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Sample records for escalated prostate radiotherapy

  1. The Impact of Dose Escalation on Secondary Cancer Risk After Radiotherapy of Prostate Cancer

    SciTech Connect

    Schneider, Uwe . E-mail: uwe.schneider@psi.ch; Lomax, Antony; Besserer, Juergen; Pemler, Peter; Lombriser, Norbert; Kaser-Hotz, Barbara D.V.M.

    2007-07-01

    Purpose: To estimate secondary cancer risk due to dose escalation in patients treated for prostatic carcinoma with three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated RT (IMRT), and spot-scanned proton RT. Methods and Materials: The organ equivalent dose (OED) concept with a linear-exponential, a plateau, and a linear dose-response curve was applied to dose distributions of 23 patients who received RT of prostate cancer. Conformal RT was used in 7 patients, 8 patients received IMRT with 6- and 15-MV photons, and 8 patients were treated with spot-scanned protons. We applied target doses ranging from 70 Gy to 100 Gy. Cancer risk was estimated as a function of target dose and tumor control probability. Results: At a 100-Gy target dose the secondary cancer risk relative to the 3D treatment plan at 70 Gy was +18.4% (15.0% for a plateau model, 22.3% for a linear model) for the 6-MV IMRT plan, +25.3% (17.0%, 14.1%) for the 15-MV IMRT plan, and -40.7% (-41.3%, -40.0%) for the spot-scanned protons. The increasing risk of developing a radiation-associated malignancy after RT with increasing dose was balanced by the enhanced cure rates at a larger dose. Conclusions: Cancer risk after dose escalation for prostate RT is expected to be equal to or lower than for conventional 3D treatment at 70 Gy, independent of treatment modality or dose-response model. Spot-scanned protons are the treatment of choice for dose escalation because this therapy can halve the risk of secondary cancers.

  2. Update of Dutch Multicenter Dose-Escalation Trial of Radiotherapy for Localized Prostate Cancer

    SciTech Connect

    Al-Mamgani, Abrahim Putten, Wim L.J. van; Heemsbergen, Wilma D.; Leenders, Geert J.L.H. van; Slot, Annerie; Dielwart, Michel F.H.; Incrocci, Luca; Lebesque, Joos V.

    2008-11-15

    Purpose: To update the analysis of the Dutch dose-escalation trial of radiotherapy for prostate cancer. Patients and Methods: A total of 669 patients with localized prostate cancer were randomly assigned to receive 68 or 78 Gy. The patients were stratified by age, institution, use of neoadjuvant or adjuvant hormonal therapy, and treatment group. The primary endpoint was freedom from failure (FFF), with failure defined as clinical or biochemical failure. Two definitions of biochemical failure were used: the American Society for Therapeutic Radiology and Oncology definition (three consecutive increases in prostate-specific antigen level) and the Phoenix definition (nadir plus 2 {mu}g/L). The secondary endpoints were freedom from clinical failure, overall survival, and genitourinary and gastrointestinal toxicity. Results: After a median follow-up of 70 months, the FFF using the American Society for Therapeutic Radiology and Oncology definition was significantly better in the 78-Gy arm than in the 68-Gy arm (7-year FFF rate, 54% vs. 47%, respectively; p = 0.04). The FFF using the Phoenix definition was also significantly better in the 78-Gy arm than in the 68-Gy arm (7-year FFF rate, 56% vs. 45%, respectively; p = 0.03). However, no differences in freedom from clinical failure or overall survival were observed. The incidence of late Grade 2 or greater genitourinary toxicity was similar in both arms (40% and 41% at 7 years; p = 0.6). However, the cumulative incidence of late Grade 2 or greater gastrointestinal toxicity was increased in the 78-Gy arm compared with the 68-Gy arm (35% vs. 25% at 7 years; p = 0.04). Conclusion: The results of our study have shown a statistically significant improvement in FFF in prostate cancer patients treated with 78 Gy but with a greater rate of late gastrointestinal toxicity.

  3. Incorporating Androgen Deprivation With Dose-Escalated External-Beam Radiotherapy for Prostate Cancer.

    PubMed

    Dosoretz, Arie P; Yu, James B

    2016-05-20

    The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.A 71-year-old man was seen by his primary care physician for routine evaluation in early 2015. On digital rectal examination, his prostate was moderately enlarged, although he had no obvious areas of palpable disease. His prostate-specific antigen (PSA) level was 7.1 ng/mL. A standard ultrasound-guided biopsy of his prostate revealed a 60-mL prostate volume and a single core (out of 12) of Gleason 3 + 3 disease. He chose to undergo surveillance. Six months later, his PSA level had risen to 10.0 ng/mL; there was still no palpable disease on digital rectal examination. Multiparametric magnetic resonance imaging of his prostate and pelvis revealed two suspicious intraprostatic lesions with restricted diffusion, focal and earlier enhancement with contrast than adjacent normal prostate, and hypointense features on T2-weighted imaging; these findings were highly suspicious for high-grade prostate cancer (Fig 1). Magnetic resonance imaging-ultrasound fusion targeted biopsy of each lesion yielded a total of four positive biopsy cores of Gleason 4 + 3 = 7, involving 50% to 80% of each core, with perineural invasion noted. The patient's medical history is notable for overweight (but not morbidly obese), hypercholesterolemia, hypertension, cataract surgeries, and inguinal hernia repair, but the patient is otherwise healthy. He has decided against prostatectomy and brachytherapy because of strong personal preference. In particular, he wanted to avoid anesthesia, and

  4. Role of Intensity-Modulated Radiotherapy in Reducing Toxicity in Dose Escalation for Localized Prostate Cancer

    SciTech Connect

    Al-Mamgani, Abrahim Heemsbergen, Wilma D.; Peeters, Stephanie T.H.; Lebesque, Joos V.

    2009-03-01

    Purpose: To compare the acute and late gastrointestinal (GI) and genitourinary (GU) toxicity in prostate cancer patients treated to a total dose of 78 Gy with either a three-conformal radiotherapy technique with a sequential boost (SEQ) or a simultaneous integrated boost using intensity-modulated radiotherapy (SIB-IMRT). Patients and Methods: A total of 78 prostate cancer patients participating in the randomized Dutch trial comparing 68 Gy and 78 Gy were the subject of this analysis. They were all treated at the same institution to a total dose of 78 Gy. The median follow-up was 76 and 56 months for the SEQ and SIB-IMRT groups, respectively. The primary endpoints were acute and late GI and GU toxicity. Results: A significantly lower incidence of acute Grade 2 or greater GI toxicity occurred in patients treated with SIB-IMRT compared with SEQ (20% vs. 61%, p = 0.001). For acute GU toxicity and late GI and GU toxicity, the incidence was lower after SIB-IMRT, but these differences were not statistically significant. No statistically significant difference were found in the 5-year freedom from biochemical failure rate (Phoenix definition) between the two groups (70% for the SIB-IMRT group vs. 61% for the SEQ group, p = 0.3). The same was true for the 5-year freedom from clinical failure rate (90% vs. 72%, p = 0.07). Conclusion: The results of our study have shown that SIB-IMRT reduced the toxicity without compromising the outcome in patients with localized prostate cancer treated to 78 Gy radiation.

  5. The role and strategy of IMRT in radiotherapy of pelvic tumors: Dose escalation and critical organ sparing in prostate cancer

    SciTech Connect

    Liu, Y.-M.; Shiau, C.-Y.; Lee, M.-L.; Huang, P.-I.; Hsieh, C.-M.; Chen, P.-H.; Lin, Y.-H.; Wang, L.-W.; Yen, S.-H. . E-mail: shyen@vghtpe.gov.tw

    2007-03-15

    Purpose: To investigate the intensity-modulated radiotherapy (IMRT) strategy in dose escalation of prostate and pelvic lymph nodes. Methods and Materials: Plan dosimetric data of 10 prostate cancer patients were compared with two-dimensional (2D) or IMRT techniques for pelvis (two-dimensional whole pelvic radiation therapy [2D-WPRT] or IM-WPRT) to receive 50 Gy or 54 Gy and additional prostate boost by three-dimensional conformal radiation therapy or IMRT (3D-PBRT or IM-PBRT) techniques up to 72 Gy or 78 Gy. Dose-volume histograms (DVHs), normal tissue complication probabilities (NTCP) of critical organ, and conformity of target volume in various combinations were calculated. Results: In DVH analysis, the plans with IM-WPRT (54 Gy) and additional boost up to 78 Gy had lower rectal and bladder volume percentage at 50 Gy and 60 Gy, compared with those with 2D-WPRT (50 Gy) and additional boost up to 72 Gy or 78 Gy. Those with IM-WPRT (54 Gy) also had better small bowel sparing at 30 Gy and 50 Gy, compared with those with 2D-WPRT (50 Gy). In NTCP, those with IM-WPRT and total dose of 78 Gy achieved lower complication rates in rectum and small bowel, compared with those of 2D-WPRT with total dose of 72 Gy. In conformity, those with IM-WPRT had better conformity compared with those with 2D-WPRT with significance (p < 0.005). No significant difference in DVHs, NTCP, or conformity was found between IM-PBRT and 3D-PBRT after IM-WPRT. Conclusions: Initial pelvic IMRT is the most important strategy in dose escalation and critical organ sparing. IM-WPRT is recommended for patients requiring WPRT. There is not much benefit for critical organ sparing by IMRT after 2D-WPRT.

  6. Sexual Function After Three-Dimensional Conformal Radiotherapy for Prostate Cancer: Results From a Dose-Escalation Trial

    SciTech Connect

    Wielen, Gerard J. van der . E-mail: g.vanderwielen@erasmusmc.nl; Putten, Wim van; Incrocci, Luca

    2007-06-01

    Purpose: The purpose of this study is to provide information about sexual function (SF) after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer while taking important factors into account that influence SF. Methods and Materials: Between June 1997 and February 2003, a total of 268 patients from a randomized dose-escalation trial comparing 68 Gy and 78 Gy agreed to participate in an additional part of the trial that evaluated SF. Results: At baseline 28% of patients had erectile dysfunction (ED). After 1 year, 27% of the pretreatment potent patients had developed ED. After 2 years this percentage had increased to 36%. After 3 years it almost stabilized at 38%. Satisfaction with sexual life was significantly correlated with ED. After 2 years one third of the pre-treatment potent patients still had considerable to very much sexual desire and found sex (very) important. No significant differences were found between the two dose-arms. Potency aids were used on a regular base by 14% of the patients. Conclusion: By taking adjuvant hormonal therapy (HT), HT during follow-up and potency aids into account, we found a lower percentage of ED after 3D-CRT than reported in previous prospective studies. A large group of patients still had sexual desire, considered sex important and 14% used potency aids after 3D-CRT.

  7. Expression of Bcl-2, p53, and MDM2 in Localized Prostate Cancer With Respect to the Outcome of Radical Radiotherapy Dose Escalation

    SciTech Connect

    Vergis, Roy; Corbishley, Catherine M.; Thomas, Karen

    2010-09-01

    Purpose: Established prognostic factors in localized prostate cancer explain only a moderate proportion of variation in outcome. We analyzed tumor expression of apoptotic markers with respect to outcome in men with localized prostate cancer in two randomized controlled trials of radiotherapy dose escalation. Methods and Materials: Between 1995 and 2001, 308 patients with localized prostate cancer received neoadjuvant androgen deprivation and radical radiotherapy at our institution in one of two dose-escalation trials. The biopsy specimens in 201 cases were used to make a biopsy tissue microarray. We evaluated tumor expression of Bcl-2, p53, and MDM2 by immunohistochemistry with respect to outcome. Results: Median follow-up was 7 years, and 5-year freedom from biochemical failure (FFBF) was 70.4% (95% CI, 63.5-76.3%). On univariate analysis, expression of Bcl-2 (p < 0.001) and p53 (p = 0.017), but not MDM2 (p = 0.224), was significantly associated with FFBF. Expression of Bcl-2 remained significantly associated with FFBF (p = 0.001) on multivariate analysis, independently of T stage, Gleason score, initial prostate-specific antigen level, and radiotherapy dose. Seven-year biochemical control was 61% vs. 41% (p = 0.0122) for 74 Gy vs. 64 Gy, respectively, among patients with Bcl-2-positive tumors and 87% vs. 81% (p = 0.423) for 74 Gy vs. 64 Gy, respectively, among patients with Bcl-2-negative tumors. There was no statistically significant interaction between dose and Bcl-2 expression. Conclusions: Bcl-2 expression was a significant, independent determinant of biochemical control after neoadjuvant androgen deprivation and radical radiotherapy for prostate cancer. These data generate the hypothesis that Bcl-2 expression could be used to inform the choice of radiotherapy dose in individual patients.

  8. Late Gastrointestinal Toxicity After Dose-Escalated Conformal Radiotherapy for Early Prostate Cancer: Results From the UK Medical Research Council RT01 Trial (ISRCTN47772397)

    SciTech Connect

    Syndikus, Isabel; Morgan, Rachel C.; Sydes, Matthew R.; Graham, John D.; Dearnaley, David P.

    2010-07-01

    Purpose: In men with localized prostate cancer, dose-escalated conformal radiotherapy (CFRT) improves efficacy outcomes at the cost of increased toxicity. We present a detailed analysis to provide further information about the incidence and prevalence of late gastrointestinal side effects. Methods and Materials: The UK Medical Research Council RT01 trial included 843 men with localized prostate cancer, who were treated for 6 months with neoadjuvant radiotherapy and were randomly assigned to either 64-Gy or 74-Gy CFRT. Toxicity was evaluated before CFRT and during long-term follow-up using Radiation Therapy Oncology Group (RTOG) grading, the Late Effects on Normal Tissue: Subjective, Objective, Management (LENT/SOM) scale, and Royal Marsden Hospital assessment scores. Patients regularly completed Functional Assessment of Cancer Therapy--Prostate (FACT-P) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) questionnaires. Results: In the dose-escalated group, the hazard ratio (HR) for rectal bleeding (LENT/SOM grade {>=}2) was 1.55 (95% CI, 1.17-2.04); for diarrhea (LENT/SOM grade {>=}2), the HR was 1.79 (95% CI, 1.10-2.94); and for proctitis (RTOG grade {>=}2), the HR was 1.64 (95% CI, 1.20-2.25). Compared to baseline scores, the prevalence of moderate and severe toxicities generally increased up to 3 years and than lessened. At 5 years, the cumulative incidence of patient-reported severe bowel problems was 6% vs. 8% (standard vs. escalated, respectively) and severe distress was 4% vs. 5%, respectively. Conclusions: There is a statistically significant increased risk of various adverse gastrointestinal events with dose-escalated CFRT. This remains at clinically acceptable levels, and overall prevalence ultimately decreases with duration of follow-up.

  9. Lack of Benefit for the Addition of Androgen Deprivation Therapy to Dose-Escalated Radiotherapy in the Treatment of Intermediate- and High-Risk Prostate Cancer

    SciTech Connect

    Krauss, Daniel; Kestin, Larry; Ye, Hong; Brabbins, Donald; Ghilezan, Michel; Gustafson, Gary; Vicini, Frank; Martinez, Alvaro

    2011-07-15

    Purpose: Assessment of androgen deprivation therapy (ADT) benefits for prostate cancer treated with dose-escalated radiotherapy (RT). Methods and Materials: From 1991 to 2004, 1,044 patients with intermediate- (n = 782) or high-risk (n = 262) prostate cancer were treated with dose-escalated RT at William Beaumont Hospital. Patients received external-beam RT (EBRT) alone, brachytherapy (high or low dose rate), or high dose rate brachytherapy plus pelvic EBRT. Intermediate-risk patients had Gleason score 7, prostate-specific antigen (PSA) 10.0-19.9 ng/mL, or Stage T2b-T2c. High-risk patients had Gleason score 8-10, PSA {>=}20, or Stage T3. Patients were additionally divided specifically by Gleason score, presence of palpable disease, and PSA level to further define subgroups benefitting from ADT. Results: Median follow-up was 5 years; 420 patients received ADT + dose-escalated RT, and 624 received dose-escalated RT alone. For all patients, no advantages in any clinical endpoints at 8 years were associated with ADT administration. No differences in any endpoints were associated with ADT administration based on intermediate- vs. high-risk group or RT modality when analyzed separately. Patients with palpable disease plus Gleason {>=}8 demonstrated improved clinical failure rates and a trend toward improved survival with ADT. Intermediate-risk patients treated with brachytherapy alone had improved biochemical control when ADT was given. Conclusion: Benefits of ADT in the setting of dose-escalated RT remain poorly defined. This question must continue to be addressed in prospective study.

  10. Hypofractionated Boost to the Dominant Tumor Region With Intensity Modulated Stereotactic Radiotherapy for Prostate Cancer: A Sequential Dose Escalation Pilot Study

    SciTech Connect

    Miralbell, Raymond; Molla, Meritxell; Rouzaud, Michel; Hidalgo, Alberto; Toscas, Jose Ignacio; Lozano, Joan; Sanz, Sergi B.Sc.; Ares, Carmen; Jorcano, Sandra; Linero, Dolors; Escude, Lluis

    2010-09-01

    Purpose: To evaluate the feasibility, tolerability, and preliminary outcomes in patients with prostate cancer treated according to a hypofractionated dose escalation protocol to boost the dominant tumor-bearing region of the prostate. Methods and Materials: After conventional fractionated external radiotherapy to 64 to 64.4Gy, 50 patients with nonmetastatic prostate cancer were treated with an intensity-modulated radiotherapy hypofractionated boost under stereotactic conditions to a reduced prostate volume to the dominant tumor region. A rectal balloon inflated with 60cc of air was used for internal organ immobilization. Five, 8, and 8 patients were sequentially treated with two fractions of 5, 6, or 7Gy, respectively (normalized total dose in 2Gy/fraction [NTD{sub 2Gy}] < 100Gy, low-dose group), whereas 29 patients received two fractions of 8Gy each (NTD{sub 2Gy} > 100Gy, high-dose group). Androgen deprivation was given to 33 patients. Acute and late toxicities were assessed according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (RTOG/EORTC) scoring system. Results: Two patients presented with Grade 3 acute urinary toxicity. The 5-year probabilities of {>=}Grade 2 late urinary and late low gastrointestinal (GI) toxicity-free survival were 82.2% {+-} 7.4% and 72.2% {+-} 7.6%, respectively. The incidence and severity of acute or late toxicities were not correlated with low- vs. high-dose groups, pelvic irradiation, age, or treatment with or without androgen deprivation. The 5-year biochemical disease-free survival (b-DFS) and disease-specific survival were 98% {+-} 1.9% and 100%, respectively. Conclusion: Intensity-modulated radiotherapy hypofractionated boost dose escalation under stereotactic conditions was feasible, and showed excellent outcomes with acceptable long-term toxicity. This approach may well be considered an alternative to high-dose-rate brachytherapy.

  11. Intensity-Modulated Radiotherapy as Primary Therapy for Prostate Cancer: Report on Acute Toxicity After Dose Escalation With Simultaneous Integrated Boost to Intraprostatic Lesion

    SciTech Connect

    Fonteyne, Valerie Villeirs, Geert; Speleers, Bruno; Neve, Wilfried de; Wagter, Carlos de; Lumen, Nicolas; Meerleer, Gert de

    2008-11-01

    Purpose: To report on the acute toxicity of a third escalation level using intensity-modulated radiotherapy for prostate cancer (PCa) and the acute toxicity resulting from delivery of a simultaneous integrated boost (SIB) to an intraprostatic lesion (IPL) detected on magnetic resonance imaging (MRI), with or without spectroscopy. Methods and Materials: Between January 2002 and March 2007, we treated 230 patients with intensity-modulated radiotherapy to a third escalation level as primary therapy for prostate cancer. If an IPL (defined by MRI or MRI plus spectroscopy) was present, a SIB was delivered to the IPL. To report on acute toxicity, patients were seen weekly during treatment and 1 and 3 months after treatment. Toxicity was scored using the Radiation Therapy Oncology Group toxicity scale, supplemented by an in-house-developed scoring system. Results: The median dose to the planning target volume was 78 Gy. An IPL was found in 118 patients. The median dose to the MRI-detected IPL and MRI plus spectroscopy-detected IPL was 81 Gy and 82 Gy, respectively. No Grade 3 or 4 acute gastrointestinal toxicity developed. Grade 2 acute gastrointestinal toxicity was present in 26 patients (11%). Grade 3 genitourinary toxicity was present in 15 patients (7%), and 95 patients developed Grade 2 acute genitourinary toxicity (41%). No statistically significant increase was found in Grade 2-3 acute gastrointestinal or genitourinary toxicity after a SIB to an IPL. Conclusion: The results of our study have shown that treatment-induced acute toxicity remains low when intensity-modulated radiotherapy to 80 Gy as primary therapy for prostate cancer is used. In addition, a SIB to an IPL did not increase the severity or incidence of acute toxicity.

  12. Percentage of Cancer Volume in Biopsy Cores Is Prognostic for Prostate Cancer Death and Overall Survival in Patients Treated With Dose-Escalated External Beam Radiotherapy

    SciTech Connect

    Vance, Sean M.; Stenmark, Matthew H.; Blas, Kevin; Halverson, Schulyer; Hamstra, Daniel A.; Feng, Felix Y.

    2012-07-01

    Purpose: To investigate the prognostic utility of the percentage of cancer volume (PCV) in needle biopsy specimens for prostate cancer patients treated with dose-escalated external beam radiotherapy. Methods and Materials: The outcomes were analyzed for 599 men treated for localized prostate cancer with external beam radiotherapy to a minimal planning target volume dose of 75 Gy (range, 75-79.2). We assessed the effect of PCV and the pretreatment and treatment-related factors on the freedom from biochemical failure, freedom from metastasis, cause-specific survival, and overall survival. Results: The median number of biopsy cores was 7 (interquartile range, 6-12), median PCV was 10% (interquartile range, 2.5-25%), and median follow-up was 62 months. The PCV correlated with the National Comprehensive Cancer Network risk group and individual risk features, including T stage, prostate-specific antigen level, Gleason score, and percentage of positive biopsy cores. On log-rank analysis, the PCV stratified by quartile was prognostic for all endpoints, including overall survival. In addition, the PCV was a stronger prognostic factor than the percentage of positive biopsy cores when the two metrics were analyzed together. On multivariate analysis, the PCV predicted a worse outcome for all endpoints, including freedom from biochemical failure, (hazard ratio, 1.9; p = .0035), freedom from metastasis (hazard ratio, 1.7, p = .09), cause-specific survival (hazard ratio, 3.9, p = .014), and overall survival (hazard ratio, 1.8, p = .02). Conclusions: For patients treated with dose-escalated external beam radiotherapy, the volume of cancer in the biopsy specimen adds prognostic value for clinically relevant endpoints, particularly in intermediate- and high-risk patients. Although the PCV determination is more arduous than the percentage of positive biopsy cores, it provides superior risk stratification.

  13. Long-term outcomes from dose-escalated image-guided intensity-modulated radiotherapy with androgen deprivation: encouraging results for intermediate- and high-risk prostate cancer

    PubMed Central

    Wilcox, Shea W; Aherne, Noel J; Benjamin, Linus C; Wu, Bosco; de Campos Silva, Thomaz; McLachlan, Craig S; McKay, Michael J; Last, Andrew J; Shakespeare, Thomas P

    2014-01-01

    Purpose Dose-escalated (DE) radiotherapy in the setting of localized prostate cancer has been shown to improve biochemical disease-free survival (bDFS) in several studies. In the same group of patients, androgen deprivation therapy (ADT) has been shown to confer a survival benefit when combined with radiotherapy doses of up to 70 Gy; however, there is currently little long-term data on patients who have received high-dose intensity-modulated radiotherapy (IMRT) with ADT. We report the long-term outcomes in a large cohort of patients treated with the combination of DE image-guided IMRT (IG-IMRT) and ADT. Methods and materials Patients with localized prostate cancer were identified from a centralized database across an integrated cancer center. All patients received DE IG-IMRT, combined with ADT, and had a minimum follow up of 12 months post-radiotherapy. All relapse and toxicity data were collected prospectively. Actuarial bDFS, metastasis-free survival, prostate cancer-specific survival, and multivariate analyses were calculated using the SPSS v20.0 statistical package. Results Seven hundred and eighty-two eligible patients were identified with a median follow up of 46 months. Overall, 4.3% of patients relapsed, 2.0% developed distant metastases, and 0.6% died from metastatic prostate cancer. At 5-years, bDFS was 88%, metastasis-free survival was 95%, and prostate cancer-specific survival was 98%. Five-year grade 2 genitourinary and gastrointestinal toxicity was 2.1% and 3.4%, respectively. No grade 3 or 4 late toxicities were reported. Pretreatment prostate specific antigen (P=0.001) and Gleason score (P=0.03) were significant in predicting biochemical failure on multivariate analysis. Conclusion There is a high probability of tumor control with DE IG-IMRT combined with androgen deprivation, and this is a technique with a low probability of significant late toxicity. Our long term results corroborate the safety and efficacy of treating with IG-IMRT to high doses

  14. Dose Escalation and Quality of Life in Patients With Localized Prostate Cancer Treated With Radiotherapy: Long-Term Results of the Dutch Randomized Dose-Escalation Trial (CKTO 96-10 Trial)

    SciTech Connect

    Al-Mamgani, Abrahim; Putten, Wim L.J. van; Wielen, Gerard J. van der; Levendag, Peter C.; Incrocci, Luca

    2011-03-15

    Purpose: To assess the impact of dose escalation of radiotherapy on quality of life (QoL) in prostate cancer patients. Patients and Methods: Three hundred prostate cancer patients participating in the Dutch randomized trial (CKTO 69-10) comparing 68 Gy with 78 Gy were the subject of this analysis. These patients filled out the SF-36 QoL questionnaire before radiotherapy (baseline) and 6, 12, 24, and 36 months thereafter. Changes in QoL over time of {>=}10 points were considered clinically relevant. Repeated-measures regression analyses were applied to estimate and test the QoL changes over time, the differences between the two arms, and for association with a number of covariates. Results: At 3-year follow-up, the summary score physical health was 73.2 for the 68-Gy arm vs. 71.6 for the 78-Gy arm (p = 0.81), and the summary score mental health was 76.7 for the 68-Gy arm vs. 76.1 for the 78-Gy arm (p = 0.97). Statistically significant (p < 0.01) deterioration in QoL scores over time was registered in both arms in six scales. The deterioration over time was more pronounced in the high-dose arm for most scales. However, clinically relevant deterioration (>10 points) was seen for only two scales. None of the tested covariates were significantly correlated with QoL scores. Conclusion: Dose escalation did not result in significant deterioration of QoL in prostate cancer patients. In both randomization arms, statistically significant decreases in QoL scores over time were seen in six scales. The deterioration of QoL was more pronounced in the physical than in the mental health domain and in some scales more in the high- than in the low-dose arm, but the differences between arms were not statistically significant.

  15. The Natural History and Predictors of Outcome Following Biochemical Relapse in the Dose Escalation Era for Prostate Cancer Patients Undergoing Definitive External Beam Radiotherapy

    PubMed Central

    Zumsteg, Zachary S.; Spratt, Daniel E.; Romesser, Paul B.; Pei, Xin; Zhang, Zhigang; Polkinghorn, William; McBride, Sean; Kollmeier, Marisa; Yamada, Yoshiya; Zelefsky, Michael J.

    2016-01-01

    Background The management of biochemical failure (BF) following external beam radiotherapy (EBRT) for prostate cancer is controversial, due to both the heterogeneous disease course following a BF and a lack of clinical trials in this setting. Objective We sought to characterize the natural history and predictors of outcome for patients experiencing BF in a large cohort of men with localized prostate cancer undergoing definitive dose-escalated EBRT. Design, setting, and participants This retrospective analysis included 2694 patients with localized prostate cancer treated with EBRT at a large academic center. Of these, 609 experienced BF, defined as prostate-specific antigen (PSA) nadir + 2 ng/ml. The median follow-up was 83 mo for all patients and 122 mo for BF patients. Intervention(s) All patients received EBRT at doses of 75.6–86.4 Gy. Outcome measurements and statistical analysis The primary objective of this study was to determine predictors of distant progression at the time of BF. Cox proportional hazards models were used in univariate and multivariate analyses of distant metastases (DM), and a competing risks method was used to analyze prostate cancer–specific mortality (PCSM). Results and limitations From the date of BF, the median times to DM and PCSM mortality were 5.4 yr and 10.5 yr, respectively. Shorter posttreatment PSA doubling time, a higher initial clinical tumor stage, a higher pretreatment Gleason score, and a shorter interval from the end of radiotherapy to BF were independent predictors for clinical progression following BF. Patients with two of these risk factors had a significantly higher incidence of DM and PCSM following BF than those with zero or one risk factor. The main limitations of this study are its retrospective nature and heterogeneous salvage interventions. Conclusions Clinical and pathologic factors can help identify patients at high risk of clinical progression following BF. Patient summary In this report, we look at

  16. Five-year prospective patient evaluation of bladder and bowel symptoms after dose-escalated radiotherapy for prostate cancer with the BeamCath (registered) technique

    SciTech Connect

    Fransson, Per . E-mail: Per.Fransson@onkologi.umu.se; Bergstroem, Per; Loefroth, Per-Olov; Widmark, Anders

    2006-10-01

    Purpose: Late side effects were prospectively evaluated up to 5 years after dose-escalated external beam radiotherapy (EBRT) and were compared with a previously treated series with conventional conformal technique. Methods and Materials: Bladder and bowel symptoms were prospectively evaluated with the Prostate Cancer Symptom Scale (PCSS) questionnaire up to 5 years posttreatment. In all, 257 patients completed the questionnaire 5 years posttreatment. A total of 168 patients were treated with the conformal technique at doses <71 Gy, and 195 were treated with the dose-escalated stereotactic BeamCath (registered) technique comprising three dose levels: 74 Gy (n = 68), 76 Gy (n = 74), and 78 Gy (n = 53). Results: For all dose groups analyzed together, 5 years after treatment, urinary starting problems decreased and urinary incontinence increased in comparison to baseline values. No increase in other bladder symptoms or frequency was detected. When comparing dose groups after 5 years, both the 74-Gy and 78-Gy groups reported increased urinary starting problems compared with patients given the conventional dose (<71 Gy). No increased incontinence was seen in the 76-Gy or the 78-Gy groups. Bowel symptoms were slightly increased during the follow-up period in comparison to baseline. Dose escalation with stereotactic EBRT (74-78 Gy) did not increase gastrointestinal late side effects after 5 years in comparison to doses <71 Gy. Conclusion: Dose-escalated EBRT with the BeamCath (registered) technique with doses up to 78 Gy is tolerable, and the toxicity profile is similar to that observed with conventional doses <71 Gy.

  17. Twice-Weekly Hypofractionated Intensity-Modulated Radiotherapy for Localized Prostate Cancer With Low-Risk Nodal Involvement: Toxicity and Outcome From a Dose Escalation Pilot Study

    SciTech Connect

    Zilli, Thomas; Jorcano, Sandra; Rouzaud, Michel; Dipasquale, Giovanna; Nouet, Philippe; Toscas, Jose Ignacio; Casanova, Nathalie; Wang, Hui; Escude, Lluis; Molla, Meritxell; Linero, Dolors; Weber, Damien C.; Miralbell, Raymond

    2011-10-01

    Purpose: To evaluate the toxicity and preliminary outcome of patients with localized prostate cancer treated with twice-weekly hypofractionated intensity-modulated radiotherapy (IMRT). Methods and Materials: Between 2003 and 2006, 82 prostate cancer patients with a nodal involvement risk {<=}20% (Roach index) have been treated to the prostate with or without seminal vesicles with 56 Gy (4 Gy/fraction twice weekly) and an overall treatment time of 6.5 weeks. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were scored according to the Radiation Therapy Oncology Group (RTOG) grading system. Median follow-up was 48 months (range, 9-67 months). Results: All patients completed the treatment without interruptions. No patient presented with Grade {>=}3 acute GU or GI toxicity. Of the patients, 4% presented with Grade 2 GU or GI persistent acute toxicity 6 weeks after treatment completion. The estimated 4-year probability of Grade {>=}2 late GU and GI toxicity-free survival were 94.2% {+-} 2.9% and 96.1% {+-} 2.2%, respectively. One patient presented with Grade 3 GI and another patient with Grade 4 GU late toxicity, which were transitory in both cases. The 4-year actuarial biochemical relapse-free survival was 91.3% {+-} 5.9%, 76.4% {+-} 8.8%, and 77.5% {+-} 8.9% for low-, intermediate-, and high-risk groups, respectively. Conclusions: In patients with localized prostate cancer, acute and late toxicity were minimal after dose-escalation administering twice-weekly 4 Gy to a total dose of 56 Gy, with IMRT. Further prospective trials are warranted to further assess the best fractionation schemes for these patients.

  18. Dose-Volume Parameters of the Corpora Cavernosa Do Not Correlate With Erectile Dysfunction After External Beam Radiotherapy for Prostate Cancer: Results From a Dose-Escalation Trial

    SciTech Connect

    Wielen, Gerard J. van der Hoogeman, Mischa S.; Dohle, Gert R.; Putten, Wim L.J. van; Incrocci, Luca

    2008-07-01

    Purpose: To analyze the correlation between dose-volume parameters of the corpora cavernosa and erectile dysfunction (ED) after external beam radiotherapy (EBRT) for prostate cancer. Methods and Materials: Between June 1997 and February 2003, a randomized dose-escalation trial comparing 68 Gy and 78 Gy was conducted. Patients at our institute were asked to participate in an additional part of the trial evaluating sexual function. After exclusion of patients with less than 2 years of follow-up, ED at baseline, or treatment with hormonal therapy, 96 patients were eligible. The proximal corpora cavernosa (crura), the superiormost 1-cm segment of the crura, and the penile bulb were contoured on the planning computed tomography scan and dose-volume parameters were calculated. Results: Two years after EBRT, 35 of the 96 patients had developed ED. No statistically significant correlations between ED 2 years after EBRT and dose-volume parameters of the crura, the superiormost 1-cm segment of the crura, or the penile bulb were found. The few patients using potency aids typically indicated to have ED. Conclusion: No correlation was found between ED after EBRT for prostate cancer and radiation dose to the crura or penile bulb. The present study is the largest study evaluating the correlation between ED and radiation dose to the corpora cavernosa after EBRT for prostate cancer. Until there is clear evidence that sparing the penile bulb or crura will reduce ED after EBRT, we advise to be careful in sparing these structures, especially when this involves reducing treatment margins.

  19. 70 Gy Versus 80 Gy in Localized Prostate Cancer: 5-Year Results of GETUG 06 Randomized Trial;Prostate cancer; Dose escalation; Conformal radiotherapy; Randomized trial

    SciTech Connect

    Beckendorf, Veronique; Guerif, Stephane; Le Prise, Elisabeth; Cosset, Jean-Marc; Bougnoux, Agnes; Chauvet, Bruno; Salem, Naji; Chapet, Olivier; Bourdain, Sylvain; Bachaud, Jean-Marc; Maingon, Philippe; Hannoun-Levi, Jean-Michel; Malissard, Luc; Simon, Jean-Marc; Pommier, Pascal; Hay, Men; Dubray, Bernard; Lagrange, Jean-Leon; Luporsi, Elisabeth; Bey, Pierre

    2011-07-15

    Purpose: To perform a randomized trial comparing 70 and 80 Gy radiotherapy for prostate cancer. Patients and Methods: A total of 306 patients with localized prostate cancer were randomized. No androgen deprivation was allowed. The primary endpoint was biochemical relapse according to the modified 1997-American Society for Therapeutic Radiology and Oncology and Phoenix definitions. Toxicity was graded using the Radiation Therapy Oncology Group 1991 criteria and the late effects on normal tissues-subjective, objective, management, analytic scales (LENT-SOMA) scales. The patients' quality of life was scored using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item cancer-specific and 25-item prostate-specific modules. Results: The median follow-up was 61 months. According to the 1997-American Society for Therapeutic Radiology and Oncology definition, the 5-year biochemical relapse rate was 39% and 28% in the 70- and 80-Gy arms, respectively (p = .036). Using the Phoenix definition, the 5-year biochemical relapse rate was 32% and 23.5%, respectively (p = .09). The subgroup analysis showed a better biochemical outcome for the higher dose group with an initial prostate-specific antigen level >15 ng/mL. At the last follow-up date, 26 patients had died, 10 of their disease and none of toxicity, with no differences between the two arms. According to the Radiation Therapy Oncology Group scale, the Grade 2 or greater rectal toxicity rate was 14% and 19.5% for the 70- and 80-Gy arms (p = .22), respectively. The Grade 2 or greater urinary toxicity was 10% at 70 Gy and 17.5% at 80 Gy (p = .046). Similar results were observed using the LENT-SOMA scale. Bladder toxicity was more frequent at 80 Gy than at 70 Gy (p = .039). The quality-of-life questionnaire results before and 5 years after treatment were available for 103 patients with no differences found between the 70- and 80-Gy arms. Conclusion: High-dose radiotherapy provided a

  20. [Postoperative radiotherapy of prostate cancer].

    PubMed

    Guérif, S; Latorzeff, I; Lagrange, J-L; Hennequin, C; Supiot, S; Garcia, A; François, P; Soulié, M; Richaud, P; Salomon, L

    2014-10-01

    Between 10 and 40% of patients who have undergone a radical prostatectomy may have a biologic recurrence. Local or distant failure represents the possible patterns of relapse. Patients at high-risk for local relapse have extraprostatic disease, positive surgical margins or seminal vesicles infiltration or high Gleason score at pathology. Three phase-III randomized clinical trials have shown that, for these patients, adjuvant irradiation reduces the risk of tumoral progression without higher toxicity. Salvage radiotherapy for late relapse allows a disease control in 60-70% of the cases. Several research in order to improve the therapeutic ratio of the radiotherapy after prostatectomy are evaluate in the French Groupe d'Étude des Tumeurs Urogénitales (Gétug) and of the French association of urology (Afu). The Gétug-Afu 17 trial will provide answers to the question of the optimal moment for postoperative radiotherapy for pT3-4 R1 pN0 Nx patients, with the objective of comparing an immediate treatment to a differed early treatment initiated at biological recurrence. The Gétug-Afu 22 questions the place of a short hormonetherapy combined with image-guided, intensity-modulated radiotherapy (IMRT) in adjuvant situation for a detectable prostate specific antigen (PSA). The implementation of a multicenter quality control within the Gétug-Afu in order to harmonize a modern postoperative radiotherapy will allow the development of a dose escalation IMRT after surgery. PMID:25195116

  1. The Percent of Positive Biopsy Cores Improves Prediction of Prostate Cancer-Specific Death in Patients Treated With Dose-Escalated Radiotherapy

    SciTech Connect

    Qian Yushen; Feng, Felix Y.; Halverson, Schuyler; Blas, Kevin; Sandler, Howard M.; Hamstra, Daniel A.

    2011-11-01

    Purpose: To examine the prognostic utility of the percentage of positive cores (PPC) at the time of prostate biopsy for patients treated with dose-escalated external beam radiation therapy. Methods and Materials: We performed a retrospective analysis of patients treated at University of Michigan Medical Center to at least 75 Gy. Patients were stratified according to PPC by quartile, and freedom from biochemical failure (nadir + 2 ng/mL), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival (OS) were assessed by log-rank test. Receiver operator characteristic (ROC) curve analysis was used to determine the optimal cut point for PPC stratification. Finally, Cox proportional hazards multivariate regression was used to assess the impact of PPC on clinical outcome when adjusting for National Comprehensive Cancer Network (NCCN) risk group and androgen deprivation therapy. Results: PPC information was available for 651 patients. Increasing-risk features including T stage, prostate-specific antigen, Gleason score, and NCCN risk group were all directly correlated with increasing PPC. On log-rank evaluation, all clinical endpoints, except for OS, were associated with PPC by quartile, with worse clinical outcomes as PPC increased, with the greatest impact seen in the highest quartile (>66.7% of cores positive). ROC curve analysis confirmed that a cut point using two-thirds positive cores was most closely associated with CSS (p = 0.002; area under ROC curve, 0.71). On univariate analysis, stratifying patients according to PPC less than or equal to 66.7% vs. PPC greater than 66.7% was prognostic for freedom from biochemical failure (p = 0.0001), FFM (p = 0.0002), and CSS (p = 0.0003) and marginally prognostic for OS (p = 0.055). On multivariate analysis, after adjustment for NCCN risk group and androgen deprivation therapy use, PPC greater than 66.7% increased the risk for biochemical failure (p = 0.0001; hazard ratio [HR], 2.1 [95% confidence

  2. Dose-Escalated Radiotherapy for High-Risk Prostate Cancer: Outcomes in Modern Era With Short-Term Androgen Deprivation Therapy

    SciTech Connect

    Liauw, Stanley L.; Stadler, Walter M.; Correa, David B.S.; Weichselbaum, Ralph R.; Jani, Ashesh B.

    2010-05-01

    Purpose: Randomized data have supported the use of long-term androgen deprivation therapy (ADT) combined with radiotherapy (RT) for men with high-risk prostate cancer. The present study reviewed the outcomes of intermediate- and high-risk men treated with RT and short-term ADT. Materials and Methods: A total of 184 men with any single risk factor of prostate-specific antigen >=10 ng/mL, clinical Stage T2b or greater, or Gleason score >=7 were treated with primary external beam RT for nonmetastatic adenocarcinoma of the prostate. The median radiation dose was 74 Gy; 55% were treated with intensity-modulated RT. All patients received ADT for 1 to 6 months (median, 4), consisting of a gonadotropin-releasing hormone analog. Univariate and multivariable analyses were performed for risk factors, including T stage, Gleason score, radiation dose, and prostate-specific antigen level. Results: With a median follow-up of 51 months, the 4-year freedom from biochemical failure (FFBF) using the nadir plus 2 ng/mL definition was 83% for all patients. Clinical Stage T3 disease was the only variable tested associated with FFBF on univariate (4-year FFBF rate, 46% vs. 87% for Stage T1-T2c disease; p = .0303) and multivariable analysis (hazard ratio, 3.9; p = .0016). On a subset analysis of high-risk patients (National Comprehensive Cancer Network criteria), those with clinical Stage T3 disease (4-year FFBF rate, 46% vs. 80%; p = .0303) and a radiation dose <74 Gy (4-year FFBF rate, 64% vs. 80%) had a poorer outcome on univariate analysis. However, clinical Stage T3 disease and radiation dose were not significant on multivariable analysis, although a statistical multivariable trend was seen for both (p = .0650 and p = .0597, respectively). Conclusion: Short-term ADT and RT might be acceptable for men with intermediate- and high-risk prostate cancer, especially for clinically localized disease treated with doses of >=74 Gy.

  3. SU-C-BRA-01: 18F-NaF PET/CT-Directed Dose Escalation in Stereotactic Body Radiotherapy for Spine Oligometastases From Prostate Cancer

    SciTech Connect

    Wu, L; Zhang, W; Li, M; Peng, X; Xie, L; Lin, Z; Kwee, S; Wang, H; Kuang, Y

    2015-06-15

    Purpose: To investigate the technical feasibility of SBRT dose painting using {sup 18}F-NaF positron emission tomography (PET) scans guidance in patients with spine oligometastases from prostate cancer. Methods: As a proof of concept, six patients with 14 spine oligometastatic lesions from prostate cancer who had {sup 18}F-NaF PET/CT scan prior to treatment were retrospectively included. GTV{sub reg} was delineated according to the regular tumor boundary shown on PET and/or CT images; and GTV{sub MATV} was contoured based on a net metabolically active tumor volume (MATV) defined by 60% of the SUV{sub max} values on {sup 18}F-NaF PET images. The PTVs (PTV{sub reg} and PTV{sub MATV}) were defined as respective GTVs (plus involved entire vertebral body for PTV{sub reg}) with a 3-mm isotropic expansion margin. Three 1-fraction SBRT plans using VMAT technique along with 10 MV FFF beams (Plan{sub 24Gy}, Plan{sub 24–27Gy}, and Plan{sub 24–30Gy}) were generated for each patient. All plans included a dose of 24 Gy prescribed to PTV{sub reg}. The Plan{sub 24–27Gy} and Plan{sub 24–30Gy} also included a simultaneous boost dose of 27 Gy or 30 Gy prescribed to the PTV{sub MATV}, respectively. The feasibility of 18F-NaF PET-guided SBRT dose escalation was evaluated by its ability to achieve the prescription dose objectives while adhering to organ-at-risk (OAR) dose constraints. The normal tissue complication probabilities (NTCP) calculated by radiological models were also compared between the plans. Results: In all 33 SBRT plans generated, the planning objectives and dose constraints were met without exception. Plan{sub 24–27Gy} and Plan{sub 24–30Gy} had a significantly higher dose in PTV{sub MATV} than Plan{sub 24Gy} (p < 0.05), respectively, while maintaining a similar OAR sparing profile and NTCP values. Conclusion: Using VMAT with FFF beams to incorporate a simultaneous {sup 18}F-NaF PET-guided radiation boost dose up to 30 Gy into a SBRT plan is technically

  4. Stereotactic body radiotherapy for prostate cancer.

    PubMed

    Henderson, D R; Tree, A C; van As, N J

    2015-05-01

    The use of stereotactic body radiotherapy (SBRT) for localised prostate cancer is now supported by a substantial body of non-randomised data, with medium-term outcomes consistent with current standard radiotherapy. The ability to deliver profoundly hypofractionated treatment, combined with the relatively low α/β ratio of prostate cancer, may result in a more favourable therapeutic ratio, presenting an opportunity for isotoxic dose escalation. Furthermore, as treatment can be given in five attendances, SBRT has the potential both to reduce costs and improve patient quality of life. However, in a treatment landscape with many competing options of broadly similar efficacy, randomised trials are essential to define the relative benefits of this approach. SBRT also has an emerging application in oligometastatic prostate cancer, with promising early outcomes for delaying disease progression and deferring the need for androgen deprivation therapy. PMID:25707911

  5. Hypofractionated External-Beam Radiotherapy for Prostate Cancer

    PubMed Central

    Cho, L. Chinsoo; Timmerman, Robert; Kavanagh, Brian

    2013-01-01

    There are radiobiological rationales supporting hypofractionated radiotherapy for prostate cancer. The recent advancements in treatment planning and delivery allow sophisticated radiation treatments to take advantage of the differences in radiobiology of prostate cancer and the surrounding normal tissues. The preliminary results from clinical studies indicate that abbreviated fractionation programs can result in successful treatment of localized prostate cancer without escalation of late toxicity. PMID:23533777

  6. [Prostate cancer external beam radiotherapy].

