); the latter was estimated to be equivalent to 84.4 Gy in 2.0 Gy fractions. High-risk patients received long-term androgen deprivation therapy (ADT), and some intermediate-risk patients received short-term ADT. The primary end point was the cumulative incidence of BCDF. Secondarily, toxicity was assessed. There were 303 assessable patients with a median follow-up of 68.4 months. No significant differences were seen between the treatment arms in terms of the distribution of patients by clinicopathologic or treatment-related (ADT use and length) factors. The 5-year rates of BCDF were 21.4% (95% CI, 14.8% to 28.7%) for CIMRT and 23.3% (95% CI, 16.4% to 31.0%) for HIMRT (P = .745). There were no statistically significant differences in late toxicity between the arms; however, in subgroup analysis, patients with compromised urinary function before enrollment had significantly worse urinary function after HIMRT. The hypofractionation regimen did not result in a significant reduction in BCDF; however, it is delivered in 2.5 fewer weeks. Men with compromised urinary function before treatment may not be ideal candidates for this approach.
    Journal of Clinical Oncology 10/2013; · 17.88 Impact Factor
  • International Journal of Radiation OncologyBiologyPhysics 10/2013; 87(2):S368-S369. · 4.18 Impact Factor
  • International Journal of Radiation OncologyBiologyPhysics 10/2013; 87(2):S378. · 4.18 Impact Factor
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    ABSTRACT: This study attempted to determine whether the Gleason score (GS) assigned at a comprehensive cancer center better predicts risk of biochemical failure (BF) after prostate radiotherapy compared with the GS of the referring institution (RI). Between 1994 and 2007, 1649 men received radiotherapy for prostate cancer at Fox Chase Cancer Center (FCCC). The Cox proportional hazard regression was used for inferences about the relationship of time to BF and GS. Harrell's C-index (HCI) was used to assess concordance in the Cox regression between predicted and observed events. The discordance rate was 26% for any change in either major or minor Gleason pattern. In the RI GS 2 through 6 group, 79 (8%) patients were upgraded to GS 7. Twenty percent of patients with RI GS 7 were downgraded and 2% were upgraded. In the RI GS 8 through 9 group, 58% were downgraded to GS 6 (12%) or GS 7 (88%). The FCCC GS altered the NCCN risk group assignment in 144 men (9%): 92 (64%) men to lower risk and 52 (36%) to higher risk. FCCC GS was a stronger predictor of BF; the hazard ratios for GS 2 through 6 (ref), 3+4, 4+3, and 8 through 9 were 1.00 (ref), 1.82, 4.14, and 2.92, respectively. In contrast, the hazard ratios for the RI GS were 1.00 (ref), 1.53, 2.44, and 1.76, respectively. FCCC GS (HCI=0.76) had improved performance compared with RI GS (HCI=0.74). Changes in GS were common and the GS assigned by a comprehensive cancer center provided better BF risk stratification and prognostication for patients. Changes in GS may impact treatment recommendations in 9% to 26% of patients.
    Journal of the National Comprehensive Cancer Network: JNCCN 07/2013; 11(7):812-819. · 4.24 Impact Factor
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    ABSTRACT: We assessed effectiveness, safety, and tolerability of paclitaxel or fluorouracil when added to radiation plus cisplatin followed by adjuvant chemotherapy in a programme of selected bladder preservation for patients with muscle invasive bladder cancer. In our randomised phase 2 trial, we enrolled patients with T2-4a transitional cell carcinoma of the bladder at 24 medical centres in the USA. We randomly allocated patients to receive paclitaxel plus cisplatin (paclitaxel group) or fluorouracil plus cisplatin (fluorouracil group) with twice-daily radiation in random block sizes per site on the basis of clinical T-stage (T2 vs T3-4). Patients and physicians were aware of treatment assignment. All patients had transurethral resection of bladder tumour and twice-daily radiotherapy to 40·3 Gy, along with allocated chemotherapy, followed by cystoscopic and biopsy assessment of response. Patients who had a tumour response with downstaging to T0, Tcis, or Ta received consolidation chemoradiotherapy to 64·3 Gy, with the same chemotherapy regimen as in the induction phase. Patients received adjuvant cisplatin-gemcitabine-paclitaxel after the end of chemoradiotherapy. If, after induction, persistent disease was graded as T1 or worse, we recommended patients undergo cystectomy and adjuvant chemotherapy. We assessed the primary endpoints of rates of treatment completion and toxic effects in all randomly allocated patients. This study is registered with, number NCT00055601. Between Dec 13, 2002, and Jan 11, 2008, we enrolled 97 patients, of whom 93 were eligible for analysis. Median follow-up was 5·0 years (IQR 5·0-6·2). Of 46 patients in the paclitaxel group, 45 (98%) completed induction (16 [35%] with grade 3-4 toxicity), 39 (85%) completed induction and consolidation (11 [24%] with grade 3-4 toxicity due to consolidation), and 31 (67%) completed the entire protocol with adjuvant chemotherapy. 34 (85%) of 40 assessable patients in the paclitaxel group had grade 3-4 toxicity during adjuvant chemotherapy. Of 47 patients in the fluorouracil group, 45 (96%) completed induction (nine [19%] with grade 3-4 toxicity), 39 (83%) completed induction and consolidation (12 [26%] had grade 3-4 toxicity due to consolidation), and 25 (53%) completed the entire protocol with adjuvant chemotherapy. 31 (76%) of 41 assessable patients in the fluorouracil group had grade 3-4 toxicity during adjuvant chemotherapy. Five (11%) patients treated with the paclitaxel regimen and three (6%) patients treated with the fluorouracil regimen developed late grade 3-4 radiotherapy toxicities. 11 (24%) patients treated with the paclitaxel regimen and 16 (34%) patients treated with the fluorouracil regimen developed late grade 3-4 toxicities unrelated to radiotherapy. One patient (in the fluorouracil group) died during follow-up. Six (13%) patients in the paclitaxel group and in three (6%) patients in the fluorouracil group discontinued due to treatment-related toxicity. In the absence of phase 3 data, our findings could inform selection of a bladder-sparing trimodality chemotherapy regimen for patients with muscle invasive bladder cancer. US National Cancer Institute.