    PubMed

    de Crevoisier, R; Pommier, P; Latorzeff, I; Chapet, O; Chauvet, B; Hennequin, C

    2016-09-01

    The prostate external beam radiotherapy techniques are described, when irradiating the prostate or after prostatectomy, with and without pelvic lymph nodes. The following parts are presented: indications of radiotherapy, total dose and fractionation, planning CT image acquisition, volume of interest delineation (target volumes and organs at risk) and margins, Intensity modulated radiotherapy planning and corresponding dose-volume constraints, and finally Image guided radiotherapy. PMID:27516051

  7. Phase II dose escalation study of image-guided adaptive radiotherapy for prostate cancer: Use of dose-volume constraints to achieve rectal isotoxicity

    SciTech Connect

    Vargas, Carlos; Yan Di; Kestin, Larry L.; Krauss, Daniel; Lockman, David M.; Brabbins, Donald S.; Martinez, Alvaro A. . E-mail: amartinez@beaumont.edu

    2005-09-01

    Purpose: In our Phase II prostate cancer Adaptive Radiation Therapy (ART) study, the highest possible dose was selected on the basis of normal tissue tolerance constraints. We analyzed rectal toxicity rates in different dose levels and treatment groups to determine whether equivalent toxicity rates were achieved as hypothesized when the protocol was started. Methods and Materials: From 1999 to 2002, 331 patients with clinical stage T1 to T3, node-negative prostate cancer were prospectively treated with three-dimensional conformal adaptive RT. A patient-specific confidence-limited planning target volume was constructed on the basis of 5 CT scans and 4 sets of electronic portal images after the first 4 days of treatment. For each case, the rectum (rectal solid) was contoured in its entirety. The rectal wall was defined by use of a 3-mm wall thickness (median volume: 29.8 cc). The prescribed dose level was chosen using the following rectal wall dose constraints: (1) Less than 30% of the rectal wall volume can receive more than 75.6 Gy. (2) Less than 5% of the rectal wall can receive more than 82 Gy. Low-risk patients (PSA < 10, Stage {<=} T2a, Gleason score < 7) were treated to the prostate alone (Group 1). All other patients, intermediate and high risk, where treated to the prostate and seminal vesicles (Group 2). The risk of chronic toxicity (NCI Common Toxicity Criteria 2.0) was assessed for the different dose levels prescribed. HIC approval was acquired for all patients. Median follow-up was 1.6 years. Results: Grade 2 chronic rectal toxicity was experienced by 34 patients (10%) (9% experienced rectal bleeding, 6% experienced proctitis, 3% experienced diarrhea, and 1% experienced rectal pain) at a median interval of 1.1 year. Nine patients (3%) experienced grade 3 or higher chronic rectal toxicity (1 Grade 4) at a median interval of 1.2 years. The 2-year rates of Grade 2 or higher and Grade 3 or higher chronic rectal toxicity were 17% and 3%, respectively. No

  8. Phase II Trial of Radiation Dose Escalation With Conformal External Beam Radiotherapy and High-Dose-Rate Brachytherapy Combined With Long-Term Androgen Suppression in Unfavorable Prostate Cancer: Feasibility Report

    SciTech Connect

    Valero, Jeanette; Cambeiro, Mauricio; Galan, Carlos; Teijeira, Mercedes; Romero, Pilar; Zudaire, Javier; Moreno, Marta; Ciervide, Raquel; Aristu, Jose Javier; Martinez-Monge, Rafael

    2010-02-01

    Purpose: To determine the feasibility of combined long-term luteinizing hormone-releasing hormone agonist-based androgen suppressive therapy (AST) and dose escalation with high-dose-rate (HDR) brachytherapy for high-risk (HRPC) or very-high-risk prostate cancer (VHRPC). Methods and Materials: Between January 2001 and October 2006, 134 patients (median age, 70 years) with either National Comprehensive Cancer Network criteria-defined HRPC (n = 47, 35.1%) or VHRPC (n = 87, 64.9%) were prospectively enrolled in this Phase II trial. Tumor characteristics included a median pretreatment prostate-specific antigen level of 14.6 ng/mL, a median clinical stage of T2c, and a median Gleason score of 7. Three-dimensional conformal radiotherapy (54 Gy in 30 fractions) was followed by HDR brachytherapy (19 Gy in 4 b.i.d. treatments). Androgen suppressive therapy started 0-3 months before three-dimensional conformal radiotherapy and continued for 2 years. Results: One implant was repositioned with a new procedure (0.7%). Five patients (3.7%) discontinued AST at a median of 13 months (range, 6-18 months) because of disease progression (n = 1), hot flashes (n = 2), fatigue (n = 1), and impotence (n = 1). After a median follow-up of 37.4 months (range, 24-90 months), the highest Radiation Therapy Oncology Group-defined late urinary toxicities were Grade 0 in 47.8%, Grade 1 in 38.1%, Grade 2 in 7.5%, and Grade 3 in 6.7% of patients. Maximal late gastrointestinal toxicities were Grade 0 in 73.1%, Grade 1 in 16.4%, Grade 2 in 7.5%, and Grade 3 in 2.9% of patients. There were no Grade 4 or 5 events. Conclusions: Intermediate-term results show that dose escalation with HDR brachytherapy combined with long-term AST is feasible and has a toxicity profile similar to that reported by previous HDR brachytherapy studies.

  9. Online image-guided intensity-modulated radiotherapy for prostate cancer: How much improvement can we expect? A theoretical assessment of clinical benefits and potential dose escalation by improving precision and accuracy of radiation delivery

    SciTech Connect

    Ghilezan, Michel; Yan Di . E-mail: dyan@beaumont.edu; Liang Jian; Jaffray, David; Wong, John; Martinez, Alvaro

    2004-12-01

    Purpose: To quantify the theoretical benefit, in terms of improvement in precision and accuracy of treatment delivery and in dose increase, of using online image-guided intensity-modulated radiotherapy (IG-IMRT) performed with onboard cone-beam computed tomography (CT), in an ideal setting of no intrafraction motion/deformation, in the treatment of prostate cancer. Methods and materials: Twenty-two prostate cancer patients treated with conventional radiotherapy underwent multiple serial CT scans (median 18 scans per patient) during their treatment. We assumed that these data sets were equivalent to image sets obtainable by an onboard cone-beam CT. Each patient treatment was simulated with conventional IMRT and online IG-IMRT separately. The conventional IMRT plan was generated on the basis of pretreatment CT, with a clinical target volume to planning target volume (CTV-to-PTV) margin of 1 cm, and the online IG-IMRT plan was created before each treatment fraction on the basis of the CT scan of the day, without CTV-to-PTV margin. The inverse planning process was similar for both conventional IMRT and online IG-IMRT. Treatment dose for each organ of interest was quantified, including patient daily setup error and internal organ motion/deformation. We used generalized equivalent uniform dose (EUD) to compare the two approaches. The generalized EUD (percentage) of each organ of interest was scaled relative to the prescription dose at treatment isocenter for evaluation and comparison. On the basis of bladder wall and rectal wall EUD, a dose-escalation coefficient was calculated, representing the potential increment of the treatment dose achievable with online IG-IMRT as compared with conventional IMRT. Results: With respect to radiosensitive tumor, the average EUD for the target (prostate plus seminal vesicles) was 96.8% for conventional IMRT and 98.9% for online IG-IMRT, with standard deviations (SDs) of 5.6% and 0.7%, respectively (p < 0.0001). The average EUDs of

  10. Magnetic resonance imaging for prostate cancer radiotherapy.

    PubMed

    Dinh, Cuong V; Steenbergen, Peter; Ghobadi, Ghazaleh; Heijmink, Stijn W T J P; Pos, Floris J; Haustermans, Karin; van der Heide, Uulke A

    2016-03-01

    For radiotherapy of prostate cancer, MRI is used increasingly for delineation of the prostate gland. For focal treatment of low-risk prostate cancer or focal dose escalation for intermediate and high-risk cancer, delineation of the tumor is also required. While multi-parametric MRI is well established for detection of tumors and for staging of the disease, delineation of the tumor inside the prostate is not common practice. Guidelines, such as the PI-RADS classification, exist for tumor detection and staging, but no such guidelines are available for tumor delineation. Indeed, interobserver studies show substantial variation in tumor contours. Computer-aided tumor detection and delineation may help improve the robustness of the interpretation of multi-parametric MRI data. Comparing the performance of an earlier developed model for tumor segmentation with expert delineations, we found a significant correlation between tumor probability in a voxel and the number of experts identifying this voxel as tumor. This suggests that the model agrees with 'the wisdom of the crowd', and thus could serve as a reference for individual physicians in their decision making. With multi-parametric MRI it becomes feasible to revisit the GTV-CTV concept in radiotherapy of prostate cancer. While detection of index lesions is quite reliable, contouring variability and the low sensitivity to small lesions suggest that the remainder of the prostate should be treated as CTV. Clinical trials that investigate the options for dose differentiation, for example with dose escalation to the visible tumor or dose reduction to the CTV, are therefore warranted. PMID:26858164

  11. Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

    PubMed Central

    Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

    2016-01-01

    Aim Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients and methods Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3–6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. Results In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. Conclusion There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered. PMID:27274277

  12. Dose-Escalated Robotic SBRT for Stage I-II Prostate Cancer.

    PubMed

    Meier, Robert

    2015-01-01

    Stereotactic body radiotherapy (SBRT) is the precise external delivery of very high-dose radiotherapy to targets in the body, with treatment completed in one to five fractions. SBRT should be an ideal approach for organ-confined prostate cancer because (I) dose-escalation should yield improved rates of cancer control; (II) the unique radiobiology of prostate cancer favors hypofractionation; and (III) the conformal nature of SBRT minimizes high-dose radiation delivery to immediately adjacent organs, potentially reducing complications. This approach is also more convenient for patients, and is cheaper than intensity-modulated radiotherapy (IMRT). Several external beam platforms are capable of delivering SBRT for early-stage prostate cancer, although most of the mature reported series have employed a robotic non-coplanar platform (i.e., CyberKnife). Several large studies report 5-year biochemical relapse rates which compare favorably to IMRT. Rates of late GU toxicity are similar to those seen with IMRT, and rates of late rectal toxicity may be less than with IMRT and low-dose rate brachytherapy. Patient-reported quality of life (QOL) outcomes appear similar to IMRT in the urinary domain. Bowel QOL may be less adversely affected by SBRT than with other radiation modalities. After 5 years of follow-up, SBRT delivered on a robotic platform is yielding outcomes at least as favorable as IMRT, and may be considered appropriate therapy for stage I-II prostate cancer. PMID:25905037

  13. Dose-Escalated Robotic SBRT for Stage I–II Prostate Cancer

    PubMed Central

    Meier, Robert

    2015-01-01

    Stereotactic body radiotherapy (SBRT) is the precise external delivery of very high-dose radiotherapy to targets in the body, with treatment completed in one to five fractions. SBRT should be an ideal approach for organ-confined prostate cancer because (I) dose-escalation should yield improved rates of cancer control; (II) the unique radiobiology of prostate cancer favors hypofractionation; and (III) the conformal nature of SBRT minimizes high-dose radiation delivery to immediately adjacent organs, potentially reducing complications. This approach is also more convenient for patients, and is cheaper than intensity-modulated radiotherapy (IMRT). Several external beam platforms are capable of delivering SBRT for early-stage prostate cancer, although most of the mature reported series have employed a robotic non-coplanar platform (i.e., CyberKnife). Several large studies report 5-year biochemical relapse rates which compare favorably to IMRT. Rates of late GU toxicity are similar to those seen with IMRT, and rates of late rectal toxicity may be less than with IMRT and low-dose rate brachytherapy. Patient-reported quality of life (QOL) outcomes appear similar to IMRT in the urinary domain. Bowel QOL may be less adversely affected by SBRT than with other radiation modalities. After 5 years of follow-up, SBRT delivered on a robotic platform is yielding outcomes at least as favorable as IMRT, and may be considered appropriate therapy for stage I–II prostate cancer. PMID:25905037

  14. Recent advancements in toxicity prediction following prostate cancer radiotherapy.

    PubMed

    Ospina, J D; Fargeas, A; Dréan, G; Simon, A; Acosta, O; de Crevoisier, R

    2015-01-01

    In external beam radiotherapy for prostate cancer limiting toxicities for dose escalation are bladder and rectum toxicities. Normal tissue complication probability models aim at quantifying the risk of developping adverse events following radiotherapy. These models, originally proposed in the context of uniform irradiation, have evolved to implementations based on the state-of-the-art classification methods which are trained using empirical data. Recently, the use of image processing techniques combined with population analysis methods has led to a new generation of models to understand the risk of normal tissue complications following radiotherapy. This paper overviews those methods in the case of prostate cancer radiation therapy and propose some lines of future research. PMID:26737471

  15. Dose Escalation Improves Cancer-Related Events at 10 Years for Intermediate- and High-Risk Prostate Cancer Patients Treated With Hypofractionated High-Dose-Rate Boost and External Beam Radiotherapy

    SciTech Connect

    Martinez, Alvaro A.; Gonzalez, Jose; Ye Hong; Ghilezan, Mihai; Shetty, Sugandh; Kernen, Kenneth; Gustafson, Gary; Krauss, Daniel; Vicini, Frank; Kestin, Larry

    2011-02-01

    Purpose: To evaluate the 10-year outcomes of intermediate- and high-risk prostate cancer patients treated with a prospective dose escalation hypofractionated trial of pelvic external beam radiation therapy (P-EBRT) with a high-dose-rate (HDR) brachytherapy boost. Methods and Materials: From 1992 to 2007, 472 patients were treated with a HDR boost at William Beaumont Hospital. They had at least one of the following: a prostate-specific antigen (PSA) level of >10 ng/ml, a Gleason score of {>=}7, or clinical stage {>=}T2b. Patients received 46-Gy P-EBRT and an HDR boost. The HDR dose fractionation was divided into two dose levels. The prostate biologically equivalent dose (BED) low-dose-level group received <268 Gy, and the high-dose group received >268 Gy . Phoenix biochemical failure (BF) definition was used. Results: Median follow-up was 8.2 years (range, 0.4-17 years). The 10-year biochemical failure rate of 43.1% vs. 18.9%, (p < 0.001), the clinical failure rate of 23.4% vs. 7.7%, (p < 0.001), and the distant metastasis of 12.4% vs. 5.7%, (p = 0.028) were all significantly better for the high-dose level group. On Cox multivariate analysis, higher BED levels (p = 0.017; hazard ratio [HR]= 0.586), pretreatment PSA assays (p < 0.001, HR = 1.022), and Gleason scores (p = 0.004) were significant variables for reduced biochemical failure. Higher dose levels (p, 0.002; HR, 0.397) and Gleason scores (p < 0.001) were significant for clinical failure. Grade 3 genitourinary complications were 2% and 3%, respectively, and grade 3 gastrointestinal complication was <0.5%. Conclusions: This prospective trial using P-EBRT with HDR boost and hypofractionated dose escalation demonstrates a strong dose-response relationship for intermediate- and high-risk prostate cancer patients. The improvement at 10 years for locoregional control with higher radiation doses (BED, > 268Gy) has significantly decreased biochemical and clinical failures as well as distant metastasis.

  16. Prostate Radiotherapy in the Era of Advanced Imaging and Precision Medicine

    PubMed Central

    Dulaney, Caleb R.; Osula, Daniel O.; Yang, Eddy S.; Rais-Bahrami, Soroush

    2016-01-01

    Tremendous technological advancements in prostate radiotherapy have decreased treatment toxicity and improved clinical outcomes for men with prostate cancer. While these advances have allowed for significant treatment volume reduction and whole-organ dose escalation, further improvement in prostate radiotherapy has been limited by classic techniques for diagnosis and risk stratification. Developments in prostate imaging, image-guided targeted biopsy, next-generation gene expression profiling, and targeted molecular therapies now provide information to stratify patients and select treatments based on tumor biology. Image-guided targeted biopsy improves detection of clinically significant cases of prostate cancer and provides important information about the biological behavior of intraprostatic lesions which can further guide treatment decisions. We review the evolution of prostate magnetic resonance imaging (MRI) and MRI-ultrasound fusion-guided prostate biopsy. Recent advancements in radiation therapy including dose escalation, moderate and extreme hypofractionation, partial prostate radiation therapy, and finally dose escalation by simultaneous integrated boost are discussed. We also review next-generation sequencing and discuss developments in targeted molecular therapies. Last, we review ongoing clinical trials and future treatment paradigms that integrate targeted biopsy, molecular profiling and therapy, and prostate radiotherapy. PMID:27022486

  17. Prostate Radiotherapy in the Era of Advanced Imaging and Precision Medicine.

    PubMed

    Dulaney, Caleb R; Osula, Daniel O; Yang, Eddy S; Rais-Bahrami, Soroush

    2016-01-01

    Tremendous technological advancements in prostate radiotherapy have decreased treatment toxicity and improved clinical outcomes for men with prostate cancer. While these advances have allowed for significant treatment volume reduction and whole-organ dose escalation, further improvement in prostate radiotherapy has been limited by classic techniques for diagnosis and risk stratification. Developments in prostate imaging, image-guided targeted biopsy, next-generation gene expression profiling, and targeted molecular therapies now provide information to stratify patients and select treatments based on tumor biology. Image-guided targeted biopsy improves detection of clinically significant cases of prostate cancer and provides important information about the biological behavior of intraprostatic lesions which can further guide treatment decisions. We review the evolution of prostate magnetic resonance imaging (MRI) and MRI-ultrasound fusion-guided prostate biopsy. Recent advancements in radiation therapy including dose escalation, moderate and extreme hypofractionation, partial prostate radiation therapy, and finally dose escalation by simultaneous integrated boost are discussed. We also review next-generation sequencing and discuss developments in targeted molecular therapies. Last, we review ongoing clinical trials and future treatment paradigms that integrate targeted biopsy, molecular profiling and therapy, and prostate radiotherapy. PMID:27022486

  18. MRI-guided prostate adaptive radiotherapy - A systematic review.

    PubMed

    McPartlin, A J; Li, X A; Kershaw, L E; Heide, U; Kerkmeijer, L; Lawton, C; Mahmood, U; Pos, F; van As, N; van Herk, M; Vesprini, D; van der Voort van Zyp, J; Tree, A; Choudhury, A

    2016-06-01

    Dose escalated radiotherapy improves outcomes for men with prostate cancer. A plateau for benefit from dose escalation using EBRT may not have been reached for some patients with higher risk disease. The use of increasingly conformal techniques, such as step and shoot IMRT or more recently VMAT, has allowed treatment intensification to be achieved whilst minimising associated increases in toxicity to surrounding normal structures. To support further safe dose escalation, the uncertainties in the treatment target position will need be minimised using optimal planning and image-guided radiotherapy (IGRT). In particular the increasing usage of profoundly hypo-fractionated stereotactic therapy is predicated on the ability to confidently direct treatment precisely to the intended target for the duration of each treatment. This article reviews published studies on the influences of varies types of motion on daily prostate position and how these may be mitigated to improve IGRT in future. In particular the role that MRI has played in the generation of data is discussed and the potential role of the MR-Linac in next-generation IGRT is discussed. PMID:27162159

  19. Penile bulb dose and impotence after three-dimensional conformal radiotherapy for prostate cancer on RTOG 9406: Findings from a prospective, multi-institutional, phase I/II dose-escalation study

    SciTech Connect

    Roach, Mack . E-mail: roach@radonc17.ucsf.edu; Winter, Kathryn; Michalski, Jeffrey M.; Cox, James D.; Purdy, James A.; Bosch, Walter; Lin Xiao; Shipley, William S.

    2004-12-01

    Purpose: To assess the relationship between the dose to the bulb of the penis and the risk of impotence in men treated on Radiation Therapy Oncology Group (RTOG) 9406. Methods and materials: Men enrolled on a Phase I/II dose-escalation study, RTOG 9406, who were reported to be potent at entry and evaluable (n = 158) were selected for inclusion. Follow-up evaluations were scheduled every 3, 4, and 6 months for the first, second, and the third through fifth years, then annually. At each follow-up visit an assessment of potency status was made. Penile structures were defined by a single observer blinded to the potency status, using Web-based, on-line software. The dosimetry for penile structures was calculated at the Quality Assurance Center at Washington University and provided to RTOG Statistical Headquarters to determine whether there was a relationship between dose and impotence. Results: Patients whose median penile dose was {>=}52.5 Gy had a greater risk of impotence compared with those receiving <52.5 Gy (p = 0.039). In a multivariate analysis neither age, the dose to the prostate, nor the use of hormonal therapy correlated with the risk of impotence. Conclusions: Dose to the bulb of the penis seems to be associated with the risk of radiation-induced impotence.

  20. Efficacy of Dose-Escalated Radiotherapy for Recurrent Colorectal Cancer

    PubMed Central

    Jo, Sunmi; Park, Sung-Kwang; Kim, Jin-Young; Kim, Hyun Jung; Lee, Yun-Han; Oh, Won Yong; Cho, Heunglae; Ahn, Ki Jung

    2016-01-01

    Purpose This study aimed to evaluate the effects of radiotherapy (RT) on progression-free survival (PFS) for patients with recurrent colorectal cancer. Methods We reviewed the records of 22 patients with recurrent colorectal cancer treated with RT between 2008 and 2014. The median radiation dose for recurrent disease was 57.6 Gy (range, 45–75.6 Gy). Patients were divided into 2 groups according to the type of RT: patients underwent RT without previous history of irradiation (n = 14) and those treated with secondary RT (reirradiation: n = 8) at the time of recurrence. Results The median follow-up period was 24.9 months (range, 4.5–66.6 months). Progression was observed in 14 patients (including 8 with loco-regional failure and 9 with distant metastases). Distant metastases were related to the RT dose (<70 Gy, P = 0.031). The 2-year loco-regional control (LRC), PFS, and overall survival (OS) rates were 74.6%, 45.1%, and 82.0%, respectively. The LRC rate was not different between the patients treated with RT for the first time and those treated with reirradiation (P = 0.101, 2-year LRC 79.5% vs. 41.7%). However, reirradiation was related to poor PFS (P = 0.022) and OS (P = 0.002). An escalated RT dose (≥70 Gy) was associated with a higher PFS (P = 0.014, 2-year PFS 63.5% vs. 20.8%). Conclusion Salvage RT for locally recurrent colorectal cancer can be offered when surgery is impossible. Dose-escalated RT shows a possible benefit in reducing the risk of progression. PMID:27218097

  1. Current role of spacers for prostate cancer radiotherapy

    PubMed Central

    Pinkawa, Michael

    2015-01-01

    Radiotherapy is an established curative treatment method for prostate cancer. Optimal tumor control rates can only be achieved with high local doses, associated with a considerable risk of rectal toxicity. Apart from already widely adapted technical advances, as intensity-modulated radiation therapy, the application of spacers placed between the prostate and rectum has been increasingly used in the last years. Biodegradable spacers, including hydrogel, hyaluronic acid, collagen or an implantable balloon, can be injected or inserted in a short procedure under transrectal ultrasound guidance via a transperineal approach. A distance of about 1.0-1.5 cm is usually achieved between the rectum and prostate, excluding the rectal wall from the high isodoses. Several studies have shown well tolerated injection procedures and treatments. Apart from considerable reduction of rectal irradiation, a prospective randomized trial demonstrated a reduction of rectal toxicity after hydrogel injection in men undergoing prostate image-guided intensity-modulated radiation therapy. The results are encouraging for continuing evaluation in dose escalation, hypofractionation, stereotactic radiotherapy or re-irradiation trials in the future. PMID:26677428

  2. Can we avoid dose escalation for intermediate-risk prostate cancer in the setting of short-course neoadjuvant androgen deprivation?

    PubMed Central

    Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

    2016-01-01

    Background Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve the outcomes in patients with intermediate-risk prostate cancer. Despite this, there are only few reports evaluating DE-EBRT for patients with intermediate-risk prostate cancer receiving neoadjuvant ADT, and virtually no studies investigating dose escalation >74 Gy in this setting. We aimed to determine whether DE-EBRT >74 Gy improved the outcomes for patients with intermediate-risk prostate cancer who received neoadjuvant ADT. Findings In our institution, patients with intermediate-risk prostate cancer were treated with neoadjuvant ADT and DE-EBRT, with doses sequentially increasing from 74 Gy to 76 Gy and then to 78 Gy between 2006 and 2012. We identified 435 patients treated with DE-EBRT and ADT, with a median follow-up of 70 months. For the 74 Gy, 76 Gy, and 78 Gy groups, five-year biochemical disease-free survival rates were 95.0%, 97.8%, and 95.3%, respectively; metastasis-free survival rates were 99.1%, 100.0%, and 98.6%, respectively; and prostate cancer-specific survival rate was 100% for all three dose levels. There was no significant benefit for dose escalation either on univariate or multivariate analysis for any outcome. Conclusion There was no benefit for DE-EBRT >74 Gy in our cohort of intermediate-risk prostate cancer patients treated with neoadjuvant ADT. Given the higher risks of toxicity associated with dose escalation, it may be feasible to omit dose escalation in this group of patients. Randomized studies evaluating dose de-escalation should be considered. PMID:27073327

  3. Increasing Use of Dose-Escalated External Beam Radiation Therapy for Men With Nonmetastatic Prostate Cancer

    SciTech Connect

    Swisher-McClure, Samuel; Mitra, Nandita; Woo, Kaitlin; Smaldone, Marc; Uzzo, Robert; Bekelman, Justin E.

    2014-05-01

    Purpose: To examine recent practice patterns, using a large national cancer registry, to understand the extent to which dose-escalated external beam radiation therapy (EBRT) has been incorporated into routine clinical practice for men with prostate cancer. Methods and Materials: We conducted a retrospective observational cohort study using the National Cancer Data Base, a nationwide oncology outcomes database in the United States. We identified 98,755 men diagnosed with nonmetastatic prostate cancer between 2006 and 2011 who received definitive EBRT and classified patients into National Comprehensive Cancer Network (NCCN) risk groups. We defined dose-escalated EBRT as total prescribed dose of ≥75.6 Gy. Using multivariable logistic regression, we examined the association of patient, clinical, and demographic characteristics with the use of dose-escalated EBRT. Results: Overall, 81.6% of men received dose-escalated EBRT during the study period. The use of dose-escalated EBRT did not vary substantially by NCCN risk group. Use of dose-escalated EBRT increased from 70.7% of patients receiving treatment in 2006 to 89.8% of patients receiving treatment in 2011. On multivariable analysis, year of diagnosis and use of intensity modulated radiation therapy were significantly associated with receipt of dose-escalated EBRT. Conclusions: Our study results indicate that dose-escalated EBRT has been widely adopted by radiation oncologists treating prostate cancer in the United States. The proportion of patients receiving dose-escalated EBRT increased nearly 20% between 2006 and 2011. We observed high utilization rates of dose-escalated EBRT within all disease risk groups. Adoption of intensity modulated radiation therapy was strongly associated with use of dose-escalated treatment.

  4. Dosimetric Impact and Theoretical Clinical Benefits of Fiducial Markers for Dose Escalated Prostate Cancer Radiation Treatment

    SciTech Connect

    Gauthier, Isabelle Carrier, Jean-Francois; Beliveau-Nadeau, Dominic; Fortin, Bernard; Taussky, Daniel

    2009-07-15

    Purpose: To assess the impact of fiducial markers and daily kilovoltage imaging (FM-kV) on dose-volume histogram (DVH) parameters and normal tissue complication probabilities (NTCPs) for the rectum and bladder during prostate cancer radiotherapy. Methods and Materials: Two different setup scenarios were compared for 20 patients treated with three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer to a total dose of 76 Gy: a traditional setup with planning target volume (PTV) margins associated with skin mark alignment vs. another setup using FM-kV. Various DVH parameters were compared, including Radiation Therapy Oncology Group (RTOG) dose-volume constraints for the rectum and bladder. Analysis of NTCPs was also performed according to the Lyman model. Results: With the traditional setup, 85% of patients had rectal V70{sub Gy} >25% compared with 45% with FM-kV. Moreover, 30% of patients with traditional setup vs. 5% with FM-kV did not fulfill at least 3 RTOG constraint parameters for the rectum. Mean rectal and bladder dose were 4.7 Gy and 6.7 Gy less, respectively, with FM-kV. The NTCP for the rectum was 11.5% with the traditional setup and 9% with FM-kV. This indicates that with FM-kV, the prescription dose could be increased by 2.1 Gy while keeping the same level of late rectal toxicity as with the traditional setup. Conclusions: Use of FM-kV is an efficient way of lowering the proportion of patients not fulfilling RTOG rectal and bladder dose-volume constraints. The results of the NTCP analysis suggest that the PTV margin reduction allowed by FM-kV should decrease the rate of late rectal toxicities or may allow moderate dose escalation.

  5. Intensified autophagy compromises the efficacy of radiotherapy against prostate cancer

    SciTech Connect

    Koukourakis, Michael I.

    2015-05-29

    Introduction: Radiotherapy is an equivalent alternative or complement to radical prostatectomy, with high therapeutic efficacy. High risk patients, however, experience high relapse rates, so that research on radio-sensitization is the most evident route to improve curability of this common disease. Materials and methods: In the current study we investigated the autophagic activity in a series of patients with localized prostate tumors treated with radical radiotherapy, using the LC3A and the LAMP2a proteins as markers of autophagosome and lysosome cellular content, respectively. The role of autophagy on prostate cancer cell line resistance to radiation was also examined. Results: Using confocal microscopy on tissue biopsies, we showed that prostate cancer cells have, overall, high levels of LC3A and low levels of LAMP2a compared to normal prostate glands. Tumors with a ‘highLC3A/lowLAMP2a’ phenotype, suggestive of intensified lysosomal consumption, had a significantly poorer biochemical relapse free survival. The PC3 radioresistant cell line sustained remarkably its autophagic flux ability after radiation, while the DU145 radiosensitive one experiences a prolonged blockage of the autophagic process. This was assessed with aggresome accumulation detection and LC3A/LAMP2a double immunofluorescence, as well as with sequestrosome/p62 protein detection. By silencing the LC3A or LAMP2a expression, both cell lines became more sensitive to escalated doses of radiation. Conclusions: High base line autophagy activity and cell ability to sustain functional autophagy define resistance of prostate cancer cells to radiotherapy. This can be reversed by blocking up-regulated components of the autophagy pathway, which may prove of importance in the field of clinical radiotherapy. - Highlights: • High LC3A and low LAMP2a levels is a frequent expression pattern of prostate carcinoma. • This pattern of intensified autophagic flux relates with high relapse rates after

  6. Computer-assisted targeted therapy (CATT) for prostate radiotherapy planning by fusion of CT and MRI

    NASA Astrophysics Data System (ADS)

    Chappelow, Jonathan; Both, Stefan; Viswanath, Satish; Hahn, Stephen; Feldman, Michael; Rosen, Mark; Tomaszewski, John; Vapiwala, Neha; Patel, Pratik; Madabhushi, Anant

    2010-02-01

    In this paper, we present a comprehensive, quantitative imaging framework for improved treatment of prostate cancer via computer-assisted targeted therapy (CATT) to facilitate radiotherapy dose escalation to regions with a high likelihood of disease presence. The framework involves identification of high likelihood prostate cancer regions using computer-aided detection (CAD) classifier on diagnostic MRI, followed by mapping of these regions from MRI onto planning computerized tomography (CT) via image registration. Treatment of prostate cancer by targeted radiotherapy requires CT to formulate a dose plan. While accurate delineation of the prostate and cancer can provide reduced exposure of benign tissue to radiation, as well as a higher dose to the cancer, CT is ineffective in localizing intraprostatic lesions and poor for highlighting the prostate boundary. MR imagery on the other hand allows for greatly improved visualization of the prostate. Further, several studies have demonstrated the utility of CAD for identifying the location of tumors on in vivo multi-functional prostate MRI. Consequently, our objective is to improve the accuracy of radiotherapy dose plans via multimodal fusion of MR and CT. To achieve this objective, the CATT framework presented in this paper comprises the following components: (1) an unsupervised pixel-wise classifier to identify suspicious regions within the prostate on diagnostic MRI, (2) elastic image registration to align corresponding diagnostic MRI, planning MRI, and CT of the prostate, (3) mapping of the suspect regions from diagnostic MRI onto CT, and (4) calculation of a modified radiotherapy plan with escalated dose for cancer. Qualitative comparison of the dose plans (with and without CAD) over a total of 79 2D slices obtained from 10 MR-CT patient studies, suggest that our CATT framework could help in improved targeted treatment of prostate cancer.

  7. Phase I Trial of Pelvic Nodal Dose Escalation With Hypofractionated IMRT for High-Risk Prostate Cancer

    SciTech Connect

    Adkison, Jarrod B.; McHaffie, Derek R.; Bentzen, Soren M.; Patel, Rakesh R.; Khuntia, Deepak; Petereit, Daniel G.; Hong, Theodore S.; Tome, Wolfgang; Ritter, Mark A.

    2012-01-01

    Purpose: Toxicity concerns have limited pelvic nodal prescriptions to doses that may be suboptimal for controlling microscopic disease. In a prospective trial, we tested whether image-guided intensity-modulated radiation therapy (IMRT) can safely deliver escalated nodal doses while treating the prostate with hypofractionated radiotherapy in 5 Vulgar-Fraction-One-Half weeks. Methods and Materials: Pelvic nodal and prostatic image-guided IMRT was delivered to 53 National Comprehensive Cancer Network (NCCN) high-risk patients to a nodal dose of 56 Gy in 2-Gy fractions with concomitant treatment of the prostate to 70 Gy in 28 fractions of 2.5 Gy, and 50 of 53 patients received androgen deprivation for a median duration of 12 months. Results: The median follow-up time was 25.4 months (range, 4.2-57.2). No early Grade 3 Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events v.3.0 genitourinary (GU) or gastrointestinal (GI) toxicities were seen. The cumulative actuarial incidence of Grade 2 early GU toxicity (primarily alpha blocker initiation) was 38%. The rate was 32% for Grade 2 early GI toxicity. None of the dose-volume descriptors correlated with GU toxicity, and only the volume of bowel receiving {>=}30 Gy correlated with early GI toxicity (p = 0.029). Maximum late Grades 1, 2, and 3 GU toxicities were seen in 30%, 25%, and 2% of patients, respectively. Maximum late Grades 1 and 2 GI toxicities were seen in 30% and 8% (rectal bleeding requiring cautery) of patients, respectively. The estimated 3-year biochemical control (nadir + 2) was 81.2 {+-} 6.6%. No patient manifested pelvic nodal failure, whereas 2 experienced paraaortic nodal failure outside the field. The six other clinical failures were distant only. Conclusions: Pelvic IMRT nodal dose escalation to 56 Gy was delivered concurrently with 70 Gy of hypofractionated prostate radiotherapy in a convenient, resource-efficient, and well-tolerated 28-fraction schedule. Pelvic nodal dose

  8. Dose Escalation for Prostate Cancer Using the Three-Dimensional Conformal Dynamic Arc Technique: Analysis of 542 Consecutive Patients

    SciTech Connect

    Jereczek-Fossa, Barbara A. Vavassori, Andrea; Fodor, Cristiana; Santoro, Luigi; Zerini, Dario; Cattani, Federica; Garibaldi, Cristina; Cambria, Raffaella; Fodor, Andrei; Boboc, Genoveva Ionela; Vitolo, Viviana; Ivaldi, Giovanni Battista; Musi, Gennaro; De Cobelli, Ottavio; Orecchia, Roberto

    2008-07-01

    Purpose: To present the results of dose escalation using three-dimensional conformal dynamic arc radiotherapy (3D-ART) for prostate cancer. Methods and Materials: Five hundred and forty two T1-T3N0M0 prostate cancer patients were treated with 3D-ART. Dose escalation (from 76 Gy/38 fractions to 80 Gy/40 fractions) was introduced in September 2003; 32% of patients received 80 Gy. In 366 patients, androgen deprivation was added to 3D-ART. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and Houston definition (nadir + 2) were used for toxicity and biochemical failure evaluation, respectively. Median follow-up was 25 months. Results: Acute toxicity included rectal (G1-2 28.9%; G3 0.5%) and urinary events (G1-2 57.9%; G3-4 2.4%). Late toxicity included rectal (G1-2 15.8%; G3-4 3.1%) and urinary events (G1-2 26.9%; G3-4 1.6%). Two-year failure-free survival and overall survival rates were 94.1% and 97.9%, respectively. Poor prognostic group (GS, iPSA, T), transurethral prostate resection, and dose >76 Gy showed significant association to high risk of progression in multivariate analysis (p = 0.014, p = 0.045, and p 0.04, respectively). The negative effect of dose >76 Gy was not observed (p 0.10), when the analysis was limited to 353 patients treated after September 2003 (when dose escalation was introduced). Higher dose was not associated with higher late toxicity. Conclusions: Three-dimensional-ART is a feasible modality allowing for dose escalation (no increase in toxicity has been observed with higher doses). However, the dose increase from 76 to 80 Gy was not associated with better tumor outcome. Further investigation is warranted for better understanding of the dose effect for prostate cancer.

  9. Image-guided radiotherapy for prostate cancer by CT-linear accelerator combination: Prostate movements and dosimetric considerations

    SciTech Connect

    Wong, James R.; Grimm, Lisa; Oren, Reva

    2005-02-01

    Purpose: Multiple studies have indicated that the prostate is not stationary and can move as much as 2 cm. Such prostate movements are problematic for intensity-modulated radiotherapy, with its associated tight margins and dose escalation. Because of these intrinsic daily uncertainties, a relative generous 'margin' is necessary to avoid marginal misses. Using the CT-linear accelerator combination in the treatment suite (Primatom, Siemens), we found that the daily intrinsic prostate movements can be easily corrected before each radiotherapy session. Dosimetric calculations were performed to evaluate the amount of discrepancy of dose to the target if no correction was done for prostate movement. Methods and materials: The Primatom consists of a Siemens Somatom CT scanner and a Siemens Primus linear accelerator installed in the same treatment suite and sharing a common table/couch. The patient is scanned by the CT scanner, which is movable on a pair of horizontal rails. During scanning, the couch does not move. The exact location of the prostate, seminal vesicles, and rectum are identified and localized. These positions are then compared with the planned positions. The daily movement of the prostate and rectum were corrected for and a new isocenter derived. The patient was treated immediately using the new isocenter. Results: Of the 108 patients with primary prostate cancer studied, 540 consecutive daily CT scans were performed during the last part of the cone down treatment. Of the 540 scans, 46% required no isocenter adjustments for the AP-PA direction, 54% required a shift of {>=}3 mm, 44% required a shift of >5 mm, and 15% required a shift of >10 mm. In the superoinferior direction, 27% required a shift of >3 mm, 25% required a shift of >5 mm, and 4% required a shift of >10 mm. In the right-left direction, 34% required a shift of >3 mm, 24% required a shift of >5 mm, and 5% required a shift of >10 mm. Dosimetric calculations for a typical case of prostate cancer

  10. Long-Term Failure Patterns and Survival in a Randomized Dose-Escalation Trial for Prostate Cancer. Who Dies of Disease?

    SciTech Connect

    Kuban, Deborah A.; Levy, Lawrence B.; Cheung, M. Rex; Lee, Andrew K.; Choi, Seungtaek; Frank, Steven; Pollack, Alan

    2011-04-01

    Purpose: To report long-term failure patterns and survival in a randomized radiotherapy dose escalation trial for prostate cancer. Materials and Methods: A total of 301 patients with Stage T1b-T3 prostate cancer treated to 70 Gy versus 78 Gy now have a median follow-up of 9 years. Failure patterns and survival were compared between dose levels. The cumulative incidence of death from prostate cancer versus other causes was examined and regression analysis was used to establish predictive factors. Results: Patients with pretreatment prostate-specific antigen (PSA) >10 ng/mL or high-risk disease had higher biochemical and clinical failures rates when treated to 70 Gy. These patients also had a significantly higher risk of dying of prostate cancer. Patients <70 years old at treatment died of prostate cancer nearly three times more frequently than of other causes when they were radiated to 70 Gy, whereas those treated to 78 Gy died of other causes more frequently. Patients age 70 or older treated to 70 Gy died of prostate cancer as often as other causes, and those receiving 78 Gy never died of prostate cancer within 10 years of follow-up. In regression analysis, factors predicting for death from prostate cancer were pretreatment PSA >10.5 ng/mL, Gleason score 9 and 10, recurrence within 2.6 years of radiation, and doubling time of <3.6 months at the time of recurrence. Conclusions: Moderate dose escalation (78 Gy) decreases biochemical and clinical failure as well as prostate cancer death in patients with pretreatment PSA >10 ng/mL or high-risk disease.

  11. Hypofractionated Intensity-Modulated Radiotherapy for Carcinoma of the Prostate: Analysis of Toxicity

    SciTech Connect

    Coote, Joanna H.; Wylie, James P.; Cowan, Richard A.; Logue, John P.; Swindell, Ric; Livsey, Jacqueline E.

    2009-07-15

    Purpose: Dose escalation for prostate cancer improves biological control but with a significant increase in late toxicity. Recent estimates of low {alpha}/{beta} ratio for prostate cancer suggest that hypofractionation may result in biological advantage. Intensity-modulated radiotherapy (IMRT) should enable dose escalation to the prostate while reducing toxicity to local organs. We report late toxicity data of a hypofractionated IMRT regime. Methods and Materials: Eligible men had T2-3N0M0 adenocarcinoma prostate, and either Gleason score {>=} 7 or prostate-specific antigen 20-50 ng/L. Patients received 57-60 Gy to prostate in 19-20 fractions using five-field IMRT. All received hormonal therapy for 3 months before radiotherapy to a maximum of 6 months. Toxicity was assessed 2 years postradiotherapy using the RTOG criteria, LENT/SOMA, and UCLA prostate index assessment tools. Results: Acute toxicity was favorable with no RTOG Grade 3 or 4 toxicity. At 2 years, there was 4% Grade 2 bowel and 4.25% Grade 2 bladder toxicity. There was no Grade 3 or 4 bowel toxicity; one patient developed Grade 3 bladder toxicity. UCLA data showed a slight improvement in urinary function at 2 years compared with pretreatment. LENT/SOMA assessments demonstrated general worsening of bowel function at 2 years. Patients receiving 60 Gy were more likely to develop problems with bowel function than those receiving 57 Gy. Conclusions: These data demonstrate that hypofractionated radiotherapy using IMRT for prostate cancer is well tolerated with minimal late toxicity at 2 years posttreatment. Ongoing studies are looking at the efficacy of hypofractionated regimes with respect to biological control.

  12. Hypofractionated Radiotherapy for Favorable Risk Prostate Cancer

    SciTech Connect

    Rene, Nicholas; Faria, Sergio; Cury, Fabio; David, Marc; Duclos, Marie; Shenouda, George; Souhami, Luis

    2010-07-01

    Purpose: Since the recognition that prostate cancer probably has a low {alpha}/{beta} ratio, hypofractionated radiotherapy has become an attractive treatment option for localized prostate cancer. However, there is little experience with the use of hypofractionation delivering a high biologically equivalent dose. We report our experience with high-dose hypofractionated radiotherapy. Material and Methods: A total of 129 patients with favorable risk prostate cancer were treated with three-dimensional conformal radiotherapy treatment plans to the dose of 66 Gy in 22 fractions, prescribed at the isocenter. Planning target volume consisted of the prostate plus a uniform 7-mm margin, including the rectal margin. No patient received hormonal therapy. Toxicity was prospectively graded by the Common Toxicity Criteria version3. Biochemical relapse was defined as postradiotherapy nadir prostate-specific antigen + 2 ng/mL. Results: With a median follow-up of 51 months, the 5-year actuarial biochemical control rate is 98%. The only 3 cases with biochemical failure did not have a clinical local relapse. More than 50% of patients did not develop acute toxicity. For late toxicity, the worst crude rate of Grade {>=}2 genitourinary (GU) and gastrointestinal (GI) toxicity seen at any time during follow-up were 32% and 25%, respectively. There was no Grade 4 or 5 toxicity. At the last follow-up, persistent Grade {>=}2 late GU and GI toxicity were 2% and 1.5%, respectively. Conclusions: This hypofractionated regimen provides excellent biochemical control in favorable risk prostate cancer with an acceptable rate of late toxicity. Further studies exploring this hypofractionation regimen are warranted.

  13. Pelvic Nodal Radiotherapy in Patients With Unfavorable Intermediate and High-Risk Prostate Cancer: Evidence, Rationale, and Future Directions

    SciTech Connect

    Morikawa, Lisa K.; Roach, Mack

    2011-05-01

    Over the past 15 years, there have been three major advances in the use of external beam radiotherapy in the management of men with clinically localized prostate made. They include: (1) image guided (IG) three-dimensional conformal/intensity modulated radiotherapy; (2) radiation dose escalation; and (3) androgen deprivation therapy. To date only the last of these three advances have been shown to improve overall survival. The presence of occult pelvic nodal involvement could explain the failure of increased conformality and dose escalation to prolong survival, because the men who appear to be at the greatest risk of death from clinically localized prostate cancer are those who are likely to have lymph node metastases. This review discusses the evidence for prophylactic pelvic nodal radiotherapy, including the key trials and controversies surrounding this issue.

  14. FTY720 (fingolimod) sensitizes prostate cancer cells to radiotherapy by inhibition of sphingosine kinase-1.

    PubMed

    Pchejetski, Dmitri; Bohler, Torsten; Brizuela, Leyre; Sauer, Lysann; Doumerc, Nicolas; Golzio, Muriel; Salunkhe, Vishal; Teissié, Justin; Malavaud, Bernard; Waxman, Jonathan; Cuvillier, Olivier

    2010-11-01

    Radiotherapy is widely used as a radical treatment for prostate cancer, but curative treatments are elusive for poorly differentiated tumors where survival is just 15% at 15 years. Dose escalation improves local response rates but is limited by tolerance in normal tissues. A sphingosine analogue, FTY720 (fingolimod), a drug currently in phase III studies for treatment of multiple sclerosis, has been found to be a potent apoptosis inducer in prostate cancer cells. Using in vitro and in vivo approaches, we analyzed the impact of FTY720 on sphingolipid metabolism in hormone-refractory metastatic prostate cancer cells and evaluated its potential as a radiosensitizer on cell lines and prostate tumor xenografts. In prostate cancer cell lines, FTY720 acted as a sphingosine kinase 1 (SphK1) inhibitor that induced prostate cancer cell apoptosis in a manner independent of sphingosine-1-phosphate receptors. In contrast, γ irradiation did not affect SphK1 activity in prostate cancer cells yet synergized with FTY720 to inhibit SphK1. In mice bearing orthotopic or s.c. prostate cancer tumors, we show that FTY720 dramatically increased radiotherapeutic sensitivity, reducing tumor growth and metastasis without toxic side effects. Our findings suggest that low, well-tolerated doses of FTY720 could offer significant improvement to the clinical treatment of prostate cancer. PMID:20959468

  15. Online Adaptive Replanning Method for Prostate Radiotherapy

    SciTech Connect

    Ahunbay, Ergun E.; Peng Cheng; Holmes, Shannon; Godley, Andrew; Lawton, Colleen; Li, X. Allen

    2010-08-01

    Purpose: To report the application of an adaptive replanning technique for prostate cancer radiotherapy (RT), consisting of two steps: (1) segment aperture morphing (SAM), and (2) segment weight optimization (SWO), to account for interfraction variations. Methods and Materials: The new 'SAM+SWO' scheme was retroactively applied to the daily CT images acquired for 10 prostate cancer patients on a linear accelerator and CT-on-Rails combination during the course of RT. Doses generated by the SAM+SWO scheme based on the daily CT images were compared with doses generated after patient repositioning using the current planning target volume (PTV) margin (5 mm, 3 mm toward rectum) and a reduced margin (2 mm), along with full reoptimization scans based on the daily CT images to evaluate dosimetry benefits. Results: For all cases studied, the online replanning method provided significantly better target coverage when compared with repositioning with reduced PTV (13% increase in minimum prostate dose) and improved organ sparing when compared with repositioning with regular PTV (13% decrease in the generalized equivalent uniform dose of rectum). The time required to complete the online replanning process was 6 {+-} 2 minutes. Conclusion: The proposed online replanning method can be used to account for interfraction variations for prostate RT with a practically acceptable time frame (5-10 min) and with significant dosimetric benefits. On the basis of this study, the developed online replanning scheme is being implemented in the clinic for prostate RT.

  16. [18F]fluoroethylcholine-PET/CT imaging for radiation treatment planning of recurrent and primary prostate cancer with dose escalation to PET/CT-positive lymph nodes

    PubMed Central

    2011-01-01

    Background At present there is no consensus on irradiation treatment volumes for intermediate to high-risk primary cancers or recurrent disease. Conventional imaging modalities, such as CT, MRI and transrectal ultrasound, are considered suboptimal for treatment decisions. Choline-PET/CT might be considered as the imaging modality in radiooncology to select and delineate clinical target volumes extending the prostate gland or prostate fossa. In conjunction with intensity modulated radiotherapy (IMRT) and imaged guided radiotherapy (IGRT), it might offer the opportunity of dose escalation to selected sites while avoiding unnecessary irradiation of healthy tissues. Methods Twenty-six patients with primary (n = 7) or recurrent (n = 19) prostate cancer received Choline-PET/CT planned 3D conformal or intensity modulated radiotherapy. The median age of the patients was 65 yrs (range 45 to 78 yrs). PET/CT-scans with F18-fluoroethylcholine (FEC) were performed on a combined PET/CT-scanner equipped for radiation therapy planning. The majority of patients had intermediate to high risk prostate cancer. All patients received 3D conformal or intensity modulated and imaged guided radiotherapy with megavoltage cone beam CT. The median dose to primary tumours was 75.6 Gy and to FEC-positive recurrent lymph nodal sites 66,6 Gy. The median follow-up time was 28.8 months. Results The mean SUVmax in primary cancer was 5,97 in the prostate gland and 3,2 in pelvic lymph nodes. Patients with recurrent cancer had a mean SUVmax of 4,38. Two patients had negative PET/CT scans. At 28 months the overall survival rate is 94%. Biochemical relapse free survival is 83% for primary cancer and 49% for recurrent tumours. Distant disease free survival is 100% and 75% for primary and recurrent cancer, respectively. Acute normal tissue toxicity was mild in 85% and moderate (grade 2) in 15%. No or mild late side effects were observed in the majority of patients (84%). One patient had a severe bladder

  17. Influence of 11C-choline PET/CT on radiotherapy planning in prostate cancer

    PubMed Central

    López, Escarlata; Lazo, Antonio; Gutiérrez, Antonio; Arregui, Gregorio; Núñez, Isabel; Sacchetti, Antonio

    2014-01-01

    Aim To evaluate the influence of 11C-choline PET/CT on radiotherapy planning in prostate cancer patients. Background Precise information on the extension of prostate cancer is crucial for the choice of an appropriate therapeutic strategy. 11C-choline positron emission tomography (11C-choline PET/CT) has two roles in radiation oncology (RT): (1) patient selection for treatment and (2) target volume selection and delineation. In conjunction with high-accuracy techniques, it might offer an opportunity of dose escalation and better tumour control while sparing healthy tissues. Materials and methods We carried out a retrospective study in order to analyse RT planning modification based on 11C-choline PET/CT in 16 prostate cancer patients. Patients were treated with hypofractionated step-and-shoot Intensity Modulated Radiotherapy (IMRT), or Volumetric Modulated Arc Therapy (VMAT), and a daily cone-beam CT for Image Guided Radiation Therapy (IGRT). All patients underwent a 11C-choline-PET/CT scan prior to radiotherapy. Results In 37.5% of cases, a re-delineation and new dose prescription occurred. Data show good preliminary clinical results in terms of biochemical control and toxicity. No gastrointestinal (GI)/genitourinary (GU) grade III toxicities were observed after a median follow-up of 9.5 months. Conclusions In our experience, concerning the treatment of prostate cancer (PCa), 11C-choline PET/CT may be helpful in radiotherapy planning, either for dose escalation or exclusion of selected sites. PMID:25859399

  18. Evolving Paradigm of Radiotherapy for High-Risk Prostate Cancer: Current Consensus and Continuing Controversies

    PubMed Central

    Juloori, Aditya; Shah, Chirag; Stephans, Kevin; Vassil, Andrew; Tendulkar, Rahul

    2016-01-01

    High-risk prostate cancer is an aggressive form of the disease with an increased risk of distant metastasis and subsequent mortality. Multiple randomized trials have established that the combination of radiation therapy and long-term androgen deprivation therapy improves overall survival compared to either treatment alone. Standard of care for men with high-risk prostate cancer in the modern setting is dose-escalated radiotherapy along with 2-3 years of androgen deprivation therapy (ADT). There are research efforts directed towards assessing the efficacy of shorter ADT duration. Current research has been focused on assessing hypofractionated and stereotactic body radiation therapy (SBRT) techniques. Ongoing randomized trials will help assess the utility of pelvic lymph node irradiation. Research is also focused on multimodality therapy with addition of a brachytherapy boost to external beam radiation to help improve outcomes in men with high-risk prostate cancer. PMID:27313896

  19. External Beam Radiotherapy for Prostate Cancer Patients on Anticoagulation Therapy: How Significant is the Bleeding Toxicity?

    SciTech Connect

    Choe, Kevin S.; Jani, Ashesh B.; Liauw, Stanley L.

    2010-03-01

    Purpose: To characterize the bleeding toxicity associated with external beam radiotherapy for prostate cancer patients receiving anticoagulation (AC) therapy. Methods and Materials: The study cohort consisted of 568 patients with adenocarcinoma of the prostate who were treated with definitive external beam radiotherapy. Of these men, 79 were receiving AC therapy with either warfarin or clopidogrel. All patients were treated with three-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Bleeding complications were recorded during treatment and subsequent follow-up visits. Results: With a median follow-up of 48 months, the 4-year actuarial risk of Grade 3 or worse bleeding toxicity was 15.5% for those receiving AC therapy compared with 3.6% among those not receiving AC (p < .0001). On multivariate analysis, AC therapy was the only significant factor associated with Grade 3 or worse bleeding (p < .0001). For patients taking AC therapy, the crude rate of bleeding was 39.2%. Multivariate analysis within the AC group demonstrated that a higher radiotherapy dose (p = .0408), intensity-modulated radiotherapy (p = 0.0136), and previous transurethral resection of the prostate (p = .0001) were associated with Grade 2 or worse bleeding toxicity. Androgen deprivation therapy was protective against bleeding, with borderline significance (p = 0.0599). Dose-volume histogram analysis revealed that Grade 3 or worse bleeding was minimized if the percentage of the rectum receiving >=70 Gy was <10% or the rectum receiving >=50 Gy was <50%. Conclusion: Patients taking AC therapy have a substantial risk of bleeding toxicity from external beam radiotherapy. In this setting, dose escalation or intensity-modulated radiotherapy should be used judiciously. With adherence to strict dose-volume histogram criteria and minimizing hotspots, the risk of severe bleeding might be reduced.

  20. Feasibility of IMRT to Cover Pelvic Nodes While Escalating the Dose to the Prostate Gland: Dosimetric Data on 35 Consecutive Patients

    SciTech Connect

    Bayouth, John E. Pena, John; Culp, Laura; Brack, Collin; Sanguineti, Giuseppe

    2008-10-01

    Utilizing available dosimetric and acute toxicity data, we confirm the feasibility of intensity modulated radiotherapy (IMRT) to include treatment of the pelvic nodes (PN) while escalating the dose to the prostate. Data were obtained from 35 consecutive patients with prostate cancer with {>=}15% risk of PN involvement. Patients received an initial boost to the prostate, delivering 16 Gy over 8 fractions using a 6-field conformal technique, followed by an 8-field coplanar inverse planning IMRT technique delivering an additional 60 Gy over 30 fractions to the prostate (76 Gy total) and 54 Gy over 30 fractions to the seminal vesicles (SV) and PN. Dose-volume histogram analysis was performed for planning target volumes and organs at risk. Acute toxicity (RTOG/EORTC scale) was prospectively and independently scored weekly for each patient. The maximum, mean, minimum dose, and D95 to each planning target volume is provided: prostate (82.2, 78.2, 72.6, 75.2 Gy), SV (79.0, 72.5, 56.9, 61.1 Gy), and PN (80.4, 59.7, 46.5, 53.3 Gy), respectively. The percent volume receiving a dose at or above 'x' Gy (Vx) was recorded for V75, V70, V65, V60, and V50 as: bladder (14%, 24%, 32%, 39%, and 54%) and rectum (3%, 18%, 26%, 34%, and 51%), respectively. Acute toxicity was as follows: 54% grade 2+ GI (n = 19), 25% grade 2+ GU (n = 9). IMRT enables treatment of pelvic nodes while escalating dose to the prostate and is clinically feasible with acute toxicity within expected ranges.

  1. Big Data Analytics for Prostate Radiotherapy

    PubMed Central

    Coates, James; Souhami, Luis; El Naqa, Issam

    2016-01-01

    Radiation therapy is a first-line treatment option for localized prostate cancer and radiation-induced normal tissue damage are often the main limiting factor for modern radiotherapy regimens. Conversely, under-dosing of target volumes in an attempt to spare adjacent healthy tissues limits the likelihood of achieving local, long-term control. Thus, the ability to generate personalized data-driven risk profiles for radiotherapy outcomes would provide valuable prognostic information to help guide both clinicians and patients alike. Big data applied to radiation oncology promises to deliver better understanding of outcomes by harvesting and integrating heterogeneous data types, including patient-specific clinical parameters, treatment-related dose–volume metrics, and biological risk factors. When taken together, such variables make up the basis for a multi-dimensional space (the “RadoncSpace”) in which the presented modeling techniques search in order to identify significant predictors. Herein, we review outcome modeling and big data-mining techniques for both tumor control and radiotherapy-induced normal tissue effects. We apply many of the presented modeling approaches onto a cohort of hypofractionated prostate cancer patients taking into account different data types and a large heterogeneous mix of physical and biological parameters. Cross-validation techniques are also reviewed for the refinement of the proposed framework architecture and checking individual model performance. We conclude by considering advanced modeling techniques that borrow concepts from big data analytics, such as machine learning and artificial intelligence, before discussing the potential future impact of systems radiobiology approaches. PMID:27379211

  2. Big Data Analytics for Prostate Radiotherapy.

    PubMed

    Coates, James; Souhami, Luis; El Naqa, Issam

    2016-01-01

    Radiation therapy is a first-line treatment option for localized prostate cancer and radiation-induced normal tissue damage are often the main limiting factor for modern radiotherapy regimens. Conversely, under-dosing of target volumes in an attempt to spare adjacent healthy tissues limits the likelihood of achieving local, long-term control. Thus, the ability to generate personalized data-driven risk profiles for radiotherapy outcomes would provide valuable prognostic information to help guide both clinicians and patients alike. Big data applied to radiation oncology promises to deliver better understanding of outcomes by harvesting and integrating heterogeneous data types, including patient-specific clinical parameters, treatment-related dose-volume metrics, and biological risk factors. When taken together, such variables make up the basis for a multi-dimensional space (the "RadoncSpace") in which the presented modeling techniques search in order to identify significant predictors. Herein, we review outcome modeling and big data-mining techniques for both tumor control and radiotherapy-induced normal tissue effects. We apply many of the presented modeling approaches onto a cohort of hypofractionated prostate cancer patients taking into account different data types and a large heterogeneous mix of physical and biological parameters. Cross-validation techniques are also reviewed for the refinement of the proposed framework architecture and checking individual model performance. We conclude by considering advanced modeling techniques that borrow concepts from big data analytics, such as machine learning and artificial intelligence, before discussing the potential future impact of systems radiobiology approaches. PMID:27379211

  3. Predicting toxicity in radiotherapy for prostate cancer.

    PubMed

    Landoni, Valeria; Fiorino, Claudio; Cozzarini, Cesare; Sanguineti, Giuseppe; Valdagni, Riccardo; Rancati, Tiziana

    2016-03-01

    This comprehensive review addresses most organs at risk involved in planning optimization for prostate cancer. It can be considered an update of a previous educational review that was published in 2009 (Fiorino et al., 2009). The literature was reviewed based on PubMed and MEDLINE database searches (from January 2009 up to September 2015), including papers in press; for each section/subsection, key title words were used and possibly combined with other more general key-words (such as radiotherapy, dose-volume effects, NTCP, DVH, and predictive model). Publications generally dealing with toxicity without any association with dose-volume effects or correlations with clinical risk factors were disregarded, being outside the aim of the review. A focus was on external beam radiotherapy, including post-prostatectomy, with conventional fractionation or moderate hypofractionation (<4Gy/fraction); extreme hypofractionation is the topic of another paper in this special issue. Gastrointestinal and urinary toxicity are the most investigated endpoints, with quantitative data published in the last 5years suggesting both a dose-response relationship and the existence of a number of clinical/patient related risk factors acting as dose-response modifiers. Some results on erectile dysfunction, bowel toxicity and hematological toxicity are also presented. PMID:27068274

  4. Improved survival with the addition of radiotherapy to androgen deprivation: questions answered and a review of current controversies in radiotherapy for non-metastatic prostate cancer.

    PubMed

    Amini, Arya; Kavanagh, Brian D; Rusthoven, Chad G

    2016-01-01

    The contemporary standard of care for locally advanced high-risk prostate cancer includes a combination of dose-escalated radiotherapy (RT) plus androgen-deprivation therapy (ADT). However, 20 years ago, at the inception of the National Cancer Institute of Canada (NCIC) led study (NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110), the survival impact of prostate RT for high-risk disease was uncertain. Recently, Mason, Warde and colleagues presented the final results of this NCIC/MRC study (PMID: 25691677) randomizing 1,205 high-risk prostate cancer patients to ADT + RT vs. ADT alone. These updated results confirm substantial improvements with the addition of RT to ADT for the endpoints of overall survival (OS), disease-free survival (DFS), and biochemical recurrence. Close examination of subtleties of this trial's design highlight some of the most salient controversies in the field of prostate RT, including the risk-stratified roles of ADT, optimal ADT duration, and RT field design in the dose-escalated and intensity-modulated radiotherapy (IMRT) era. PMID:26855950

  5. Transitioning from conventional radiotherapy to intensity-modulated radiotherapy for localized prostate cancer: changing focus from rectal bleeding to detailed quality of life analysis.

    PubMed

    Yamazaki, Hideya; Nakamura, Satoaki; Nishimura, Takuya; Yoshida, Ken; Yoshioka, Yasuo; Koizumi, Masahiko; Ogawa, Kazuhiko

    2014-11-01

    With the advent of modern radiation techniques, we have been able to deliver a higher prescribed radiotherapy dose for localized prostate cancer without severe adverse reactions. We reviewed and analyzed the change of toxicity profiles of external beam radiation therapy (EBRT) from the literature. Late rectal bleeding is the main adverse effect, and an incidence of >20% of Grade ≥2 adverse events was reported for 2D conventional radiotherapy of up to 70 Gy. 3D conformal radiation therapy (3D-CRT) was found to reduce the incidence to ∼10%. Furthermore, intensity-modulated radiation therapy (IMRT) reduced it further to a few percentage points. However, simultaneously, urological toxicities were enhanced by dose escalation using highly precise external radiotherapy. We should pay more attention to detailed quality of life (QOL) analysis, not only with respect to rectal bleeding but also other specific symptoms (such as urinary incontinence and impotence), for two reasons: (i) because of the increasing number of patients aged >80 years, and (ii) because of improved survival with elevated doses of radiotherapy and/or hormonal therapy; age is an important prognostic factor not only for prostate-specific antigen (PSA) control but also for adverse reactions. Those factors shift the main focus of treatment purpose from survival and avoidance of PSA failure to maintaining good QOL, particularly in older patients. In conclusion, the focus of toxicity analysis after radiotherapy for prostate cancer patients is changing from rectal bleeding to total elaborate quality of life assessment. PMID:25204643

  6. Intensity-Modulated Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer: A Dose-Escalation Planning Study

    SciTech Connect

    Lievens, Yolande; Nulens, An; Gaber, Mousa Amr; Defraene, Gilles; De Wever, Walter; Stroobants, Sigrid; Van den Heuvel, Frank

    2011-05-01

    Purpose: To evaluate the potential for dose escalation with intensity-modulated radiotherapy (IMRT) in positron emission tomography-based radiotherapy planning for locally advanced non-small-cell lung cancer (LA-NSCLC). Methods and Materials: For 35 LA-NSCLC patients, three-dimensional conformal radiotherapy and IMRT plans were made to a prescription dose (PD) of 66 Gy in 2-Gy fractions. Dose escalation was performed toward the maximal PD using secondary endpoint constraints for the lung, spinal cord, and heart, with de-escalation according to defined esophageal tolerance. Dose calculation was performed using the Eclipse pencil beam algorithm, and all plans were recalculated using a collapsed cone algorithm. The normal tissue complication probabilities were calculated for the lung (Grade 2 pneumonitis) and esophagus (acute toxicity, grade 2 or greater, and late toxicity). Results: IMRT resulted in statistically significant decreases in the mean lung (p <.0001) and maximal spinal cord (p = .002 and 0005) doses, allowing an average increase in the PD of 8.6-14.2 Gy (p {<=}.0001). This advantage was lost after de-escalation within the defined esophageal dose limits. The lung normal tissue complication probabilities were significantly lower for IMRT (p <.0001), even after dose escalation. For esophageal toxicity, IMRT significantly decreased the acute NTCP values at the low dose levels (p = .0009 and p <.0001). After maximal dose escalation, late esophageal tolerance became critical (p <.0001), especially when using IMRT, owing to the parallel increases in the esophageal dose and PD. Conclusion: In LA-NSCLC, IMRT offers the potential to significantly escalate the PD, dependent on the lung and spinal cord tolerance. However, parallel increases in the esophageal dose abolished the advantage, even when using collapsed cone algorithms. This is important to consider in the context of concomitant chemoradiotherapy schedules using IMRT.

  7. Clinical Outcome of Dose-Escalated Image-Guided Radiotherapy for Spinal Metastases

    SciTech Connect

    Guckenberger, Matthias; Goebel, Joachim; Wilbert, Juergen; Baier, Kurt; Richter, Anne; Sweeney, Reinhart A.; Bratengeier, Klaus; Flentje, Michael

    2009-11-01

    Purpose: To evaluate the outcomes after dose-escalated radiotherapy (RT) for spinal metastases and paraspinal tumors. Methods and Materials: A total of 14 patients, 12 with spinal metastases and a long life expectancy and 2 with paraspinal tumors, were treated for 16 lesions with intensity-modulated, image-guided RT. A median biologic effective dose of 74 Gy{sub 10} (range, 55-86) in a median of 20 fractions (range, 3-34) was prescribed to the target volume. The spinal canal was treated to 40 Gy in 20 fractions using a second intensity-modulated RT dose level in the case of epidural involvement. Results: After median follow-up of 17 months, one local recurrence was observed, for an actuarial local control rate of 88% after 2 years. Local control was associated with rapid and long-term pain relief. Of 11 patients treated for a solitary spinal metastasis, 6 developed systemic disease progression. The actuarial overall survival rate for metastatic patients was 85% and 63% after 1 and 2 years, respectively. Acute Grade 2-3 skin toxicity was seen in 2 patients with no late toxicity greater than Grade 2. No radiation-induced myelopathy was observed. Conclusion: Dose-escalated irradiation of spinal metastases was safe and resulted in excellent local control. Oligometastatic patients with a long life expectancy and epidural involvement are considered to benefit the most from fractionated RT.

  8. Decision Regret in Men Undergoing Dose-Escalated Radiation Therapy for Prostate Cancer

    SciTech Connect

    Steer, Anna N.; Aherne, Noel J.; Gorzynska, Karen; Hoffman, Matthew; Last, Andrew; Hill, Jacques; Shakespeare, Thomas P.

    2013-07-15

    Purpose: Decision regret (DR) is a negative emotion associated with medical treatment decisions, and it is an important patient-centered outcome after therapy for localized prostate cancer. DR has been found to occur in up to 53% of patients treated for localized prostate cancer, and it may vary depending on treatment modality. DR after modern dose-escalated radiation therapy (DE-RT) has not been investigated previously, to our knowledge. Our primary aim was to evaluate DR in a cohort of patients treated with DE-RT. Methods and Materials: We surveyed 257 consecutive patients with localized prostate cancer who had previously received DE-RT, by means of a validated questionnaire. Results: There were 220 responses (85.6% response rate). Image-guided intensity modulated radiation therapy was given in 85.0% of patients and 3-dimensional conformal radiation therapy in 15.0%. Doses received included 73.8 Gy (34.5% patients), 74 Gy (53.6%), and 76 Gy (10.9%). Neoadjuvant androgen deprivation (AD) was given in 51.8% of patients and both neoadjuvant and adjuvant AD in 34.5%. The median follow-up time was 23 months (range, 12-67 months). In all, 3.8% of patients expressed DR for their choice of treatment. When asked whether they would choose DE-RT or AD again, only 0.5% probably or definitely would not choose DE-RT again, compared with 8.4% for AD (P<.01). Conclusion: Few patients treated with modern DE-RT express DR, with regret appearing to be lower than in previously published reports of patients treated with radical prostatectomy or older radiation therapy techniques. Patients experienced more regret with the AD component of treatment than with the radiation therapy component, with implications for informed consent. Further research should investigate regret associated with individual components of modern therapy, including AD, radiation therapy and surgery.

  9. Parameters Favorable to Intraprostatic Radiation Dose Escalation in Men With Localized Prostate Cancer

    SciTech Connect

    Housri, Nadine; Ning, Holly; Ondos, John; Choyke, Peter; Camphausen, Kevin; Citrin, Deborah; Arora, Barbara; Shankavaram, Uma; Kaushal, Aradhana

    2011-06-01

    Purpose: To identify , within the framework of a current Phase I trial, whether factors related to intraprostatic cancer lesions (IPLs) or individual patients predict the feasibility of high-dose intraprostatic irradiation. Methods and Materials: Endorectal coil MRI scans of the prostate from 42 men were evaluated for dominant IPLs. The IPLs, prostate, and critical normal tissues were contoured. Intensity-modulated radiotherapy plans were generated with the goal of delivering 75.6 Gy in 1.8-Gy fractions to the prostate, with IPLs receiving a simultaneous integrated boost of 3.6 Gy per fraction to a total dose of 151.2 Gy, 200% of the prescribed dose and the highest dose cohort in our trial. Rectal and bladder dose constraints were consistent with those outlined in current Radiation Therapy Oncology Group protocols. Results: Dominant IPLs were identified in 24 patients (57.1%). Simultaneous integrated boosts (SIB) to 200% of the prescribed dose were achieved in 12 of the 24 patients without violating dose constraints. Both the distance between the IPL and rectum and the hip-to-hip patient width on planning CT scans were associated with the feasibility to plan an SIB (p = 0.002 and p = 0.0137, respectively). Conclusions: On the basis of this small cohort, the distance between an intraprostatic lesion and the rectum most strongly predicted the ability to plan high-dose radiation to a dominant intraprostatic lesion. High-dose SIB planning seems possible for select intraprostatic lesions.

  10. Dose Escalation of Whole-Brain Radiotherapy for Brain Metastases From Melanoma

    SciTech Connect

    Rades, Dirk; Heisterkamp, Christine; Huttenlocher, Stefan; Bohlen, Guenther; Dunst, Juergen; Haatanen, Tiina; Schild, Steven E.

    2010-06-01

    Purpose: The majority of patients with brain metastases from melanoma receive whole-brain radiotherapy (WBRT). However, the results are poor. Hypofractionation regimens failed to improve the outcome of these patients. This study investigates a potential benefit from escalation of the WBRT dose beyond the 'standard' regimen 30 Gy in 10 fractions (10x3 Gy). Methods and Materials: Data from 51 melanoma patients receiving WBRT alone were retrospectively analyzed. A dosage of 10x3 Gy (n = 33) was compared with higher doses including 40 Gy/20 fractions (n = 11) and 45 Gy/15 fractions (n = 7) for survival (OS) and local (intracerebral) control (LC). Additional potential prognostic factors were evaluated: age, gender, performance status, number of metastases, extracerebral metastases, and recursive partitioning analysis (RPA) class. Results: At 6 months, OS rates were 27% after 10x3 Gy and 50% after higher doses (p = 0.009). The OS rates at 12 months were 4% and 20%. On multivariate analysis, higher WBRT doses (p = 0.010), fewer than four brain metastases (p = 0.012), no extracerebral metastases (p = 0.006), and RPA class 1 (p = 0.005) were associated with improved OS. The LC rates at 6 months were 23% after 10x3 Gy and 50% after higher doses (p = 0.021). The LC rates at 12 months were 0% and 13%. On multivariate analysis, higher WBRT doses (p = 0.020) and fewer than brain metastases (p = 0.002) were associated with better LC. Conclusions: Given the limitations of a retrospective study, the findings suggest that patients with brain metastases from melanoma receiving WBRT alone may benefit from dose escalation beyond 10x3 Gy. The hypothesis generated by this study must be confirmed in a randomized trial stratifying for significant prognostic factors.

  11. Prostate motion during standard radiotherapy as assessed by fiducial markers.

    PubMed

    Crook, J M; Raymond, Y; Salhani, D; Yang, H; Esche, B

    1995-10-01

    From November 1993 to August 1994, 55 patients with localized prostate carcinoma had three gold seeds placed in the prostate under transrectal ultrasound guidance prior to the start of radiotherapy in order to track prostate motion. Patients had a planning CT scan before initial simulation and again at about 40 Gy, just prior to simulation of a field reduction. Seed position relative to fixed bony landmarks (pubic symphysis and both ischial tuberosities) was digitized from each pair of orthogonal films from the initial and boost simulation using the Nucletron brachytherapy planning system. Vector analysis was performed to rule out the possibility of independent seed migration within the prostate between the time of initial and boost simulation. Prostate motion was seen in the posterior (mean: 0.56 cm; SD: 0.41 cm) and inferior directions (mean: 0.59 cm; SD: 0.45 cm). The base of the prostate was displaced more than 1 cm posteriorly in 30% of patients and in 11% in the inferior direction. Prostate position is related to rectal and bladder filling. Distension of these organs displaces the prostate in an anterosuperior direction, with lesser degrees of filling allowing the prostate to move posteriorly and inferiorly. Conformal therapy planning must take this motion into consideration. Changes in prostate position of this magnitude preclude the use of standard margins. PMID:8539455

  12. Impact of conventional fractionated RT to pelvic lymph nodes and dose-escalated hypofractionated RT to prostate gland using IMRT treatment delivery in high-risk prostate cancer

    NASA Astrophysics Data System (ADS)

    Pervez, Nadeem

    Prostate cancer is the most common cancer among Canadian men. The standard treatment in high-risk category is radical radiation, with androgen suppression treatment (AST). Significant disease progression is reported despite this approach. Radiation dose escalation has been shown to improve disease-free survival; however, it results in higher toxicities. Hypofractionated radiation schedules (larger dose each fraction in shorter overall treatment time) are expected to deliver higher biological doses. A hypofractionated scheme was used in this study to escalate radiation doses with AST. Treatment was well tolerated acutely. Early results of self-administered quality of life reported by patients shows a decrease in QOL which is comparable to other treatment schedules. Significant positional variation of the prostate was observed during treatment. Therefore, we suggest daily target verification to avoid a target miss. Initial late effects are reasonable and early treatment outcomes are promising. Longer follow-up is required for full outcomes assessments.

  13. Toxicity Profile With a Large Prostate Volume After External Beam Radiotherapy for Localized Prostate Cancer

    SciTech Connect

    Pinkawa, Michael Fischedick, Karin; Asadpour, Branka; Gagel, Bernd; Piroth, Marc D.; Nussen, Sandra; Eble, Michael J.

    2008-01-01

    Purpose: To assess the impact of prostate volume on health-related quality of life (HRQOL) before and at different intervals after radiotherapy for prostate cancer. Methods and Materials: A group of 204 patients was surveyed prospectively before (Time A), at the last day (Time B), 2 months after (Time C), and 16 months (median) after (Time D) radiotherapy, with a validated questionnaire (Expanded Prostate Cancer Index Composite). The group was divided into subgroups with a small (11-43 cm{sup 3}) and a large (44-151 cm{sup 3}) prostate volume. Results: Patients with large prostates presented with lower urinary bother scores (median 79 vs. 89; p = 0.01) before treatment. Urinary function/bother scores for patients with large prostates decreased significantly compared to patients with small prostates due to irritative/obstructive symptoms only at Time B (pain with urination more than once daily in 48% vs. 18%; p < 0.01). Health-related quality of life did not differ significantly between both patient groups at Times C and D. In contrast to a large prostate, a small initial bladder volume (with associated higher dose-volume load) was predictive for lower urinary bother scores both in the acute and late phase; at Time B it predisposed for pollakiuria but not for pain. Patients with neoadjuvant hormonal therapy reached significantly lower HRQOL scores in several domains (affecting only incontinence in the urinary domain), despite a smaller prostate volume (34 cm{sup 3} vs. 47 cm{sup 3}; p < 0.01). Conclusions: Patients with a large prostate volume have a great risk of irritative/obstructive symptoms (particularly dysuria) in the acute radiotherapy phase. These symptoms recover rapidly and do not influence long-term HRQOL.

  14. Insufficiency Fractures After Pelvic Radiotherapy in Patients With Prostate Cancer

    SciTech Connect

    Igdem, Sefik; Alco, Guel; Ercan, Tuelay; Barlan, Metin; Ganiyusufoglu, Kuersat; Unalan, Buelent; Turkan, Sedat; Okkan, Sait

    2010-07-01

    Purpose: To assess the incidence, predisposing factors, and clinical characteristics of insufficiency fractures (IF) in patients with prostate cancer, who received pelvic radiotherapy as part of their definitive treatment. Methods and Materials: The charts of 134 prostate cancer patients, who were treated with pelvic radiotherapy between 1998 and 2007 were retrospectively reviewed. IF was diagnosed by bone scan and/or CT and/or MRI. The cumulative incidence of symptomatic IF was estimated by actuarial methods. Results: Eight patients were identified with symptomatic IF after a median follow-up period of 68 months (range, 12-116 months). The 5-year cumulative incidence of symptomatic IF was 6.8%. All patients presented with lower back pain. Insufficiency fracture developed at a median time of 20 months after the end of radiotherapy and was managed conservatively without any need for hospitalization. Three patients were thought to have metastatic disease because of increased uptake in their bone scans. However, subsequent CT and MR imaging revealed characteristic changes of IF, avoiding any further intervention. No predisposing factors for development of IF could be identified. Conclusions: Pelvic IF is a rare complication of pelvic radiotherapy in prostate cancer. Knowledge of pelvic IF is essential to rule out metastatic disease and prevent unnecessary treatment, especially in a patient cohort with high-risk features for distant spread.

  15. Perineural Invasion Predicts Increased Recurrence, Metastasis, and Death From Prostate Cancer Following Treatment With Dose-Escalated Radiation Therapy

    SciTech Connect

    Feng, Felix Y.; Qian Yushen; Stenmark, Matthew H.; Halverson, Schuyler; Blas, Kevin; Vance, Sean; Sandler, Howard M.; Hamstra, Daniel A.

    2011-11-15

    Purpose: To assess the prognostic value of perineural invasion (PNI) for patients treated with dose-escalated external-beam radiation therapy for prostate cancer. Methods and Materials: Outcomes were analyzed for 651 men treated for prostate cancer with EBRT to a minimum dose {>=}75 Gy. We assessed the impact of PNI as well as pretreatment and treatment-related factors on freedom from biochemical failure (FFBF), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival. Results: PNI was present in 34% of specimens at biopsy and was significantly associated with higher Gleason score (GS), T stage, and prostate-specific antigen level. On univariate and multivariate analysis, the presence of PNI was associated with worse FFBF (hazard ratio = 1.7, p <0.006), FFM (hazard ratio = 1.8, p <0.03), and CSS (HR = 1.4, p <0.05) compared with absence of PNI; there was no difference in overall survival. Seven-year rates of FFBF, FFM, and CCS were 64% vs. 80%, 84% vs. 92%, and 91% vs. 95% for those patients with and without PNI, respectively. On recursive partitioning analysis, PNI predicted for worse FFM and CSS in patients with GS 8-10, with FFM of 67% vs. 89% (p <0.02), and CSS of 69% vs. 91%, (p <0.04) at 7 years for those with and without PNI, respectively. Conclusions: The presence of PNI in the prostate biopsy predicts worse clinical outcome for patients treated with dose-escalated external-beam radiation therapy. Particularly in patients with GS 8-10 disease, the presence of PNI suggests an increased risk of metastasis and prostate cancer death.

  16. Volumetric Arc Therapy and Intensity-Modulated Radiotherapy for Primary Prostate Radiotherapy With Simultaneous Integrated Boost to Intraprostatic Lesion With 6 and 18 MV: A Planning Comparison Study

    SciTech Connect

    Ost, Piet; Speleers, Bruno; De Meerleer, Gert; De Neve, Wilfried; Fonteyne, Valerie; Villeirs, Geert; De Gersem, Werner

    2011-03-01

    Purpose: The aim of the present study was to compare intensity-modulated radiotherapy (IMRT) with volumetric arc therapy (VMAT), in the treatment of prostate cancer with maximal dose escalation to the intraprostatic lesion (IPL), without violating the organ-at-risk constraints. Additionally, the use of 6-MV photons was compared with 18-MV photons for all techniques. Methods and Materials: A total of 12 consecutive prostate cancer patients with an IPL on magnetic resonance imaging were selected for the present study. Plans were made for three IMRT field setups (three, five, and seven fields) and one VMAT field setup (single arc). First, optimal plans were created for every technique using biologic and physical planning aims. Next, an additional escalation to the IPL was planned as high as possible without violating the planning aims of the first step. Results: No interaction between the technique and photon energy (p = .928) occurred. No differences were found between the 6- and 18-MV photon beams, except for a reduction in the number of monitor units needed for 18 MV (p < .05). All techniques, except for three-field IMRT, allowed for dose escalation to a median dose of {>=}93 {+-} 6 Gy (mean {+-} standard deviation) to the IPL. VMAT was superior to IMRT for rectal volumes receiving 20-50 Gy (p < .05). Conclusion: VMAT allowed for dose escalation to the IPL with better sparing of the rectum than static three-, five-, and seven-field IMRT setups. High-energy photons had no advantage over low-energy photons.

  17. Biological dose volume histograms during conformal hypofractionated accelerated radiotherapy for prostate cancer

    SciTech Connect

    Koukourakis, Michael I.; Abatzoglou, Ioannis; Touloupidis, Stavros; Manavis, Ioannis

    2007-01-15

    Radiobiological data suggest that prostate cancer has a low {alpha}/{beta} ratio. Large radiotherapy fractions may, therefore, prove more efficacious than standard radiotherapy, while radiotherapy acceleration should further improve control rates. This study describes the radiobiology of a conformal hypofractionated accelerated radiotherapy scheme for the treatment of high risk prostate cancer. Anteroposterior fields to the pelvis deliver a daily dose of 2.7 Gy, while lateral fields confined to the prostate and seminal vesicles deliver an additional daily dose of 0.7 Gy. Radiotherapy is accomplished within 19 days (15 fractions). Dose volume histograms, calculated for tissue specific {alpha}/{beta} ratios and time factors, predict a high biological dose to the prostate and seminal vesicles (77-93 Gy). The biological dose to normal pelvic tissues is maintained at standard levels. Radiobiological dosimetry suggests that, using hypofractionated and accelerated radiotherapy, high biological radiation dose can be given to the prostate without overdosing normal tissues.

  18. Impact of hydrogel spacer injections on interfraction prostate motion during prostate cancer radiotherapy.

    PubMed

    Picardi, Cristina; Rouzaud, Michel; Kountouri, Melpomeni; Lestrade, Laetitia; Vallée, Jean Paul; Caparrotti, Francesca; Dubouloz, Angèle; Miralbell, Raymond; Zilli, Thomas

    2016-07-01

    Background The dosimetric advantage of prostate-rectum spacers to displace the anterior rectal wall outside of the high-dose radiation regions has been clearly established in prostate cancer radiotherapy (RT). The aim of this study was to assess the impact of hydrogel spacer (HS) in the interfraction prostate motion in patients undergoing RT for prostate cancer. Material and methods Twenty prostate cancer patients implanted with three fiducial markers (FM) with (n = 10) or without (n = 10) HS were analyzed. Displacements between the prostate isocenter based on the FM's position and the bony anatomy were quantified in the left-right (LR), anterior-posterior (AP), superior-inferior (SI) axes by offline analyses of 122 cone beam computed tomography scans. Group systematic (M), systematic (Σ) and random (σ) setup errors were determined. Results In patients with or without HS, the overall mean interfraction prostate displacements were 0.4 versus -0.4 mm (p = 0.0001), 0.6 versus 0.6 mm (p = 0.85), and -0.6 mm versus -0.3 mm (p = 0.48) for the LR, AP, and SI axes, respectively. Prostate displacements >5 mm in the AP and SI directions were similar for both groups. No differences in M, Σ and σ setup errors were observed in the three axes between HS + or HS- patients. Conclusions HS implantation does not significantly influence the interfraction prostate motion in patients treated with RT for prostate cancer. The major expected benefit of HS is a reduction of the high-dose levels to the rectal wall without influence in prostate immobilization. PMID:26796870

  19. Whole Pelvic Radiotherapy Versus Prostate Only Radiotherapy in the Management of Locally Advanced or Aggressive Prostate Adenocarcinoma

    SciTech Connect

    Aizer, Ayal A.; Yu, James B.; McKeon, Anne M.; Decker, Roy H.; Colberg, John W.; Peschel, Richard E.

    2009-12-01

    Purpose: To determine whether whole pelvic radiotherapy (WPRT) or prostate-only radiotherapy (PORT) yields improved biochemical disease-free survival (BDFS) in patients with advanced or aggressive prostate adenocarcinoma. Methods and Materials: Between 2000 and 2007, a consecutive sample of 277 patients with prostate adenocarcinoma and at least a 15% likelihood of lymph node involvement who had undergone WPRT (n = 68) or PORT (n = 209) at two referral centers was analyzed. The median radiation dose in both arms was 75.6 Gy. The outcome measure was BDFS, as determined using the prostate-specific antigen nadir + 2 ng/mL definition of failure. BDFS was calculated using the Kaplan-Meier method and compared with the log-rank test. A multivariate analysis was performed to assess for confounding. Treatment-related toxicity was assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events guidelines. The median follow-up was 30 months. Results: WPRT patients had more advanced and aggressive disease at baseline (p < .001). The 4-year BDFS rate was 69.4% in the PORT cohort and 86.3% in the WPRT cohort (p = .02). Within the entire cohort, after adjustment for confounding variables, the pretreatment prostate-specific antigen (p < .001), Gleason score (p < .001), use of hormonal therapy (p = .002), and use of WPRT (vs. PORT, p = .006) predicted for BDFS. Patients undergoing WPRT had increased acute gastrointestinal toxicity (p = .048), but no significant difference in acute genitourinary toxicity was seen (p = .09). No difference in late toxicity was found. Conclusion: WPRT may yield improved BDFS in patients with advanced or aggressive prostate adenocarcinoma, but results in a greater incidence of acute toxicity.

  20. Is Androgen Deprivation Therapy Necessary in All Intermediate-Risk Prostate Cancer Patients Treated in the Dose Escalation Era?

    SciTech Connect

    Castle, Katherine O.; Hoffman, Karen E.; Levy, Lawrence B.; Lee, Andrew K.; Choi, Seungtaek; Nguyen, Quynh N.; Frank, Steven J.; Pugh, Thomas J.; McGuire, Sean E.; Kuban, Deborah A.

    2013-03-01

    Purpose: The benefit of adding androgen deprivation therapy (ADT) to dose-escalated radiation therapy (RT) for men with intermediate-risk prostate cancer is unclear; therefore, we assessed the impact of adding ADT to dose-escalated RT on freedom from failure (FFF). Methods: Three groups of men treated with intensity modulated RT or 3-dimensional conformal RT (75.6-78 Gy) from 1993-2008 for prostate cancer were categorized as (1) 326 intermediate-risk patients treated with RT alone, (2) 218 intermediate-risk patients treated with RT and ≤6 months of ADT, and (3) 274 low-risk patients treated with definitive RT. Median follow-up was 58 months. Recursive partitioning analysis based on FFF using Gleason score (GS), T stage, and pretreatment PSA concentration was applied to the intermediate-risk patients treated with RT alone. The Kaplan-Meier method was used to estimate 5-year FFF. Results: Based on recursive partitioning analysis, intermediate-risk patients treated with RT alone were divided into 3 prognostic groups: (1) 188 favorable patients: GS 6, ≤T2b or GS 3+4, ≤T1c; (2) 71 marginal patients: GS 3+4, T2a-b; and (3) 68 unfavorable patients: GS 4+3 or T2c disease. Hazard ratios (HR) for recurrence in each group were 1.0, 2.1, and 4.6, respectively. When intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT, the greatest benefit from ADT was seen for the unfavorable intermediate-risk patients (FFF, 74% vs 94%, respectively; P=.005). Favorable intermediate-risk patients had no significant benefit from the addition of ADT to RT (FFF, 94% vs 95%, respectively; P=.85), and FFF for favorable intermediate-risk patients treated with RT alone approached that of low-risk patients treated with RT alone (98%). Conclusions: Patients with favorable intermediate-risk prostate cancer did not benefit from the addition of ADT to dose-escalated RT, and their FFF was nearly as good as patients with low-risk disease

  1. Influence of intrafraction motion on margins for prostate radiotherapy

    SciTech Connect

    Litzenberg, Dale W. . E-mail: litzen@umich.edu; Balter, James M.; Hadley, Scott W.; Sandler, Howard M.; Willoughby, Twyla R.; Kupelian, Patrick A.; Levine, Lisa

    2006-06-01

    Purpose: To assess the impact of intrafraction intervention on margins for prostate radiotherapy. Methods and Materials: Eleven supine prostate patients with three implanted transponders were studied. The relative transponder positions were monitored for 8 min and combined with previously measured data on prostate position relative to skin marks. Margins were determined for situations of (1) skin-based positioning, and (2) pretreatment transponder positioning. Intratreatment intervention was simulated assuming conditions of (1) continuous tracking, and (2) a 3-mm threshold for position correction. Results: For skin-based setup without and with inclusion of intrafraction motion, prostate treatments would have required average margins of 8.0, 7.3, and 10.0 mm and 8.2, 10.2, and 12.5 mm, about the left-right, anterior-posterior, and cranial-caudal directions, respectively. Positioning by prostate markers at the start of the treatment fraction reduced these values to 1.8, 5.8, and 7.1 mm, respectively. Interbeam adjustment further reduced margins to an average of 1.4, 2.3, and 1.8 mm. Intrabeam adjustment yielded margins of 1.3, 1.5, and 1.5 mm, respectively. Conclusion: Significant reductions in margins might be achieved by repositioning the patient before each beam, either radiographically or electromagnetically. However, 2 of the 11 patients would have benefited from continuous target tracking and threshold-based intervention.

  2. Positron Emission Tomography-Guided, Focal-Dose Escalation Using Intensity-Modulated Radiotherapy for Head and Neck Cancer

    SciTech Connect

    Madani, Indira . E-mail: indira@krtkg1.ugent.be; Duthoy, Wim; Derie, Cristina R.N.; De Gersem, Werner Ir.; Boterberg, Tom; Saerens, Micky; Jacobs, Filip Ir.; Gregoire, Vincent; Lonneux, Max; Vakaet, Luc; Vanderstraeten, Barbara; Bauters, Wouter; Bonte, Katrien; Thierens, Hubert; Neve, Wilfried de

    2007-05-01

    Purpose: To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided dose escalation, and to determine the maximum tolerated dose in head and neck cancer. Methods and Materials: A Phase I clinical trial was designed to escalate the dose limited to the [{sup 18}-F]fluoro-2-deoxy-D-glucose positron emission tomography ({sup 18}F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10 fractions. Standard IMRT was applied for the remaining 22 fractions of 2.16 Gy. Results: Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level I, and 18 at dose level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of dose-limiting toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at dose level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted {sup 18}F-FDG-PET-delineated region. Conclusions: For head and neck cancer, PET-guided dose escalation appears to be well-tolerated. The maximum tolerated dose was not reached at the investigated dose levels.

  3. Clinical commissioning of online seed matching protocol for prostate radiotherapy

    PubMed Central

    Duffton, A; McNee, S; Muirhead, R; Alhasso, A

    2012-01-01

    Objectives Our aim was to clinically commission an online seed matching image-guided radiotherapy (IGRT) protocol using modern hardware/software for patients undergoing prostate radiotherapy. An essential constraint was to achieve this within a busy centre without reducing patient throughput, which had been reported with other techniques. Methods 45 patients had 3 fiducial markers inserted into the prostate and were imaged daily using kilovoltage orthogonal images with online correction applied before treatment. A total of 1612 image pairs were acquired and analysed to identify interfractional motion, seed migration and interobserver variability, and assess ease of use. Results This method of IGRT was implemented successfully in our centre with no impact on treatment times and patient throughput. Systematic (Σ) interfractional set-up errors were 2.2, 2.7 and 3.9 mm in right–left (RL), superoinferior (SI) and anteroposterior (AP) directions, respectively. Random (σ) interfractional set-up errors were 3.2 (RL), 3.7 (SI) and 5.7 mm (AP). There were significant differences between patients. Seed migration and interobserver variability were not significant issues. Conclusions The described technique is facilitated by the advanced imaging system, allowing a fast and effective method of correcting set-up errors before treatment. Extended implementation of this technique has improved treatment delivery to the majority of our prostate radiotherapy patients. The measurement of interfractional motion in this study is potentially valuable for margin reduction in intensity-modulated radiotherapy/volumetric arc therapy. Advances in knowledge This technique can be used within treatment time constraints, benefiting large numbers of patients by helping to avoid geographical miss and potentially reducing toxicity to organs at risk. PMID:23175493

  4. Acute Toxicity in High-Risk Prostate Cancer Patients Treated With Androgen Suppression and Hypofractionated Intensity-Modulated Radiotherapy

    SciTech Connect

    Pervez, Nadeem; Small, Cormac; MacKenzie, Marc; Yee, Don; Parliament, Matthew; Ghosh, Sunita; Mihai, Alina; Amanie, John; Murtha, Albert; Field, Colin; Murray, David; Fallone, Gino; Pearcey, Robert

    2010-01-15

    Purpose: To report acute toxicity resulting from radiotherapy (RT) dose escalation and hypofractionation using intensity-modulated RT (IMRT) treatment combined with androgen suppression in high-risk prostate cancer patients. Methods and Materials: Sixty patients with a histological diagnosis of high-risk prostatic adenocarcinoma (having either a clinical Stage of >=T3a or an initial prostate-specific antigen [PSA] level of >=20 ng/ml or a Gleason score of 8 to 10 or a combination of a PSA concentration of >15 ng/ml and a Gleason score of 7) were enrolled. RT prescription was 68 Gy in 25 fractions (2.72 Gy/fraction) over 5 weeks to the prostate and proximal seminal vesicles. The pelvic lymph nodes and distal seminal vesicles concurrently received 45 Gy in 25 fractions. The patients were treated with helical TomoTherapy-based IMRT and underwent daily megavoltage CT image-guided verification prior to each treatment. Acute toxicity scores were recorded weekly during RT and at 3 months post-RT, using Radiation Therapy Oncology Group acute toxicity scales. Results: All patients completed RT and follow up for 3 months. The maximum acute toxicity scores were as follows: 21 (35%) patients had Grade 2 gastrointestinal (GI) toxicity; 4 (6.67%) patients had Grade 3 genitourinary (GU) toxicity; and 30 (33.33%) patients had Grade 2 GU toxicity. These toxicity scores were reduced after RT; there were only 8 (13.6%) patients with Grade 1 GI toxicity, 11 (18.97%) with Grade 1 GU toxicity, and 5 (8.62%) with Grade 2 GU toxicity at 3 months follow up. Only the V60 to the rectum correlated with the GI toxicity. Conclusion: Dose escalation using a hypofractionated schedule to the prostate with concurrent pelvic lymph node RT and long-term androgen suppression therapy is well tolerated acutely. Longer follow up for outcome and late toxicity is required.

  5. Image-guided adaptive radiation therapy (IGART): Radiobiological and dose escalation considerations for localized carcinoma of the prostate.

    PubMed

    Song, William; Schaly, Bryan; Bauman, Glenn; Battista, Jerry; Van Dyk, Jake

    2005-07-01

    The goal of this work was to evaluate the efficacy of various image-guided adaptive radiation therapy (IGART) techniques to deliver and escalate dose to the prostate in the presence of geometric uncertainties. Five prostate patients with 15-16 treatment CT studies each were retrospectively analyzed. All patients were planned with an 18 MV, six-field conformal technique with a 10 mm margin size and an initial prescription of 70 Gy in 35 fractions. The adaptive strategy employed in this work for patient-specific dose escalation was to increase the prescription dose in 2 Gy-per-fraction increments until the rectum normal tissue complication probability (NTCP) reached a level equal to that of the nominal plan NTCP (i.e., iso-NTCP dose escalation). The various target localization techniques simulated were: (1) daily laser-guided alignment to skin tattoo marks that represents treatment without image-guidance, (2) alignment to bony landmarks with daily portal images, and (3) alignment to the clinical target volume (CTV) with daily CT images. Techniques (1) and (3) were resimulated with a reduced margin size of 5 mm to investigate further dose escalation. When delivering the original clinical prescription dose of 70 Gy in 35 fractions, the "CTV registration" technique yielded the highest tumor control probability (TCP) most frequently, followed by the "bone registration" and "tattoo registration" techniques. However, the differences in TCP among the three techniques were minor when the margin size was 10 mm (< or = 1.1 %). Reducing the margin size to 5 mm significantly degraded the TCP values of the "tattoo registration" technique in two of the five patients, where a large difference was found compared to the other techniques (< or = 11.8 %). The "CTV registration" technique, however, did maintain similar TCP values compared to their 10 mm margin counterpart. In terms of normal tissue sparing, the technique producing the lowest NTCP varied from patient to patient. Reducing

  6. Feasibility of dose escalation using intensity-modulated radiotherapy in posthysterectomy cervical carcinoma

    SciTech Connect

    D'Souza, Warren D. . E-mail: wdsou001@umaryland.edu; Ahamad, Anesa A.; Iyer, Revathy B.; Salehpour, Mohammad R.; Jhingran, Anuja; Eifel, Patricia J.