    The Lancet Oncology 06/2013; · 25.12 Impact Factor
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    ABSTRACT: This study aims to quantify the reduction of the intrafractional motion when the prostate intensity modulated radiation therapy (IMRT) treatment time is shortened. Prostate intrafractional motion data recorded by the Calypso system for 105 patients was analyzed. Statistical distributions of the prostate displacements for the regular IMRT treatment and the first 1, 2, 3 and 5 min of the treatment were calculated and used for treatment margin estimation for all the selected patients. The treatment margins estimated for the first 1, 2, 3 and 5 min were compared with those for the regular IMRT treatment to quantify the reduction of the motion. If the treatment can be completed within 5 (3) min, the standard deviation of the prostate displacement could be reduced by up to 45% and the required treatment margins could be reduced to 1.2 (1.1), 0.9 (0.8), 2.2 (1.9), 1.9 (1.5), 1.9 (1.7) and 2.8 (2.4) mm from 1.5, 1.1, 2.8, 3.0, 2.4 and 3.9 mm in the left, right, superior, inferior, anterior and posterior directions, respectively. The same work was also performed for 19 of the 105 patients who exhibited the largest motion with 30% of their treatment time having 3D motion more than 3 mm. For this group of patients, the required margins change to 1.4 (1.2), 0.8 (0.8), 1.8 (1.6), 2.3 (1.8), 1.7 (1.5) and 3.4 (2.8) mm from 1.9, 1.2, 1.7, 3.7, 1.6 and 4.9 mm in the six directions when the treatment time is reduced to 5 (3) min. The intrafractional motion effects on prostate treatment are significantly smaller and the required margins can be therefore reduced when the treatment is shortened.
    Physics in Medicine and Biology 06/2013; 58(14):4921-4932. · 2.92 Impact Factor
  • Mark K Buyyounouski
    Nature Reviews Urology 06/2013; · 4.79 Impact Factor
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    ABSTRACT: BACKGROUND: There are no well-established normal tissue sparing dose-volume histogram (DVH) criteria that limit the risk of urinary toxicity from prostate radiation therapy (RT). The aim of this study was to determine which criteria predict late toxicity among various DVH parameters when contouring the entire solid bladder and its contents versus the bladder wall. The area under the histogram curve (AUHC) was also analyzed. METHODS AND MATERIALS: From 1993 to 2000, 503 men with prostate cancer received 3-dimensional conformal RT (median follow-up time, 71 months). The whole bladder and the bladder wall were contoured in all patients. The primary endpoint was grade ≥2 genitourinary (GU) toxicity occurring ≥3 months after completion of RT. Cox regressions of time to grade ≥2 toxicity were estimated separately for the entire bladder and bladder wall. Concordance probability estimates (CPE) assessed model discriminative ability. Before training the models, an external random test group of 100 men was set aside for testing. Separate analyses were performed based on the mean age (≤ 68 vs >68 years). RESULTS: Age, pretreatment urinary symptoms, mean dose (entire bladder and bladder wall), and AUHC (entire bladder and bladder wall) were significant (P<.05) in multivariable analysis. Overall, bladder wall CPE values were higher than solid bladder values. The AUHC for bladder wall provided the greatest discrimination for late bladder toxicity when compared with alternative DVH points, with CPE values of 0.68 for age ≤68 years and 0.81 for age >68 years. CONCLUSION: The AUHC method based on bladder wall volumes was superior for predicting late GU toxicity. Age >68 years was associated with late grade ≥2 GU toxicity, which suggests that risk-adapted dose constraints based on age should be explored.
    International journal of radiation oncology, biology, physics 05/2013; · 4.59 Impact Factor
  • International journal of radiation oncology, biology, physics 05/2013; 86(1):6-7. · 4.59 Impact Factor
  • M E Johnson, K Ruth, M K Buyyounouski, E M Horwitz
    Practical radiation oncology. 04/2013; 3(2 Suppl 1):S31-2.

Publication Stats

1k Citations
574.60 Total Impact Points


  • 2013–2014
    • Stanford University
      • Department of Radiation Oncology
      Palo Alto, California, United States
    • Thomas Jefferson University Hospitals
      Philadelphia, Pennsylvania, United States
    • Temple University
      Philadelphia, Pennsylvania, United States
  • 2002–2013
    • Fox Chase Cancer Center
      • Department of Radiation Oncology
      Philadelphia, PA, United States
  • 2012
    • University of Miami Miller School of Medicine
      • Department of Radiation Oncology
      Miami, FL, United States
  • 2011
    • Mayo Foundation for Medical Education and Research
      • Department of Urology
      Scottsdale, AZ, United States
    • Cooper University Hospital
      • Department of Radiation Oncology
      Camden, New Jersey, United States
  • 2009
    • University of Melbourne
      Melbourne, Victoria, Australia