    2005-03-15

    Purpose: To evaluate retrospectively the utility of intensity-modulated radiotherapy (IMRT) in reducing the volume of normal tissues receiving radiation at varying dose levels when the female pelvis after hysterectomy is treated to doses of 50.4 Gy and 54 Gy. Methods and materials: Computed tomography scans from 10 patients who had previously undergone conventional postoperative RT were selected. The clinical tumor volume (vaginal apex and iliac nodes) and organs at risk were contoured. Margins were added to generate the planning tumor volume. The Pinnacle and Corvus planning systems were used to develop conventional and IMRT plans, respectively. Conventional four-field plans were prescribed to deliver 45 Gy (4F{sub 45Gy}) or 50.4 Gy; eight-field IMRT plans were prescribed to deliver 50.4 Gy (IMRT{sub 50.4Gy}) or 54 Gy (IMRT{sub 54Gy}) to the planning tumor volume. All plans were normalized so that {>=}97% of the planning tumor volume received the prescribed dose. Student's t test was used to compare the volumes of organs at risk receiving the same doses with different plans. Results: The mean volume of bowel receiving {>=}45 Gy was lower with the IMRT{sub 50.4Gy} (33% lower) and IMRT{sub 54Gy} (18% lower) plans than with the 4F{sub 45Gy} plan. The mean volume of rectum receiving {>=}45 Gy or {>=}50 Gy was also significantly reduced with the IMRT plans despite an escalation of the prescribed dose from 45 Gy with the conventional plans to 54 Gy with IMRT. The mean volume of bladder treated to 45 Gy was the same or slightly lower with the IMRT{sub 50.4Gy} and IMRT{sub 54Gy} plans compared with the 4F{sub 45Gy} plan. Compared with the 4F{sub 45Gy} plan, the IMRT{sub 50.4Gy} plan resulted in a smaller volume of bowel receiving 35-45 Gy and a larger volume of bowel receiving 50-55 Gy. Compared with the 4F{sub 45Gy} plan, the IMRT{sub 54Gy} plan resulted in smaller volumes of bowel receiving 45-50 Gy; however, small volumes of bowel received 55-60 Gy with the IMRT plan

  7. Automatic localization of the prostate for on-line or off-line image-guided radiotherapy

    SciTech Connect

    Smitsmans, Monique H.P.; Wolthaus, Jochem W.H.; Artignan, Xavier; Bois, Josien de; Jaffray, David A.; Lebesque, Joos V.; Herk, Marcel van . E-mail: portal@nki.nl

    2004-10-01

    Purpose: With higher radiation dose, higher cure rates have been reported in prostate cancer patients. The extra margin needed to account for prostate motion, however, limits the level of dose escalation, because of the presence of surrounding organs at risk. Knowledge of the precise position of the prostate would allow significant reduction of the treatment field. Better localization of the prostate at the time of treatment is therefore needed, e.g. using a cone-beam computed tomography (CT) system integrated with the linear accelerator. Localization of the prostate relies upon manual delineation of contours in successive axial CT slices or interactive alignment and is fairly time-consuming. A faster method is required for on-line or off-line image-guided radiotherapy, because of prostate motion, for patient throughput and efficiency. Therefore, we developed an automatic method to localize the prostate, based on 3D gray value registration. Methods and materials: A study was performed on conventional repeat CT scans of 19 prostate cancer patients to develop the methodology to localize the prostate. For each patient, 8-13 repeat CT scans were made during the course of treatment. First, the planning CT scan and the repeat CT scan were registered onto the rigid bony structures. Then, the delineated prostate in the planning CT scan was enlarged by an optimum margin of 5 mm to define a region of interest in the planning CT scan that contained enough gray value information for registration. Subsequently, this region was automatically registered to a repeat CT scan using 3D gray value registration to localize the prostate. The performance of automatic prostate localization was compared to prostate localization using contours. Therefore, a reference set was generated by registering the delineated contours of the prostates in all scans of all patients. Gray value registrations that showed large differences with respect to contour registrations were detected with a {chi

  8. Radiation dose escalation by simultaneous modulated accelerated radiotherapy combined with chemotherapy for esophageal cancer: a phase II study

    PubMed Central

    Zhai, Tiantian; Chang, Daniel; Chen, Zhijian; Huang, Ruihong; Zhang, Wuzhe; Lin, Kun; Guo, Longjia; Zhou, Mingzhen; Li, Dongsheng; Li, Derui; Chen, Chuangzhen

    2016-01-01

    The outcomes for patients with esophageal cancer (EC) underwent standard-dose radical radiotherapy were still disappointing. This phase II study investigated the feasibility, safety and efficacy of radiation dose escalation using simultaneous modulated accelerated radiotherapy (SMART) combined with chemotherapy in 60 EC patients. Radiotherapy consisted of 66Gy at 2.2 Gy/fraction to the gross tumor and 54Gy at 1.8 Gy/fraction to subclinical diseases simultaneously. Chemotherapy including cisplatin and 5fluorouracil were administered to all patients during and after radiotherapy. The data showed that the majority of patients (98.3%) completed the whole course of radiotherapy and concurrent chemotherapy. The most common ≥ grade 3 acute toxicities were neutropenia (16.7%), followed by esophagitis (6.7%) and thrombopenia (5.0%). With a median follow-up of 24 months (5-38) for all patients and 30 months (18-38) for those still alive, 11 patients (18.3%) developed ≥ Grade 3 late toxicities and 2 (3.3%) of them died subsequently due to esophageal hemorrhage. The 1- and 2-year local-regional control, distant metastasis-free survival, disease-free survival and overall survival rates were 87.6% and 78.6%, 86.0% and 80.5%, 75.6% and 64.4%, 86.7% and 72.7%, respectively. SMART combined with concurrent chemotherapy is feasible in EC patients with tolerable acute toxicities. They showed a trend of significant improvements in local-regional control and overall survival. Further follow-up is needed to evaluate the late toxicities. PMID:26992206

  9. Prostate Bed Motion During Intensity-Modulated Radiotherapy Treatment

    SciTech Connect

    Klayton, Tracy; Price, Robert; Buyyounouski, Mark K.; Sobczak, Mark; Greenberg, Richard; Li, Jinsheng; Keller, Lanea; Sopka, Dennis; Kutikov, Alexander; Horwitz, Eric M.

    2012-09-01

    Purpose: Conformal radiation therapy in the postprostatectomy setting requires accurate setup and localization of the prostatic fossa. In this series, we report prostate bed localization and motion characteristics, using data collected from implanted radiofrequency transponders. Methods and Materials: The Calypso four-dimensional localization system uses three implanted radiofrequency transponders for daily target localization and real-time tracking throughout a course of radiation therapy. We reviewed the localization and tracking reports for 20 patients who received ultrasonography-guided placement of Calypso transponders within the prostate bed prior to a course of intensity-modulated radiation therapy at Fox Chase Cancer Center. Results: At localization, prostate bed displacement relative to bony anatomy exceeded 5 mm in 9% of fractions in the anterior-posterior (A-P) direction and 21% of fractions in the superior-inferior (S-I) direction. The three-dimensional vector length from skin marks to Calypso alignment exceeded 1 cm in 24% of all 652 fractions with available setup data. During treatment, the target exceeded the 5-mm tracking limit for at least 30 sec in 11% of all fractions, generally in the A-P or S-I direction. In the A-P direction, target motion was twice as likely to move posteriorly, toward the rectum, than anteriorly. Fifteen percent of all treatments were interrupted for repositioning, and 70% of patients were repositioned at least once during their treatment course. Conclusion: Set-up errors and motion of the prostatic fossa during radiotherapy are nontrivial, leading to potential undertreatment of target and excess normal tissue toxicity if not taken into account during treatment planning. Localization and real-time tracking of the prostate bed via implanted Calypso transponders can be used to improve the accuracy of plan delivery.

  10. Vesicocutaneous fistula following adjuvant radiotherapy for prostate cancer

    PubMed Central

    Hennessey, Derek Barry; Bolton, Eva; Thomas, Arun Z; Lynch, Thomas H

    2013-01-01

    Vesicocutaneous fistulas (VCF) are a rare complication of radical radiotherapy to the pelvis. Timely diagnosis and management are often difficult and complex. We report the unusual case of a 64-year-old gentleman who presented to the emergency department with worsening sepsis and profuse discharge from a cutaneous opening in the left groin. This presentation was 6 weeks following the completion of external beam radiotherapy for apical margin-positive prostate cancer (pT3a). A diagnosis of a VCF was confirmed after CT scanning of the abdomen and pelvis with contrast. Urinary diversion was achieved by a temporary urethral catheter insertion. Full resolution of this gentleman's symptoms was accomplished. In this article, we present a non-invasive approach to the management of VCF. This case raises intricate management issues in the atypical development of an early urinary tract fistula postradiotherapy. PMID:23625668

  11. Testicular Doses in Image-Guided Radiotherapy of Prostate Cancer

    SciTech Connect

    Deng Jun; Chen Zhe; Yu, James B.; Roberts, Kenneth B.; Peschel, Richard E.; Nath, Ravinder

    2012-01-01

    Purpose: To investigate testicular doses contributed by kilovoltage cone-beam computed tomography (kVCBCT) during image-guided radiotherapy (IGRT) of prostate cancer. Methods and Materials: An EGS4 Monte Carlo code was used to calculate three-dimensional dose distributions from kVCBCT on 3 prostate cancer patients. Absorbed doses to various organs were compared between intensity-modulated radiotherapy (IMRT) treatments and kVCBCT scans. The impact of CBCT scanning mode, kilovoltage peak energy (kVp), and CBCT field span on dose deposition to testes and other organs was investigated. Results: In comparison with one 10-MV IMRT treatment, a 125-kV half-fan CBCT scan delivered 3.4, 3.8, 4.1, and 5.7 cGy to the prostate, rectum, bladder, and femoral heads, respectively, accounting for 1.7%, 3.2%, 3.2%, and 8.4% of megavoltage photon dose contributions. However, the testes received 2.9 cGy from the same CBCT scan, a threefold increase as compared with 0.7 cGy received during IMRT. With the same kVp, full-fan mode deposited much less dose to organs than half-fan mode, ranging from 9% less for prostate to 69% less for testes, except for rectum, where full-fan mode delivered 34% more dose. As photon beam energy increased from 60 to 125 kV, kVCBCT-contributed doses increased exponentially for all organs, irrespective of scanning mode. Reducing CBCT field span from 30 to 10 cm in the superior-inferior direction cut testicular doses from 5.7 to 0.2 cGy in half-fan mode and from 1.5 to 0.1 cGy in full-fan mode. Conclusions: Compared with IMRT, kVCBCT-contributed doses to the prostate, rectum, bladder, and femoral heads are clinically insignificant, whereas dose to the testes is threefold more. Full-fan CBCT usually deposits much less dose to organs (except for rectum) than half-fan mode in prostate patients. Kilovoltage CBCT-contributed doses increase exponentially with photon beam energy. Reducing CBCT field significantly cuts doses to testes and other organs.

  12. Intrafractional Motion of the Prostate During Hypofractionated Radiotherapy

    SciTech Connect

    Xie Yaoqin; Djajaputra, David; King, Christopher R.; Hossain, Sabbir; Ma Lijun; Xing Lei

    2008-09-01

    Purpose: To report the characteristics of prostate motion as tracked by the stereoscopic X-ray images of the implanted fiducials during hypofractionated radiotherapy with CyberKnife. Methods and Materials: Twenty-one patients with prostate cancer who were treated with CyberKnife between January 2005 and September 2007 were selected for this retrospective study. The CyberKnife uses a stereoscopic X-ray system to obtain the position of the prostate target through the monitoring of implanted gold fiducial markers. If there is a significant deviation, the treatment is paused while the patient is repositioned by moving the couch. The deviations calculated from X-ray images acquired within the time interval between two consecutive couch motions constitute a data set. Results: Included in the analysis were 427 data sets and 4,439 time stamps of X-ray images. The mean duration for each data set was 697 sec. At 30 sec, a motion >2 mm exists in about 5% of data sets. The percentage is increased to 8%, 11%, and 14% at 60 sec, 90 sec, and 120 sec, respectively. A similar trend exists for other values of prostate motion. Conclusions: With proper monitoring and intervention during treatment, the prostate shifts observed among patients can be kept within the tracking range of the CyberKnife. On average, a sampling rate of {approx}40 sec between consecutive X-rays is acceptable to ensure submillimeter tracking. However, there is significant movement variation among patients, and a higher sampling rate may be necessary in some patients.

  13. Does Treatment Duration Affect Outcome After Radiotherapy for Prostate Cancer?

    SciTech Connect

    D'Ambrosio, David J.; Li Tianyu; Horwitz, Eric M.; Chen, David Y.T.; Pollack, Alan; Buyyounouski, Mark K.

    2008-12-01

    Purpose: The protraction of external beam radiotherapy (RT) time is detrimental in several disease sites. In prostate cancer, the overall treatment time can be considerable, as can the potential for treatment breaks. We evaluated the effect of elapsed treatment time on outcome after RT for prostate cancer. Methods and Materials: Between April 1989 and November 2004, 1,796 men with prostate cancer were treated with RT alone. The nontreatment day ratio (NTDR) was defined as the number of nontreatment days divided by the total elapsed days of RT. This ratio was used to account for the relationship between treatment duration and total RT dose. Men were stratified into low risk (n = 789), intermediate risk (n = 798), and high risk (n = 209) using a single-factor model. Results: The 10-year freedom from biochemical failure (FFBF) rate was 68% for a NTDR <33% vs. 58% for NTDR {>=}33% (p = 0.02; BF was defined as a prostate-specific antigen nadir + 2 ng/mL). In the low-risk group, the 10-year FFBF rate was 82% for NTDR <33% vs. 57% for NTDR {>=}33% (p = 0.0019). The NTDR was independently predictive for FFBF (p = 0.03), in addition to T stage (p = 0.005) and initial prostate-specific antigen level (p < 0.0001) on multivariate analysis, including Gleason score and radiation dose. The NTDR was not a significant predictor of FFBF when examined in the intermediate-risk group, high-risk group, or all risk groups combined. Conclusions: A proportionally longer treatment duration was identified as an adverse factor in low-risk patients. Treatment breaks resulting in a NTDR of {>=}33% (e.g., four or more breaks during a 40-fraction treatment, 5 d/wk) should be avoided.

  14. Stereotactic body radiotherapy for primary prostate cancer: a systematic review.

    PubMed

    Tan, Tze-Jian; Siva, Shankar; Foroudi, Farshad; Gill, Suki

    2014-10-01

    Stereotactic body radiotherapy (SBRT) for prostate cancer allows overall treatment times to be reduced to as little as 1 week while maintaining a non-invasive approach. This study provides a comprehensive summary of the literature relating to SBRT in prostate cancer. A systematic review of the relevant literature was performed using structured search terms. Fourteen phase I-II trials and retrospective studies using SBRT for the treatment of prostate cancer were used. Three studies were identified which addressed cost. Dose fractionation, radiotherapy procedures, biochemical progression-free survival, toxicity, cost and quality of life were critically appraised. A total of 1472 patients were examined across studies. Median follow-up ranged from 11 to 60 months. The most common dose fractionation was 35-36.25 Gy in five fractions, used in nine out of 14 studies. Ten of 14 studies used CyberKnife. The overall biochemical progression-free survival ranged 81-100%. Acute grade 2 urinary and rectal toxicities were reported in 5-42% and 0-27% of patients, respectively. Acute grade 3 or more urinary and rectal toxicity were 0.5% and 0%, respectively. Late grade 2 urinary toxicity was reported in 0-29% of patients, while 1.3% had a late grade 3 urinary toxicity. There were no late grade 4 urinary toxicities seen. Late grade 2 rectal toxicity was reported in 0-11%, while 0.5% had a late grade 3 rectal toxicity. Late grade 4 rectal toxicity was reported in 0.2% of patients. PMID:25155286

  15. Results of the Phase I Dose-Escalating Study of Motexafin Gadolinium With Standard Radiotherapy in Patients With Glioblastoma Multiforme

    SciTech Connect

    Ford, Judith M. Seiferheld, Wendy; Alger, Jeffrey R.; Wu, Genevieve; Endicott, Thyra J.; Mehta, Minesh; Curran, Walter; Phan, See-Chun

    2007-11-01

    Purpose: Motexafin gadolinium (MGd) is a putative radiation enhancer initially evaluated in patients with brain metastases. This Phase I trial studied the safety and tolerability of a 2-6-week course (10-22 doses) of MGd with radiotherapy for glioblastoma multiforme. Methods and Materials: A total of 33 glioblastoma multiforme patients received one of seven MGd regimens starting at 10 doses of 4 mg/kg/d MGd and escalating to 22 doses of 5.3 mg/kg/d MGd (5 or 10 daily doses then three times per week). The National Cancer Institute Cancer Therapy Evaluation Program toxicity and stopping rules were applied. Results: The maximal tolerated dose was 5.0 mg/kg/d MGd (5 d/wk for 2 weeks, then three times per week) for 22 doses. The dose-limiting toxicity was reversible transaminase elevation. Adverse reactions included rash/pruritus (45%), chills/fever (30%), and self-limiting vesiculobullous rash of the thumb and fingers (42%). The median survival of 17.6 months prompted a case-matched analysis. In the case-matched analysis, the MGd patients had a median survival of 16.1 months (n = 31) compared with the matched Radiation Therapy Oncology Group database patients with a median survival of 11.8 months (hazard ratio, 0.43; 95% confidence interval, 0.20-0.94). Conclusion: The maximal tolerated dose of MGd with radiotherapy for glioblastoma multiforme in this study was 5 mg/kg/d for 22 doses (daily for 2 weeks, then three times weekly). The baseline survival calculations suggest progression to Phase II trials is appropriate, with the addition of MGd to radiotherapy with concurrent and adjuvant temozolomide.

  16. Short-term Androgen-Deprivation Therapy Improves Prostate Cancer-Specific Mortality in Intermediate-Risk Prostate Cancer Patients Undergoing Dose-Escalated External Beam Radiation Therapy

    SciTech Connect

    Zumsteg, Zachary S.; Spratt, Daniel E.; Pei, Xin; Yamada, Yoshiya; Kalikstein, Abraham; Kuk, Deborah; Zhang, Zhigang; Zelefsky, Michael J.

    2013-03-15

    Purpose: We investigated the benefit of short-term androgen-deprivation therapy (ADT) in patients with intermediate-risk prostate cancer (PC) receiving dose-escalated external beam radiation therapy. Methods and Materials: The present retrospective study comprised 710 intermediate-risk PC patients receiving external beam radiation therapy with doses of ≥81 Gy at a single institution from 1992 to 2005, including 357 patients receiving neoadjuvant and concurrent ADT. Prostate-specific antigen recurrence-free survival (PSA-RFS) and distant metastasis (DM) were compared using the Kaplan-Meier method and Cox proportional hazards models. PC-specific mortality (PCSM) was assessed using competing-risks analysis. Results: The median follow-up was 7.9 years. Despite being more likely to have higher PSA levels, Gleason score 4 + 3 = 7, multiple National Comprehensive Cancer Network intermediate-risk factors, and older age (P≤.001 for all comparisons), patients receiving ADT had improved PSA-RFS (hazard ratio [HR], 0.598; 95% confidence interval [CI], 0.435-0.841; P=.003), DM (HR, 0.424; 95% CI, 0.219-0.819; P=.011), and PCSM (HR, 0.380; 95% CI, 0.157-0.921; P=.032) on univariate analysis. Using multivariate analysis, ADT was an even stronger predictor of improved PSA-RFS (adjusted HR [AHR], 0.516; 95% CI, 0.360-0.739; P<.001), DM (AHR, 0.347; 95% CI, 0.176-0.685; P=.002), and PCSM (AHR, 0.297; 95% CI, 0.128-0.685; P=.004). Gleason score 4 + 3 = 7 and ≥50% positive biopsy cores were other independent predictors of PCSM. Conclusions: Short-term ADT improves PSA-RFS, DM, and PCSM in patients with intermediate-risk PC undergoing dose-escalated external beam radiation therapy.

  17. Benchmarking Dosimetric Quality Assessment of Prostate Intensity-Modulated Radiotherapy

    SciTech Connect

    Senthi, Sashendra; Gill, Suki S.; Haworth, Annette; Kron, Tomas; Cramb, Jim; Rolfo, Aldo; Thomas, Jessica; Duchesne, Gillian M.; Hamilton, Christopher H.; Joon, Daryl Lim; Bowden, Patrick; Foroudi, Farshad

    2012-02-01

    Purpose: To benchmark the dosimetric quality assessment of prostate intensity-modulated radiotherapy and determine whether the quality is influenced by disease or treatment factors. Patients and Methods: We retrospectively analyzed the data from 155 consecutive men treated radically for prostate cancer using intensity-modulated radiotherapy to 78 Gy between January 2007 and March 2009 across six radiotherapy treatment centers. The plan quality was determined by the measures of coverage, homogeneity, and conformity. Tumor coverage was measured using the planning target volume (PTV) receiving 95% and 100% of the prescribed dose (V{sub 95%} and V{sub 100%}, respectively) and the clinical target volume (CTV) receiving 95% and 100% of the prescribed dose. Homogeneity was measured using the sigma index of the PTV and CTV. Conformity was measured using the lesion coverage factor, healthy tissue conformity index, and the conformity number. Multivariate regression models were created to determine the relationship between these and T stage, risk status, androgen deprivation therapy use, treatment center, planning system, and treatment date. Results: The largest discriminatory measurements of coverage, homogeneity, and conformity were the PTV V{sub 95%}, PTV sigma index, and conformity number. The mean PTV V{sub 95%} was 92.5% (95% confidence interval, 91.3-93.7%). The mean PTV sigma index was 2.10 Gy (95% confidence interval, 1.90-2.20). The mean conformity number was 0.78 (95% confidence interval, 0.76-0.79). The treatment center independently influenced the coverage, homogeneity, and conformity (all p < .0001). The planning system independently influenced homogeneity (p = .038) and conformity (p = .021). The treatment date independently influenced the PTV V{sub 95%} only, with it being better at the start (p = .013). Risk status, T stage, and the use of androgen deprivation therapy did not influence any aspect of plan quality. Conclusion: Our study has benchmarked measures

  18. The Effect of Changing Technique, Dose, and PTV Margin on Therapeutic Ratio During Prostate Radiotherapy

    SciTech Connect

    Huang Shaohui; Catton, Charles; Jezioranski, John M.Math.; Bayley, Andrew; Rose, Stuart; Rosewall, Tara

    2008-07-15

    Purpose: To quantify the dosimetric and radiobiological changes seen when using intensity-modulated radiation therapy (IMRT) or planning target volume (PTV) margin reduction with consistent planning parameters in a representative sample of localized prostate cancer patients. Methods and Materials: Twenty patients were randomly selected from a cohort that received 79.8 Gy using six-field conformal radiotherapy. Using the clinical contours, PTV margin, planning system, and dose constraints, five-field IMRT plans were generated for 79.8, 83.8, and 88.0 Gy. The 88.0-Gy IMRT plan was then reoptimized with a PTV margin reduced to 3 mm. These plans were then compared using various dosimetric and radiobiological endpoints calculated for various {alpha}/{beta}. Results: Intensity-modulated RT resulted in greater conformity to the PTV (p < 0.001). No improvement in mean normal tissue complication probabilities in the rectal wall (NTCPrw) was seen, and the modified therapeutic ratio (TR{sub mod}) was largely unchanged between six-field conformal and IMRT for the majority of the patients. When IMRT was used to escalate dose, NTCPrw increased by 9% at each 5% prescription increase (p < 0.001). Reducing the posterior PTV margin from 7 mm to 3 mm for an IMRT plan reduced the mean NTCPrw by 12% (p < 0.001) and resulted in a trend toward increased TR{sub mod}(p = 0.005). Changes in TR{sub mod} between conformal and IMRT planning or PTV reduction showed large interpatient variability. Conclusions: Changing from conformal to IMRT, or from PTV{sub 10-7} to PTV{sub 3}, did not produce a uniform interpatient increase in TR{sub mod}when the CTV contained the prostate alone. Radiobiological benefits of these two methods seem to be dependent on the particular anatomy of individual patients, supporting the use of patient-specific margin, planning, and dose prescription strategies.

  19. An Endorectal Balloon Reduces Intrafraction Prostate Motion During Radiotherapy

    SciTech Connect

    Smeenk, Robert Jan; Louwe, Robert J.W.; Langen, Katja M.; Shah, Amish P.; Kupelian, Patrick A.; Lin, Emile N.J.Th. van; Kaanders, Johannes H.A.M.

    2012-06-01

    Purpose: To investigate the effect of endorectal balloons (ERBs) on intrafraction and interfraction prostate motion during radiotherapy. Methods and Materials: Thirty patients were treated with intensity-modulated radiotherapy, to a total dose of 80 Gy in 40 fractions. In 15 patients, a daily-inserted air-filled ERB was applied. Prostate motion was tracked, in real-time, using an electromagnetic tracking system. Interfraction displacements, measured before each treatment, were quantified by calculating the systematic and random deviations of the center of mass of the implanted transponders. Intrafraction motion was analyzed in timeframes of 150 s, and displacements >1 mm, >3 mm, >5 mm, and >7 mm were determined in the anteroposterior, left-right, and superoinferior direction, and for the three-dimensional (3D) vector. Manual table corrections, made during treatment sessions, were retrospectively undone. Results: A total of 576 and 567 tracks have been analyzed in the no-ERB group and ERB group, respectively. Interfraction variation was not significantly different between both groups. After 600 s, 95% and 98% of the treatments were completed in the respective groups. Significantly fewer table corrections were performed during treatment fractions with ERB: 88 vs. 207 (p = 0.02). Intrafraction motion was significantly reduced with ERB. During the first 150 s, only negligible deviations were observed, but after 150 s, intrafraction deviations increased with time. This resulted in cumulative percentages of 3D-vector deviations >1 mm, >3 mm, >5 mm, and >7 mm that were 57.7%, 7.0%, 0.7%, and 0.3% in the ERB-group vs. 70.2%, 18.1%, 4.6%, and 1.4% in the no-ERB group after 600 s. The largest reductions in the ERB group were observed in the AP direction. These data suggest that a 5 mm CTV-to-PTV margin is sufficient to correct for intrafraction prostate movements when using an ERB. Conclusions: ERB significantly reduces intrafraction prostate motion, but not interfraction

  20. SU-E-T-183: Feasibility of Extreme Dose Escalation for Glioblastoma Multiforme Using 4π Radiotherapy

    SciTech Connect

    Nguyen, D; Rwigema, J; Yu, V; Kaprealian, T; Kupelian, P; Selch, M; Low, D; Sheng, K

    2014-06-01

    Purpose: GBM recurrence primarily occurs inside or near the high-dose radiation field of original tumor site requiring greater than 100 Gy to significantly improve local control. We utilize 4π non-coplanar radiotherapy to test the feasibility of planning target volume (PTV) margin expansions or extreme dose escalations without incurring additional radiation toxicities. Methods: 11 GBM patients treated with VMAT to a prescription dose of 59.4 Gy or 60 Gy were replanned with 4π. Original VMAT plans were created with 2 to 4 coplanar or non-coplanar arcs using 3 mm hi-res MLC. The 4π optimization, using 5 mm MLC, selected and inverse optimized 30 beams from a candidate pool of 1162 beams evenly distributed through 4π steradians. 4π plans were first compared to clinical plans using the same prescription dose. Two more studies were then performed to respectively escalate the GTV and PTV doses to 100 Gy, followed by a fourth plan expanding the PTV by 5 mm and maintaining the prescription dose. Results: The standard 4π plan significantly reduced (p<0.01) max and mean doses to critical structures by a range of 47.0–98.4% and 61.0–99.2%, respectively. The high dose PTV/high dose GTV/expanded PTV studies showed a reduction (p<0.05) or unchanged* (p>0.05) maximum dose of 72.1%/86.7%/77.1% (chiasm), 7.2%*/27.7%*/30.7% (brainstem), 39.8%*/84.2%/51.9%* (spinal cord), 69.0%/87.0%/66.9% (L eye), 76.2%/88.1%/84.1% (R eye), 95.0%/98.6%/97.5% (L lens), 93.9%/98.8%/97.6% (R lens), 74.3%/88.5%/72.4% (L optical nerve), 80.4%/91.3%/75.7% (R optical nerve), 64.8%/84.2%/44.9%* (L cochlea), and 85.2%/93.0%/78.0% (R cochlea), respectively. V30 and V36 for both brain and (brain - PTV) were reduced for all cases except the high dose PTV plan. PTV dose coverage increased for all 4π plans. Conclusion: Extreme dose escalation or further margin expansion is achievable using 4π, maintaining or reducing OAR doses. This study indicates that clinical trials employing 4π delivery using

  1. Salvage of locally recurrent prostate cancer after definitive radiotherapy.

    PubMed

    Mendenhall, William M; Henderson, Randal H; Hoppe, Bradford S; Nichols, Romaine C; Mendenhall, Nancy P

    2014-08-01

    Although a significant proportion of patients with localized prostate cancer are cured after definitive radiotherapy, solitary local recurrence is observed in a subset of patients and poses a management challenge. Curative-intent treatment options include prostatectomy, reirradiation, cryotherapy, and high-intensity-focused ultrasound. Outcomes data after any of these options are relatively limited. The 5-year biochemical progression-free survival rate is approximately 50% after salvage prostatectomy. However, the morbidity rate of the procedure is significantly higher compared with that observed in previously untreated patients. The likelihood of cure after low dose rate brachytherapy is similar to that observed after salvage prostatectomy, and the morbidity, although significant is less. Although cryotherapy and high-intensity-focused ultrasound may be less morbid than a prostatectomy, the probability of cure is probably lower. PMID:22772432

  2. Integral dose: Comparison between four techniques for prostate radiotherapy

    PubMed Central

    Ślosarek, Krzysztof; Osewski, Wojciech; Grządziel, Aleksandra; Radwan, Michał; Dolla, Łukasz; Szlag, Marta; Stąpór-Fudzińska, Małgorzata

    2014-01-01

    Aim Comparisons of integral dose delivered to the treatment planning volume and to the whole patient body during stereotactic, helical and intensity modulated radiotherapy of prostate. Background Multifield techniques produce large volumes of low dose inside the patient body. Delivered dose could be the result of the cytotoxic injuries of the cells even away from the treatment field. We calculated the total dose absorbed in the patient body for four radiotherapy techniques to investigate whether some methods have a potential to reduce the exposure to the patient. Materials and methods We analyzed CyberKnife plans for 10 patients with localized prostate cancer. Five alternative plans for each patient were calculated with the VMAT, IMRT and TomoTherapy techniques. Alternative dose distributions were calculated to achieve the same coverage for PTV. Integral Dose formula was used to calculate the total dose delivered to the PTV and whole patient body. Results Analysis showed that the same amount of dose was deposited to the treated volume despite different methods of treatment delivery. The mean values of total dose delivered to the whole patient body differed significantly for each treatment technique. The highest integral dose in the patient's body was at the TomoTherapy and CyberKnife treatment session. VMAT was characterized by the lowest integral dose deposited in the patient body. Conclusions The highest total dose absorbed in normal tissue was observed with the use of a robotic radiosurgery system and TomoTherapy. These results demonstrate that the exposure of healthy tissue is a dosimetric factor which differentiates the dose delivery methods. PMID:25859398

  3. Superiority of helical tomotherapy on liver sparing and dose escalation in hepatocellular carcinoma: a comparison study of three-dimensional conformal radiotherapy and intensity-modulated radiotherapy

    PubMed Central

    Zhao, Qianqian; Wang, Renben; Zhu, Jian; Jin, Linzhi; Zhu, Kunli; Xu, Xiaoqing; Feng, Rui; Jiang, Shumei; Qi, Zhonghua; Yin, Yong

    2016-01-01

    Background and purpose To compare the difference of liver sparing and dose escalation between three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and helical tomotherapy (HT) for hepatocellular carcinoma. Patients and methods Sixteen unresectable HCC patients were enrolled in this study. First, some evaluation factors of 3DCRT, IMRT, and HT plans were calculated with prescription dose at 50 Gy/25 fractions. Then, the doses were increased using HT or IMRT independently until either the plans reached 70 Gy or any normal tissue reached the dose limit according to quantitative analysis of normal tissue effects in the clinic criteria. Results The conformal index of 3DCRT was lower than that of IMRT (P<0.001) or HT (P<0.001), and the homogeneity index of 3DCRT was higher than that of IMRT (P<0.001) or HT (P<0.001). HT took the longest treatment time (P<0.001). For V50% (fraction of normal liver treated to at least 50% of the isocenter dose) of the normal liver, there was a significant difference: 3DCRT > IMRT > HT (P<0.001). HT had a lower Dmean (mean dose) and V20 (Vn, the percentage of organ volume receiving ≥n Gy) of liver compared with 3DCRT (P=0.005 and P=0.005, respectively) or IMRT (P=0.508 and P=0.007, respectively). Dmean of nontarget normal liver and V30 of liver were higher for 3DCRT than IMRT (P=0.005 and P=0.005, respectively) or HT (P=0.005 and P=0.005, respectively). Seven patients in IMRT (43.75%) and nine patients in HT (56.25%) reached the isodose 70 Gy, meeting the dose limit of the organs at risk. Conclusion HT may provide significantly better liver sparing and allow more patients to achieve higher prescription dose in HCC radiotherapy. PMID:27445485

  4. Strategies to evaluate the impact of rectal volume on prostate motion during three-dimensional conformal radiotherapy for prostate cancer*

    PubMed Central

    Poli, Ana Paula Diniz Fortuna; Dias, Rodrigo Souza; Giordani, Adelmo José; Segreto, Helena Regina Comodo; Segreto, Roberto Araujo

    2016-01-01

    Objective To evaluate the rectal volume influence on prostate motion during three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. Materials and Methods Fifty-one patients with prostate cancer underwent a series of three computed tomography scans including an initial planning scan and two subsequent scans during 3D-CRT. The organs of interest were outlined. The prostate contour was compared with the initial CT images considering the anterior, posterior, superior, inferior and lateral edges of the organ. Variations in the anterior limits and volume of the rectum were assessed and correlated with prostate motion in the anteroposterior direction. Results The maximum range of prostate motion was observed in the superoinferior direction, followed by the anteroposterior direction. A significant correlation was observed between prostate motion and rectal volume variation (p = 0.037). A baseline rectal volume superior to 70 cm3 had a significant influence on the prostate motion in the anteroposterior direction (p = 0.045). Conclusion The present study showed a significant interfraction motion of the prostate during 3D-CRT with greatest variations in the superoinferior and anteroposterior directions, and that a large rectal volume influences the prostate motion with a cutoff value of 70 cm3. Therefore, the treatment of patients with a rectal volume > 70 cm3 should be re-planned with appropriate rectal preparation. PMID:26929456

  5. Magnetic resonance assessment of prostate localization variability in intensity-modulated radiotherapy for prostate cancer

    SciTech Connect

    Villeirs, Geert M. . E-mail: Geert.Villeirs@ugent.be; Meerleer, Gert O. de; Verstraete, Koenraad L.; Neve, Wilfried J. de

    2004-12-01

    Purpose: To measure prostate motion with magnetic resonance imaging (MRI) during a course of intensity-modulated radiotherapy. Methods and materials: Seven patients with prostate carcinoma were scanned supine on a 1.5-Tesla MRI system with weekly pretreatment and on-treatment HASTE T2-weighted images in 3 orthogonal planes. The bladder and rectal volumes and position of the prostatic midpoint (PMP) and margins relative to the bony pelvis were measured. Results: All pretreatment positions were at the mean position as computed from the on-treatment scans in each patient. The PMP variability (given as 1 SD) in the anterior-posterior (AP), superior-inferior (SI), and right-left (RL) directions was 2.6, 2.4, and 1.0 mm, respectively. The largest variabilities occurred at the posterior (3.2 mm), superior (2.6 mm), and inferior (2.6 mm) margins. A strong correlation was found between large rectal volume (>95th percentile) and anterior PMP displacement. A weak correlation was found between bladder volume and superior PMP displacement. Conclusions: All pretreatment positions were representative of the subsequent on-treatment positions. A clinical target volume (CTV) expansion of 5.3 mm in any direction was sufficient to ascertain a 95% coverage of the CTV within the planning target volume (PTV), provided that a rectal suppository is administered to avoid rectal overdistension and that the patient has a comfortably filled bladder (<300 mL)

  6. The Missing Pieces in Reporting of Randomized Controlled Trials of External Beam Radiation Therapy Dose Escalation for Prostate Cancer.

    PubMed

    Zaorsky, Nicholas G; Egleston, Brian L; Horwitz, Eric M; Dicker, Adam P; Nguyen, Paul L; Showalter, Timothy N; Den, Robert B

    2016-08-01

    Randomized controlled trials (RCTs) are the most rigorous way of determining whether a cause-effect relation exists between treatment and outcome and for assessing the cost-effectiveness of a treatment. For many patients, cancer is a chronic illness; RCTs evaluating treatments for indolent cancers must evolve to facilitate medical decision-making, as "concrete" patient outcomes (eg, survival) will likely be excellent independent of the intervention, and detecting a difference between trial arms may be impossible. In this commentary, we articulate 9 recommendations that we hope future clinical trialists and funding agencies (including those under the National Cancer Institute) will take into consideration when planning RCTs to help guide subsequent interpretation of results and clinical decision making, based on RCTs of external beam radiation therapy dose escalation for the most common indolent cancer in men, that is, prostate cancer. We recommend routinely reporting: (1) race; (2) medical comorbidities; (3) psychiatric comorbidities; (4) insurance status; (5) education; (6) marital status; (7) income; (8) sexual orientation; and (9) facility-related characteristics (eg, number of centers involved, type of facilities, yearly hospital volumes). We discuss how these factors independently affect patient outcomes and toxicities; future clinicians and governing organizations should consider this information to plan RCTs accordingly (to maximize patient accrual and total n), select appropriate endpoints (eg, toxicity, quality of life, sexual function), actively monitor RCTs, and report results so as to identify the optimal treatment among subpopulations. PMID:27322694

  7. PSA Response to Neoadjuvant Androgen Deprivation Therapy Is a Strong Independent Predictor of Survival in High-Risk Prostate Cancer in the Dose-Escalated Radiation Therapy Era

    SciTech Connect

    McGuire, Sean E.; Lee, Andrew K.; Cerne, Jasmina Z.; Munsell, Mark F.; Levy, Lawrence B.; Kudchadker, Rajat J.; Choi, Seungtaek L.; Nguyen, Quynh N.; Hoffman, Karen E.; Pugh, Thomas J.; Frank, Steven J.; Corn, Paul G.; Logothetis, Christopher J.; Kuban, Deborah A.

    2013-01-01

    Purpose: The aim of the study was to evaluate the prognostic value of prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) prior to dose-escalated radiation therapy (RT) and long-term ADT in high-risk prostate cancer. Methods and Materials: We reviewed the charts of all patients diagnosed with high-risk prostate cancer and treated with a combination of long-term ADT (median, 24 months) and dose-escalated (median, 75.6 Gy) RT between 1990 and 2007. The associations among patient, tumor, and treatment characteristics with biochemical response to neoadjuvant ADT and their effects on failure-free survival (FFS), time to distant metastasis (TDM), prostate cancer-specific mortality (PCSM) and overall survival (OS) were examined. Results: A total of 196 patients met criteria for inclusion. Median follow-up time for patients alive at last contact was 7.0 years (range, 0.5-18.1 years). Multivariate analysis identified the pre-RT PSA concentration (<0.5 vs {>=}0.5 ng/mL) as a significant independent predictor of FFS (P=.021), TDM (P=.009), PCSM (P=.039), and OS (P=.037). On multivariate analysis, pretreatment PSA (iPSA) and African-American race were significantly associated with failure to achieve a pre-RT PSA of <0.5 ng/mL. Conclusions: For high-risk prostate cancer patients treated with long-term ADT and dose-escalated RT, a pre-RT PSA level {>=}0.5 ng/mL after neoadjuvant ADT predicts for worse survival measures. Both elevated iPSA and African-American race are associated with increased risk of having a pre-RT PSA level {>=}0.5 ng/mL. These patients should be considered for clinical trials that test newer, more potent androgen-depleting therapies such as abiraterone and MDV3100 in combination with radiation.

  8. Salvage brachytherapy for locally recurrent prostate cancer after external beam radiotherapy.

    PubMed

    Yamada, Yasuhiro; Okihara, Koji; Iwata, Tsuyoshi; Masui, Koji; Kamoi, Kazumi; Yamada, Kei; Miki, Tsuneharu

    2015-01-01

    External beam radiotherapy (EBRT) is a standard treatment for prostate cancer. Despite the development of novel radiotherapy techniques such as intensity-modulated conformal radiotherapy, the risk of local recurrence after EBRT has not been obviated. Various local treatment options (including salvage prostatectomy, brachytherapy, cryotherapy, and high-intensity focused ultrasound [HIFU]) have been employed in cases of local recurrence after primary EBRT. Brachytherapy is the first-line treatment for low-risk and selected intermediate-risk prostate tumors. However, few studies have examined the use of brachytherapy to treat post-EBRT recurrent prostate cancer. The purpose of this paper is to analyze the current state of our knowledge about the effects of salvage brachytherapy in patients who develop locally recurrent prostate cancer after primary EBRT. This article also introduces our novel permanent brachytherapy salvage method. PMID:26112477

  9. Method comparison of ultrasound and kilovoltage x-ray fiducial marker imaging for prostate radiotherapy targeting.

    PubMed

    Fuller, Clifton David; Thomas, Charles R; Schwartz, Scott; Golden, Nanalei; Ting, Joe; Wong, Adrian; Erdogmus, Deniz; Scarbrough, Todd J

    2006-10-01

    Several measurement techniques have been developed to address the capability for target volume reduction via target localization in image-guided radiotherapy; among these have been ultrasound (US) and fiducial marker (FM) software-assisted localization. In order to assess interchangeability between methods, US and FM localization were compared using established techniques for determination of agreement between measurement methods when a 'gold-standard' comparator does not exist, after performing both techniques daily on a sequential series of patients. At least 3 days prior to CT simulation, four gold seeds were placed within the prostate. FM software-assisted localization utilized the ExacTrac X-Ray 6D (BrainLab AG, Germany) kVp x-ray image acquisition system to determine prostate position; US prostate targeting was performed on each patient using the SonArray (Varian, Palo Alto, CA). Patients were aligned daily using laser alignment of skin marks. Directional shifts were then calculated by each respective system in the X, Y and Z dimensions before each daily treatment fraction, previous to any treatment or couch adjustment, as well as a composite vector of displacement. Directional shift agreement in each axis was compared using Altman-Bland limits of agreement, Lin's concordance coefficient with Partik's grading schema, and Deming orthogonal bias-weighted correlation methodology. 1,019 software-assisted shifts were suggested by US and FM in 39 patients. The 95% limits of agreement in X, Y and Z axes were +/-9.4 mm, +/-11.3 mm and +/-13.4, respectively. Three-dimensionally, measurements agreed within 13.4 mm in 95% of all paired measures. In all axes, concordance was graded as 'poor' or 'unacceptable'. Deming regression detected proportional bias in both directional axes and three-dimensional vectors. Our data suggest substantial differences between US and FM image-guided measures and subsequent suggested directional shifts. Analysis reveals that the vast

  10. Real-Time Study of Prostate Intrafraction Motion During External Beam Radiotherapy With Daily Endorectal Balloon

    SciTech Connect

    Both, Stefan; Wang, Ken Kang-Hsin; Plastaras, John P.; Deville, Curtiland; Bar Ad, Voika; Tochner, Zelig; Vapiwala, Neha

    2011-12-01

    Purpose: To prospectively investigate intrafraction prostate motion during radiofrequency-guided prostate radiotherapy with implanted electromagnetic transponders when daily endorectal balloon (ERB) is used. Methods and Materials: Intrafraction prostate motion from 24 patients in 787 treatment sessions was evaluated based on three-dimensional (3D), lateral, cranial-caudal (CC), and anterior-posterior (AP) displacements. The mean percentage of time with 3D, lateral, CC, and AP prostate displacements >2, 3, 4, 5, 6, 7, 8, 9, and 10 mm in 1 minute intervals was calculated for up to 6 minutes of treatment time. Correlation between the mean percentage time with 3D prostate displacement >3 mm vs. treatment week was investigated. Results: The percentage of time with 3D prostate movement >2, 3, and 4 mm increased with elapsed treatment time (p < 0.05). Prostate movement >5 mm was independent of elapsed treatment time (p = 0.11). The overall mean time with prostate excursions >3 mm was 5%. Directional analysis showed negligible lateral prostate motion; AP and CC motion were comparable. The fraction of time with 3D prostate movement >3 mm did not depend on treatment week of (p > 0.05) over a 4-minute mean treatment time. Conclusions: Daily endorectal balloon consistently stabilizes the prostate, preventing clinically significant displacement (>5 mm). A 3-mm internal margin may sufficiently account for 95% of intrafraction prostate movement for up to 6 minutes of treatment time. Directional analysis suggests that the lateral internal margin could be further reduced to 2 mm.

  11. Ultrasonographic changes in the normal and malignant prostate after definitive radiotherapy

    SciTech Connect

    Egawa, S.; Carter, S.S.; Wheeler, T.M.; Scardino, P.T. )

    1989-11-01

    As treatments for early localized prostate cancer come under closer scrutiny, the fundamental problem of documenting the success of radiotherapy becomes more obvious. Currently, no satisfactory method exists to determine tumor viability after radiotherapy. Transrectal ultrasonography is particularly valuable for monitoring the response of prostate cancer to radiotherapy. Persistent cancer retains its hypoechoic appearance after definitive radiotherapy. Hypoechoic lesions greater than 5 mm in diameter found more than 12 months after radiotherapy should be suspected of representing persistent local disease. In our study, albeit in a selected group of patients undergoing salvage radical prostatectomy, 92 per cent of such findings were associated with what we interpreted as viable tumor by light microscopy. Ultrasound-guided biopsy should be considered in such circumstances. The persistence of hypoechoic lesions in more than 65 per cent of patients 12 to 36 months after radiotherapy also suggests that local treatment failure may be underestimated by digital rectal examination and random digitally guided biopsy. Serial measurement of the diameter of hypoechoic lesions may provide a valuable indicator of progress in an individual patient. Patients with enlarging foci of tumor within the prostate after radiotherapy might be selected for biopsy and further treatment. If such a policy is employed, it is likely that a higher incidence of persistent cancer will be found after radiotherapy than has previously been discovered by random digitally guided biopsy.

  12. Treatment of Breast and Prostate Cancer by Hypofractionated Radiotherapy: Potential Risks and Benefits.

    PubMed

    Ray, K J; Sibson, N R; Kiltie, A E

    2015-07-01

    Breast cancer and prostate cancer are the most common cancers diagnosed in women and men, respectively, in the UK, and radiotherapy is used extensively in the treatment of both. In vitro data suggest that tumours in the breast and prostate have unique properties that make a hypofractionated radiotherapy treatment schedule advantageous in terms of therapeutic index. Many clinical trials of hypofractionated radiotherapy treatment schedules have been completed to establish the extent to which hypofractionation can improve patient outcome. Here we present a concise description of hypofractionation, the mathematical description of converting between conventional and hypofractionated schedules, and the motivation for using hypofractionation in the treatment of breast and prostate cancer. Furthermore, we summarise the results of important recent hypofractionation trials and highlight the limitations of a hypofractionated treatment regimen. PMID:25752244

  13. Treatment of Breast and Prostate Cancer by Hypofractionated Radiotherapy: Potential Risks and Benefits

    PubMed Central

    Ray, K.J.; Sibson, N.R.; Kiltie, A.E.

    2015-01-01

    Breast cancer and prostate cancer are the most common cancers diagnosed in women and men, respectively, in the UK, and radiotherapy is used extensively in the treatment of both. In vitro data suggest that tumours in the breast and prostate have unique properties that make a hypofractionated radiotherapy treatment schedule advantageous in terms of therapeutic index. Many clinical trials of hypofractionated radiotherapy treatment schedules have been completed to establish the extent to which hypofractionation can improve patient outcome. Here we present a concise description of hypofractionation, the mathematical description of converting between conventional and hypofractionated schedules, and the motivation for using hypofractionation in the treatment of breast and prostate cancer. Furthermore, we summarise the results of important recent hypofractionation trials and highlight the limitations of a hypofractionated treatment regimen. PMID:25752244

  14. A tensor-based population value decomposition to explain rectal toxicity after prostate cancer radiotherapy

    PubMed Central

    Ospina, Juan David; Commandeur, Frédéric; Ríos, Richard; Dréan, Gaël; Correa, Juan Carlos; Simon, Antoine; Haigron, Pascal; De Crevoisier, Renaud; Acosta, Oscar

    2013-01-01

    In prostate cancer radiotherapy the association between the dose distribution and the occurrence of undesirable side-effects is yet to be revealed. In this work a method to perform population analysis by comparing the dose distributions is proposed. The method is a tensor-based approach that generalises an existing method for 2D images and allows for the highlighting of over irradiated zones correlated with rectal bleeding after prostate cancer radiotherapy. Thus, the aim is to contribute to the elucidation of the dose patterns correlated with rectal toxicity. The method was applied to a cohort of 63 patients and it was able to build up a dose pattern characterizing the difference between patients presenting rectal bleeding after prostate cancer radiotherapy and those who did not. PMID:24579164

  15. Repeated stereotactic body radiotherapy for oligometastatic prostate cancer recurrence

    PubMed Central

    2014-01-01

    Purpose To assess the outcome of prostate cancer (PCa) patients diagnosed with oligometastatic disease at recurrence and treated with stereotactic body radiotherapy (SBRT). Methods Non-castrate patients with up to 3 synchronous metastases (bone and/or lymph nodes) diagnosed on positron emission tomography - computed tomography, following biochemical recurrence after local curative treatment, were treated with (repeated) SBRT to a dose of 50 Gy in 10 fractions or 30 Gy in 3 fractions. Androgen deprivation therapy-free survival (ADT-FS) defined as the time interval between the first day of SBRT and the initiation of ADT was the primary endpoint. ADT was initiated if more than 3 metastases were detected during follow-up even when patients were still asymptomatic. Secondary endpoints were local control, progression free survival (PFS) and toxicity. Toxicity was scored using the Common Terminology Criteria for Adverse Events. Results With a median follow-up from time of SBRT of 2 years, we treated 50 patients with 70 metastatic lesions with a local control rate of 100%. The primary involved metastatic sites were lymph nodes (54%), bone (44%), and viscera (2%). The median PFS was 19 mo (95% CI: 13–25 mo) with 75% of recurring patients having ≤3 metastases. A 2nd and 3rd course of SBRT was delivered in 19 and 6 patients respectively. This results in a median ADT-FS of 25 months (20–30 mo). On univariate analysis, only a short PSA doubling time was a significant predictor for both PFS (HR: 0.90, 95% CI: 0.82 – 0.99) and ADT-FS (HR: 0.83; 95% CI: 0.71 – 0.97). Ten patients (20%) developed toxicity following treatment, which was classified as grade I in 7 and grade II in 3 patients. Conclusion Repeated SBRT for oligometastatic prostate cancer postpones palliative androgen deprivation therapy with 2 years without grade III toxicity. PMID:24920079

  16. Does Radiotherapy for the Primary Tumor Benefit Prostate Cancer Patients with Distant Metastasis at Initial Diagnosis?

    PubMed Central

    Cho, Yeona; Chang, Jee Suk; Rha, Koon Ho; Hong, Sung Joon; Choi, Young Deuk; Ham, Won Sik; Kim, Jun Won; Cho, Jaeho

    2016-01-01

    Purpose/Objectives Treatment of the primary tumor reportedly improves survival in several types of metastatic cancer. We herein evaluated the efficacy and toxicity of radiotherapy for the primary tumor in prostate cancer with metastasis. Materials/Methods The study cohort included 140 men with metastatic prostate cancer at initial diagnosis. Metastatic sites were divided into 4 groups as follows: solitary bone, 2–4 bones, ≥5 bones, and visceral organs. Patient, tumor, and treatment characteristics, and clinical outcomes were compared between patients treated with (prostate radiotherapy [PRT] group) or without radiotherapy to the primary tumor. Results Patients in PRT group presented with a statistically significantly younger age (p = .02), whereas other characteristics showed no significant difference. Overall survival (OS) and biochemical failure-free survival (BCFFS) were improved in PRT patients (3-year OS: 69% vs. 43%, p = 0.004; 3-year BCFFS: 52% vs. 16%, p = 0.002). Multivariate analysis identified PRT as a significant predictor of both OS (hazard ratio [HR] = 0.43, p = 0.015). None of the 38 PRT patients experienced severe (grade ≥3) genitourinary or gastrointestinal toxicity. Conclusions Our data suggest that radiotherapy to the primary tumor was associated with improved OS and BCFFS in metastatic prostate cancer. The results of this study warrant prospective controlled clinical trials of this approach in stage IV prostate cancer patients with limited extent of bone metastasis and good performance status. PMID:26807740

  17. Definitive radiotherapy of prostatic cancer: the Norwegian Radium Hospital's experience (1976-1982)

    SciTech Connect

    Telhaug, R.; Fossa, S.D.O.; Ous, S.

    1987-01-01

    During the years 1976 to 1982 definitive curatively aimed radiotherapy to the primary tumor was given to 53 patients with prostatic cancer confined to the true pelvis (T0, 2; T1-2, 19; T3, 24; T4, 8; N0, 18; N+, 2; Nx, 33); all patients were of the Mo-category. The pelvic lymph nodes received a total dose of 2 Gy X 25 by means of an anterior and posterior radiation field. The prostatic gland was irradiated by an additional booster dose of 2 Gy X 10 given to a perineal field. Twenty-four patients have relapsed after their prostatic radiotherapy, only three of them within the irradiated area. For the patients with T0-T2 tumors, the 5-year crude survival was 69%, whereas it was only 37% for patients with T3 tumors. Thirty-five patients developed intestinal (26 patients) and/or urogenital (23 patients) radiation side effects. In three patients a colostomy had to be performed owing to rectal stricture or fistula. The poor survival after radiotherapy in the present series is probably due to a high incidence of unrecognized pelvic lymph node metastases. In the future only prostatic cancer patients without pelvic lymph node spread will be considered candidates for definitive radiotherapy. An optimal radiation technique is mandatory in order to avoid major radiotherapy-induced toxicity.

  18. Method comparison of ultrasound and kilovoltage x-ray fiducial marker imaging for prostate radiotherapy targeting

    NASA Astrophysics Data System (ADS)

    Fuller, Clifton David; Thomas, Charles R., Jr.; Schwartz, Scott; Golden, Nanalei; Ting, Joe; Wong, Adrian; Erdogmus, Deniz; Scarbrough, Todd J.

    2006-10-01

    Several measurement techniques have been developed to address the capability for target volume reduction via target localization in image-guided radiotherapy; among these have been ultrasound (US) and fiducial marker (FM) software-assisted localization. In order to assess interchangeability between methods, US and FM localization were compared using established techniques for determination of agreement between measurement methods when a 'gold-standard' comparator does not exist, after performing both techniques daily on a sequential series of patients. At least 3 days prior to CT simulation, four gold seeds were placed within the prostate. FM software-assisted localization utilized the ExacTrac X-Ray 6D (BrainLab AG, Germany) kVp x-ray image acquisition system to determine prostate position; US prostate targeting was performed on each patient using the SonArray (Varian, Palo Alto, CA). Patients were aligned daily using laser alignment of skin marks. Directional shifts were then calculated by each respective system in the X, Y and Z dimensions before each daily treatment fraction, previous to any treatment or couch adjustment, as well as a composite vector of displacement. Directional shift agreement in each axis was compared using Altman-Bland limits of agreement, Lin's concordance coefficient with Partik's grading schema, and Deming orthogonal bias-weighted correlation methodology. 1019 software-assisted shifts were suggested by US and FM in 39 patients. The 95% limits of agreement in X, Y and Z axes were ±9.4 mm, ±11.3 mm and ±13.4, respectively. Three-dimensionally, measurements agreed within 13.4 mm in 95% of all paired measures. In all axes, concordance was graded as 'poor' or 'unacceptable'. Deming regression detected proportional bias in both directional axes and three-dimensional vectors. Our data suggest substantial differences between US and FM image-guided measures and subsequent suggested directional shifts. Analysis reveals that the vast majority of

  19. Evaluating changes in tumor volume using magnetic resonance imaging during the course of radiotherapy treatment of high-grade gliomas: Implications for conformal dose-escalation studies

    SciTech Connect

    Tsien, Christina . E-mail: ctsien@umich.edu; Gomez-Hassan, Diana; Haken, Randall K. ten; Tatro, Daniel C.; Junck, L.; Chenevert, T.L.; Lawrence, T.

    2005-06-01

    tumors had tumor progression, based on MRI obtained during Week 3 of radiotherapy. Median increase in GTV (Week 3) was 11.7 cc (range, 9.8-21.3). Retrospective DVH analysis of PTV (Pre-Rx) and PTV (Week 3) demonstrated a decrease in V{sub 95%}(PTV volume receiving 95% of the prescribed dose) in those 3 cases. Conclusions: Routine MR imaging during radiotherapy may be essential in ensuring tumor coverage if highly conformal radiotherapy techniques such as stereotactic boost and intensity-modulated radiotherapy are used in dose-escalation trials that utilize smaller treatment margins.

  20. Stereotactic Body Radiation Therapy for Prostate Cancer: Review of Experience of a Multicenter Phase I/II Dose-Escalation Study

    PubMed Central

    Kim, D. W. Nathan; Straka, Christopher; Cho, L. Chinsoo; Timmerman, Robert D.

    2014-01-01

    Introduction: Stereotactic body radiation therapy (SBRT) is an area of active investigation for treatment of prostate cancer. In our phase I dose-escalation study, maximum-tolerated dose (MTD) was not reached, and subsequently phase II study has been completed. The purpose of this article is to review our experiences of dose-escalated SBRT for localized prostate cancer. Methods and materials: Patients enrolled to phase I/II study from 2006 to 2011 were reviewed. Prescription dose groups were 45, 47.5, and 50 Gray (Gy) in five fractions over 2.5 weeks. Toxicity and quality of life questionnaire data were collected and analyzed. Descriptive statistics were obtained in the form of means, medians, and ranges for the continuous variables, and frequencies and percentages for the categoric variables. Results: Ninety-one patients were enrolled from five institutions. Median follow-up for prostate specific antigen (PSA) evaluation was 42 months. PSA control remains at 99%. While the MTD was not reached in the phase I study, excess high grade rectal toxicity (10.6%) was noted in the phase II study. The 13 patients treated to 50 Gy in the phase I study that did not have high grade rectal toxicity, in retrospect met these parameters and have not had further events on longer follow-up. Conclusion: Prostate specific antigen control rate, even for patients with intermediate risk, is thus far excellent at these dose levels. This study provides a platform for exploration of SBRT based clinical trials aimed at optimizing outcome for intermediate and high risk patients. High grade toxicities specifically related to the rectum were observed in a small but meaningful minority at the highest dose level. Dose constraints based on physiologic parameters have been defined to mitigate this risk, and strategies to minimize rectal exposure to such doses are being explored. PMID:25505731

  1. Surgical Management of Ureteral Strictures Arising From Radiotherapy for Prostate Cancer

    PubMed Central

    Orchard, J.; Tward, Jonathan D.; Lenherr, Sara; Hotaling, James M.; Brant, William O.; Myers, Jeremy B.

    2016-01-01

    Ureteral strictures arising from radiotherapy for the treatment of prostate cancer are rare. We describe four cases of these ureteral strictures emphasizing pre-operative factors that may have contributed to development of the strictures, their ultimate surgical management, and the patients' short-term outcomes. PMID:27175344

  2. Relationship between delay in radiotherapy and biochemical control in prostate cancer

    SciTech Connect

    Kwan, Winkle . E-mail: wkwan@bccancer.bc.ca; Pickles, Tom; Duncan, Graeme; Liu, Mitchell; Paltiel, Chuck

    2006-11-01

    Purpose: The aim of this study was to investigate whether a delay in radiotherapy is associated with a poorer biochemical control for prostate cancer. Methods: The time to treatment (TTT) from diagnosis of prostate cancer to radiotherapy was analyzed with respect to prostate-specific antigen (PSA) control in 1024 hormone-naive patients. The Kaplan-Meier PSA control curves for patients with TTT less than the median were compared with those for patients with TTT greater than the median in 3 predefined risk groups. Statistical significant differences in PSA control were further analyzed using Cox multivariate analysis with pretreatment PSA, Gleason score, T stage, and radiotherapy dose as covariates. Results: The median TTT and median follow-up are 3.7 months and 49 months respectively. Patients with a longer TTT have a statistically significant better PSA control than patients with a shorter TTT if they have intermediate- or high-risk disease. However in multivariate analysis TTT was not found to be significant in predicting PSA control, with pretreatment PSA and Gleason score emerging as highly significant in predicting PSA failure in both intermediate- and high-risk disease. Conclusion: In this study in prostate cancer patients in British Columbia, there was no evidence that a longer time interval between diagnosis and radiotherapy was associated with poorer PSA control.

  3. Interfraction Prostate Movement in Bone Alignment After Rectal Enema for Radiotherapy

    PubMed Central

    Seo, Young Eun; Kim, Tae Hyo; Lee, Ki Soo; Cho, Won Yeol; Lee, Hyung-Sik; Hur, Won-Joo

    2014-01-01

    Purpose To assess the effect of a rectal enema on interfraction prostate movement in bone alignment (BA) for prostate radiotherapy (RT), we analyzed the spatial difference in prostates in a bone-matched setup. Materials and Methods We performed BA retrospectively with data from prostate cancer patients who underwent image-guided RT (IGRT). The prostate was identified with implanted fiducial markers. The setup for the IGRT was conducted with the matching of three fiducial markers on RT planning computed tomography images and those on two oblique kV x-ray images. Offline BA was performed at the same position. The coordinates of a virtual prostate in BA and a real prostate were obtained by use of the ExaxTrac/NovalisBody system, and the distance between them was calculated as the spatial difference. Interfraction prostate displacement was drawn from the comparison of the spatial differences. Results A total of 15 patients with localized prostate cancer treated with curative hypofractionated IGRT were enrolled. A total of 420 fractions were analyzed. The mean of the interfraction prostate displacements after BA was 3.12±2.00 mm (range, 0.20-10.53 mm). The directional difference was profound in the anterior-posterior and supero-inferior directions (2.14±1.73 mm and 1.97±1.44 mm, respectively) compared with the right-left direction (0.26±0.22 mm, p<0.05). The required margin around the clinical target volume was 4.97 mm with the formula of van Herk et al. Conclusions The interfraction prostate displacement was less frequent when a rectal enema was performed before the procedure. A rectal enema can be used to reduce interfraction prostate displacement and resulting clinical target volume-to-planning target volume margin. PMID:24466393

  4. Potential of Adaptive Radiotherapy to Escalate the Radiation Dose in Combined Radiochemotherapy for Locally Advanced Non-Small Cell Lung Cancer

    SciTech Connect

    Guckenberger, Matthias; Wilbert, Juergen; Richter, Anne; Baier, Kurt; Flentje, Michael

    2011-03-01

    Purpose: To evaluate the potential of adaptive radiotherapy (ART) for advanced-stage non-small cell lung cancer (NSCLC) in terms of lung sparing and dose escalation. Methods and Materials: In 13 patients with locally advanced NSCLC, weekly CT images were acquired during radio- (n = 1) or radiochemotherapy (n = 12) for simulation of ART. Three-dimensional (3D) conformal treatment plans were generated: conventionally fractionated doses of 66 Gy were prescribed to the planning target volume without elective lymph node irradiation (Plan{sub 3}D). Using a surface-based algorithm of deformable image registration, accumulated doses were calculated in the CT images acquired during the treatment course (Plan{sub 4}D). Field sizes were adapted to tumor shrinkage once in week 3 or 5 and twice in weeks 3 and 5. Results: A continuous tumor regression of 1.2% per day resulted in a residual gross tumor volume (GTV) of 49% {+-} 15% after six weeks of treatment. No systematic differences between Plan{sub 3}D and Plan{sub 4}D were observed regarding doses to the GTV, lung, and spinal cord. Plan adaptation to tumor shrinkage resulted in significantly decreased lung doses without compromising GTV coverage: single-plan adaptation in Week 3 or 5 and twice-plan adaptation in Weeks 3 and 5 reduced the mean lung dose by 5.0% {+-} 4.4%, 5.6% {+-} 2.9% and 7.9% {+-} 4.8%, respectively. This lung sparing with twice ART allowed an iso-mean lung dose escalation of the GTV dose from 66.8 Gy {+-} 0.8 Gy to 73.6 Gy {+-} 3.8 Gy. Conclusions: Adaptation of radiotherapy to continuous tumor shrinkage during the treatment course reduced doses to the lung, allowed significant dose escalation and has the potential of increased local control.

  5. External beam radiotherapy for palliation of pain from metastatic carcinoma of the prostate

    SciTech Connect

    Benson, R.C. Jr.; Hasan, S.M.; Jones, A.G.; Schlise, S.

    1982-01-01

    Radiotherapy often is used for palliation of bone pain from metastatic cancer of the prostate but an objective evaluation of its efficacy in a large series of patients is unavailable. We report the results of external beam irradiation in 62 patients who had bone pain secondary to stage D carcinoma of the prostate. The variables used to judge pain before and after radiotherapy included subjective evaluation of pain, status of activity and quantitation of analgesic use. Complete relief of pain was achieved in 26 patients (42 per cent), partial relief in 22 (35 per cent) and no relief in 14 (23 per cent). On the basis of our experience external beam irradiation is useful palliative therapy for pain from metastatic cancer of the prostate.

  6. Prostate-specific antigen kinetics following hypofractionated stereotactic body radiotherapy boost as post-external beam radiotherapy versus conventionally fractionated external beam radiotherapy for localized prostate cancer

    PubMed Central

    Phak, Jeong Hoon; Kim, Hun Jung; Kim, Woo Chul

    2015-01-01

    Background Stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for localized prostate cancer. The purpose of this study was to compare the prostate-specific antigen (PSA) kinetics between conventionally fractionated external beam radiotherapy (CF-EBRT) and SBRT boost after whole pelvis EBRT (WP-EBRT) in localized prostate cancer. Methods A total of 77 patients with localized prostate cancer [T-stage, T1–T3; Gleason score (GS) 5–9; PSA < 20 ng/mL] were enrolled. A total of 35 patients were treated with SBRT boost (21 Gy in 3 fractions) after WP-EBRT and 42 patients were treated with CF-EBRT (45 Gy WP-EBRT and boost of 25.2–30.6 Gy in 1.8-Gy fractions). PSA nadir and rate of change in PSA (slope) were calculated and compared. Results With a median follow-up of 52.4 months (range, 14–74 months), the median PSA nadir and slope for SBRT boost were 0.29 ng/mL and −0.506, −0.235, −0.129, and −0.092 ng/mL/mo, respectively, for durations of 1 year, 2 years, 3 years, and 4 years postradiotherapy. Similarly, for CF-EBRT, the median PSA nadir and slopes were 0.39 ng/mL and −0.720 ng/mL/mo, −0.204 ng/mL/mo, −0.121 ng/mL/mo, and −0.067 ng/mL/mo, respectively. The slope of CF-EBRT was significantly different with a greater median rate of change for 1 year postradiotherapy than that of SBRT boost (P = 0.018). Contrastively, the slopes of SBRT boost for durations of 2 years, 3 years, and 4 years tended to be continuously greater than that of CF-EBRT. The significantly lower PSA nadir was observed in SBRT boost (median nadir 0.29 ng/mL) compared with CF-EBRT (median nadir 0.35 ng/mL, P = 0.025). Five-year biochemical failure (BCF) free survival was 94.3% for SBRT boost and 78.6% for CF-EBRT (P = 0.012). Conclusion Patients treated with SBRT boost after WP-EBRT experienced a lower PSA nadir and there tended to be a continuously greater rate of decline of PSA for durations of 2 years, 3 years, and

  7. Hypofractionated intensity-modulated radiotherapy in patients with localized prostate cancer: a preliminary study

    PubMed Central

    Kang, Hye Jin; Son, Seok Hyun; Kim, Myungsoo; Jo, In Young; Lee, So Jung; Lee, Dong Hwan; Suh, Hong Jin; Choi, Yong Sun

    2016-01-01

    Purpose The aim of this work was to assess the efficacy and tolerability of hypofractionated intensity-modulated radiotherapy (IMRT) in patients with localized prostate cancer. Materials and Methods Thirty-nine patients who received radical hypofractionated IMRT were retrospectively reviewed. Based on a pelvic lymph node involvement risk of 15% as the cutoff value, we decided whether to deliver treatment prostate and seminal vesicle only radiotherapy (PORT) or whole pelvis radiotherapy (WPRT). Sixteen patients (41%) received PORT with prostate receiving 45 Gy in 4.5 Gy per fraction in 2 weeks and the other 23 patients (59%) received WPRT with the prostate receiving 72 Gy in 2.4 Gy per fraction in 6 weeks. The median equivalent dose in 2 Gy fractions to the prostate was 79.9 Gy based on the assumption that the α/β ratio is 1.5 Gy. Results The median follow-up time was 38 months (range, 4 to 101 months). The 3-year biochemical failure-free survival rate was 88.2%. The 3-year clinical failure-free and overall survival rates were 94.5% and 96.3%, respectively. The rates of grade 2 acute genitourinary (GU) and gastrointestinal (GI) toxicities were 20.5% and 12.8%, respectively. None of the patients experienced grade ≥3 acute GU and GI toxicities. The grade 2-3 late GU and GI toxicities were found in 8.1% and 5.4% of patients, respectively. No fatal late toxicity was observed. Conclusion Favorable biochemical control with low rates of toxicity was observed after hypofractionated IMRT, suggesting that our radiotherapy schedule can be an effective treatment option in the treatment of localized prostate cancer. PMID:27104166

  8. High-Dose Radiotherapy With or Without Androgen Deprivation Therapy for Intermediate-Risk Prostate Cancer: Cancer Control and Toxicity Outcomes

    SciTech Connect

    Edelman, Scott; Liauw, Stanley L.; Rossi, Peter J.; Cooper, Sherrie; Jani, Ashesh B.

    2012-08-01

    Purpose: To evaluate the impact of short-course androgen deprivation therapy (ADT) on cancer control outcomes and toxicity in intermediate-risk prostate cancer treated with dose-escalated external beam radiotherapy (high-dose radiotherapy [HDRT]). Methods and Materials: Demographic, disease, and treatment characteristics of prostate cancer patients at 2 institution consortiums were charted. Of 296 men with intermediate-risk prostate cancer (defined as {>=}T2b, prostate-specific antigen level >10 ng/mL, or Gleason score [GS] of 7, with none of the following: {>=}T3, prostate-specific antigen level >20 ng/mL, GS {>=}8, or positive nodes) treated with HDRT to a dose of 72 Gy or greater, 123 received short-course ADT and 173 did not. Univariate and multivariate analyses on biochemical failure-free survival (BFFS) (including subset analysis by disease factors) and on overall survival (OS) were performed, as were comparisons of gastrointestinal (GI) and genitourinary (GU) toxicity rates. Results: For the whole group, the median dose was 75.6 Gy; the minimum follow-up was 2 years, and the median follow-up was 47.4 months. For ADT vs. no ADT, the 5-year BFFS rate was 86% vs. 79% (p = 0.138) and the 5-year OS rate was 87% vs. 80% (p = 0.159). On multivariate analysis, percent positive cores (PPC) (p = 0.002) and GS (p = 0.008) were significantly associated with BFFS, with ADT showing a trend (p = 0.055). The impact of ADT was highest in the subsets with PPC greater than 50% (p = 0.019), GS 4+3 (p = 0.078), and number of risk factors greater than 1 (p = 0.022). Only intensity-modulated radiotherapy use (p = 0.012) and GS (p = 0.023) reached significance for OS, and there were no significant differences in GU or GI toxicity. Conclusions: Although the use of ADT with HDRT did not influence BFFS, our study suggests a benefit in patients with PPC greater than 50%, GS 4+3, or multiple risk factors. No OS benefit was shown, and ADT was not associated with additional radiotherapy

  9. Does Hormone Therapy Reduce Disease Recurrence in Prostate Cancer Patients Receiving Dose-Escalated Radiation Therapy? An Analysis of Radiation Therapy Oncology Group 94-06

    SciTech Connect

    Valicenti, Richard K.; Bae, Kwounghwa; Michalski, Jeff; Sandler, Howard; Shipley, William; Lin, Alex; Cox, James

    2011-04-01

    Purpose: The purpose of this study was to evaluate the effect on freedom from biochemical failure (bNED) or disease-free survival (DFS) by adding hormone therapy (HT) to dose-escalated radiation therapy (HDRT). Methods and Materials: We used 883 analyzable prostate cancer patients who enrolled on Radiation Therapy Oncology Group (RTOG) 94-06, a Phase I/II dose escalation trial, and whose mean planning target volume dose exceeded 73.8 Gy (mean, 78.5 Gy; maximum, 84.3 Gy). We defined biochemical failure according to the Phoenix definition. Results: A total of 259 men started HT 2 to 3 months before HDRT, but not longer than 6 months, and 66 men with high-risk prostate cancer received HT for a longer duration. At 5 years, the biochemical failure rates after HDRT alone were 12%, 18%, and 29% for low-, intermediate-, and high-risk patients, respectively (p < 0.0001). Cox proportional hazards regression analysis adjusted for covariates revealed that pretreatment PSA level was a significant factor, whereas risk group, Gleason score, T-stage, and age were not. When the patients were stratified by risk groups, the Cox proportion hazards regression model (after adjusting for pretreatment PSA, biopsy Gleason score, and T stage) did not reveal a significant effect on bNED or DFS by adding HT to HDRT Conclusion: The addition of HT did not significantly improve bNED survival or DFS in all prostate cancer patients receiving HDRT, but did approach significance in high-risk patient subgroup. The result of this study is hypothesis generating and requires testing in a prospective randomized trial.

  10. The importance of prostate bed tilt during postprostatectomy intensity-modulated radiotherapy

    SciTech Connect

    Bell, Linda J.; Cox, Jennifer; Eade, Thomas; Rinks, Marianne; Kneebone, Andrew

    2014-10-01

    Variations in rectal and bladder filling can create a tilt of the prostate bed, which generates the potential for a geographic miss during postprostatectomy radiotherapy. The aim of this study is to assess the effect that bladder and rectum filling has on planning target volume angle, to determine a method to assess prostate bed tilt leading to potential geographic miss, and to discuss possible implementation issues. The cone-beam computed tomography images (n = 377) of 40 patients who received postprostatectomy radiotherapy with intensity-modulated radiotherapy were reviewed. The amount of tilt in the prostate bed was defined as the angle change between 2 surgical clips, one in the upper prostate bed and another in the lower. A potential geographic miss was defined as movement of any clip of more than 1 cm in any direction or 0.5 cm posteriorly when aligned to bone anatomy. Variations in bladder and rectum size were correlated with the degree of prostate bed tilt, and the rate of potential geographic miss was determined. A possible clinical use of prostate bed tilt was then assessed for different imaging techniques. A tilt of more than 10° was seen in 20.2% of images, which resulted in a 57.9% geographic miss rate of the superior clip. When tilt remained within 10°, there was only a 9% rate of geographic miss. Potential geographic miss of the inferior surgical clip was rare, occurring in only 1.9% of all images reviewed. The most common occurrence when the prostate bed tilt increased by more than 10° was a smaller bladder and larger rectum (6.4% of all images). The most common occurrence when the prostate bed tilt decreased by more than 10° was a larger bladder and smaller rectum (1.3% of all images). Significant prostate bed tilt (>± 10°) occurred in more than 20% of images, creating a 58% rate of geographic miss. Greatest prostate bed tilt occurred when the bladder size increased or reduced by more than 2 cm or the superior rectum size increased by more

  11. Radiotherapy Combined With Androgen Deprivation for Bone Oligometastases After Primary Curative Radiotherapy for Prostate Cancer

    PubMed Central

    Wu, Jun-Xin; Lin, Li-Mei; He, Jun-Yan; Hong, Liang; Li, Jin-Luan

    2016-01-01

    Abstract To evaluate the effects and toxicity of radiotherapy (RT) combined with androgen deprivation (AD) for bone oligometastases after primary curative RT for prostate cancer (PCa). We retrospectively analyzed 30 consecutively treated PCa patients with bone oligometastases from April 2005 to July 2014. All patients underwent RT combined with AD for oligometastatic bones after curative RT for PCa. Measured outcomes included overall survival (OS) rate, local control (LC), progression-free survival (PFS), pain relief, and toxicities. Statistical analysis was performed with SPSS17.0. The median follow-up was 32.5 months (range, 0.6–50.3). The 3-year PFS and OS rates were 22.8% (95% CI, 13.4–37.5%) and 69% (95% CI, 51.7–81.1%), respectively. The number of bone oligometastases and RT schedule were found to be significantly associated with OS on univariate analysis (P < 0.05, respectively). The 3-year OS for patients with 1 and >1 metastases was 78.8% versus 42.2%, respectively (P = 0.037). The long-course RT was associated with better 3-year OS compared with short-course (76.4% vs 44.1%, P = 0.03). A total of 15 (83.3%, 15/18) patients achieved pain relief. No grade 3 toxicity was observed. Long-course RT combined with ADT was effective and well-tolerated in PCa patients with bone oligometastases after curative RT for PCa. Further randomized controlled trials are needed to corroborate the findings. PMID:26871838

  12. Predictors of Rectal Tolerance Observed in a Dose-Escalated Phase 1-2 Trial of Stereotactic Body Radiation Therapy for Prostate Cancer

    SciTech Connect

    Kim, D.W. Nathan; Cho, L. Chinsoo; Straka, Christopher; Christie, Alana; Lotan, Yair; Pistenmaa, David; Kavanagh, Brian D.; Nanda, Akash; Kueplian, Patrick; Brindle, Jeffrey; Cooley, Susan; Perkins, Alida; Raben, David; Xie, Xian-Jin; Timmerman, Robert D.

    2014-07-01

    Purpose: To convey the occurrence of isolated cases of severe rectal toxicity at the highest dose level tested in 5-fraction stereotactic body radiation therapy (SBRT) for localized prostate cancer; and to rationally test potential causal mechanisms to guide future studies and experiments to aid in mitigating or altogether avoiding such severe bowel injury. Methods and Materials: Clinical and treatment planning data were analyzed from 91 patients enrolled from 2006 to 2011 on a dose-escalation (45, 47.5, and 50 Gy in 5 fractions) phase 1/2 clinical study of SBRT for localized prostate cancer. Results: At the highest dose level, 6.6% of patients treated (6 of 91) developed high-grade rectal toxicity, 5 of whom required colostomy. Grade 3+ delayed rectal toxicity was strongly correlated with volume of rectal wall receiving 50 Gy >3 cm{sup 3} (P<.0001), and treatment of >35% circumference of rectal wall to 39 Gy (P=.003). Grade 2+ acute rectal toxicity was significantly correlated with treatment of >50% circumference of rectal wall to 24 Gy (P=.010). Conclusion: Caution is advised when considering high-dose SBRT for treatment of tumors near bowel structures, including prostate cancer. Threshold dose constraints developed from physiologic principles are defined, and if respected can minimize risk of severe rectal toxicity.

  13. Second malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis

    PubMed Central

    Wallis, Christopher J D; Mahar, Alyson L; Choo, Richard; Herschorn, Sender; Kodama, Ronald T; Shah, Prakesh S; Danjoux, Cyril; Narod, Steven A

    2016-01-01

    Objective To determine the association between exposure to radiotherapy for the treatment of prostate cancer and subsequent second malignancies (second primary cancers). Design Systematic review and meta-analysis of observational studies. Data sources Medline and Embase up to 6 April 2015 with no restrictions on year or language. Study selection Comparative studies assessing the risk of second malignancies in patients exposed or unexposed to radiotherapy in the course of treatment for prostate cancer were selected by two reviewers independently with any disagreement resolved by consensus. Data extraction and synthesis Two reviewers independently extracted study characteristics and outcomes. Risk of bias was assessed with the Newcastle-Ottawa scale. Outcomes were synthesized with random effects models and Mantel-Haenszel weighting. Unadjusted odds ratios and multivariable adjusted hazard ratios, when available, were pooled. Main outcome measures Second cancers of the bladder, colorectal tract, rectum, lung, and hematologic system. Results Of 3056 references retrieved, 21 studies were selected for analysis. Most included studies were large multi-institutional reports but had moderate risk of bias. The most common type of radiotherapy was external beam; 13 studies used patients treated with surgery as controls and eight used patients who did not undergo radiotherapy as controls. The length of follow-up among studies varied. There was increased risk of cancers of the bladder (four studies; adjusted hazard ratio 1.67, 95% confidence interval 1.55 to 1.80), colorectum (three studies; 1.79, 1.34 to 2.38), and rectum (three studies; 1.79, 1.34 to 2.38), but not cancers of the hematologic system (one study; 1.64, 0.90 to 2.99) or lung (two studies; 1.45, 0.70 to 3.01), after radiotherapy compared with the risk in those unexposed to radiotherapy. The odds of a second cancer varied depending on type of radiotherapy: treatment with external beam radiotherapy was

  14. Continued Benefit to Androgen Deprivation Therapy for Prostate Cancer Patients Treated With Dose-Escalated Radiation Therapy Across Multiple Definitions of High-Risk Disease

    SciTech Connect

    Stenmark, Matthew H.; Blas, Kevin; Halverson, Schuyler; Sandler, Howard M.; Feng, Felix Y.; Hamstra, Daniel A.

    2011-11-15

    Purpose: To analyze prognostic factors in patients with high-risk prostate cancer treated with dose-escalated external-beam radiation therapy (EBRT) and androgen deprivation (ADT). Methods and Materials: Between 1998 and 2008 at University of Michigan Medical Center, 718 men were consecutively treated with EBRT to at least 75 Gy. Seven definitions of high-risk prostate cancer, applying to 11-33% of patients, were evaluated. Biochemical failure (BF), salvage ADT use, metastatic progression, and prostate cancer-specific mortality (PCSM) were estimated by the Kaplan-Meier method and Cox proportional hazards regression. Results: Each high-risk definition was associated with increased BF (hazard ratio [HR] 2.8-3.9, p < 0.0001), salvage ADT use (HR 3.9-6.3, p < 0.0001), metastasis (HR 3.7-6.6, p < 0.0001), and PCSM (HR 3.7-16.2, p < 0.0001). Furthermore, an increasing number of high-risk features predicted worse outcome. Adjuvant ADT yielded significant reductions in both metastases (HR 0.19-0.38, p < 0.001) and PCSM (HR 0.38-0.50, p < 0.05) for all high-risk definitions (with the exception of clinical Stage T3-4 disease) but improved BF only for those with elevated Gleason scores (p < 0.03, HR 0.25-0.48). When treated with ADT and dose-escalated EBRT, patients with Gleason scores 8 to 10, without other high-risk features, had 8-year freedom from BF of 74%, freedom from distant metastases of 93%, and cause-specific survival of 92%, with salvage ADT used in 16% of patients. Conclusion: Adjuvant ADT results in a significant improvement in clinical progression and PCSM across multiple definitions of high-risk disease even with dose-escalated EBRT. There is a subset of patients, characterized by multiple high-risk features or the presence of Gleason Pattern 5, who remain at significant risk for metastasis and PCSM despite current treatment.

  15. Radiation-induced complications in prostate cancer patients treated with radiotherapy

    SciTech Connect

    Azuddin, A. Yusof; Rahman, I. Abdul; Mohamed, F.; Siah, N. J.; Saadc, M.; Ismail, F.

    2014-09-03

    The purpose of the study is to determine the relationship between radiation-induced complications with dosimetric and radiobiological parameters for prostate cancer patients that underwent the conformal radiotherapy treatment. 17 prostate cancer patients that have been treated with conformal radiotherapy were retrospectively analysed. The dosimetric data was retrieved in the form of dose-volume histogram (DVH) from Radiotherapy Treatment Planning System. The DVH was utilised to derived Normal Tissue Complication Probability (NTCP) in radiobiological data. Follow-up data from medical records were used to grade the occurrence of acute gastrointestinal (GI) and genitourinary (GU) complications using Radiation Therapy Oncology Group (RTOG) scoring system. The chi-square test was used to determine the relationship between radiation-induced complication with dosimetric and radiobiological parameters. 8 (47%) and 7 (41%) patients were having acute GI and GU complications respectively. The acute GI complication can be associated with V60{sub rectum}, rectal mean dose and NTCP{sub rectum} with p-value of 0.016, 0.038 and 0.049 respectively. There are no significant relationships of acute GU complication with dosimetric and radiobiological variables. Further study can be done by increase the sample size and follow up duration for deeper understanding of the factors that effecting the GU and GI complication in prostate cancer radiotherapy.

  16. Radiation-induced complications in prostate cancer patients treated with radiotherapy

    NASA Astrophysics Data System (ADS)

    Azuddin, A. Yusof; Rahman, I. Abdul; Siah, N. J.; Mohamed, F.; Saadc, M.; Ismail, F.

    2014-09-01

    The purpose of the study is to determine the relationship between radiation-induced complications with dosimetric and radiobiological parameters for prostate cancer patients that underwent the conformal radiotherapy treatment. 17 prostate cancer patients that have been treated with conformal radiotherapy were retrospectively analysed. The dosimetric data was retrieved in the form of dose-volume histogram (DVH) from Radiotherapy Treatment Planning System. The DVH was utilised to derived Normal Tissue Complication Probability (NTCP) in radiobiological data. Follow-up data from medical records were used to grade the occurrence of acute gastrointestinal (GI) and genitourinary (GU) complications using Radiation Therapy Oncology Group (RTOG) scoring system. The chi-square test was used to determine the relationship between radiation-induced complication with dosimetric and radiobiological parameters. 8 (47%) and 7 (41%) patients were having acute GI and GU complications respectively. The acute GI complication can be associated with V60rectum, rectal mean dose and NTCPrectum with p-value of 0.016, 0.038 and 0.049 respectively. There are no significant relationships of acute GU complication with dosimetric and radiobiological variables. Further study can be done by increase the sample size and follow up duration for deeper understanding of the factors that effecting the GU and GI complication in prostate cancer radiotherapy.

  17. Cross-Linked Hyaluronan Gel Reduces the Acute Rectal Toxicity of Radiotherapy for Prostate Cancer

    SciTech Connect

    Wilder, Richard B.; Barme, Greg A.; Gilbert, Ronald F.; Holevas, Richard E.; Kobashi, Luis I.; Reed, Richard R.; Solomon, Ronald S.; Walter, Nancy L.; Chittenden, Lucy; Mesa, Albert V.; Agustin, Jeffrey; Lizarde, Jessica; Macedo, Jorge; Ravera, John; Tokita, Kenneth M.

    2010-07-01

    Purpose: To prospectively analyze whether cross-linked hyaluronan gel reduces the mean rectal dose and acute rectal toxicity of radiotherapy for prostate cancer. Methods and Materials: Between September 2008 and March 2009, we transperitoneally injected 9mL of cross-linked hyaluronan gel (Hylaform; Genzyme Corporation, Cambridge, MA) into the anterior perirectal fat of 10 early-stage prostate cancer patients to increase the separation between the prostate and rectum by 8 to 18mm at the start of radiotherapy. Patients then underwent high-dose rate brachytherapy to 2,200cGy followed by intensity-modulated radiation therapy to 5,040cGy. We assessed acute rectal toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grading scheme. Results: Median follow-up was 3 months. The anteroposterior dimensions of Hylaform at the start and end of radiotherapy were 13 {+-} 3mm (mean {+-} SD) and 10 {+-} 4mm, respectively. At the start of intensity-modulated radiation therapy, daily mean rectal doses were 73 {+-} 13cGy with Hylaform vs. 106 {+-} 20cGy without Hylaform (p = 0.005). There was a 0% incidence of National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 Grade 1, 2, or 3 acute diarrhea in 10 patients who received Hylaform vs. a 29.7% incidence (n = 71) in 239 historical controls who did not receive Hylaform (p = 0.04). Conclusions: By increasing the separation between the prostate and rectum, Hylaform decreased the mean rectal dose. This led to a significant reduction in the acute rectal toxicity of radiotherapy for prostate cancer.

  18. Salvage Hypofractionated Radiotherapy for Biochemically Recurrent Prostate Cancer After Radical Prostatectomy

    SciTech Connect

    Wong, Gordon W.; Palazzi-Churas, Kerrin L.; Jarrard, David F.; Paolone, David R.; Graf, Andrew K.; Hedican, Sean P.; Wegenke, John D.; Ritter, Mark A.

    2008-02-01

    Purpose: To evaluate whether hypofractionation is well tolerated and to preliminarily assess biochemical control of this regimen in a postprostatectomy, salvage setting. Methods and Materials: A retrospective analysis was performed in 50 patients treated between May 2003 and December 2005 with hypofractionated radiotherapy for biochemical recurrence after radical prostatectomy. Radiotherapy was prescribed to the prostatic fossa to 65-70 Gy in 26-28 fractions of 2.5 Gy each, using intensity-modulated radiotherapy with daily image localization. Toxicities were scored using a modified Radiation Therapy Oncology Group scale and the Fox Chase modification of Late Effects Normal Tissue scale. The median follow-up was 18.9 months (range, 5.3-35.9). Results: No Grade 3 or greater acute or late toxicities were observed. Grade 2 toxicities included four acute genitourinary, one acute gastrointestinal, two late genitourinary, and two late gastrointestinal toxicities. Of the 50 patients, 39 demonstrated a continuous biochemical response after salvage therapy, 3 had an initial response before prostate-specific antigen failure, and 7 had prostate-specific antigen progression, 1 of whom died of progressive metastatic disease. Finally, 1 patient discontinued therapy because of the diagnosis of a metachronous pancreatic cancer and died without additional prostate cancer follow-up. All remaining patients were alive at the last follow-up visit. A lower presalvage prostate-specific antigen level was the only significant prognostic factor for improved biochemical control. The estimated actuarial biochemical control rate at 2 years was 72.9%. Conclusions: The toxicity and early biochemical response rates were consistent with expectations from conventional fractionation. Additional follow-up is required to better document the biochemical control, but these results suggest that hypofractionation is a well-tolerated approach for salvage radiotherapy.

  19. The predictive value of 2-year posttreatment biopsy after prostate cancer radiotherapy for eventual biochemical outcome

    SciTech Connect

    Vance, Waseet; Tucker, Susan L.; Crevoisier, Renaud de; Kuban, Deborah A.; Cheung, M. Rex . E-mail: mrcheung@mdanderson.org

    2007-03-01

    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.

  20. Retrospective Evaluation Reveals That Long-term Androgen Deprivation Therapy Improves Cause-Specific and Overall Survival in the Setting of Dose-Escalated Radiation for High-Risk Prostate Cancer

    SciTech Connect

    Feng, Felix Y.; Blas, Kevin; Olson, Karin; Stenmark, Matthew; Sandler, Howard; Hamstra, Daniel A.

    2013-05-01

    Purpose: To evaluate the role of androgen deprivation therapy (ADT) and duration for high-risk prostate cancer patients treated with dose-escalated radiation therapy (RT). Methods and Materials: A retrospective analysis of high-risk prostate cancer patients treated with dose-escalated RT (minimum 75 Gy) with or without ADT was performed. The relationship between ADT use and duration with biochemical failure (BF), metastatic failure (MF), prostate cancer-specific mortality (PCSM), non-prostate cancer death (NPCD), and overall survival (OS) was assessed as a function of pretreatment characteristics, comorbid medical illness, and treatment using Fine and Gray's cumulative incidence methodology. Results: The median follow-up time was 64 months. In men with National Comprehensive Cancer Network defined high-risk prostate cancer treated with dose-escalated RT, on univariate analysis, both metastasis (P<.0001; hazard ratio 0.34; 95% confidence interval 0.18-0.67; cumulative incidence at 60 months 13% vs 35%) and PCSM (P=.015; hazard ratio 0.41; 95% confidence interval 0.2-1.0; cumulative incidence at 60 months 6% vs 11%) were improved with the use of ADT. On multivariate analysis for all high-risk patients, Gleason score was the strongest negative prognostic factor, and long-term ADT (LTAD) improved MF (P=.002), PCSM (P=.034), and OS (P=.001). In men with prostate cancer and Gleason scores 8 to 10, on multivariate analysis after adjustment for other risk features, there was a duration-dependent improvement in BF, metastasis, PCSM, and OS, all favoring LTAD in comparison with STAD or RT alone. Conclusion: For men with high-risk prostate cancer treated with dose-escalated EBRT, this retrospective study suggests that the combination of LTAD and RT provided a significant improvement in clinical outcome, which was especially true for those with Gleason scores of 8 to 10.

  1. Geometric-model-based segmentation of the prostate and surrounding structures for image-guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Tang, Xiaoli; Jeong, Yongwon; Radke, Richard J.; Chen, George T. Y.

    2004-01-01

    We present a computer vision tool to improve the clinical outcome of patients undergoing radiation therapy for prostate cancer by improving irradiation technique. While intensity modulated radiotherapy (IMRT) allows one to irradiate a specific region in the body with high accuracy, it is still difficult to know exactly where to aim the radiation beam on every day of the 30~40 treatments that are necessary. This paper presents a geometric model-based technique to accurately segment the prostate and other surrounding structures in a daily serial CT image, compensating for daily motion and shape variation. We first acquire a collection of serial CT scans of patients undergoing external beam radiotherapy, and manual segmentation of the prostate and other nearby structures by radiation oncologists. Then we train shape and local appearance models for the structures of interest. When new images are available, an iterative algorithm is applied to locate the prostate and surrounding structures automatically. Our experimental results show that excellent matches can be given to the prostate and surrounding structure. Convergence is declared after 10 iterations. For 256 x 256 images, the mean distance between the hand-segmented contour and the automatically estimated contour is about 1.5 pixels (2.44 mm), with variance about 0.6 pixel (1.24 mm).

  2. Influence of Antiflatulent Dietary Advice on Intrafraction Motion for Prostate Cancer Radiotherapy

    SciTech Connect

    Lips, Irene M.; Kotte, Alexis N.T.J.; Gils, Carla H. van; Leerdam, Monique E. van; Heide, Uulke A. van der; Vulpen, Marco van

    2011-11-15

    Purpose: To evaluate the effect of an antiflatulent dietary advice on the intrafraction prostate motion in patients treated with intensity-modulated radiotherapy (IMRT) for prostate cancer. Methods and Materials: Between February 2002 and December 2009, 977 patients received five-beam IMRT for prostate cancer to a dose of 76 Gy in 35 fractions combined with fiducial markers for position verification. In July 2008, the diet, consisting of dietary guidelines to obtain regular bowel movements and to reduce intestinal gas by avoiding certain foods and air swallowing, was introduced to reduce the prostate motion. The intrafraction prostate movement was determined from the portal images of the first segment of all five beams. Clinically relevant intrafraction motion was defined as {>=}50% of the fractions with an intrafraction motion outside a range of 3 mm. Results: A total of 739 patients were treated without the diet and 105 patients were treated with radiotherapy after introduction of the diet. The median and interquartile range of the average intrafraction motion per patient was 2.53 mm (interquartile range, 2.2-3.0) without the diet and 3.00 mm (interquartile range, 2.4-3.5) with the diet (p < .0001). The percentage of patients with clinically relevant intrafraction motion increased statistically significant from 19.1% without diet to 42.9% with a diet (odds ratio, 3.18; 95% confidence interval, 2.07-4.88; p < .0001). Conclusions: The results of the present study suggest that antiflatulent dietary advice for patients undergoing IMRT for prostate cancer does not reduce the intrafraction movement of the prostate. Therefore, antiflatulent dietary advice is not recommended in clinical practice for this purpose.

  3. MR-CT registration using a Ni-Ti prostate stent in image-guided radiotherapy of prostate cancer

    SciTech Connect

    Korsager, Anne Sofie; Ostergaard, Lasse Riis; Carl, Jesper

    2013-06-15

    Purpose: In image-guided radiotherapy of prostate cancer defining the clinical target volume often relies on magnetic resonance (MR). The task of transferring the clinical target volume from MR to standard planning computed tomography (CT) is not trivial due to prostate mobility. In this paper, an automatic local registration approach is proposed based on a newly developed removable Ni-Ti prostate stent.Methods: The registration uses the voxel similarity measure mutual information in a two-step approach where the pelvic bones are used to establish an initial registration for the local registration.Results: In a phantom study, the accuracy was measured to 0.97 mm and visual inspection showed accurate registration of all 30 data sets. The consistency of the registration was examined where translation and rotation displacements yield a rotation error of 0.41 Degree-Sign {+-} 0.45 Degree-Sign and a translation error of 1.67 {+-} 2.24 mm.Conclusions: This study demonstrated the feasibility for an automatic local MR-CT registration using the prostate stent.

  4. Assessment of Planning Target Volume Margins for Intensity-Modulated Radiotherapy of the Prostate Gland: Role of Daily Inter- and Intrafraction Motion

    SciTech Connect

    Tanyi, James A.; He, Tongming; Summers, Paige A.; Mburu, Ruth G.; Kato, Catherine M.; Rhodes, Stephen M.; Hung, Arthur Y.; Fuss, Martin

    2010-12-01

    Purpose: To determine planning target volume margins for prostate intensity-modulated radiotherapy based on inter- and intrafraction motion using four daily localization techniques: three-point skin mark alignment, volumetric imaging with bony landmark registration, volumetric imaging with implanted fiducial marker registration, and implanted electromagnetic transponders (beacons) detection. Methods and Materials: Fourteen patients who underwent definitive intensity-modulated radiotherapy for prostate cancer formed the basis of this study. Each patient was implanted with three electromagnetic transponders and underwent a course of 39 treatment fractions. Daily localization was based on three-point skin mark alignment followed by transponder detection and patient repositioning. Transponder positioning was verified by volumetric imaging with cone-beam computed tomography of the pelvis. Relative motion between the prostate gland and bony anatomy was quantified by offline analyses of daily cone-beam computed tomography. Intratreatment organ motion was monitored continuously by the Calypso (registered) System for quantification of intrafraction setup error. Results: As expected, setup error (that is, inter- plus intrafraction motion, unless otherwise stated) was largest with skin mark alignment, requiring margins of 7.5 mm, 11.4 mm, and 16.3 mm, in the lateral (LR), longitudinal (SI), and vertical (AP) directions, respectively. Margin requirements accounting for intrafraction motion were smallest for transponder detection localization techniques, requiring margins of 1.4 mm (LR), 2.6 mm (SI), and 2.3 mm (AP). Bony anatomy alignment required 2.1 mm (LR), 9.4 mm (SI), and 10.5 mm (AP), whereas image-guided marker alignment required 2.8 mm (LR), 3.7 mm (SI), and 3.2 mm (AP). No marker migration was observed in the cohort. Conclusion: Clinically feasible, rapid, and reliable tools such as the electromagnetic transponder detection system for pretreatment target localization

  5. Postoperative Radiotherapy in Prostate Cancer: The Case of the Missing Target

    SciTech Connect

    Croke, Jennifer; Malone, Shawn; Roustan Delatour, Nicolas; Belanger, Eric; Avruch, Leonard; Morash, Christopher; Kayser, Cathleen; Underhill, Kathryn; Spaans, Johanna

    2012-07-15

    Purpose: Postoperative radiotherapy (XRT) increases survival in high-risk prostate cancer patients. Approximately 50% of patients on long-term follow-up relapse despite adjuvant XRT and the predominant site of failure remains local. Four consensus guidelines define postoperative clinical target volume (CTV) in prostate cancer. We explore the possibility that inadequate CTV coverage is an important cause of local failure. This study evaluates the utility of preoperative magnetic resonance imaging (MRI) in defining prostate bed CTV. Methods and Materials: Twenty prostate cancer patients treated with postoperative XRT who also had preoperative staging MRI were included. The four guidelines were applied and the CTVs were expanded to create planning target volumes (PTVs). Preoperative MRIs were fused with postoperative planning CT scans. MRI-based prostate and gross visible tumors were contoured. Three-dimensional (3D) conformal four- and six-field XRT plans were developed and dose-volume histograms analyzed. Subtraction analysis was conducted to assess the adequacy of prostate/gross tumor coverage. Results: Gross tumor was visible in 18 cases. In all 20 cases, the consensus CTVs did not fully cover the MRI-defined prostate. On average, 35% of the prostate volume and 32% of the gross tumor volume were missed using six-field 3D treatment plans. The entire MRI-defined gross tumor volume was completely covered in only two cases (six-field plans). The expanded PTVs did not cover the entire prostate bed in 50% of cases. Prostate base and mid-zones were the predominant site of inadequate coverage. Conclusions: Current postoperative CTV guidelines do not adequately cover the prostate bed and/or gross tumor based on preoperative MRI imaging. Additionally, expanded PTVs do not fully cover the prostate bed in 50% of cases. Inadequate CTV definition is likely a major contributing factor for the high risk of relapse despite adjuvant XRT. Preoperative imaging may lead to more

  6. A Double-Blind Placebo-Controlled Randomized Clinical Trial With Magnesium Oxide to Reduce Intrafraction Prostate Motion for Prostate Cancer Radiotherapy

    SciTech Connect

    Lips, Irene M.; Gils, Carla H. van; Kotte, Alexis N.T.J.; Leerdam, Monique E. van; Franken, Stefan P.G.; Heide, Uulke A. van der; Vulpen, Marco van

    2012-06-01

    Purpose: To investigate whether magnesium oxide during external-beam radiotherapy for prostate cancer reduces intrafraction prostate motion in a double-blind, placebo-controlled randomized trial. Methods and Materials: At the Department of Radiotherapy, prostate cancer patients scheduled for intensity-modulated radiotherapy (77 Gy in 35 fractions) using fiducial marker-based position verification were randomly assigned to receive magnesium oxide (500 mg twice a day) or placebo during radiotherapy. The primary outcome was the proportion of patients with clinically relevant intrafraction prostate motion, defined as the proportion of patients who demonstrated in {>=}50% of the fractions an intrafraction motion outside a range of 2 mm. Secondary outcome measures included quality of life and acute toxicity. Results: In total, 46 patients per treatment arm were enrolled. The primary endpoint did not show a statistically significant difference between the treatment arms with a percentage of patients with clinically relevant intrafraction motion of 83% in the magnesium oxide arm as compared with 80% in the placebo arm (p = 1.00). Concerning the secondary endpoints, exploratory analyses demonstrated a trend towards worsened quality of life and slightly more toxicity in the magnesium oxide arm than in the placebo arm; however, these differences were not statistically significant. Conclusions: Magnesium oxide is not effective in reducing the intrafraction prostate motion during external-beam radiotherapy, and therefore there is no indication to use it in clinical practice for this purpose.

  7. Causes of Mortality After Dose-Escalated Radiation Therapy and Androgen Deprivation for High-Risk Prostate Cancer

    SciTech Connect

    Tendulkar, Rahul D.; Hunter, Grant K.; Reddy, Chandana A.; Stephans, Kevin L.; Ciezki, Jay P.; Abdel-Wahab, May; Stephenson, Andrew J.; Klein, Eric A.; Mahadevan, Arul; Kupelian, Patrick A.

    2013-09-01

    Purpose: Men with high-risk prostate cancer have other competing causes of mortality; however, current risk stratification schema do not account for comorbidities. We aim to identify the causes of death and factors predictive for mortality in this population. Methods and Materials: A total of 660 patients with high-risk prostate cancer were treated with definitive high-dose external beam radiation therapy (≥74 Gy) and androgen deprivation (AD) between 1996 and 2009 at a single institution. Cox proportional hazards regression analysis was conducted to determine factors predictive of survival. Results: The median radiation dose was 78 Gy, median duration of AD was 6 months, and median follow-up was 74 months. The 10-year overall survival (OS) was 60.6%. Prostate cancer was the leading single cause of death, with 10-year mortality of 14.1% (95% CI 10.7-17.6), compared with other cancers (8.4%, 95% CI 5.7-11.1), cardiovascular disease (7.3%, 95% CI 4.7-9.9), and all other causes (10.4%, 95% CI 7.2-13.6). On multivariate analysis, older age (HR 1.55, P=.002) and Charlson comorbidity index score (CS) ≥1 (HR 2.20, P<.0001) were significant factors predictive of OS, whereas Gleason score, T stage, prostate-specific antigen, duration of AD, radiation dose, smoking history, and body mass index were not. Men younger than 70 years of age with CS = 0 were more likely to die of prostate cancer than any other cause, whereas older men or those with CS ≥1 more commonly suffered non-prostate cancer death. The cumulative incidences of prostate cancer-specific mortality were similar regardless of age or comorbidities (P=.60). Conclusions: Men with high-risk prostate cancer are more likely to die of causes other than prostate cancer, except for the subgroup of men younger than 70 years of age without comorbidities. Only older age and presence of comorbidities significantly predicted for OS, whereas prostate cancer- and treatment-related factors did not.

  8. Quantification of shape variation of prostate and seminal vesicles during external beam radiotherapy

    SciTech Connect

    Deurloo, Kirsten; Rasch, Coen . E-mail: portal@nki.nl

    2005-01-01

    Purpose: The prostate is known to translate and rotate under influence of rectal filling changes and many studies have addressed the magnitude of these motions. However, prostate shape variations also have been reported. For image-guided radiotherapy, it is essential to know the relative magnitude of translations, rotations, and shape variation so that the most appropriate correction strategy can be chosen. However, no quantitative analysis of shape variation has been performed. It is, therefore, the purpose of this article to develop a method to determine shape variation of complex organs and apply it to determine shape variation during external beam radiotherapy of a GTV (gross tumor volume) consisting of prostate and seminal vesicles. Methods and materials: For this study, the data of 19 patients with prostate cancer were used. Each patient received a planning computed tomography (CT) scan and 8-12 (11 on average) repeat CT scans that were made during the course of conformal radiotherapy. One observer delineated the GTV in all scans, and volume variations were measured. After matching the GTVs for each patient for translation and rotation, a coverage probability matrix was constructed and the 50% isosurface was taken to determine the average GTV surface. Perpendicular distances between the average GTV and the individual GTVs were calculated for each point of the average GTV, and their variation was expressed in terms of local standard deviation (SD). The local SDs of the shape variation of all 19 patients were mapped onto a reference case by matching and morphing of the individual average GTVs. Repeated delineation of the GTV was done for 6 patients to determine intraobserver variation. Finally, the measured shape variation was corrected for intraobserver variation to estimate the 'real' shape variation. Results: No significant variations in GTV volume were observed. The measured shape variation (including delineation variation) was largest at the tip of the

  9. Dosimetric comparison of four target alignment methods for prostate cancer radiotherapy

    SciTech Connect

    O'Daniel, Jennifer C.; Dong Lei . E-mail: ldong@mdanderson.org; Zhang Lifei; Crevoisier, Renaud de; Wang He; Lee, Andrew K.; Cheung, Rex; Tucker, Susan L.; Kudchadker, Rajat J.; Bonnen, Mark D.; Cox, James D.; Mohan, Radhe; Kuban, Deborah A.

    2006-11-01

    Purpose: The aim of this study was to compare the dosimetric consequences of 4 treatment delivery techniques for prostate cancer patients treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: During an 8-week course of radiotherapy, 10 patients underwent computed tomography (CT) scans 3 times per week (243 total) before daily treatment with a CT-linear accelerator. Treatment delivery was simulated by realigning a fixed-margin treatment plan on each CT scan and calculating doses. The alignment methods were those based on the following: skin marks, bony registration, ultrasonography (United States), and in-room CT. For the last two methods, prostate was the alignment target. The dosimetric effects of these alignment methods on the prostate, seminal vesicles, rectum, and bladder were compared. The average daily minimum dose to 0.1 cm{sup 3} was used as the metric for target coverage. Results: Skin and bone alignments provided acceptable prostate coverage for only 70% of patients, US alignment for 90%, and CT alignment for 100%. CT-based alignment of the prostate provided seminal vesicle (SV) coverage of {>=}69 Gy for all patients; US and bone alignments provided SV coverage of {>=}60 Gy. This SV coverage may be acceptable for early-stage cancer (equivalent SV dose = 55.8 Gy at 1.8 Gy per fraction), but unacceptable for late-stage cancer (SV dose = 75.6 Gy). At 75.6 Gy, the acceptable rate for SV coverage was 40% for skin and bone alignments, 70% for US, and 80% for CT. Conclusions: Direct target alignment methods (US and CT) provided better target coverage. CT-guided alignment provided the best and most consistent dosimetric coverage. A larger planning target volume margin is needed for SV coverage when the alignment target is the prostate.

  10. Calcifications Are Potential Surrogates for Prostate Localization in Image-Guided Radiotherapy

    SciTech Connect

    Zeng, Grace G. McGowan, Tom S.; Larsen, Tessa M.; Bruce, Lisa M.; Moran, Natasha K.; Tsao, Jonathan R.; MacPherson, Miller S.

    2008-11-15

    Purpose: To investigate the feasibility of using calcifications as surrogates for the prostate position during cone-beam computed tomography (CBCT) image-guided radiotherapy. Methods and Materials: The twice-weekly CBCT images taken during the treatment course of 4 patients were retrospectively studied for the stability of the calcifications. The geometric center of three fiducial markers was used as the reference. The planning CT images of 131 prostate patients recently treated with external beam radiotherapy at our center were reviewed to estimate the calcification occurrence rate. Analysis was conducted using the Varian Eclipse treatment planning system. Two patients were treated using prostate calcifications as the landmark in on-line registration. Both the Varian standard and the low-dose CBCT modes were used for imaging. Results: The calcifications were found to be stable during the treatment course. At the 95% confidence interval, the difference between the distance from an identified calcification to the fiducial markers on CBCT and the distance on the planning CT scans was 0.2 {+-} 2.0 mm, 0.8 {+-} 2.2 mm, and 0.4 {+-} 2.4 mm in the left-right, anteroposterior, and superoinferior direction, respectively. Of the 131 patients, 46 (35%) had well-defined calcifications either inside the prostate or near the borders. Our experience in treating the first 2 patients demonstrated that the calcifications are easily distinguished on low-dose scans and that calcification registration can be precisely performed. Conclusion: The results of our study have shown that calcifications can be reliable markers of prostate position and allow for precise image guidance with a low-imaging dose. With this approach, potentially about one-third of prostate patients could benefit from precise image guidance without the invasive use of markers.

  11. Daily Bone Alignment With Limited Repeat CT Correction Rivals Daily Ultrasound Alignment for Prostate Radiotherapy

    SciTech Connect

    O'Daniel, Jennifer C.; Dong Lei Zhang Lifei; Wang He; Tucker, Susan L.; Kudchadker, Rajat J.; Lee, Andrew K.; Cheung, Rex; Cox, James D.; Kuban, Deborah A.; Mohan, Radhe

    2008-05-01

    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{sub 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{sub ID} after three off-line CT scans (bone+3CT), (2) bone alignment plus CF{sub 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{sub ID} was compared. The target dosimetric effect was quantified. Results: The CF{sub 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{sub ID} for internal systematic prostate displacement provided better daily alignment precision and equivalent dose coverage compared with daily US alignment. The CF{sub 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{sub ID} provides another option for accurate prostate cancer patient positioning.

  12. Strategies for Online Organ Motion Correction for Intensity-Modulated Radiotherapy of Prostate Cancer: Prostate, Rectum, and Bladder Dose Effects

    SciTech Connect

    Rijkhorst, Erik-Jan; Lakeman, Annemarie; Nijkamp, Jasper; Bois, Josien de; Herk, Marcel van; Lebesque, Joos V.; Sonke, Jan-Jakob

    2009-11-15

    Purpose: To quantify and evaluate the accumulated prostate, rectum, and bladder dose for several strategies including rotational organ motion correction for intensity-modulated radiotherapy (IMRT) of prostate cancer using realistic organ motion data. Methods and Materials: Repeat computed tomography (CT) scans of 19 prostate patients were used. Per patient, two IMRT plans with different uniform margins were created. To quantify prostate and seminal vesicle motion, repeat CT clinical target volumes (CTVs) were matched onto the planning CTV using deformable registration. Four different strategies, from online setup to full motion correction, were simulated. Rotations were corrected for using gantry and collimator angle adjustments. Prostate, rectum, and bladder doses were accumulated for each patient, plan, and strategy. Minimum CTV dose (D{sub min}), rectum equivalent uniform dose (EUD, n = 0.13), and bladder surface receiving >=78 Gy (S78), were calculated. Results: With online CTV translation correction, a 7-mm margin was sufficient (i.e., D{sub min} >= 95% of the prescribed dose for all patients). A 4-mm margin required additional rotational correction. Margin reduction lowered the rectum EUD(n = 0.13) by approx2.6 Gy, and the bladder S78 by approx1.9%. Conclusions: With online correction of both translations and rotations, a 4-mm margin was sufficient for 15 of 19 patients, whereas the remaining four patients had an underdosed CTV volume <1%. Margin reduction combined with online corrections resulted in a similar or lower dose to the rectum and bladder. The more advanced the correction strategy, the better the planned and accumulated dose agreed.

  13. Stereotactic hypofractionated accurate radiotherapy of the prostate (SHARP), 33.5 Gy in five fractions for localized disease: First clinical trial results

    SciTech Connect

    Madsen, Berit L. . E-mail: ronblm@vmmc.org; Hsi, R. Alex; Pham, Huong T.; Fowler, Jack F.; Esagui, Laura C.; Corman, John

    2007-03-15

    Purpose: To evaluate the feasibility and toxicity of stereotactic hypofractionated accurate radiotherapy (SHARP) for localized prostate cancer. Methods and Materials: A Phase I/II trial of SHARP performed for localized prostate cancer using 33.5 Gy in 5 fractions, calculated to be biologically equivalent to 78 Gy in 2 Gy fractions ({alpha}/{beta} ratio of 1.5 Gy). Noncoplanar conformal fields and daily stereotactic localization of implanted fiducials were used for treatment. Genitourinary (GU) and gastrointestinal (GI) toxicity were evaluated by American Urologic Association (AUA) score and Common Toxicity Criteria (CTC). Prostate-specific antigen (PSA) values and self-reported sexual function were recorded at specified follow-up intervals. Results: The study includes 40 patients. The median follow-up is 41 months (range, 21-60 months). Acute toxicity Grade 1-2 was 48.5% (GU) and 39% (GI); 1 acute Grade 3 GU toxicity. Late Grade 1-2 toxicity was 45% (GU) and 37% (GI). No late Grade 3 or higher toxicity was reported. Twenty-six patients reported potency before therapy; 6 (23%) have developed impotence. Median time to PSA nadir was 18 months with the majority of nadirs less than 1.0 ng/mL. The actuarial 48-month biochemical freedom from relapse is 70% for the American Society for Therapeutic Radiology and Oncology definition and 90% by the alternative nadir + 2 ng/mL failure definition. Conclusions: SHARP for localized prostate cancer is feasible with minimal acute or late toxicity. Dose escalation should be possible.

  14. Phase I Dose-Escalation Study of the Novel Anti-androgen BMS-641988 in Patients with Castration-Resistant Prostate Cancer

    PubMed Central

    Rathkopf, Dana; Liu, Glenn; Carducci, Michael A; Eisenberger, Mario A; Anand, Aseem; Morris, Michael J; Slovin, Susan F; Sasaki, Yasutsuna; Takahashi, Shunji; Ozono, Seiichiro; Fung, Nga Kit Eliza; Cheng, Shinta; Gan, Jinping; Gottardis, Marco; Obermeier, Mary T.; Reddy, Jyotsna; Zhang, Steven; Vakkalagadda, Blisse J.; Wilding, George; Scher, Howard I.

    2011-01-01

    Purpose BMS-641988 is an androgen receptor antagonist with increased potency relative to bicalutamide in both in vitro and in vivo prostate cancer models. A first-in-man phase I study was conducted to define the safety and tolerability of oral BMS-641988 in patients with castration-resistant prostate cancer (CRPC). Experimental Design Doses were escalated from 5 to 150 mg based on discrete pharmacokinetic parameters in cohorts of 3 to 6 subjects. After establishing safety with 20 mg of BMS-641988 in the United States, a companion study was opened in Japan to assess differences in drug metabolism between populations. Results Sixty-one men with CRPC were treated with daily BMS-641988. The pharmacokinetics of BMS-641988 and its active metabolites were proportional to dose. One patient experienced an epileptic seizure at a dose of 60 mg administered twice. Despite achieving target drug exposures, anti-tumor activity was limited to 1 partial response. Seventeen of 23 evaluable patients (74%) exhibited stable disease on imaging (median 15 weeks; range 8–32), and 10 of 61 patients (16%) achieved a ≥30%. decline in levels of prostate-specific antigen (PSA). Partial agonism was seen within the context of this study upon removal of the drug as evidenced by a decrease in PSA. Conclusions Although the clinical outcomes of predominantly stable disease and partial agonism were similar to what was observed in the preclinical evaluation of the compound, the limited anti-tumor activity of BMS-641988 at therapeutic dose levels coupled with an episode of seizure activity led to study closure. PMID:21131556

  15. Prostate-specific antigen kinetics after stereotactic body radiotherapy as monotherapy or boost after whole pelvic radiotherapy for localized prostate cancer

    PubMed Central

    Kim, Hun Jung; Phak, Jung Hoon; Kim, Woo Chul

    2015-01-01

    Purpose Stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for localized prostate cancer. However, prostate-specific antigen (PSA) kinetics after SBRT has not been well characterized. The purpose of the current study is to assess the kinetics of PSA for low- and intermediate-risk prostate cancer patients treated with SBRT using Cyberknife as both monotherapy and boost after whole pelvic radiotherapy (WPRT) in the absence of androgen deprivation therapy. Methods A total of 61 patients with low- and intermediated-risk prostate cancer treated with SBRT as monotherapy (36.25 Gy in 5 fractions in 32 patients) and SBRT (21 Gy in 3 fractions in 29 patients) boost combined with WPRT (45 Gy in 25 fractions). Patients were excluded if they failed therapy by the Phoenix definition or had androgen deprivation therapy. PSA nadir and rate of change in PSA over time (slope) were calculated and compared. Results With a median follow-up of 52.4 months (range, 14–74 months), for SBRT monotherapy, the median PSA nadir was 0.31 ng/mL (range, 0.04–1.15 ng/mL) and slopes were –0.41 ng/mL/mo, –0.17 ng/mL/mo, –0.12 ng/mL/mo, and –0.09 ng/mL/mo, respectively, for durations of 1 year, 2 years, 3 years, and 4 years postradiotherapy. Similarly, for SBRT boost after WPRT, the median PSA nadir was 0.34 ng/mL (range, 0.04–1.44 ng/mL) and slopes were –0.53 ng/mL/mo, –0.25 ng/mL/mo, –0.14 ng/mL/mo, and –0.09 ng/mL/mo, respectively. The median nadir and slopes of SBRT monotherapy did not differ significantly from those of SBRT boost after WPRT. Benign PSA bounces were common in 30.4% of all cohorts, and the median time to PSA bounce was 12 months (range, 6–25 months). Conclusions In this report of low- and intermediate-risk prostate cancer patients, an initial period of rapid PSA decline was followed by a slow decline, which resulted in a lower PSA nadir. The PSA kinetics of SBRT monotherapy appears to be comparable to those achieved

  16. Dose-escalated intensity-modulated radiotherapy and irradiation of subventricular zones in relation to tumor control outcomes of patients with glioblastoma multiforme

    PubMed Central

    Kusumawidjaja, Grace; Gan, Patricia Zhun Hong; Ong, Whee Sze; Teyateeti, Achiraya; Dankulchai, Pittaya; Tan, Daniel Yat Harn; Chua, Eu Tiong; Chua, Kevin Lee Min; Tham, Chee Kian; Wong, Fuh Yong; Chua, Melvin Lee Kiang

    2016-01-01

    Background Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with high relapse rate. In this study, we aimed to determine if dose-escalated (DE) radiotherapy improved tumor control and survival in GBM patients. Methods We conducted a retrospective analysis of 49 and 23 newly-diagnosed histology-proven GBM patients, treated with DE radiotherapy delivered in 70 Gy (2.33 Gy per fraction) and conventional doses (60 Gy), respectively, between 2007 and 2013. Clinical target volumes for 70 and 60 Gy were defined by 0.5 and 2.0 cm expansion of magnetic resonance imaging T1-gadolinium-enhanced tumor/surgical cavity, respectively. Bilateral subventricular zones (SVZ) were contoured on a co-registered pre-treatment magnetic resonance imaging and planning computed tomography dataset as a 5 mm wide structure along the lateral margins of the lateral ventricles. Survival outcomes of both cohorts were compared using log-rank test. Radiation dose to SVZ in the DE cohort was evaluated. Results Median follow-up was 13.6 and 15.1 months for the DE- and conventionally-treated cohorts, respectively. Median overall survival (OS) of patients who received DE radiotherapy was 15.2 months (95% confidence interval [CI] =11.0–18.6), while median OS of the latter cohort was 18.4 months (95% CI =12.5–31.4, P=0.253). Univariate analyses of clinical and dosimetric parameters among the DE cohort demonstrated a trend of longer progression-free survival, but not OS, with incremental radiation doses to the ipsilateral SVZ (hazard ratio [HR] =0.95, 95% CI =0.90–1.00, P=0.052) and proportion of ipsilateral SVZ receiving 50 Gy (HR =0.98, 95% CI =0.97–1.00, P=0.017). Conclusion DE radiotherapy did not improve survival in patients with GBM. Incorporation of ipsilateral SVZ as a radiotherapy target volume for patients with GBM requires prospective validation. PMID:27042103

  17. Triple course external beam radiotherapy for carcinoma of the prostate

    SciTech Connect

    El-Mahdi, A.M.; Turalba, C.I.C.; Schellhammer, P.F.; Peeples, W.J.

    1984-04-01

    In 1976 this hospital began using a triple-course technique of external beam irradiation for localized carcinoma of the prostate. The treatment consisted of 2 courses of 20 Gy in 2 weeks to the pelvis and a third course of 20-25 Gy in 2-2 1/2 weeks as a boost to the prostate. A 2 week rest followed the first and second courses. The results of this treatment technique are reported on the first 50 patients who had been followed for at least 3 years. Although 96% of these patients developed bladder and/or bowel reactions, the majority of the symptoms were in the very mild to mild category, with only 2% severe reactions referrable to each organ. The incidence of late complications in this series compared favorably to those reported by other authors. Clinical local control was 96% while postreatment needle biopsy performed on 22/50 patients yielded a negative rate of 86%. This study has shown that with triple course external beam irradiation, excellent control of localized carcinoma of the prostate can be achieved with minimal acute morbidity.

  18. Inverse Relationship Between Biochemical Outcome and Acute Toxicity After Image-Guided Radiotherapy for Prostate Cancer

    SciTech Connect

    Vesprini, Danny; Catton, Charles; Jacks, Lindsay; Lockwood, Gina; Rosewall, Tara; Bayley, Andrew; Chung, Peter; Gospodarowicz, Mary; Menard, Cynthia; Milosevic, Michael; Nichol, Alan; Skala, Marketa; Warde, Padraig; Bristow, Robert G.

    2012-06-01

    Purpose: Prostate cancer patients exhibit variability in normal tissue reactions and biochemical failure. With the use of image-guided radiotherapy (IGRT), there is a greater likelihood that the differences in normal tissue and tumor response are due to biological rather than physical factors. We tested the hypothesis that prospectively scored acute toxicity is associated with biochemical failure-free rate (BFFR) in prostate cancer patients treated with IGRT. Methods and Materials: We retrospectively analyzed BFFR in 362 patients with localized prostate cancer treated with IGRT. We compared BFFR with prospectively collected Radiation Therapy Oncology Group (RTOG) maximum acute gastrointestinal (GI) and genitourinary (GU) toxicity scores. Median follow-up for all patients was 58.3 months after total radiotherapy doses of 75.6-79.8 Gy. Results: Patients reporting RTOG acute GU or GI toxicity scores of {>=}2 were considered 'sensitive' (n = 141, 39%) and patients reporting scores <2 were considered 'nonsensitive' (n = 221, 61%). When calculating biochemical failure (BF) using the American Society for Therapeutic Radiology and Oncology definition at 5 years, 76% (CI 70-82%) of the 'nonsensitive' patients were failure free, compared with only 53% (CI 43-62%) of the 'sensitive' patients (log-rank test, p < 0.0001). This difference was also observed using the Phoenix definition; 'nonsensitive' 5-year BFFR was 81% (CI 74-86%) vs. 'sensitive' BFFR was 68% (CI 58-76%; log-rank test p = 0.0012). The difference in BF between cohorts remained significant when controlled for radiation dose (75.6 vs. 79.8 Gy), prognostic stratification (T category, prostate-specific antigen, and Gleason score), and prostate volume. Conclusions: This study unexpectedly shows that prostate cancer patients who develop {>=}Grade 2 RTOG acute toxicity during radiotherapy are less likely to remain BFF at 5 years. These results deserve further study and, if validated in other large IGRT cohorts

  19. External Beam Radiotherapy for Prostate Cancer: Urinary Outcomes for Men With High International Prostate Symptom Scores (IPSS)

    SciTech Connect

    Malik, Renuka; Jani, Ashesh B.; Liauw, Stanley L.

    2011-07-15

    Purpose: To report the urinary outcome of men treated for prostate cancer with external beam radiotherapy (EBRT) who have pretreatment obstructive urinary symptoms (International Prostate Symptom Score [IPSS] {>=}15). Methods and Materials: We treated 368 patients with EBRT for localized prostate cancer, and pre- and post-radiotherapy (RT) IPSSs were recorded. In total, 80 men had an IPSS {>=}15, 48% of whom were taking genitourinary (GU) medications before RT. The IPSS was followed over time and analyzed as a pretreatment factor against Radiation Therapy Oncology Group acute and late GU toxicity. Results: The median follow-up was 44 months. Among men with a pre-RT IPSS {>=}15, the median IPSS at baseline, first follow-up, and last follow-up was 18 (range, 15 to 34), 17 (range, 0 to 32), and 13 (range, 0 to 34), respectively. The mean patient declines in IPSS from baseline to first and last follow-up were -3.6 points (p < 0.0004) and -6.9 points (p < 0.0001), respectively. At last follow-up, 43 men (54%) took GU medications. Pre-RT IPSS {>=}15 vs. {<=}14 was associated with a higher incidence of Grade {>=}2 acute GU toxicity (64% vs. 42%, p = 0.0005), and 4-year freedom from Grade {>=}2 late GU toxicity was 38% vs. 64% (p < 0.0001). There was no greatly increased risk of Grade {>=}3 late GU toxicity for men with IPSS {>=}15 (4-year freedom from Grade {>=}3 late GU toxicity of 90% vs. 96%, p = 0.0964). Conclusions: Although the improvement is not immediate, men with moderate to severe obstructive GU symptoms can have improvement in urinary function after EBRT, without significant risk for severe morbidity.

  20. Fractionated changes in prostate cancer radiotherapy using cone-beam computed tomography

    SciTech Connect

    Huang, Tzung-Chi; Chou, Kuei-Ting; Yang, Shih-Neng; Chang, Chih-Kai; Liang, Ji-An; Zhang, Geoffrey

    2015-10-01

    The high mobility of the bladder and the rectum causes uncertainty in radiation doses prescribed to patients with prostate cancer who undergo radiotherapy (RT) multifraction treatments. The purpose of this study was to estimate the dose received by the bladder, rectum, and prostate from multifraction treatments using daily cone-beam computed tomography (CBCT). Overall, 28 patients with prostate cancer who planned to receive radiation treatments were enrolled in the study. The acquired CBCT before the treatment delivery was registered with the planning CT to map the dose distribution used in the treatment plan for estimating the received dose during clinical treatment. For all 28 patients with 112 data sets, the mean percentage differences (± standard deviation) in the volume and radiation dose were 44% (± 41) and 18% (± 17) for the bladder, 20% (± 21) and 2% (± 2) for the prostate, and 36% (± 29) and 22% (± 15) for the rectum, respectively. Substantial differences between the volumes and radiation dose and those specified in treatment plans were observed. Besides the use of image-guided RT to improve patient setup accuracy, further consideration of large changes in bladder and rectum volumes is strongly suggested when using external beam radiation for prostate cancer.

  1. DNA-PKcs Expression Predicts Response to Radiotherapy in Prostate Cancer

    SciTech Connect

    Bouchaert, Patrick; Guerif, Stephane; Debiais, Celine; Irani, Jacques; Fromont, Gaelle

    2012-12-01

    Purpose: Double-strand breaks, the most lethal DNA lesions induced by ionizing radiation, are mainly repaired by the nonhomologous end-joining system. The expression of the nonhomologous end-joining pathway has never been studied in prostate cancer, and its prognostic value for patients undergoing radiotherapy remains unknown. Methods: Pretreatment biopsies from 238 patients treated with exclusive external beam radiotherapy for localized prostate cancer with {>=}2 years of follow-up were reviewed to reassess the Gleason score. Of these 238 cases, 179 were suitable for in situ analysis and were included in the tissue microarrays. Expression of the nonhomologous end-joining proteins Ku70, Ku80, DNA-dependent protein kinase, catalytic subunits (DNA-PKcs), and X-ray repair cross complementing 4-like factor was studied by immunohistochemistry, together with the proliferation marker Ki67. Results: The predictive value of the Gleason score for biochemical relapse (using the Phoenix criteria) was markedly improved after review (P<.0001) compared with the initial score (P=.003). The clinical stage, pretreatment prostate-specific antigen level, and perineural invasion status were also associated with progression-free survival (P=.005, P<.0001, and P=.03, respectively). High proliferation (>4%) tends to be associated with biochemical recurrence; however, the difference did not reach statistical significance (P=.06). Although the expression of Ku70, Ku80, and X-ray repair cross complementing 4-like factor was not predictive of relapse, positive DNA-PKcs nuclear staining was closely associated with biochemical recurrence (P=.0002). On multivariate analysis, only the Gleason score, prostate-specific antigen level, and DNA-PKcs status remained predictive of recurrence (P=.003, P=.002, and P=.01, respectively). Conclusions: The results of the present study highly suggest that DNA-PKcs could be a predictive marker of recurrence after radiotherapy, independently of the classic

  2. Intraoperative Radiotherapy During Radical Prostatectomy for Locally Advanced Prostate Cancer: Technical and Dosimetric Aspects

    SciTech Connect

    Krengli, Marco; Terrone, Carlo; Ballare, Andrea; Loi, Gianfranco; Tarabuzzi, Roberto; Marchioro, Giansilvio; Beldi, Debora; Mones, Eleonora; Bolchini, Cesare R.T.; Volpe, Alessandro; Frea, Bruno

    2010-03-15

    Purpose: To analyze the feasibility of intraoperative radiotherapy (IORT) in patients with high-risk prostate cancer and candidates for radical prostatectomy. Methods and Materials: A total of 38 patients with locally advanced prostate cancer were enrolled. No patients had evidence of lymph node or distant metastases, probability of organ-confined disease >25%, or risk of lymph node involvement >15% according to the Memorial Sloan-Kettering Cancer Center Nomogram. The IORT was delivered after exposure of the prostate by a dedicated linear accelerator with beveled collimators using electrons of 9 to 12 MeV to a total dose of 10-12 Gy. Rectal dose was measured in vivo by radiochromic films placed on a rectal probe. Administration of IORT was followed by completion of radical prostatectomy and regional lymph node dissection. All cases with extracapsular extension and/or positive margins were scheduled for postoperative radiotherapy. Patients with pT3 to pT4 disease or positive nodes received adjuvant hormonal therapy. Results: Mean dose detected by radiochromic films was 3.9 Gy (range, 0.4-8.9 Gy) to the anterior rectal wall. The IORT procedure lasted 31 min on average (range, 15-45 min). No major intra- or postoperative complications occurred. Minor complications were observed in 10/33 (30%) of cases. Of the 27/31 patients who completed the postoperative external beam radiotherapy, 3/27 experienced Grade 2 rectal toxicity and 1/27 experienced Grade 2 urinary toxicity. Conclusions: Use of IORT during radical prostatectomy is feasible and allows safe delivery of postoperative external beam radiotherapy to the tumor bed without relevant acute rectal toxicity.

  3. Sexual Function After Stereotactic Body Radiotherapy for Prostate Cancer: Results of a Prospective Clinical Trial

    SciTech Connect

    Wiegner, Ellen A.; King, Christopher R.

    2010-10-01

    Purpose: To study the sexual quality of life for prostate cancer patients after stereotactic body radiotherapy (SBRT). Methods and Materials: Using the Expanded Prostate Cancer Index Composite (EPIC)-validated quality-of-life questionnaire, the sexual function of 32 consecutive patients who received prostate SBRT in a prospective Phase II clinical trial were analyzed at baseline, and at median times of 4, 12, 20, and 50 months after treatment. SBRT consisted of 36.25 Gy in five fractions of 7.25 Gy using the Cyberknife. No androgen deprivation therapy was given. The use of erectile dysfunction (ED) medications was monitored. A comprehensive literature review for radiotherapy-alone modalities based on patient self-reported questionnaires served as historical comparison. Results: Median age at treatment was 67.5 years, and median follow-up was 35.5 months (minimum 12 months). The mean EPIC sexual domain summary score, sexual function score, and sexual bother score decreased by 45%, 49%, and 25% respectively at 50 months follow-up. These differences reached clinical relevance by 20 months after treatment. Baseline ED rate was 38% and increased to 71% after treatment (p = 0.024). Use of ED medications was 3% at baseline and progressed to 25%. For patients aged <70 years at follow-up, 60% maintained satisfactory erectile function after treatment compared with only 12% aged {>=}70 years (p = 0.008). Penile bulb dose was not associated with ED. Conclusions: The rates of ED after treatment appear comparable to those reported for other modalities of radiotherapy. Given the modest size of this study and the uncertainties in the physiology of radiotherapy-related ED, these results merit further investigations.

  4. External Beam Radiotherapy for Clinically Localized Hormone-Refractory Prostate Cancer: Clinical Significance of Nadir Prostate-Specific Antigen Value Within 12 Months

    SciTech Connect

    Ogawa, Kazuhiko Nakamura, Katsumasa; Sasaki, Tomonari; Onishi, Hiroshi; Koizumi, Masahiko; Shioyama, Yoshiyuki; Araya, Masayuki; Mukumoto, Nobutaka M.S.; Mitsumori, Michihide; Teshima, Teruki

    2009-07-01

    Purpose: To analyze retrospectively the results of external beam radiotherapy for clinically localized hormone-refractory prostate cancer and investigate the clinical significance of nadir prostate-specific antigen (PSA) value within 12 months (nPSA12) as an early estimate of clinical outcomes after radiotherapy. Methods and Materials: Eighty-four patients with localized hormone-refractory prostate cancer treated with external beam radiotherapy were retrospectively reviewed. The total radiation doses ranged from 30 to 76 Gy (median, 66 Gy), and the median follow-up period for all 84 patients was 26.9 months (range, 2.7-77.3 months). Results: The 3-year actuarial overall survival, progression-free survival (PFS), and local control rates in all 84 patients after radiotherapy were 67%, 61%, and 93%, respectively. Although distant metastases and/or regional lymph node metastases developed in 34 patients (40%) after radiotherapy, local progression was observed in only 5 patients (6%). Of all 84 patients, the median nPSA12 in patients with clinical failure and in patients without clinical failure was 3.1 ng/mL and 0.5 ng/mL, respectively. When dividing patients according to low (<0.5 ng/mL) and high ({>=}0.5 ng/mL) nPSA12 levels, the 3-year PFS rate in patients with low nPSA12 and in those with high nPSA12 was 96% and 44%, respectively (p < 0.0001). In univariate analysis, nPSA12 and pretreatment PSA value had a significant impact on PFS, and in multivariate analysis nPSA12 alone was an independent prognostic factor for PFS after radiotherapy. Conclusions: External beam radiotherapy had an excellent local control rate for clinically localized hormone-refractory prostate cancer, and nPSA12 was predictive of clinical outcomes after radiotherapy.

  5. Investigation of Linac-Based Image-Guided Hypofractionated Prostate Radiotherapy

    SciTech Connect

    Pawlicki, Todd . E-mail: tpaw@stanford.edu; Kim, Gwe-Ya; Hsu, Annie; Cotrutz, Cristian; Boyer, Arthur L.; Xing Lei; King, Christopher R.; Luxton, Gary

    2007-07-01

    A hypofractionation treatment protocol for prostate cancer was initiated in our department in December 2003. The treatment regimen consists of a total dose of 36.25 Gy delivered at 7.25 Gy per fraction over 10 days. We discuss the rationale for such a prostate hypofractionation protocol and the need for frequent prostate imaging during treatment. The CyberKnife (Accuray Inc., Sunnyvale, CA), a linear accelerator mounted on a robotic arm, is currently being used as the radiation delivery device for this protocol, due to its incorporation of near real-time kV imaging of the prostate via 3 gold fiducial seeds. Recently introduced conventional linac kV imaging with intensity modulated planning and delivery may add a new option for these hypofractionated treatments. The purpose of this work is to investigate the use of intensity modulated radiotherapy (IMRT) and the Varian Trilogy Accelerator with on-board kV imaging (Varian Medical Systems Inc., Palo Alto, CA) for treatment of our hypofractionated prostate patients. The dose-volume histograms and dose statistics of 2 patients previously treated on the CyberKnife were compared to 7-field IMRT plans. A process of acquiring images to observe intrafraction prostate motion was achieved in an average time of about 1 minute and 40 seconds, and IMRT beam delivery takes about 40 seconds per field. A complete 7-field IMRT plan can therefore be imaged and delivered in 10 to 17 minutes. The Varian Trilogy Accelerator with on-board imaging and IMRT is well suited for image-guided hypofractionated prostate treatments. During this study, we have also uncovered opportunities for improvement of the on-board imaging hardware/software implementation that would further enhance performance in this regard.

  6. Stereotactic Body Radiotherapy for Localized Prostate Cancer: Interim Results of a Prospective Phase II Clinical Trial

    SciTech Connect

    King, Christopher R. Brooks, James D.; Gill, Harcharan; Pawlicki, Todd; Cotrutz, Cristian; Presti, Joseph C.

    2009-03-15

    Purpose: The radiobiology of prostate cancer favors a hypofractionated dose regimen. We report results of a prospective Phase II clinical trial of stereotactic body radiotherapy (SBRT) for localized prostate cancer. Methods and Materials: Forty-one low-risk prostate cancer patients with 6 months' minimum follow-up received 36.25 Gy in five fractions of 7.25 Gy with image-guided SBRT alone using the CyberKnife. The early (<3 months) and late (>6 months) urinary and rectal toxicities were assessed using validated quality of life questionnaires (International Prostate Symptom Score, Expanded Prostate Cancer Index Composite) and the Radiation Therapy Oncology Group (RTOG) toxicity criteria. Patterns of prostate-specific antigen (PSA) response are analyzed. Results: The median follow-up was 33 months. There were no RTOG Grade 4 acute or late rectal/urinary complications. There were 2 patients with RTOG Grade 3 late urinary toxicity and none with RTOG Grade 3 rectal complications. A reduced rate of severe rectal toxicities was observed with every-other-day vs. 5 consecutive days treatment regimen (0% vs. 38%, p = 0.0035). A benign PSA bounce (median, 0.4 ng/mL) was observed in 12 patients (29%) occurring at 18 months (median) after treatment. At last follow-up, no patient has had a PSA failure regardless of biochemical failure definition. Of 32 patients with 12 months minimum follow-up, 25 patients (78%) achieved a PSA nadir {<=}0.4 ng/mL. A PSA decline to progressively lower nadirs up to 3 years after treatment was observed. Conclusions: The early and late toxicity profile and PSA response for prostate SBRT are highly encouraging. Continued accrual and follow-up will be necessary to confirm durable biochemical control rates and low toxicity profiles.

  7. Prostate cancer radiation therapy: A physician's perspective.

    PubMed

    Dal Pra, Alan; Souhami, Luis

    2016-03-01

    Prostate cancer is the second most common cancer in men and a major cause of cancer deaths worldwide. Ionizing radiation has played a substantial role in the curative treatment of this disease. The historical evolution of radiotherapy techniques through 3D-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and image-guided radiotherapy (IGRT) has allowed more accurate and precise treatments toward significant improvements in the therapeutic ratio. The addition of androgen deprivation therapy has significantly improved overall survival becoming the standard therapy for intermediate- and high-risk disease. Many randomized controlled trials have shown improved local control with dose escalation, and hypofractionated RT has been consolidated with proven efficacy and safe clinical results. However, several questions remain open in the radiotherapeutic management of prostate cancer patients and hopefully ongoing studies will shed light on these uncertainties. More individualized approaches are essential through better prognostic and novel predictive biomarkers of prostate radiotherapy response. Clinicians should critically interpret the evolving technologies in prostate cancer radiotherapy with important optimism but balancing the costs and the actual magnitude of clinical benefit. This article provides an overview of the basic aspects of radiotherapy treatment in localized prostate cancer from a physician's perspective. PMID:27056435

  8. Inter- and Intrafraction Uncertainty in Prostate Bed Image-Guided Radiotherapy

    SciTech Connect

    Huang, Kitty; Palma, David A.; Scott, Danielle; McGregor, Danielle; Gaede, Stewart; Yartsev, Slav; Bauman, Glenn; Louie, Alexander V.; Rodrigues, George

    2012-10-01

    Purpose: The goals of this study were to measure inter- and intrafraction setup error and prostate bed motion (PBM) in patients undergoing post-prostatectomy image-guided radiotherapy (IGRT) and to propose appropriate population-based three-dimensional clinical target volume to planning target volume (CTV-PTV) margins in both non-IGRT and IGRT scenarios. Methods and Materials: In this prospective study, 14 patients underwent adjuvant or salvage radiotherapy to the prostate bed under image guidance using linac-based kilovoltage cone-beam CT (kV-CBCT). Inter- and intrafraction uncertainty/motion was assessed by offline analysis of three consecutive daily kV-CBCT images of each patient: (1) after initial setup to skin marks, (2) after correction for positional error/immediately before radiation treatment, and (3) immediately after treatment. Results: The magnitude of interfraction PBM was 2.1 mm, and intrafraction PBM was 0.4 mm. The maximum inter- and intrafraction prostate bed motion was primarily in the anterior-posterior direction. Margins of at least 3-5 mm with IGRT and 4-7 mm without IGRT (aligning to skin marks) will ensure 95% of the prescribed dose to the clinical target volume in 90% of patients. Conclusions: PBM is a predominant source of intrafraction error compared with setup error and has implications for appropriate PTV margins. Based on inter- and estimated intrafraction motion of the prostate bed using pre- and post-kV-CBCT images, CBCT IGRT to correct for day-to-day variances can potentially reduce CTV-PTV margins by 1-2 mm. CTV-PTV margins for prostate bed treatment in the IGRT and non-IGRT scenarios are proposed; however, in cases with more uncertainty of target delineation and image guidance accuracy, larger margins are recommended.

  9. Dose-Escalated Intensity-Modulated Radiotherapy Is Feasible and May Improve Locoregional Control and Laryngeal Preservation in Laryngo-Hypopharyngeal Cancers

    SciTech Connect

    Miah, Aisha B.; Bhide, Shreerang A.; Guerrero-Urbano, M. Teresa; Clark, Catharine; Bidmead, A. Margaret; St Rose, Suzanne; Barbachano, Yolanda; A'Hern, Roger; Tanay, Mary; Hickey, Jennifer; Nicol, Robyn; Newbold, Kate L.; Harrington, Kevin J.; Nutting, Christopher M.

    2012-02-01

    Purpose: To determine the safety and outcomes of induction chemotherapy followed by dose-escalated intensity-modulated radiotherapy (IMRT) with concomitant chemotherapy in locally advanced squamous cell cancer of the larynx and hypopharynx (LA-SCCL/H). Methods and Materials: A sequential cohort Phase I/II trial design was used to evaluate moderate acceleration and dose escalation. Patients with LA-SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions (Fx) to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Acute and late toxicities and tumor control rates were recorded. Results: Between September 2002 and January 2008, 60 patients (29 DL1, 31 DL2) with Stage III (41% DL1, 52% DL2) and Stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 51.2 (12.1-77.3) months and for DL2 was 36.2 (4.2-63.3) months. Acute Grade 3 (G3) dysphagia was higher in DL2 (87% DL2 vs. 59% DL1), but other toxicities were equivalent. One patient in DL1 required dilatation of a pharyngeal stricture (G3 dysphagia). In DL2, 2 patients developed benign pharyngeal strictures at 1 year. One underwent a laryngo-pharyngectomy and the other a dilatation. No other G3/G4 toxicities were reported. Overall complete response was 79% (DL1) and 84% (DL2). Two-year locoregional progression-free survival rates were 64.2% (95% confidence interval, 43.5-78.9%) in DL1 and 78.4% (58.1-89.7%) in DL2. Two-year laryngeal preservation rates were 88.7% (68.5-96.3%) in DL1 and 96.4% (77.7-99.5%) in DL2. Conclusions: At a mean follow-up of 36 months, dose-escalated chemotherapy-IMRT at DL2 has so far been safe to deliver. In this study, DL2 delivered high rates of locoregional control, progression-free survival, and organ preservation and has been selected as the experimental arm in a Cancer Research UK Phase III

  10. Radiotherapy for urinary bladder pheochromocytoma with invasion of the prostate: A case report and literature review

    PubMed Central

    YOU, DONG; REN, RUIZHEN; CHEN, ERCHENG; CHEN, SHULIN; WANG, DAWEI; LIU, JIANHUI

    2016-01-01

    Malignant pheochromocytoma is a rare tumor, for which there is currently no effective therapy. Cytoreductive surgery is recommended to reduce tumor burden and relieve the symptoms of catecholamine excess, although complete eradication of the lesions is often not feasible. In patients with advanced disease, for whom surgical resection is not an option, systemic chemotherapy, radiotherapy and treatment with iodine-131-meta-iodobenzylguanidine may be used to achieve symptomatic relief. Although malignant pheochromocytoma is considered to be unresponsive to radiotherapy, a limited number of case reports, although not large patient samples, have been published on the effectiveness of radiotherapy for the treatment of this disease. This is the case report of a 23-year-old male patient with bladder pheochromocytoma invading the prostate, who refused to undergo surgery. The tumor shrank following radiotherapy and had not increased in size 1.5 years after treatment. Similarly, the blood pressure of the patient remained within normal limits without antihypertensive medication; the levels of catecholamines and their metabolites also remained normal. Our case demonstrated that radiotherapy was effective for malignant pheochromocytoma to a certain extent and, therefore, it may be selected when surgery is not feasible.

  11. Radiobiologically optimized couch shift: A new localization paradigm using cone-beam CT for prostate radiotherapy

    SciTech Connect

    Huang, Yimei Gardner, Stephen J.; Wen, Ning; Zhao, Bo; Gordon, James; Brown, Stephen; Chetty, Indrin J.

    2015-10-15

    Purpose: To present a novel positioning strategy which optimizes radiation delivery by utilizing radiobiological response knowledge and evaluate its use during prostate external beam radiotherapy. Methods: Five patients with low or intermediate risk prostate cancer were evaluated retrospectively in this IRB-approved study. For each patient, a VMAT plan with one 358° arc was generated on the planning CT (PCT) to deliver 78 Gy in 39 fractions. Five representative pretreatment cone beam CTs (CBCT) were selected for each patient. The CBCT images were registered to PCT by a human observer, which consisted of an initial automated registration with three degrees-of-freedom, followed by manual adjustment for agreement at the prostate/rectal wall interface. To determine the optimal treatment position for each CBCT, a search was performed centering on the observer-matched position (OM-position) utilizing a score function based on radiobiological and dosimetric indices (EUD{sub prostate}, D99{sub prostate}, NTCP{sub rectum}, and NTCP{sub bladder}) for the prostate, rectum, and bladder. We termed the optimal treatment position the radiobiologically optimized couch shift position (ROCS-position). Results: The dosimetric indices, averaged over the five patients’ treatment plans, were (mean ± SD) 79.5 ± 0.3 Gy (EUD{sub prostate}), 78.2 ± 0.4 Gy (D99{sub prostate}), 11.1% ± 2.7% (NTCP{sub rectum}), and 46.9% ± 7.6% (NTCP{sub bladder}). The corresponding values from CBCT at the OM-positions were 79.5 ± 0.6 Gy (EUD{sub prostate}), 77.8 ± 0.7 Gy (D99{sub prostate}), 12.1% ± 5.6% (NTCP{sub rectum}), and 51.6% ± 15.2% (NTCP{sub bladder}), respectively. In comparison, from CBCT at the ROCS-positions, the dosimetric indices were 79.5 ± 0.6 Gy (EUD{sub prostate}), 77.3 ± 0.6 Gy (D99{sub prostate}), 8.0% ± 3.3% (NTCP{sub rectum}), and 46.9% ± 15.7% (NTCP{sub bladder}). Excessive NTCP{sub rectum} was observed on Patient 5 (19.5% ± 6.6%) corresponding to localization at OM

  12. Second Tumor Induction Risk in IMRT for Prostate Cancer: An Unbalanced Comparison Between Surgery and Radiotherapy?

    PubMed

    Calandrino, Riccardo; Perna, Lucia; Belli, Maria Luisa; Botti, Andrea; Cattaneo, Mauro; Fiorino, Claudio; Cozzarini, Cesare; Iori, Mauro

    2015-12-01

    The aim of this study was to evaluate the risk of second tumor induction for prostate patients treated with volumetric modulated arc therapy in age classes 50-70. Based on both age-dependent models and doses to critical organs, the risk of second tumor induction was evaluated simulating the small field (prostate and seminal vesicles) and large field (whole pelvis) for Helical Tomotherapy and Rapid Arc. The doses to the organs closest to the treatment volume were derived from treatment planning system data. Whereas, due to the lack of calculation algorithms where leakage and internal radiation scattering are unreliable at a large distance from target, the doses to the organs outside the treatment volume were measured in an anthropomorphic phantom. Doses from Image Guided Radiotherapy (IGRT) were also assessed on phantom measurements. The Lifetime Attributable Risk (LAR) for second tumor induction increases from 2.2 to 13.7% as irradiated volume increases and age decreases. IGRT could add a non-negligible factor to the risk when daily set-up verification with high-resolution modality is included. As prostate cancer is detected earlier, the probability of an increase in early stage patients rises, and life expectancy thus increases. Radiotherapy has improved its capability in the tailoring of the dose around the target at the cost of a greater dose to surrounding organs, thus increasing the risk of second tumor induction, especially for those patients expected to survive 15 y or more. PMID:26509622

  13. Inhibition of Fatty Acid Synthase Sensitizes Prostate Cancer Cells to Radiotherapy.

    PubMed

    Rae, Colin; Haberkorn, Uwe; Babich, John W; Mairs, Robert J

    2015-11-01

    Many common human cancers, including colon, prostate and breast cancer, express high levels of fatty acid synthase compared to normal human tissues. This elevated expression is associated with protection against apoptosis, increased metastasis and poor prognosis. Inhibitors of fatty acid synthase, such as the cerulenin synthetic analog C75, decrease prostate cancer cell proliferation, increase apoptosis and decrease tumor growth in experimental models. Although radiotherapy is widely used in the treatment of prostate cancer patients, the risk of damage to neighboring normal organs limits the radiation dose that can be delivered. In this study, we examined the potential of fatty acid synthase inhibition to sensitize prostate cancer cells to radiotherapy. The efficacy of C75 alone or in combination with X irradiation was examined in monolayers and in multicellular tumor spheroids. Treatment with C75 alone decreased clonogenic survival, an effect that was abrogated by the antioxidant. C75 treatment also delayed spheroid growth in a concentration-dependent manner. The radiosensitizing effect of C75 was indicated by combination index values between 0.65 and 0.71 and the reduced surviving fraction of clonogens, in response to 2 Gy X irradiation, from 0.51 to 0.30 and 0.11 in the presence of 25 and 35 μM C75, respectively. This increased sensitivity to radiation was reduced by the presence of the antioxidant. The C75 treatment also enhanced the spheroid growth delay induced by X irradiation in a supra-additive manner. The level of radiation-induced apoptosis in prostate cancer cells was increased further by C75, which induced cell cycle arrest in the G2/M phase, but only at a concentration greater than that required for radiosensitization. Radiation-induced G2/M blockade was not affected by C75 treatment. These results suggest the potential use of fatty acid synthase inhibition to enhance the efficacy of radiotherapy of prostate carcinoma and that C75-dependent cell

  14. Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

    SciTech Connect

    Hoffman, Karen E. Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

    2014-04-01

    Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

  15. How to identify rectal sub-regions likely involved in rectal bleeding in prostate cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Dréan, G.; Acosta, O.; Ospina, J. D.; Voisin, C.; Rigaud, B.; Simon, A.; Haigron, P.; de Crevoisier, R.

    2013-11-01

    Nowadays, the de nition of patient-speci c constraints in prostate cancer radiotherapy planning are solely based on dose-volume histogram (DVH) parameters. Nevertheless those DVH models lack of spatial accuracy since they do not use the complete 3D information of the dose distribution. The goal of the study was to propose an automatic work ow to de ne patient-speci c rectal sub-regions (RSR) involved in rectal bleeding (RB) in case of prostate cancer radiotherapy. A multi-atlas database spanning the large rectal shape variability was built from a population of 116 individuals. Non-rigid registration followed by voxel-wise statistical analysis on those templates allowed nding RSR likely correlated with RB (from a learning cohort of 63 patients). To de ne patient-speci c RSR, weighted atlas-based segmentation with a vote was then applied to 30 test patients. Results show the potentiality of the method to be used for patient-speci c planning of intensity modulated radiotherapy (IMRT).

  16. Pictorial review. Magnetic resonance for radiotherapy management and treatment planning in prostatic carcinoma.

    PubMed

    Lim, Christopher; Malone, Shawn C; Avruch, Leonard; Breau, Rodney H; Flood, Trevor A; Lim, Megan; Morash, Christopher; Quon, Jeff S; Walsh, Cynthia; Schieda, Nicola

    2015-10-01

    MRI has an important role for radiotherapy (RT) treatment planning in prostate cancer (PCa) providing accurate visualization of the dominant intraprostatic lesion (DIL) and locoregional anatomy, assessment of local staging and depiction of implanted devices. MRI enables the radiation oncologist to optimize RT planning by better defining target tumour volumes (thereby increasing local tumour control), as well as decreasing morbidity (by minimizing the dose to adjacent normal structures). Using MRI, radiation oncologists can define the DIL for delivery of boost doses of RT using a variety of techniques including: stereotactic body radiotherapy, intensity-modulated radiotherapy, proton RT or brachytherapy to improve tumour control. Radiologists require a familiarity with the different RT methods used to treat PCa, as well as an understanding of the advantages and disadvantages of the various MR pulse sequences available for RT planning in order to provide an optimal multidisciplinary RT treatment approach to PCa. Understanding the expected post-RT appearance of the prostate and typical characteristics of local tumour recurrence is also important because MRI is rapidly becoming an integral component for diagnosis, image-guided histological sampling and treatment planning in the setting of biochemical failure after RT or surgery. PMID:26279086

  17. Estimation of effective imaging dose for kilovoltage intratreatment monitoring of the prostate position during cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Ng, J. A.; Booth, J.; Poulsen, P.; Kuncic, Z.; Keall, P. J.

    2013-09-01

    Kilovoltage intratreatment monitoring (KIM) is a novel real-time localization modality where the tumor position is continuously measured during intensity modulated radiation therapy (IMRT) or intensity modulated arc therapy (IMAT) by a kilovoltage (kV) x-ray imager. Adding kV imaging during therapy adds radiation dose. The additional effective dose is quantified for prostate radiotherapy and compared to dose from other localization modalities. The software PCXMC 2.0 was used to calculate the effective dose delivered to a phantom as a function of imager angle and field size for a Varian On-Board Imager. The average angular effective dose was calculated for a field size of 6 cm × 6 cm. The average angular effective dose was used in calculations for different treatment scenarios. Treatment scenarios considered were treatment type and fractionation. For all treatment scenarios, (i.e. conventionally fractionated and stereotactic body radiotherapy (SBRT), IMRT and IMAT), the total KIM dose at 1 Hz ranged from 2-10 mSv. This imaging dose is less than the Navotek radioactive implant dose (64 mSv) and a standard SBRT cone beam computed tomography pretreatment scan dose (22 mSv) over an entire treatment regime. KIM delivers an acceptably low effective dose for daily use as a real-time image-guidance method for prostate radiotherapy.

  18. Feasibility of penumbra compensating filters for conformal prostate radiotherapy

    NASA Astrophysics Data System (ADS)

    Cadman, P.; Sidhu, N. P. S.

    2000-02-01

    Radiation therapy beams demonstrate a gradual dose fall-off at the field edges, due to factors affecting the physical penumbra and transport of radiation. Adequate target coverage requires an increase in field size larger than the target volume itself for a uniform dose to be delivered to that target volume. A method is presented for the design and fabrication of penumbra compensating filters (PCFs) which essentially sharpen the penumbra on a field-by-field basis and are used in conjunction with custom shielding blocks. We have explored the feasibility of using PCFs to reduce the field margins required for our four-field conformal prostate treatments. The penumbra compensation is designed based on a profile measured along the direction perpendicular to the blocked field edge that shows the greatest 50% to 95% isodose distance for a typical conformal prostate patient. Rigid foam material is milled and filled with a low melting point alloy material to create a filter which provides dose compensation in the field periphery of the custom shielding block. The accuracy of our methodology has been established using film dosimetry. By employing PCFs, the reduction in the rectal margin ranges from approximately 4 mm in the posterior region to 13 mm in the superior-posterior region, as compared with the shielding blocks alone. The reduction in bladder margin ranges from approximately 4 mm in the superior-anterior region to 10 mm in the superior region. Dose-volume histograms for an idealized cylindrical rectum indicate a substantial reduction in the volume treated to high doses. The calculated normal tissue complication probability values were 8.7% and 10.5% with and without PCFs included in the blocked fields respectively. The advantages of using PCFs, compared with multileaf collimator based techniques, are discussed.

  19. Dosimetric Study of Pelvic Proton Radiotherapy for High-Risk Prostate Cancer

    SciTech Connect

    Chera, Bhishamjit S.; Vargas, Carlos; Morris, Christopher G.; Louis, Debbie; Flampouri, Stella; Yeung, Daniel; Duvvuri, Srividya; Li Zuofeng; Mendenhall, Nancy Price

    2009-11-15

    Purpose: To compare dose distributions in targeted tissues (prostate, seminal vesicles, pelvic regional nodes) and nontargeted tissues in the pelvis with intensity-modulated radiotherapy (IMRT) and forward-planned, double-scattered, three-dimensional proton radiotherapy (3D-PRT). Methods and Materials: IMRT, IMRT followed by a prostate 3D-PRT boost (IMRT/3D-PRT), and 3D-PRT plans were created for 5 high-risk prostate cancer patients (n = 15 plans). A 78-CGE/Gy dose was prescribed to the prostate and proximal seminal vesicles and a 46-CGE/Gy was prescribed to the pelvic nodes. Various dosimetric endpoints were compared. Results: Target coverage of the prostate and nodal planning target volumes was adequate for all three plans. Compared with the IMRT and IMRT/3D-PRT plans, the 3D-PRT plans reduced the mean dose to the rectum, rectal wall, bladder, bladder wall, small bowel, and pelvis. The relative benefit of 3D-PRT (vs IMRT) at reducing the rectum and rectal wall V5-V40 was 53% to 71% (p < 0.05). For the bladder and bladder wall, the relative benefit for V5 to V40 CGE/Gy was 40% to 63% (p < 0.05). The relative benefit for reducing the volume of small bowel irradiated from 5 to 30 CGE/Gy in the 3D-PRT ranged from 62% to 69% (p < 0.05). Use of 3D-PRT did not produce the typical low-dose 'bath' of radiation to the pelvis seen with IMRT. Femoral head doses were higher for the 3D-PRT. Conclusions: Use of 3D-PRT significantly reduced the dose to normal tissues in the pelvis while maintaining adequate target coverage compared with IMRT or IMRT/3D-PRT. When treating the prostate, seminal vesicles, and pelvic lymph nodes in prostate cancer, proton therapy may improve the therapeutic ratio beyond what is possible with IMRT.

  20. Daily variations in delivered doses in patients treated with radiotherapy for localized prostate cancer

    SciTech Connect

    Kupelian, Patrick A. . E-mail: patrick.kupelian@orhs.org; Langen, Katja M.; Zeidan, Omar A.; Meeks, Sanford L.; Willoughby, Twyla R.; Wagner, Thomas H.; Jeswani, Sam; Ruchala, Kenneth J.; Haimerl, Jason; Olivera, Gustavo H.

    2006-11-01

    Purpose: The aim of this work was to study the variations in delivered doses to the prostate, rectum, and bladder during a full course of image-guided external beam radiotherapy. Methods and Materials: Ten patients with localized prostate cancer were treated with helical tomotherapy to 78 Gy at 2 Gy per fraction in 39 fractions. Daily target localization was performed using intraprostatic fiducials and daily megavoltage pelvic computed tomography (CT) scans, resulting in a total of 390 CT scans. The prostate, rectum, and bladder were manually contoured on each CT by a single physician. Daily dosimetric analysis was performed with dose recalculation. The study endpoints were D95 (dose to 95% of the prostate), rV2 (absolute rectal volume receiving 2 Gy), and bV2 (absolute bladder volume receiving 2 Gy). Results: For the entire cohort, the average D95 ({+-}SD) was 2.02 {+-} 0.04 Gy (range, 1.79-2.20 Gy). The average rV2 ({+-}SD) was 7.0 {+-} 8.1 cc (range, 0.1-67.3 cc). The average bV2 ({+-}SD) was 8.7 {+-} 6.8 cc (range, 0.3-36.8 cc). Unlike doses for the prostate, there was significant daily variation in rectal and bladder doses, mostly because of variations in volume and shape of these organs. Conclusion: Large variations in delivered doses to the rectum and bladder can be documented with daily megavoltage CT scans. Image guidance for the targeting of the prostate, even with intraprostatic fiducials, does not take into account the variation in actual rectal and bladder doses. The clinical impact of techniques that take into account such dosimetric parameters in daily patient set-ups should be investigated.

  1. Role of Intra- or Periprostatic Calcifications in Image-Guided Radiotherapy for Prostate Cancer

    SciTech Connect

    Hanna, Samir Abdallah; Neves-Junior, Wellington Furtado Pimenta; Marta, Gustavo Nader; Haddad, Cecilia Maria Kalil; Fernandes da Silva, Joao Luis

    2012-03-01

    Purpose: Image-guided radiotherapy (IGRT) allows more precise localization of the prostate, thus minimizing errors resulting from organ motion and set-up during treatment of prostate cancer. Using megavoltage cone-beam computed tomography (MVCBCT), references such as bones, the prostate itself or implanted fiducial markers can be used as surrogates to correct patient positioning immediately before each treatment fraction. However, the use of fiducials requires an invasive procedure and may increase costs. We aimed to assess whether intra- or periprostatic calcifications (IPC) could be used as natural fiducials. Methods and Materials: Data on patients treated with IGRT for prostate cancer with clearly visible IPC and implanted fiducials in both planning CT and MVCBCT images were reviewed. IPC were classified as central when inside the prostate and peripheral when within the planning target volume. Daily deviations in lateral, longitudinal, and vertical directions from baseline positioning using fiducials and using IPC were compared. Results: A total of 287 MVCBCT images were obtained and analyzed from 10 patients. The mean {+-} standard deviation daily deviation (mm) in the lateral, longitudinal, and vertical coordinates were 0.55 {+-} 3.11, 0.58 {+-} 3.45, and -0.54 {+-} 4.03, respectively, for fiducials, and 0.72 {+-} 3.22, 0.63 {+-} 3.58, and -0.69 {+-} 4.26, for IPC. The p values for comparisons (fiducials vs. IPC) were 0.003, 0.653, and 0.078 for lateral, longitudinal, and vertical coordinates, respectively. When cases with central IPC were analyzed (n = 7), no significant difference was found in such comparisons. Central IPC and fiducials exhibited a similar pattern of displacement during treatment, with equal values for daily displacements in the three directions for more than 90% of measurements. Conclusions: Our data suggest that centrally located IPC may be used as natural fiducials for treatment positioning during IGRT for prostate cancer, with potential

  2. Failure to Achieve a PSA Level {<=}1 ng/mL After Neoadjuvant LHRHA Therapy Predicts for Lower Biochemical Control Rate and Overall Survival in Localized Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Mitchell, Darren M. McAleese, Jonathan; Park, Richard M.; Stewart, David P.; Stranex, Stephen; Eakin, Ruth L.; Houston, Russell F.; O'Sullivan, Joe M.

    2007-12-01

    Purpose: To investigate whether failure to suppress the prostate-specific antigen (PSA) level to {<=}1 ng/mL after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy in patients scheduled to undergo external beam radiotherapy for localized prostate carcinoma is associated with reduced biochemical failure-free survival. Methods and Materials: A retrospective case note review of consecutive patients with intermediate- or high-risk localized prostate cancer treated between January 2001 and December 2002 with neoadjuvant hormonal deprivation therapy, followed by concurrent hormonal therapy and radiotherapy was performed. Patient data were divided for analysis according to whether the PSA level in Week 1 of radiotherapy was {<=}1.0 ng/mL. Biochemical failure was determined using the American Society for Therapeutic Radiology and Oncology (Phoenix) definition. Results: A total of 119 patients were identified. The PSA level after neoadjuvant hormonal deprivation therapy was {<=}1 ng/mL in 67 patients and >1 ng/mL in 52. At a median follow-up of 49 months, the 4-year actuarial biochemical failure-free survival rate was 84% vs. 60% (p = 0.0016) in favor of the patients with a PSA level after neoadjuvant hormonal deprivation therapy of {<=}1 ng/mL. The overall survival rate was 94% vs. 77.5% (p = 0.0045), and the disease-specific survival rate at 4 years was 98.5% vs. 82.5%. Conclusions: The results of our study have shown that patients with a PSA level >1 ng/mL at the beginning of external beam radiotherapy after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy have a significantly greater rate of biochemical failure and lower survival rate compared with those with a PSA level of {<=}1 ng/mL. Patients without adequate PSA suppression should be considered a higher risk group and considered for dose escalation or the use of novel treatments.

  3. Equivalent dose and effective dose from stray radiation during passively scattered proton radiotherapy for prostate cancer

    NASA Astrophysics Data System (ADS)

    Fontenot, Jonas; Taddei, Phillip; Zheng, Yuanshui; Mirkovic, Dragan; Jordan, Thomas; Newhauser, Wayne

    2008-03-01

    Proton therapy reduces the integral therapeutic dose required for local control in prostate patients compared to intensity-modulated radiotherapy. One proposed benefit of this reduction is an associated decrease in the incidence of radiogenic secondary cancers. However, patients are also exposed to stray radiation during the course of treatment. The purpose of this study was to quantify the stray radiation dose received by patients during proton therapy for prostate cancer. Using a Monte Carlo model of a proton therapy nozzle and a computerized anthropomorphic phantom, we determined that the effective dose from stray radiation per therapeutic dose (E/D) for a typical prostate patient was approximately 5.5 mSv Gy-1. Sensitivity analysis revealed that E/D varied by ±30% over the interval of treatment parameter values used for proton therapy of the prostate. Equivalent doses per therapeutic dose (HT/D) in specific organs at risk were found to decrease with distance from the isocenter, with a maximum of 12 mSv Gy-1 in the organ closest to the treatment volume (bladder) and 1.9 mSv Gy-1 in the furthest (esophagus). Neutrons created in the nozzle predominated effective dose, though neutrons created in the patient contributed substantially to the equivalent dose in organs near the proton field. Photons contributed less than 15% to equivalent doses.

  4. Target Definition in Salvage Radiotherapy for Recurrent Prostate Cancer: The Role of Advanced Molecular Imaging

    PubMed Central

    Amzalag, Gaël; Rager, Olivier; Tabouret-Viaud, Claire; Wissmeyer, Michael; Sfakianaki, Electra; de Perrot, Thomas; Ratib, Osman; Miralbell, Raymond; Giovacchini, Giampiero; Garibotto, Valentina; Zilli, Thomas

    2016-01-01

    Salvage radiotherapy (SRT) represents the main treatment option for relapsing prostate cancer in patients after radical prostatectomy. Several open questions remain unanswered in terms of target volumes definition and delivered doses for SRT: the effective dose necessary to achieve biochemical control in the SRT setting may be different if the tumor recurrence is micro- or macroscopic. At the same time, irradiation of only the prostatic bed or of the whole pelvis will depend on the localization of the recurrence, local or locoregional. In the “theragnostic imaging” era, molecular imaging using positron emission tomography (PET) constitutes a useful tool for clinicians to define the site of the recurrence, the extent of disease, and individualize salvage treatments. The best option currently available in clinical routine is the combination of radiolabeled choline PET imaging and multiparametric magnetic resonance imaging (MRI), associating the nodal and distant metastases identification based on PET with the local assessment by MRI. A new generation of targeted tracers, namely, prostate-specific membrane antigen, show promising results, with a contrast superior to choline imaging and a higher detection rate even for low prostate-specific antigen levels; validation studies are ongoing. Finally, imaging targeting bone remodeling, using whole-body SPECT–CT, is a relevant complement to molecular/metabolic PET imaging when bone involvement is suspected. PMID:27065024

  5. Comparison of manual and automatic MR-CT registration for radiotherapy of prostate cancer.

    PubMed

    Korsager, Anne Sofie; Carl, Jesper; Riis Østergaard, Lasse

    2016-01-01

    In image-guided radiotherapy (IGRT) of prostate cancer, delineation of the clini-cal target volume (CTV) often relies on magnetic resonance (MR) because of its good soft-tissue visualization. Registration of MR and computed tomography (CT) is required in order to add this accurate delineation to the dose planning CT. An automatic approach for local MR-CT registration of the prostate has previously been developed using a voxel property-based registration as an alternative to a manual landmark-based registration. The aim of this study is to compare the two registration approaches and to investigate the clinical potential for replacing the manual registration with the automatic registration. Registrations and analysis were performed for 30 prostate cancer patients treated with IGRT using a Ni-Ti prostate stent as a fiducial marker. The comparison included computing translational and rotational differences between the approaches, visual inspection, and computing the overlap of the CTV. The computed mean translational difference was 1.65, 1.60, and 1.80mm and the computed mean rotational difference was 1.51°, 3.93°, and 2.09° in the superior/inferior, anterior/posterior, and medial/lateral direction, respectively. The sensitivity of overlap was 87%. The results demonstrate that the automatic registration approach performs registrations comparable to the manual registration. PMID:27167285

  6. Impact of Body Mass Index on Outcomes After Conformal Radiotherapy in Patients With Prostate Cancer

    SciTech Connect

    Geinitz, Hans; Thamm, Reinhard; Mueller, Tobias; Jess, Kerstin; Zimmermann, Frank B.; Molls, Michael; Nieder, Carsten

    2011-09-01

    Purpose: Several retrospective analyses have suggested that obese men with prostate cancer treated with external beam radiotherapy (EBRT) have outcomes inferior to those of normal-weight men. However, a recently presented analysis for the first time challenged this association between body mass index (BMI) and treatment failure. It is therefore important to provide further data on this issue. Methods and Materials: This was a retrospective analysis of 564 men treated with risk-adapted conformal EBRT at a single institution. Low-risk patients received EBRT alone, and the other patients received EBRT plus endocrine treatment. In addition, high-risk patients were treated to higher EBRT doses (74 Gy). A rectal balloon catheter for internal immobilization, which can be identified on portal images, was used in 261 patients (46%). Thus, localization did not rely on bony landmarks alone in these cases. Results: The median BMI was 26, and 15% of patients had BMI {>=}30. Neither univariate nor multivariate analyses detected any significant impact of BMI on biochemical relapse, prostate cancer-specific survival, or overall survival. The 5-year biochemical relapse rate was 21% and prostate cancerspecific survival 96%. Conclusions: The present analysis of a large cohort of consecutively treated patients suggests that efforts to reduce prostate movement and geographic miss might result in comparable outcomes in obese and normal-weight patients.

  7. Stereotactic Body Radiotherapy for Recurrent Squamous Cell Carcinoma of the Head and Neck: Results of a Phase I Dose-Escalation Trial

    SciTech Connect

    Heron, Dwight E.; Ferris, Robert L.; Karamouzis, Michalis; Andrade, Regiane S.; Deeb, Erin L.; Burton, Steven; Gooding, William E.; Branstetter, Barton F.; Mountz, James M.; Johnson, Jonas T.; Argiris, Athanassios; Grandis, Jennifer R.; Lai, Stephen Y.

    2009-12-01

    Purpose: To evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) in previously irradiated patients with squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods: In this Phase I dose-escalation clinical trial, 25 patients were treated in five dose tiers up to 44 Gy, administered in 5 fractions over a 2-week course. Response was assessed according to the Response Evaluation Criteria in Solid Tumors and [{sup 18}F]-fluorodeoxyglucose standardized uptake value change on positron emission tomography-computed tomography (PET-CT). Results: No Grade 3/4 or dose-limiting toxicities occurred. Four patients had Grade 1/2 acute toxicities. Four objective responses were observed, for a response rate of 17% (95% confidence interval 2%-33%). The maximum duration of response was 4 months. Twelve patients had stable disease. Median time to disease progression was 4 months, and median overall survival was 6 months. Self-reported quality of life was not significantly affected by treatment. Fluorodeoxyglucose PET was a more sensitive early-measure response to treatment than CT volume changes. Conclusion: Reirradiation up to 44 Gy using SBRT is well tolerated in the acute setting and warrants further evaluation in combination with conventional and targeted therapies.

  8. Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity

    PubMed Central

    Ahmed, Mahbubl; Dorling, Leila; Kerns, Sarah; Fachal, Laura; Elliott, Rebecca; Partliament, Matt; Rosenstein, Barry S; Vega, Ana; Gómez-Caamaño, Antonio; Barnett, Gill; Dearnaley, David P; Hall, Emma; Sydes, Matt; Burnet, Neil; Pharoah, Paul D P; Eeles, Ros; West, Catharine M L

    2016-01-01

    Background: Numerous germline single-nucleotide polymorphisms increase susceptibility to prostate cancer, some lying near genes involved in cellular radiation response. This study investigated whether prostate cancer patients with a high genetic risk have increased toxicity following radiotherapy. Methods: The study included 1560 prostate cancer patients from four radiotherapy cohorts: RAPPER (n=533), RADIOGEN (n=597), GenePARE (n=290) and CCI (n=150). Data from genome-wide association studies were imputed with the 1000 Genomes reference panel. Individuals were genetically similar with a European ancestry based on principal component analysis. Genetic risks were quantified using polygenic risk scores. Regression models tested associations between risk scores and 2-year toxicity (overall, urinary frequency, decreased stream, rectal bleeding). Results were combined across studies using standard inverse-variance fixed effects meta-analysis methods. Results: A total of 75 variants were genotyped/imputed successfully. Neither non-weighted nor weighted polygenic risk scores were associated with late radiation toxicity in individual studies (P>0.11) or after meta-analysis (P>0.24). No individual variant was associated with 2-year toxicity. Conclusion: Patients with a high polygenic susceptibility for prostate cancer have no increased risk for developing late radiotherapy toxicity. These findings suggest that patients with a genetic predisposition for prostate cancer, inferred by common variants, can be safely treated using current standard radiotherapy regimens. PMID:27070714

  9. A phase I dose escalation study of S-1 with concurrent radiotherapy in elderly patients with esophageal cancer

    PubMed Central

    Ji, Yongling; Qiu, Guoqing; Sheng, Liming; Sun, Xiaojiang; Zheng, Yuanda; Chen, Ming

    2016-01-01

    Background Concurrent chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and cisplatin (CDDP) are often associated with significant incidence of toxic effects in elderly patients with esophageal cancer. This phase I trial was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of S-1, an oral 5-FU derivative, when given with radiotherapy in elderly patients. Methods Patients who were age of 70 years or older with histologically confirmed esophageal cancer, and had an Eastern Cooperative Oncology Group (ECOG) score of 0–2 were eligible for this study. Radiotherapy was administered in 1.8 Gy fractions 5 times weekly to a total dose of 54 Gy. S-1 was administered on days 1–14 and 29–42 at the following dosages: 60, 70, and 80 mg/m2/day. Trial registration: NCT01175447 (ClinicalTrials.gov). Results Twelve previously untreated patients were enrolled in this study. No grade 3 or 4 toxicity was observed in six patients treated at the 60 and 70 mg/m2 dose levels. DLT was observed in four of six patients treated at the 80 mg/m2 dose level. Two patients developed grade 3 esophagitis, one patient developed grade 3 esophagitis and pneumonitis, and one patient developed grade 3 thrombocytopaenia. Endoscopic complete response (CR) was observed in eight patients (66.7%). The median progression free survival (PFS) was 20 months and median overall survival was 29 months. Conclusions The MTD of S-1 was 80 mg/m2, and the recommended dose (RD) for phase II studies was 70 mg/m2. This regimen was well tolerated and active in elderly patients with esophageal cancer, meriting further investigation in phase II studies. PMID:27076940

  10. Effects of external beam radiotherapy on endocrine function in patients with carcinoma of the prostate

    SciTech Connect

    Grigsby, P.W.; Perez, C.A.

    1986-04-01

    Serum levels of testosterone, dihydrotestosterone, and follicle-stimulating and luteinizing hormones were determined prospectively in 59 patients with carcinoma of the prostate treated curatively with external beam radiotherapy. Hormone levels were determined before the initiation of therapy and up to 2 years following completion of therapy. Testosterone levels remained unchanged but dihydrotestosterone levels decreased slightly. Follicle-stimulating and luteinizing hormone levels increased significantly during therapy and remained elevated for up to 2 years after therapy. These findings are consistent with low dose irradiation of the testis.

  11. Hypofractionated Concomitant Intensity-Modulated Radiotherapy Boost for High-Risk Prostate Cancer: Late Toxicity

    SciTech Connect

    Quon, Harvey; Cheung, Patrick C.F.; Loblaw, D. Andrew; Morton, Gerard; Pang, Geordi; Szumacher, Ewa; Danjoux, Cyril; Choo, Richard; Thomas, Gillian; Kiss, Alex; Mamedov, Alexandre; Deabreu, Andrea

    2012-02-01

    Purpose: To report the acute and late toxicities of patients with high-risk localized prostate cancer treated using a concomitant hypofractionated, intensity-modulated radiotherapy boost combined with long-term androgen deprivation therapy. Methods and Materials: A prospective Phase I-II study of patients with any of the following: clinical Stage T3 disease, prostate-specific antigen level {>=}20 ng/mL, or Gleason score 8-10. A dose of 45 Gy (1.8 Gy/fraction) was delivered to the pelvic lymph nodes with a concomitant 22.5 Gy prostate intensity-modulated radiotherapy boost, to a total of 67.5 Gy (2.7 Gy/fraction) in 25 fractions within 5 weeks. Image guidance was performed using three gold seed fiducials. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, and Radiation Therapy Oncology Group late morbidity scores were used to assess the acute and late toxicities, respectively. Biochemical failure was determined using the Phoenix definition. Results: A total of 97 patients were treated and followed up for a median of 39 months, with 88% having a minimum of 24 months of follow-up. The maximal toxicity scores were recorded. The grade of acute gastrointestinal toxicity was Grade 0 in 4%, 1 in 59%, and 2 in 37%. The grade of acute urinary toxicity was Grade 0 in 8%, 1 in 50%, 2 in 39%, and 3 in 4%. The grade of late gastrointestinal toxicity was Grade 0 in 54%, 1 in 40%, and 2 in 7%. No Grade 3 or greater late gastrointestinal toxicities developed. The grade of late urinary toxicity was Grade 0 in 82%, 1 in 9%, 2 in 5%, 3 in 3%, and 4 in 1% (1 patient). All severe toxicities (Grade 3 or greater) had resolved at the last follow-up visit. The 4-year biochemical disease-free survival rate was 90.5%. Conclusions: A hypofractionated intensity-modulated radiotherapy boost delivering 67.5 Gy in 25 fractions within 5 weeks combined with pelvic nodal radiotherapy and long-term androgen deprivation therapy was well tolerated, with low rates

  12. Age and Comorbid Illness Are Associated With Late Rectal Toxicity Following Dose-Escalated Radiation Therapy for Prostate Cancer

    SciTech Connect

    Hamstra, Daniel A.; Stenmark, Matt H.; Ritter, Tim; Litzenberg, Dale; Jackson, William; Johnson, Skyler; Albrecht-Unger, Liesel; Donaghy, Alex; Phelps, Laura; Blas, Kevin; Halverson, Schuyler; Marsh, Robin; Olson, Karin; Feng, Felix Y.

    2013-04-01

    Purpose: To assess the impacts of patient age and comorbid illness on rectal toxicity following external beam radiation therapy (EBRT) for prostate cancer and to assess the Qualitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) normal tissue complication probability (NTCP) model in this context. Methods and Materials: Rectal toxicity was analyzed in 718 men previously treated for prostate cancer with EBRT (≥75 Gy). Comorbid illness was scored using the Charlson Comorbidity Index (CCMI), and the NTCP was evaluated with the QUANTEC model. The influence of clinical and treatment-related parameters on rectal toxicity was assessed by Kaplan-Meier and Cox proportional hazards models. Results: The cumulative incidence of rectal toxicity grade ≥2 was 9.5% and 11.6% at 3 and 5 years and 3.3% and 3.9% at 3 and 5 years for grade ≥3 toxicity, respectively. Each year of age predicted an increasing relative risk of grade ≥2 (P<.03; hazard ratio [HR], 1.04 [95% confidence interval (CI), 1.01-1.06]) and ≥3 rectal toxicity (P<.0001; HR, 1.14 [95% CI,1.07-1.22]). Increasing CCMI predicted rectal toxicity where a history of either myocardial infarction (MI) (P<.0001; HR, 5.1 [95% CI, 1.9-13.7]) or congestive heart failure (CHF) (P<.0006; HR, 5.4 [95% CI, 0.6-47.5]) predicted grade ≥3 rectal toxicity, with lesser correlation with grade ≥2 toxicity (P<.02 for MI, and P<.09 for CHF). An age comorbidity model to predict rectal toxicity was developed and confirmed in a validation cohort. The use of anticoagulants increased toxicity independent of age and comorbidity. NTCP was prognostic for grade ≥3 (P=.015) but not grade ≥2 (P=.49) toxicity. On multivariate analysis, age, MI, CHF, and an NTCP >20% all correlated with late rectal toxicity. Conclusions: Patient age and a history of MI or CHF significantly impact rectal toxicity following EBRT for the treatment of prostate cancer, even after controlling for NTCP.

  13. Gleason Pattern 5 Is the Greatest Risk Factor for Clinical Failure and Death From Prostate Cancer After Dose-Escalated Radiation Therapy and Hormonal Ablation

    SciTech Connect

    Sabolch, Aaron; Feng, Felix Y.; Daignault-Newton, Stephanie; Halverson, Schuyler; Blas, Kevin; Phelps, Laura; Olson, Karin B.; Sandler, Howard M.; Hamstra, Daniel A.

    2011-11-15

    Purpose: The division of Gleason score (GS) into three categories (2-6, 7, 8-10) may not fully use its prognostic power, as revealed by recent reports demonstrating the presence of Gleason Pattern 5 (GP5) as a strong predictor for biochemical recurrence. Therefore, we analyzed the clinical outcomes in patients treated with dose-escalated radiation therapy (RT) based on the presence or absence of GP5. Methods and Materials: Outcomes were analyzed for 718 men treated for localized prostate cancer with external-beam RT to a minimum planning target volume dose of at least 75 Gy. We assessed the impact of GP5 and that of pretreatment- and treatment-related factors on freedom from biochemical failure, freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival (OS). Results: At biopsy, 89% of patients had no GP5, and 11% (76/718) had GP5. There were no differences in age, comorbid illness, T stage, prostate-specific antigen, or the use or duration of androgen deprivation therapy between GS8 without GP5 and GS8-10 with GP5. The presence of GP5 predicted lower FFM (p < 0.002; hazard ratio [HR] 3.4 [1.7-7.1]); CSS (p < 0.0001; HR 12.9 [5.4-31]); and OS (p < 0.0001; HR 3.6 [2.0-6.5]) in comparison with GS8 (without GP5). The 8-year FFM, CSS, and OS were 89%, 98%, and 57%, respectively, for those with Gleason 8 prostate cancer without GP5 in comparison with 61%, 55%, and 31%, respectively, for those with GP5. In addition, both FFM and CSS were strongly influenced by androgen deprivation therapy given concurrently with RT. On multivariate analysis, GP5 was the strongest prognostic factor for all clinical endpoints, including OS. Conclusion: The presence of GP5 predicts for worse clinical behavior, which therefore needs to be accounted for by risk stratification schemes. Further intensification of local and/or systemic therapy may be appropriate for such patients.

  14. Salvage Radiotherapy for Rising Prostate-Specific Antigen Levels After Radical Prostatectomy for Prostate Cancer: Dose-Response Analysis

    SciTech Connect

    Bernard, Johnny Ray; Buskirk, Steven J.; Heckman, Michael G.; Diehl, Nancy N.; Ko, Stephen J.; Macdonald, Orlan K.; Schild, Steven E.; Pisansky, Thomas M.

    2010-03-01

    Purpose: To investigate the association between external beam radiotherapy (EBRT) dose and biochemical failure (BcF) of prostate cancer in patients who received salvage prostate bed EBRT for a rising prostate-specific antigen (PSA) level after radical prostatectomy. Methods and Materials: We evaluated patients with a rising PSA level after prostatectomy who received salvage EBRT between July 1987 and October 2007. Patients receiving pre-EBRT androgen suppression were excluded. Cox proportional hazards models were used to investigate the association between EBRT dose and BcF. Dose was considered as a numeric variable and as a categoric variable (low, <64.8 Gy; moderate, 64.8-66.6 Gy; high, >66.6 Gy). Results: A total of 364 men met study selection criteria and were followed up for a median of 6.0 years (range, 0.1-19.3 years). Median pre-EBRT PSA level was 0.6 ng/mL. The estimated cumulative rate of BcF at 5 years after EBRT was 50% overall and 57%, 46%, and 39% for the low-, moderate-, and high-dose groups, respectively. In multivariable analysis adjusting for potentially confounding variables, there was evidence of a linear trend between dose and BcF, with risk of BcF decreasing as dose increased (relative risk [RR], 0.77 [5.0-Gy increase]; p = 0.05). Compared with the low-dose group, there was evidence of a decreased risk of BcF for the high-dose group (RR, 0.60; p = 0.04), but no difference for the moderate-dose group (RR, 0.85; p = 0.41). Conclusions: Our results suggest a dose response for salvage EBRT. Doses higher than 66.6 Gy result in decreased risk of BcF.

  15. A hybrid strategy of offline adaptive planning and online image guidance for prostate cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Lei, Yu; Wu, Qiuwen

    2010-04-01

    Offline adaptive radiotherapy (ART) has been used to effectively correct and compensate for prostate motion and reduce the required margin. The efficacy depends on the characteristics of the patient setup error and interfraction motion through the whole treatment; specifically, systematic errors are corrected and random errors are compensated for through the margins. In online image-guided radiation therapy (IGRT) of prostate cancer, the translational setup error and inter-fractional prostate motion are corrected through pre-treatment imaging and couch correction at each fraction. However, the rotation and deformation of the target are not corrected and only accounted for with margins in treatment planning. The purpose of this study was to investigate whether the offline ART strategy is necessary for an online IGRT protocol and to evaluate the benefit of the hybrid strategy. First, to investigate the rationale of the hybrid strategy, 592 cone-beam-computed tomography (CBCT) images taken before and after each fraction for an online IGRT protocol from 16 patients were analyzed. Specifically, the characteristics of prostate rotation were analyzed. It was found that there exist systematic inter-fractional prostate rotations, and they are patient specific. These rotations, if not corrected, are persistent through the treatment fraction, and rotations detected in early fractions are representative of those in later fractions. These findings suggest that the offline adaptive replanning strategy is beneficial to the online IGRT protocol with further margin reductions. Second, to quantitatively evaluate the benefit of the hybrid strategy, 412 repeated helical CT scans from 25 patients during the course of treatment were included in the replanning study. Both low-risk patients (LRP, clinical target volume, CTV = prostate) and intermediate-risk patients (IRP, CTV = prostate + seminal vesicles) were included in the simulation. The contours of prostate and seminal vesicles were

  16. A Study of Image-Guided Intensity-Modulated Radiotherapy With Fiducials for Localized Prostate Cancer Including Pelvic Lymph Nodes

    SciTech Connect

    Hsu, Annie; Pawlicki, Todd; Luxton, Gary; Hara, Wendy; King, Christopher R. . E-mail: crking@stanford.edu

    2007-07-01

    Purpose: To study the impact on nodal coverage and dose to fixed organs at risk when using daily fiducial localization of the prostate to deliver intensity-modulated radiotherapy (IMRT). Methods and Materials: Five patients with prostate cancer in whom prostate and pelvic nodes were irradiated with IMRT were studied. Dose was prescribed such that 95% of the prostate planning target volume (PTV) and 90% of the nodal PTV were covered. Random and systematic prostate displacements in the anterior-posterior, superior-inferior, and left-right directions were simulated to shift the original isocenter of the IMRT plan. The composite dose during the course of treatment was calculated. Results: Compared with a static setup, simulating random shifts reduced dose by less than 1.5% for nodal hotspot (i.e., dose to 1 cm{sup 3}), by less than 1% for the 90% nodal PTV coverage, and by less than 0.5% for the nodal mean dose. Bowel and femoral head hotspots were reduced by less than 1.5% and 2%, respectively. A 10-mm systematic offset reduced nodal coverage by up to 10%. Conclusion: The use of prostate fiducials for daily localization during IMRT treatment results in negligible changes in dose coverage of pelvic nodes or normal tissue sparing in the absence of a significant systematic offset. This offers a simple and practical solution to the problem of image-guided radiotherapy for prostate cancer when including pelvic nodes.

  17. First Clinical Release of an Online, Adaptive, Aperture-Based Image-Guided Radiotherapy Strategy in Intensity-Modulated Radiotherapy to Correct for Inter- and Intrafractional Rotations of the Prostate

    SciTech Connect

    Deutschmann, Heinz; Kametriser, Gerhard; Steininger, Philipp; Scherer, Philipp; Schoeller, Helmut; Gaisberger, Christoph; Mooslechner, Michaela; Mitterlechner, Bernhard; Weichenberger, Harald; Fastner, Gert; Wurstbauer, Karl; Jeschke, Stephan; Forstner, Rosemarie; Sedlmayer, Felix

    2012-08-01

    Purpose: We developed and evaluated a correction strategy for prostate rotations using direct adaptation of segments in intensity-modulated radiotherapy (IMRT). Method and Materials: Implanted fiducials (four gold markers) were used to determine interfractional translations, rotations, and dilations of the prostate. We used hybrid imaging: The markers were automatically detected in two pretreatment planar X-ray projections; their actual position in three-dimensional space was reconstructed from these images at first. The structure set comprising prostate, seminal vesicles, and adjacent rectum wall was transformed accordingly in 6 degrees of freedom. Shapes of IMRT segments were geometrically adapted in a class solution forward-planning approach, derived within seconds on-site and treated immediately. Intrafractional movements were followed in MV electronic portal images captured on the fly. Results: In 31 of 39 patients, for 833 of 1013 fractions (supine, flat couch, knee support, comfortably full bladder, empty rectum, no intraprostatic marker migrations >2 mm of more than one marker), the online aperture adaptation allowed safe reduction of margins clinical target volume-planning target volume (prostate) down to 5 mm when only interfractional corrections were applied: Dominant L-R rotations were found to be 5.3 Degree-Sign (mean of means), standard deviation of means {+-}4.9 Degree-Sign , maximum at 30.7 Degree-Sign . Three-dimensional vector translations relative to skin markings were 9.3 {+-} 4.4 mm (maximum, 23.6 mm). Intrafractional movements in 7.7 {+-} 1.5 min (maximum, 15.1 min) between kV imaging and last beam's electronic portal images showed further L-R rotations of 2.5 Degree-Sign {+-} 2.3 Degree-Sign (maximum, 26.9 Degree-Sign ), and three-dimensional vector translations of 3.0 {+-}3.7 mm (maximum, 10.2 mm). Addressing intrafractional errors could further reduce margins to 3 mm. Conclusion: We demonstrated the clinical feasibility of an online

  18. Adaptive Radiotherapy for Prostate Cancer Using Kilovoltage Cone-Beam Computed Tomography: First Clinical Results

    SciTech Connect

    Nijkamp, Jasper; Pos, Floris J. Nuver, Tonnis T.; Jong, Rianne de; Remeijer, Peter; Sonke, Jan-Jakob; Lebesque, Joos V.

    2008-01-01

    Purpose: To evaluate the first clinical results of an off-line adaptive radiotherapy (ART) protocol for prostate cancer using kilovoltage cone-beam computed tomography (CBCT) in combination with a diet and mild laxatives. Methods and Materials: Twenty-three patients began treatment with a planning target volume (PTV) margin of 10 mm. The CBCT scans acquired during the first six fractions were used to generate an average prostate clinical target volume (AV-CTV), and average rectum (AV-Rect). Using these structures, a new treatment plan was generated with a 7-mm PTV margin. Weekly CBCT scans were used to monitor the CTV coverage. A diet and mild laxatives were introduced to improve image quality and reduce prostate motion. Results: Twenty patients were treated with conform ART protocol. For these patients, 91% of the CBCT scans could be used to calculate the AV-CTV and AV-Rect. In 96% of the follow-up CBCT scans, the CTV was located within the average PTV. In the remaining 4%, the prostate extended the PTV by a maximum of 1 mm. Systematic and random errors for organ motion were reduced by a factor of two compared with historical data without diet and laxatives. An average PTV reduction of 29% was achieved. The volume of the AV-Rect that received >65 Gy was reduced by 19%. The mean dose to the anal wall was reduced on average by 4.8 Gy. Conclusions: We safely reduced the high-dose region by 29%. The reduction in irradiated volume led to a significant reduction in the dose to the rectum. The diet and laxatives improved the image quality and tended to reduce prostate motion.

  19. Practical Method of Adaptive Radiotherapy for Prostate Cancer Using Real-Time Electromagnetic Tracking

    SciTech Connect

    Olsen, Jeffrey R.; Noel, Camille E.; Baker, Kenneth; Santanam, Lakshmi; Michalski, Jeff M.; Parikh, Parag J.

    2012-04-01

    Purpose: We have created an automated process using real-time tracking data to evaluate the adequacy of planning target volume (PTV) margins in prostate cancer, allowing a process of adaptive radiotherapy with minimal physician workload. We present an analysis of PTV adequacy and a proposed adaptive process. Methods and Materials: Tracking data were analyzed for 15 patients who underwent step-and-shoot multi-leaf collimation (SMLC) intensity-modulated radiation therapy (IMRT) with uniform 5-mm PTV margins for prostate cancer using the Calypso Registered-Sign Localization System. Additional plans were generated with 0- and 3-mm margins. A custom software application using the planned dose distribution and structure location from computed tomography (CT) simulation was developed to evaluate the dosimetric impact to the target due to motion. The dose delivered to the prostate was calculated for the initial three, five, and 10 fractions, and for the entire treatment. Treatment was accepted as adequate if the minimum delivered prostate dose (D{sub min}) was at least 98% of the planned D{sub min}. Results: For 0-, 3-, and 5-mm PTV margins, adequate treatment was obtained in 3 of 15, 12 of 15, and 15 of 15 patients, and the delivered D{sub min} ranged from 78% to 99%, 96% to 100%, and 99% to 100% of the planned D{sub min}. Changes in D{sub min} did not correlate with magnitude of prostate motion. Treatment adequacy during the first 10 fractions predicted sufficient dose delivery for the entire treatment for all patients and margins. Conclusions: Our adaptive process successfully used real-time tracking data to predict the need for PTV modifications, without the added burden of physician contouring and image analysis. Our methods are applicable to other uses of real-time tracking, including hypofractionated treatment.

  20. Intermittent androgen ablation in patients with biochemical failure after pelvic radiotherapy for localized prostate cancer

    SciTech Connect

    Cury, Fabio L.B.; Souhami, Luis . E-mail: luis.souhami@muhc.mcgill.ca; Rajan, Raghu; Tanguay, Simon; Gagnon, Bruno; Duclos, Marie; Shenouda, George; Faria, Sergio L.; David, Marc; Freeman, Carolyn R.

    2006-03-01

    Purpose: To assess the efficacy of intermittent androgen ablation (IAA) in patients with biochemical failure after radiotherapy for prostate cancer. Methods and Materials: Thirty-nine patients received a luteinizing hormone-releasing hormone analog every 2 months for a total of 4 doses. IAA was then discontinued if serum prostate-specific antigen (PSA) fell to a normal level with a castrate level of testosterone. Therapy was restarted when the serum PSA level reached {>=}10 ng/mL and was discontinued if hormone resistance or unacceptable toxicity occurred. Results: Median PSA was 9.1 ng/mL at the time of first IAA. The median time between the first and the second cycles was 20.1 months, decreasing to 15.5 months between the third and fourth cycles. Two patients discontinued the treatment because of severe hot flushes. Four patients developed hormone resistance. With a median follow-up of 56.4 months, 5-year survival is 92.3%. Three patients died of unrelated causes. The incidence of distant metastasis is 6.8%. Conclusions: The use of IAA seems to be a safe and effective treatment for patients with biochemical failure post radiotherapy and no evidence of metastatic disease. The use of IAA limits hormone-related side effects and health care costs without an apparent increase in the risk for the development of metastatic disease.

  1. Salvage High-intensity Focused Ultrasound for the Recurrent Prostate Cancer after Radiotherapy

    SciTech Connect

    Shoji, S.; Nakano, M.; Omata, T.; Harano, Y.; Nagata, Y.; Uchida, T.; Usui, Y.; Terachi, T.

    2010-03-09

    To investigate the use of minimally invasive high-intensity focused ultrasound (HIFU) as a salvage therapy in men with localized prostate cancer recurrence following external beam radiotherapy (EBRT), brachytherapy or proton therapy. A review of 20 cases treated using the Sonablate registered 500 HIFU device, between August 28, 2002 and September 1, 2009, was carried out. All men had presumed organ-confined, histologically confirmed recurrent prostate adenocarcinoma following radiation therapy. All men with presumed, organ-confined, recurrent disease following EBRT in 8 patients, brachytherapy in 7 patients or proton therapy in 5 patients treated with salvage HIFU were included. The patients were followed for a mean (range) of 16.0 (3-80) months. Biochemical disease-free survival (bDFS) rates in patients with low-intermediate and high risk groups were 86% and 50%, respectively. Side-effects included urethral stricture in 2 of the 16 patients (13%), urinary tract infection or dysuria syndrome in eight (26%), and urinary incontinence in one (6%). Recto-urethral fistula occurred in one patient (6%). Transrectal HIFU is an effective treatment for recurrence after radiotherapy especially in patients with low- and intermediate risk groups.

  2. Salvage High-intensity Focused Ultrasound for the Recurrent Prostate Cancer after Radiotherapy

    NASA Astrophysics Data System (ADS)

    Shoji, S.; Nakano, M.; Omata, T.; Harano, Y.; Nagata, Y.; Usui, Y.; Terachi, T.; Uchida, T.

    2010-03-01

    To investigate the use of minimally invasive high-intensity focused ultrasound (HIFU) as a salvage therapy in men with localized prostate cancer recurrence following external beam radiotherapy (EBRT), brachytherapy or proton therapy. A review of 20 cases treated using the Sonablate® 500 HIFU device, between August 28, 2002 and September 1, 2009, was carried out. All men had presumed organ-confined, histologically confirmed recurrent prostate adenocarcinoma following radiation therapy. All men with presumed, organ-confined, recurrent disease following EBRT in 8 patients, brachytherapy in 7 patients or proton therapy in 5 patients treated with salvage HIFU were included. The patients were followed for a mean (range) of 16.0 (3-80) months. Biochemical disease-free survival (bDFS) rates in patients with low-intermediate and high risk groups were 86% and 50%, respectively. Side-effects included urethral stricture in 2 of the 16 patients (13%), urinary tract infection or dysuria syndrome in eight (26%), and urinary incontinence in one (6%). Recto-urethral fistula occurred in one patient (6%). Transrectal HIFU is an effective treatment for recurrence after radiotherapy especially in patients with low- and intermediate risk groups.

  3. Robotic Image-Guided Stereotactic Radiotherapy, for Isolated Recurrent Primary, Lymph Node or Metastatic Prostate Cancer

    SciTech Connect

    Jereczek-Fossa, Barbara Alicja; Beltramo, Giancarlo; Fariselli, Laura; Fodor, Cristiana; Santoro, Luigi; Vavassori, Andrea; Zerini, Dario; Gherardi, Federica; Ascione, Carmen; Bossi-Zanetti, Isa; Mauro, Roberta; Bregantin, Achille; Bianchi, Livia Corinna; De Cobelli, Ottavio; Orecchia, Roberto

    2012-02-01

    Purpose: To evaluate the outcome of robotic CyberKnife (Accuray, Sunnyvale, CA)-based stereotactic radiotherapy (CBK-SRT) for isolated recurrent primary, lymph node, or metastatic prostate cancer. Methods and Materials: Between May 2007 and December 2009, 34 consecutive patients/38 lesions were treated (15 patients reirradiated for local recurrence [P], 4 patients reirradiated for anastomosis recurrence [A], 16 patients treated for single lymph node recurrence [LN], and 3 patients treated for single metastasis [M]). In all but 4 patients, [{sup 11}C]choline positron emission tomography/computed tomography was performed. CBK-SRT consisted of reirradiation and first radiotherapy in 27 and 11 lesions, respectively. The median CBK-SRT dose was 30 Gy in 4.5 fractions (P, 30 Gy in 5 fractions; A, 30 Gy in 5 fractions; LN, 33 Gy in 3 fractions; and M, 36 Gy in 3 fractions). In 18 patients (21 lesions) androgen deprivation was added to CBK-SRT (median duration, 16.6 months). Results: The median follow-up was 16.9 months. Acute toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event). Late toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event and 1 Grade 2 event). Biochemical response was observed in 32 of 38 evaluable lesions. Prostate-specific antigen stabilization was seen for 4 lesions, and in 2 cases prostate-specific antigen progression was reported. The 30-month progression-free survival rate was 42.6%. Disease progression was observed for 14 lesions (5, 2, 5, and 2 in Groups P, A, LN, and M respectively). In only 3 cases, in-field progression was seen. At the time of analysis (May 2010), 19 patients are alive with no evidence of disease and 15 are alive with disease. Conclusions: CyberKnife-based stereotactic radiotherapy is a feasible approach for isolated recurrent primary, lymph node, or metastatic prostate cancer, offering excellent in-field tumor

  4. Analysis of Prostate Bed Motion Using Daily Cone-Beam Computed Tomography During Postprostatectomy Radiotherapy

    SciTech Connect

    Ost, Piet; De Meerleer, Gert; De Gersem, Werner; Impens, Aline; De Neve, Wilfried

    2011-01-01

    Purpose: To report on the interfraction total positioning error of the postoperative prostate bed and to quantify its components (bony misalignment [BM]and prostate bed motion [PBM]) using daily kilovoltage cone-beam computed tomography (CBCT). The role of an adaptive radiotherapy schedule (ART) was investigated. Methods and Materials: A total of 547 daily CBCT images from 15 consecutive patients who had been treated with prostate bed radiotherapy were retrospectively analyzed. The positioning error was measured by rigid co-registration of the daily CBCT with pretreatment CT planning scan. The total positioning error was quantified by co-registration of the CBCT with the CT planning scan to match the anterior rectal wall. Automatic bony pelvis co-registration was performed to separate BM and PBM. The ART was determined by the average total positioning error from the first 5 CBCT images. Results: The systematic error for the total positioning error in the left-right, superoinferior, and anteroposterior direction was 2.69, 2.00, and 2.65 mm with a random error of 1.99, 1.49, and 2.25 mm, resulting in a planning target volume margin of 8, 6, and 8 mm, respectively. ART reduced the margin by 54%, 44%, and 40%, respectively. Systematic errors in the left-right, superoinferior, and anteroposterior direction for BM was 2.66, 1.83, and 2.60 mm and for PBM was 0.44, 0.92, and 2.50 mm with a random error of 1.88, 1.24, and 1.77 mm for BM and 0.99, 1.38, and 2.32 mm for PBM, respectively. Conclusion: Without treatment verifications, 6-8-mm planning target volume margins are required because of PBM and BM. The anteroposterior PBM was significant. An ART protocol can reduce these planning target volume margins.

  5. Incremental Learning With Selective Memory (ILSM): Towards Fast Prostate Localization for Image Guided Radiotherapy

    PubMed Central

    Gao, Yaozong; Zhan, Yiqiang

    2015-01-01

    Image-guided radiotherapy (IGRT) requires fast and accurate localization of the prostate in 3-D treatment-guided radiotherapy, which is challenging due to low tissue contrast and large anatomical variation across patients. On the other hand, the IGRT workflow involves collecting a series of computed tomography (CT) images from the same patient under treatment. These images contain valuable patient-specific information yet are often neglected by previous works. In this paper, we propose a novel learning framework, namely incremental learning with selective memory (ILSM), to effectively learn the patient-specific appearance characteristics from these patient-specific images. Specifically, starting with a population-based discriminative appearance model, ILSM aims to “personalize” the model to fit patient-specific appearance characteristics. The model is personalized with two steps: backward pruning that discards obsolete population-based knowledge and forward learning that incorporates patient-specific characteristics. By effectively combining the patient-specific characteristics with the general population statistics, the incrementally learned appearance model can localize the prostate of a specific patient much more accurately. This work has three contributions: 1) the proposed incremental learning framework can capture patient-specific characteristics more effectively, compared to traditional learning schemes, such as pure patient-specific learning, population-based learning, and mixture learning with patient-specific and population data; 2) this learning framework does not have any parametric model assumption, hence, allowing the adoption of any discriminative classifier; and 3) using ILSM, we can localize the prostate in treatment CTs accurately (DSC ∼0.89) and fast (∼4 s), which satisfies the real-world clinical requirements of IGRT. PMID:24495983

  6. Disturbed Colonic Motility Contributes to Anorectal Symptoms and Dysfunction After Radiotherapy for Carcinoma of the Prostate

    SciTech Connect

    Yeoh, Eric K.; Bartholomeusz, Dylan L.; Holloway, Richard H.; Fraser, Robert J.; Botten, Rochelle; Di Matteo, Addolorata; Moore, James W.; Schoeman, Mark N.

    2010-11-01

    Purpose: To evaluate the role of colonic motility in the pathogenesis of anorectal symptoms and dysfunction after radiotherapy (RT) for carcinoma of the prostate. Patients and Methods: Thirty-eight patients, median age 71 (range, 50-81) years with localized prostate carcinoma randomized to one of two radiation dose schedules underwent colonic transit scintigraphy and assessment of anorectal symptoms (questionnaire), anorectal function (manometry), and anal sphincteric morphology (endoanal ultrasound) before and at 1 month and 1 year after RT. Results: Whole and distal colonic transit increased 1 month after RT, with faster distal colonic transit only persisting at 1 year. Frequency and urgency of defecation, fecal incontinence, and rectal bleeding increased 1 month after RT and persisted at 1 year. Basal anal pressures remained unchanged, but progressive reductions occurred in anal squeeze pressures and responses to increased intra-abdominal pressure. Rectal compliance decreased progressively in the patients, although no changes in anorectal sensory function ensued. Radiotherapy had no effect on the morphology of the internal and external anal sphincters. Distal colonic retention was weakly related to rectal compliance at 1 month, but both faster colonic transit and reduced rectal compliance were more frequent with increased fecal urgency. At 1 year, a weak inverse relationship existed between colonic half-clearance time and frequency of defecation, although both faster whole-colonic transit and reduced rectal compliance occurred more often with increased stool frequency. Conclusion: Colonic dysmotility contributes to anorectal dysfunction after RT for carcinoma of the prostate. This has implications for improving the management of anorectal radiation sequelae.

  7. A Statistical Evaluation of Rules for Biochemical Failure After Radiotherapy in Men Treated for Prostate Cancer

    SciTech Connect

    Bellera, Carine A.; Hanley, James A.; Joseph, Lawrence; Albertsen, Peter C.

    2009-12-01

    Purpose: The 'PSA nadir + 2 rule,' defined as any rise of 2 ng/ml above the current prostate-specific antigen (PSA) nadir, has replaced the American Society for Therapeutic Radiology and Oncology (ASTRO) rule, defined as three consecutive PSA rises, to indicate biochemical failure (BF) after radiotherapy in patients treated for prostate cancer. We propose an original approach to evaluate BF rules based on the PSAdt as the gold standard rule and on a simulation process allowing us to evaluate the BF rules under multiple settings (different frequency, duration of follow-up, PSA doubling time [PSAdt]). Methods and Materials: We relied on a retrospective, population-based cohort of individuals identified by the Connecticut Tumor Registry and treated for localized prostate cancer with radiotherapy. We estimated the 470 underlying true PSA trajectories, including the PSAdt, using a Bayesian hierarchical changepoint model. Next, we simulated realistic, sophisticated data sets that accurately reflect the systematic and random variations observed in PSA series. We estimated the sensitivity and specificity by comparing the simulated PSA series to the underlying true PSAdt. Results: For follow-up of more than 3 years, the specificity of the PSA nadir + 2 rule was systematically greater than that of the ASTRO criterion. In few settings, the nadir + 2 rule had a lower sensitivity than the ASTRO. The PSA nadir + 2 rule appeared less dependent on the frequency and duration of follow-up than the ASTRO. Conclusions: Our results provide some refinements to earlier findings as the BF rules were evaluated according to various parameters. In most settings, the PSA nadir + 2 rule outperforms the ASTRO criterion.

  8. A self-adaptive case-based reasoning system for dose planning in prostate cancer radiotherapy

    SciTech Connect

    Mishra, Nishikant; Petrovic, Sanja; Sundar, Santhanam

    2011-12-15

    Purpose: Prostate cancer is the most common cancer in the male population. Radiotherapy is often used in the treatment for prostate cancer. In radiotherapy treatment, the oncologist makes a trade-off between the risk and benefit of the radiation, i.e., the task is to deliver a high dose to the prostate cancer cells and minimize side effects of the treatment. The aim of our research is to develop a software system that will assist the oncologist in planning new treatments. Methods: A nonlinear case-based reasoning system is developed to capture the expertise and experience of oncologists in treating previous patients. Importance (weights) of different clinical parameters in the dose planning is determined by the oncologist based on their past experience, and is highly subjective. The weights are usually fixed in the system. In this research, the weights are updated automatically each time after generating a treatment plan for a new patient using a group based simulated annealing approach. Results: The developed approach is analyzed on the real data set collected from the Nottingham University Hospitals NHS Trust, City Hospital Campus, UK. Extensive experiments show that the dose plan suggested by the proposed method is coherent with the dose plan prescribed by an experienced oncologist or even better. Conclusions: The developed case-based reasoning system enables the use of knowledge and experience gained by the oncologist in treating new patients. This system may play a vital role to assist the oncologist in making a better decision in less computational time; it utilizes the success rate of the previously treated patients and it can also be used in teaching and training processes.

  9. Rhodium-105 Bombesin Analogs for Prostate Cancer Radiotherapy

    SciTech Connect

    Silvia S. Jurisson, PhD

    2005-12-31

    Over the period of this grant (11/01/2001 to 12/31/2005), the consistent and reproducible production of Rh-105, synthesis and evaluation of three new chelate systems based on hydroxymethyl phosphines, development of a new non-hydroxymethyl phosphine N{sub 2}P{sub 2} chelate system, conjugation of two of the chelates to the bombesin peptide analog BBN[7-14]NH{sub 2}, evaluation of the bombesin conjugates and their Rh-105 complexes for stability, cell binding affinity, and in vivo biodistribution in normal mice has been developed. The BBN analogs bind to GRP receptors that are overexpressed on PC-3 prostate tumor cells. A dedicated glove box is used for the separation and isolation of {sup 105}Rh from the target ({sup 104}Ru). All tubing/connections/valves from the point of the Cl{sub 2} tank are made of Teflon to minimize/eliminate the introduction of any metal into the process (e.g., iron from stainless steel corrosion). The separation of {sup 105}Rh produced from the enriched {sup 104}Ru target involves oxidation of the enriched {sup 104}Ru metal target to ruthenium tetroxide with chlorine gas and sodium hydroxide solution to generate hypochlorite in situ. The RuO4 is removed by distillation and the {sup 105}Rh remaining in the reaction vial is converted into {sup 105}Rh-chloride by acidification with hydrochloric acid and heating. The {sup 105}Rh production process has become reproducible over the past year to consistently make 10-30 mCi of {sup 105}Rh from 1-3 mg of an enriched (99.21%) {sup 104}Ru target. The process itself involves irradiation of the enriched {sup 104}Ru target in the core of the reactor (University of Missouri Research Reactor (MURR)) for one week to yield 16-40 mCi of {sup 105}Rh. The irradiated target is processed to separate the Rh-105 in high specific activity from the {sup 104}Ru target. The irradiated target is dissolved in NaOH (2M, 3 mL) by bubbling Cl{sub 2} gas through the solution (generating NaOCl in situ) to generate RuO{sub 4

  10. Variation in Use of Androgen Suppression With External-Beam Radiotherapy for Nonmetastatic Prostate Cancer

    SciTech Connect

    Swisher-McClure, Samuel; Pollack, Craig E.; Christodouleas, John P.; Guzzo, Thomas J.; Haas, Naomi B.; Vapiwala, Neha; Bekelman, Justin E.

    2012-05-01

    Purpose: To describe practice patterns associated with androgen suppression (AS) stratified by disease risk group in patients undergoing external-beam radiotherapy (EBRT) for localized prostate cancer. Methods and Materials: We identified 2,184 low-risk, 2,339 intermediate-risk, and 2,897 high-risk patients undergoing EBRT for nonmetastatic prostate cancer diagnosed between January 1, 2004, and December 31, 2005, in the linked Surveillance, Epidemiology, and End Results-Medicare database. We examined the association of patient, clinical, and demographic characteristics with AS use by multivariate logistic regression. Results: The proportions of patients receiving AS for low-risk, intermediate-risk, and high-risk prostate cancer were 32.2%, 56.3%, and 81.5%, respectively. AS use among men in the low-risk disease category varied widely, ranging from 13.6% in Detroit to 47.8% in Kentucky. We observed a significant decline in AS use between 2004 and 2005 within all three disease risk categories. Men aged {>=}75 years or with elevated comorbidity levels were more likely to receive AS. Conclusion: Our results identified apparent overuse and underuse of AS among men within the low-risk and high-risk disease categories, respectively. These results highlight the need for clinician and patient education regarding the appropriate use of AS. Practice patterns among intermediate-risk patients reflect the clinical heterogeneity of this population and underscore the need for better evidence to guide the treatment of these patients.

  11. Voxel-based population analysis for correlating local dose and rectal toxicity in prostate cancer radiotherapy

    PubMed Central

    Acosta, Oscar; Drean, Gael; Ospina, Juan David; Simon, Antoine; Haigron, Pascal; Lafond, Caroline; De Crevoisier, Renaud

    2013-01-01

    The majority of current models utilized for predicting toxicity in prostate cancer radiotherapy are based on dose-volume histograms. One of their main drawbacks is the lack of spatial accuracy, since they consider the organs as a whole volume and thus ignore the heterogeneous intra-organ radio-sensitivity. In this paper, we propose a dose-image-based framework to reveal the relationships between local dose and toxicity. In this approach, the three-dimensional (3D) planned dose distributions across a population are non-rigidly registered into a common coordinate system and compared at a voxel level, therefore enabling the identification of 3D anatomical patterns, which may be responsible for toxicity, at least to some extent. Additionally, different metrics were employed in order to assess the quality of the dose mapping. The value of this approach was demonstrated by prospectively analyzing rectal bleeding (≥Grade 1 at 2 years) according to the CTCAE v3.0 classification in a series of 105 patients receiving 80Gy to the prostate by IMRT. Within the patients presenting bleeding, a significant dose excess (6Gy on average, p<0.01) was found in a region of the anterior rectal wall. This region, close to the prostate (1cm), represented less than 10% of the rectum. This promising voxel-wise approach allowed subregions to be defined within the organ that may be involved in toxicity and, as such, must be considered during the inverse IMRT planning step. PMID:23528429

  12. Longitudinal Study of Intestinal Symptoms and Fecal Continence in Patients With Conformal Radiotherapy for Prostate Cancer

    SciTech Connect

    Geinitz, Hans; Thamm, Reinhard; Keller, Monika; Astner, Sabrina T.; Heinrich, Christine; Scholz, Christian; Pehl, Christian; Kerndl, Simone; Prause, Nina; Busch, Raymonde; Molls, Michael; Zimmermann, Frank B.

    2011-04-01

    Purpose: To prospectively assess the intestinal symptoms and fecal continence in patients who had undergone conformal radiotherapy (CRT) for prostate cancer. Methods and Materials: A total of 78 men who had undergone definitive CRT for prostate cancer were evaluated. The patients were assessed before, during (treatment Weeks 4 and 6), and 2, 12, and 24 months after CRT completion. The intestinal symptoms and fecal continence were evaluated with comprehensive standardized questionnaires. Results: The intestinal symptoms were mostly intermittent, with only a small minority of patients affected daily. Defecation pain, fecal urge, and rectal mucous discharge increased significantly during therapy. Defecation pain and rectal mucous discharge had returned to baseline levels within 8 weeks and 1 year after CRT, respectively. However, fecal urge remained significantly elevated for {<=}1 year and then returned toward the pretreatment values. The prevalence of rectal bleeding was significantly elevated 2 years after CRT. Fecal continence deteriorated during CRT and remained impaired at 1 year after treatment. Incontinence was mostly minor, occurring less than once per week and predominantly affecting incontinence for gas. Conclusion: Intestinal symptoms and fecal incontinence increased during prostate CRT. Except for rectal bleeding, the intestinal symptoms, including fecal incontinence, returned to baseline levels within 1-2 years after CRT. Thus, the rate of long-term late radiation-related intestinal toxicity was low.

  13. Influence of Multiple Genetic Polymorphisms on Genitourinary Morbidity After Carbon Ion Radiotherapy for Prostate Cancer

    SciTech Connect

    Suga, Tomo; Iwakawa, Mayumi; Tsuji, Hiroshi; Ishikawa, Hitoshi; Oda, Eisei; Noda, Shuhei; Otsuka, Yoshimi; Ishikawa, Atsuko; Ishikawa, Ken-Ichi; Shimazaki, Jun; Mizoe, Jun-Etsu; Tsujii, Hirohiko; Imai, Takashi

    2008-11-01

    Purpose: To investigate the genetic risk of late urinary morbidity after carbon ion radiotherapy in prostate cancer patients. Methods and Materials: A total of 197 prostate cancer patients who had undergone carbon ion radiotherapy were evaluated for urinary morbidity. The distribution of patients with dysuria was as follows: Grade 0, 165; Grade 1, 28; and Grade 2, 4 patients. The patients were divided (2:1) consecutively into the training and test sets and then categorized into control (Grade 0) and case (Grade 1 or greater) groups. First, 450 single nucleotide polymorphisms (SNPs) in 118 candidate genes were genotyped in the training set. The associations between the SNP genotypes and urinary morbidity were assessed using Fisher's exact test. Then, various combinations of the markers were tested for their ability to maximize the area under the receiver operating characteristics (AUC-ROC) curve analysis results. Finally, the test set was validated for the selected markers. Results: When the SNP markers in the SART1, ID3, EPDR1, PAH, and XRCC6 genes in the training set were subjected to AUC-ROC curve analysis, the AUC-ROC curve reached a maximum of 0.86. The AUC-ROC curve of these markers in the test set was 0.77. The SNPs in these five genes were defined as 'risk genotypes.' Approximately 90% of patients in the case group (Grade 1 or greater) had three or more risk genotypes. Conclusions: Our results have shown that patients with late urinary morbidity after carbon ion radiotherapy can be stratified according to the total number of risk genotypes they harbor.

  14. Random variation in rectal position during radiotherapy for prostate cancer is two to three times greater than that predicted from prostate motion

    PubMed Central

    Harrison, K; Romanchikova, M; Parker, A; Sutcliffe, M; Bond, S; Thomas, S; Freeman, S; Jena, R; Bates, A; Burnet, N

    2014-01-01

    Objective: Radiotherapy for prostate cancer does not explicitly take into account daily variation in the position of the rectum. It is important to accurately assess accumulated dose (DA) to the rectum in order to understand the relationship between dose and toxicity. The primary objective of this work was to quantify systematic (Σ) and random (σ) variation in the position of the rectum during a course of prostate radiotherapy. Methods: The rectum was manually outlined on the kilo-voltage planning scan and 37 daily mega-voltage image guidance scans for 10 participants recruited to the VoxTox study. The femoral heads were used to produce a fixed point to which all rectal contours were referenced. Results: Σ [standard deviation (SD) of means] between planning and treatment was 4.2 mm in the anteroposterior (AP) direction and 1.3 mm left–right (LR). σ (root mean square of SDs) was 5.2 mm AP and 2.7 mm LR. Superior–inferior variation was less than one slice above and below the planning position. Conclusion: Our results for Σ are in line with published data for prostate motion. σ, however, was approximately twice as great as that seen for prostate motion. This suggests that DA may differ from planned dose in some patients treated with radiotherapy for prostate cancer. Advances in knowledge: This work is the first to use daily imaging to quantify Σ and σ of the rectum in prostate cancer. σ was found to be greater than published data, providing strong rationale for further investigation of individual DA. PMID:25138155

  15. Second Primary Cancer After Radiotherapy for Prostate Cancer-A SEER Analysis of Brachytherapy Versus External Beam Radiotherapy

    SciTech Connect

    Abdel-Wahab, May Reis, Isildinha M.; Hamilton, Kara

    2008-09-01

    Purpose: To determine the incidence of second primary cancers (SPCs) and radiotherapy-induced SPCs (RTSPCs). Patients and Methods: The incidence of SPCs and RTSPCs was compared among four treatment groups with locoregional prostate adenocarcinoma in the 1973-2002 Surveillance, Epidemiology, and End Results database. These groups were no radiotherapy (RT), no surgery (Group 1); external beam RT (EBRT) (Group 2); brachytherapy (Group 3); and a combination of EBRT and brachytherapy (Group 4). Results: The age-adjusted estimates of SPCs were greater with EBRT than with brachytherapy (2,178 vs. 1,901 SPCs/100,000; p = 0.025) or with the no RT, no surgery group (1,971 SPCs/100,000; p <0.0001). The age-adjusted rate of late SPC ({>=}5 years) for EBRT (2,425 SPCs/100,000) was only significantly greater (p <0.0001) than that for no RT, no surgery (1,950 SPCs/100,000). The hazard ratio adjusted for age, race/ethnicity, and grade was constant at 1.263 for EBRT compared with no RT, no surgery (p <0.0001) but varied with the length of follow-up in both the brachytherapy (0.721 at 5 years to 1.200 at 9 years) and combination (0.920 at 5 years to 1.317 at 9 years) groups. The incidence of RTSPCs was only significantly different between the no RT, no surgery group and the EBRT group, with an increase of 162 cases/100,000 or a 0.16% increased SPC risk (p = 0.023). No significant differences in the incidence of RTSPC were seen between the RT groups. Conclusion: No significant differences were seen in the incidence of RTSPCs between the RT groups. The initial smaller relative risk of overall SPCs in the brachytherapy group increased with time until the curves converged, suggesting that the effect had resulted from patient selection bias.

  16. Outcomes After Intensity-Modulated Versus Conformal Radiotherapy in Older Men With Nonmetastatic Prostate Cancer

    SciTech Connect

    Bekelman, Justin E.; Mitra, Nandita; Efstathiou, Jason; Liao Kaijun; Sunderland, Robert; Yeboa, Deborah N.; Armstrong, Katrina

    2011-11-15

    Purpose: There is little evidence comparing complications after intensity-modulated (IMRT) vs. three-dimensional conformal radiotherapy (CRT) for prostate cancer. The study objective was to test the hypothesis that IMRT, compared with CRT, is associated with a reduction in bowel, urinary, and erectile complications in elderly men with nonmetastatic prostate cancer. Methods and Materials: We undertook an observational cohort study using registry and administrative claims data from the SEER-Medicare database. We identified men aged 65 years or older diagnosed with nonmetastatic prostate cancer in the United States between 2002 and 2004 who received IMRT (n = 5,845) or CRT (n = 6,753). The primary outcome was a composite measure of bowel complications. Secondary outcomes were composite measures of urinary and erectile complications. We also examined specific subsets of bowel (proctitis/hemorrhage) and urinary (cystitis/hematuria) events within the composite complication measures. Results: IMRT was associated with reductions in composite bowel complications (24-month cumulative incidence 18.8% vs. 22.5%; hazard ratio [HR] 0.86; 95% confidence interval [CI], 0.79-0.93) and proctitis/hemorrhage (HR 0.78; 95% CI, 0.64-0.95). IMRT was not associated with rates of composite urinary complications (HR 0.93; 95% CI, 0.83-1.04) or cystitis/hematuria (HR 0.94; 95% CI, 0.83-1.07). The incidence of erectile complications involving invasive procedures was low and did not differ significantly between groups, although IMRT was associated with an increase in new diagnoses of impotence (HR 1.27, 95% CI, 1.14-1.42). Conclusion: IMRT is associated with a small reduction in composite bowel complications and proctitis/hemorrhage compared with CRT in elderly men with nonmetastatic prostate cancer.

  17. Effectiveness of Androgen-Deprivation Therapy and Radiotherapy for Older Men With Locally Advanced Prostate Cancer

    PubMed Central

    Bekelman, Justin E.; Mitra, Nandita; Handorf, Elizabeth A.; Uzzo, Robert G.; Hahn, Stephen A.; Polsky, Daniel; Armstrong, Katrina

    2015-01-01

    Purpose We examined whether the survival advantage of androgen-deprivation therapy with radiotherapy (ADT plus RT) relative to ADT alone for men with locally advanced prostate cancer reported in two randomized trials holds in real-world clinical practice and extended the evidence to patients poorly represented in the trials. Methods We conducted nonrandomized effectiveness studies of ADT plus RT versus ADT in three groups of patients diagnosed between 1995 and 2007 and observed through 2009 in the SEER-Medicare data set: (1) the randomized clinical trial (RCT) cohort, which included men age 65 to 75 years and was most consistent with participants in the randomized trials; (2) the elderly cohort, which included men age > 75 years with locally advanced prostate cancer; and (3) the screen-detected cohort, which included men age ≥ 65 years with screen-detected high-risk prostate cancer. We evaluated cause-specific and all-cause mortality using propensity score, instrumental variable (IV), and sensitivity analyses. Results In the RCT cohort, ADT plus RT was associated with reduced cause-specific and all-cause mortality relative to ADT alone (cause-specific propensity score–adjusted hazard ratio [HR], 0.43; 95% CI, 0.37 to 0.49; all-cause propensity score–adjusted HR, 0.63; 95% CI, 0.59 to 0.67). Effectiveness estimates for the RCT cohort were not significantly different from those from randomized trials (P > .1). In the elderly and screen-detected cohorts, ADT plus RT was also associated with reduced cause-specific and all-cause mortality. IV analyses produced estimates similar to those from propensity score–adjusted methods. Conclusion Older men with locally advanced or screen-detected high-risk prostate cancer who receive ADT alone risk decrements in cause-specific and overall survival. PMID:25559808

  18. OUTCOMES AFTER INTENSITY-MODULATED VERSUS CONFORMAL RADIOTHERAPY IN OLDER MEN WITH NONMETASTATIC PROSTATE CANCER

    PubMed Central

    Bekelman, Justin E.; Mitra, Nandita; Efstathiou, Jason; Liao, Kaijun; Sunderland, Robert; Yeboa, Deborah N.; Armstrong, Katrina

    2013-01-01

    Purpose There is little evidence comparing complications after intensity-modulated (IMRT) vs. three-dimensional conformal radiotherapy (CRT) for prostate cancer. The study objective was to test the hypothesis that IMRT, compared with CRT, is associated with a reduction in bowel, urinary, and erectile complications in elderly men with nonmetastatic prostate cancer. Methods and Materials We undertook an observational cohort study using registry and administrative claims data from the SEER-Medicare database. We identified men aged 65 years or older diagnosed with nonmetastatic prostate cancer in the United States between 2002 and 2004 who received IMRT (n = 5,845) or CRT (n = 6,753). The primary outcome was a composite measure of bowel complications. Secondary outcomes were composite measures of urinary and erectile complications. We also examined specific subsets of bowel (proctitis/hemorrhage) and urinary (cystitis/hematuria) events within the composite complication measures. Results IMRT was associated with reductions in composite bowel complications (24-month cumulative incidence 18.8% vs. 22.5%; hazard ratio [HR] 0.86; 95% confidence interval [CI], 0.79–0.93) and proctitis/hemorrhage (HR 0.78; 95% CI, 0.64–0.95). IMRT was not associated with rates of composite urinary complications (HR 0.93; 95% CI, 0.83–1.04) or cystitis/hematuria (HR 0.94; 95% CI, 0.83–1.07). The incidence of erectile complications involving invasive procedures was low and did not differ significantly between groups, although IMRT was associated with an increase in new diagnoses of impotence (HR 1.27, 95% CI, 1.14–1.42). Conclusion IMRT is associated with a small reduction in composite bowel complications and proctitis/hemorrhage compared with CRT in elderly men with nonmetastatic prostate cancer. PMID:21498008

  19. Investigation on the performance of dedicated radiotherapy positioning devices for MR scanning for prostate planning.

    PubMed

    Sun, Jidi; Dowling, Jason A; Pichler, Peter; Parker, Joel; Martin, Jarad; Stanwell, Peter; Arm, Jameen; Menk, Fred; Greer, Peter B

    2015-01-01

    The purpose of this study was to investigate performance of the couch and coil mounts designed for MR-simulation prostate scanning using data from ten volunteers. Volunteers were scanned using the standard MR scanning protocol with the MR coil directly strapped on the external body and the volunteer lying on the original scanner table. They also were scanned using a MR-simulation table top and pelvic coil mounts. MR images from both setups were compared in terms of body contour variation and image quality effects within particular organs of interest. Six-field conformal plans were generated on the two images with assigned bulk density for dose calculation. With the MR-simulation devices, the anterior skin deformation was reduced by up to 1.7 cm. The hard tabletop minimizes the posterior body deformation which can be up to 2.3 cm on the standard table, depending on the weight of volunteer. The image signal-to-noise ratio reduced by 14% and 25% on large field of view (FOV) and small FOV images, respectively, after using the coil mount; the prostate volume contoured on two images showed difference of 1.05 ± 0.66 cm3. The external body deformation caused a mean dose reduction of 0.6 ± 0.3 Gy, while the coverage reduced by 22% ± 13% and 27% ± 6% in V98 and V100, respectively. A dedicated MR simulation setup for prostate radiotherapy is essential to ensure the agreement between planning anatomy and treatment anatomy. The image signal was reduced after applying the coil mount, but no significant effect was found on prostate contouring. PMID:26103166

  20. Hypofractionated Versus Conventionally Fractionated Radiotherapy for Prostate Carcinoma: Final Results of Phase III Randomized Trial

    SciTech Connect

    Yeoh, Eric E.; Botten, Rochelle J.; Butters, Julie; Di Matteo, Addolorata C.; Holloway, Richard H.; Fowler, Jack

    2011-12-01

    Purpose: To evaluate the long-term efficacy and toxicity of a hypofractionated (55 Gy in 20 fractions within 4 weeks) vs. a conventionally fractionated (64 Gy in 32 fractions within 6.5 weeks) dose schedule for radiotherapy (RT) for localized carcinoma of the prostate. Methods and Materials: A total of 217 patients were randomized to either the hypofractionated (n = 108) or the conventional (n = 109) dose schedule. Most patients (n = 156) underwent RT planning and RT using a two-dimensional computed tomography method. Efficacy using the clinical, radiologic, and prostate-specific antigen data in each patient was evaluated before RT and at predetermined intervals after RT until death. Gastrointestinal and genitourinary toxicity using the modified Late Effect in Normal Tissue - Subjective Objective Management Analytic (LENT-SOMA) scales was also evaluated before and at intervals after RT to 60 months. Results: The whole group has now been followed for a median of 90 months (range, 3-138). Of the 217 patients, 85 developed biochemical relapse (nadir prostate-specific antigen level + 2 {mu}g/L), 36 in the hypofractionated and 49 in the conventional group. The biochemical relapse-free, but not overall, survival at 90 months was significantly better with the hypofractionated (53%) than with the conventional (34%) schedule. Gastrointestinal and genitourinary toxicity persisted 60 months after RT and did not differ between the two dose schedules. Multivariate analyses revealed that the conventional schedule was of independent prognostic significance, not only for biochemical failure, but also for an increased risk of worse genitourinary symptoms at 4 years. Conclusions: A therapeutic advantage of the hypofractionated compared with the conventional dose schedule for RT of prostate cancer was evident at 90 months in the present study.

  1. Long-Term Results After High-Dose Radiotherapy and Adjuvant Hormones in Prostate Cancer: How Curable Is High-Risk Disease?

    SciTech Connect

    Zapatero, Almudena; Garcia-Vicente, Feliciano; Martin de Vidales, Carmen; Cruz Conde, Alfonso; Ibanez, Yamile; Fernandez, Inmaculada; Rabadan, Mariano

    2011-12-01

    Purpose: To analyze long-term outcome and prognostic factors for high-risk prostate cancer defined by National Comprehensive Cancer Network criteria treated with high-dose radiotherapy and androgen deprivation in a single institution. Methods and Materials: A total of 306 patients treated between 1995 and 2007 in a radiation dose-escalation program fulfilled the National Comprehensive Cancer Network high-risk criteria. Median International Commission on Radiation Units and Measurements radiation dose was 78 Gy (range, 66.0-84.1 Gy). Long-term androgen deprivation (LTAD) was administered in 231 patients, short-term androgen deprivation (STAD) in 59 patients, and no hormones in 16 patients. The Phoenix (nadir plus 2 ng/mL) consensus definition was used for biochemical control. Multivariate analysis was performed to determine the independent prognostic impact of clinical and treatment factors. Median follow-up time was 64 months (range, 24-171 months). Results: The actuarial overall survival at 5 and 10 years was 95.7% and 89.8%, respectively, and the corresponding biochemical disease-free survival (bDFS) was 89.5% and 67.2%, respectively. Fourteen patients (4.6%) developed distant metastasis. Multivariate analysis showed that Gleason score >7 (p = 0.001), pretreatment prostate-specific antigen (PSA) level >20 ng/mL (p = 0.037), higher radiation dose (p = 0.005), and the use of adjuvant LTAD vs. STAD (p = 0.011) were independent prognostic factors affecting bDFS in high-risk disease. The 5-year bDFS for patients treated with LTAD plus radiotherapy dose >78 Gy was 97%. Conclusions: For high-risk patients the present series showed that the use of LTAD in conjunction with higher doses (>78 Gy) of radiotherapy was associated with improved biochemical tumor control. We observed that the presence of Gleason sum >7 and pretreatment PSA level >20 ng/mL in the same patient represents a 6.8 times higher risk of PSA failure. These men could be considered for clinical trials with

  2. The Benefits of Including Clinical Factors in Rectal Normal Tissue Complication Probability Modeling After Radiotherapy for Prostate Cancer

    SciTech Connect

    Defraene, Gilles; Van den Bergh, Laura; Al-Mamgani, Abrahim; Haustermans, Karin; Heemsbergen, Wilma; Van den Heuvel, Frank; Lebesque, Joos V.

    2012-03-01

    Purpose: To study the impact of clinical predisposing factors on rectal normal tissue complication probability modeling using the updated results of the Dutch prostate dose-escalation trial. Methods and Materials: Toxicity data of 512 patients (conformally treated to 68 Gy [n = 284] and 78 Gy [n = 228]) with complete follow-up at 3 years after radiotherapy were studied. Scored end points were rectal bleeding, high stool frequency, and fecal incontinence. Two traditional dose-based models (Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) and a logistic model were fitted using a maximum likelihood approach. Furthermore, these model fits were improved by including the most significant clinical factors. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminating ability of all fits. Results: Including clinical factors significantly increased the predictive power of the models for all end points. In the optimal LKB, RS, and logistic models for rectal bleeding and fecal incontinence, the first significant (p = 0.011-0.013) clinical factor was 'previous abdominal surgery.' As second significant (p = 0.012-0.016) factor, 'cardiac history' was included in all three rectal bleeding fits, whereas including 'diabetes' was significant (p = 0.039-0.048) in fecal incontinence modeling but only in the LKB and logistic models. High stool frequency fits only benefitted significantly (p = 0.003-0.006) from the inclusion of the baseline toxicity score. For all models rectal bleeding fits had the highest AUC (0.77) where it was 0.63 and 0.68 for high stool frequency and fecal incontinence, respectively. LKB and logistic model fits resulted in similar values for the volume parameter. The steepness parameter was somewhat higher in the logistic model, also resulting in a slightly lower D{sub 50}. Anal wall DVHs were used for fecal incontinence, whereas anorectal wall dose best described the other two endpoints. Conclusions: Comparable

  3. ZnFe2O4 nanoparticles as radiosensitizers in radiotherapy of human prostate cancer cells.

    PubMed

    Meidanchi, Alireza; Akhavan, Omid; Khoei, Samideh; Shokri, Ali A; Hajikarimi, Zahra; Khansari, Nakisa

    2015-01-01

    Nanoparticles of high-Z elements exhibit stronger photoelectric effects than soft tissues under gamma irradiation. Hence, they can be used as effective radiosensitizers for increasing the efficiency of current radiotherapy. In this work, superparamagnetic zinc ferrite spinel (ZnFe2O4) nanoparticles were synthesized by a hydrothermal reaction method and used as radiosensitizers in cancer therapy. The magnetic nanoparticles showed fast separation from solutions (e.g., ~1 min for 2 mg mL(-1) of the nanoparticles in ethanol) by applying an external magnetic field (~1T). The ZnFe2O4 nanoparticles were applied in an in vitro radiotherapy of lymph node carcinoma of prostate cells (as high radioresistant cells) under gamma irradiation of (60)Co source. The nanoparticles exhibited no significant effects on the cancer cells up to the high concentration of 100 μg mL(-1), in the absence of gamma irradiation. The gamma irradiation alone (2Gy dose) also showed no significant effects on the cells. However, gamma irradiation in the presence of 100 μg mL(-1) ZnFe2O4 nanoparticles resulted in ~53% inactivation of the cells (~17 times higher than the inactivation that occurred under gamma irradiation alone) after 24h. The higher cell inactivation was assigned to interaction of gamma radiation with nanoparticles (photoelectric effect), resulting in a high level electron release in the media of the radioresistant cells. Our results indicated that ZnFe2O4 nanoparticles not only can be applied in increasing the efficiency of radiotherapy, but also can be easily separated from the cell environment by using an external magnetic field after the radiotherapy. PMID:25492003

  4. Segmenting CT prostate images using population and patient-specific statistics for radiotherapy

    SciTech Connect

    Feng, Qianjin; Foskey, Mark; Chen Wufan; Shen Dinggang

    2010-08-15

    Purpose: In the segmentation of sequential treatment-time CT prostate images acquired in image-guided radiotherapy, accurately capturing the intrapatient variation of the patient under therapy is more important than capturing interpatient variation. However, using the traditional deformable-model-based segmentation methods, it is difficult to capture intrapatient variation when the number of samples from the same patient is limited. This article presents a new deformable model, designed specifically for segmenting sequential CT images of the prostate, which leverages both population and patient-specific statistics to accurately capture the intrapatient variation of the patient under therapy. Methods: The novelty of the proposed method is twofold: First, a weighted combination of gradient and probability distribution function (PDF) features is used to build the appearance model to guide model deformation. The strengths of each feature type are emphasized by dynamically adjusting the weight between the profile-based gradient features and the local-region-based PDF features during the optimization process. An additional novel aspect of the gradient-based features is that, to alleviate the effect of feature inconsistency in the regions of gas and bone adjacent to the prostate, the optimal profile length at each landmark is calculated by statistically investigating the intensity profile in the training set. The resulting gradient-PDF combined feature produces more accurate and robust segmentations than general gradient features. Second, an online learning mechanism is used to build shape and appearance statistics for accurately capturing intrapatient variation. Results: The performance of the proposed method was evaluated on 306 images of the 24 patients. Compared to traditional gradient features, the proposed gradient-PDF combination features brought 5.2% increment in the success ratio of segmentation (from 94.1% to 99.3%). To evaluate the effectiveness of online

  5. A multicenter phase 1/2a dose-escalation study of the antioxidant moiety of vitamin E 2,2,5,7,8-pentamethyl-6-chromanol (APC-100) in men with advanced prostate cancer.

    PubMed

    Kyriakopoulos, Christos E; Heath, Elisabeth I; Eickhoff, Jens C; Kolesar, Jill; Yayehyirad, Mulusew; Moll, Thomas; Wilding, George; Liu, Glenn

    2016-04-01

    Background A phase 1/2a dose escalation study of APC-100 (2,2,5,7,8-Pentamethyl-6-chromanol) was conducted to determine maximum tolerated dose (MTD), recommended phase 2 dose, toxicities and efficacy in men with castrate-resistant prostate cancer (CRPC). Methods This open label phase 1/2a study utilizes a time-to-event reassessment method (TITE-CRM) design. Patients in cohorts of 3 were treated with escalating doses of APC-100 (900 mg-2400 mg) orally once daily continuously. Cycles were 28 days. Results Twenty patients with CRPC were enrolled in the dose escalation cohort. One possible DLT (elevated ALT) was seen at dose level 1. No other DLTs were seen and no dose reductions were required. Most frequent AEs included nausea (grade 1 in 6 patients) and elevated transaminases (grade 1-3 in 5 patients). After enrolment of 20 patients the MTD was not reached, however the maximal feasible dose was exceeded due to the number of capsules ingested. Five of the 20 patients had stable disease as their best response. The median progression free survival (PFS) for the cohort was 2.8 months (range 1-8). Conclusions APC-100 is a novel agent with dual mechanism of action functioning both as potent antioxidant as well as antiandrogen. No detectable APC-100 was found in the plasma at dose level 5 (2100 mg) and it was felt that maximal feasibility was nearly reached. APC-100 is being reformulated as a tablet to allow further dose escalation. Once a recommended phase 2 dose is established, future studies in prostate cancer chemoprevention should be conducted. PMID:26924129

  6. Dose Escalation of Gemcitabine Is Possible With Concurrent Chest Three-Dimensional Rather Than Two-Dimensional Radiotherapy: A Phase I Trial in Patients With Stage III Non-Small-Cell Lung Cancer

    SciTech Connect

    Zinner, Ralph G. Cox, James D.; Glisson, Bonnie S.; Pisters, Katherine M.W.; Herbst, Roy S.; Kies, Merril; Hong, Waun K.; Fossella, Frank V.

    2009-01-01

    Purpose: To determine in a Phase I study the maximum tolerated dose of weekly gemcitabine concurrent with radiotherapy in locally advanced non-small-cell lung cancer (NSCLC), as well as the relationship between the volume of the esophagus irradiated and severe esophagitis. Methods and Materials: Twenty-one patients with Stage III NSCLC received gemcitabine initially at 150 mg/m{sup 2}/wk over 7 weeks concurrently with chest radiotherapy to 63 Gy in 34 fractions. The first 9 patients underwent treatment with two-dimensional (2D) radiotherapy; the remaining 12 patients, with three-dimensional conformal radiotherapy (3D-CRT) and target volume reduced to clinically apparent disease. Consolidation was 4 cycles of gemcitabine at 1000 mg/m{sup 2}/wk and cisplatin 60 mg/m{sup 2}. Results: In the 2D group, the dose-limiting toxicity, Grade 3 esophagitis, occurred in 3 of 6 patients in the 150-mg/m{sup 2}/wk cohort and 2 of 3 patients in the 125-mg/m{sup 2}/wk cohort. No cases of Grade 3 esophagitis occurred at these doses in the 3D group. At gemcitabine 190 mg/m{sup 2}/wk, 2 of 6 patients in the 3D cohort had Grade 3 esophagitis. The mean percentages of esophagus irradiated to 60 Gy were 68% in the 2D cohort and 18% in the 3D cohort. Conclusions: We could not escalate the dose of gemcitabine with concurrent radiotherapy when using 2D planning because of severe acute esophagitis. However, we could escalate the dose of gemcitabine to 190 mg/m{sup 2}/wk when using 3D planning. The Phase II dose is 150 mg/m{sup 2}/wk. Three-dimensional CRT permitted the use of higher doses of gemcitabine.

  7. Learning statistical correlation for fast prostate registration in image-guided radiotherapy

    SciTech Connect

    Shi Yonghong; Liao Shu; Shen Dinggang

    2011-11-15

    Purpose: In adaptive radiation therapy of prostate cancer, fast and accurate registration between the planning image and treatment images of the patient is of essential importance. With the authors' recently developed deformable surface model, prostate boundaries in each treatment image can be rapidly segmented and their correspondences (or relative deformations) to the prostate boundaries in the planning image are also established automatically. However, the dense correspondences on the nonboundary regions, which are important especially for transforming the treatment plan designed in the planning image space to each treatment image space, are remained unresolved. This paper presents a novel approach to learn the statistical correlation between deformations of prostate boundary and nonboundary regions, for rapidly estimating deformations of the nonboundary regions when given the deformations of the prostate boundary at a new treatment image. Methods: The main contributions of the proposed method lie in the following aspects. First, the statistical deformation correlation will be learned from both current patient and other training patients, and further updated adaptively during the radiotherapy. Specifically, in the initial treatment stage when the number of treatment images collected from the current patient is small, the statistical deformation correlation is mainly learned from other training patients. As more treatment images are collected from the current patient, the patient-specific information will play a more important role in learning patient-specific statistical deformation correlation to effectively reflect prostate deformation of the current patient during the treatment. Eventually, only the patient-specific statistical deformation correlation is used to estimate dense correspondences when a sufficient number of treatment images have been acquired from the current patient. Second, the statistical deformation correlation will be learned by using a

  8. Hypofractionated Accelerated Radiotherapy Using Concomitant Intensity-Modulated Radiotherapy Boost Technique for Localized High-Risk Prostate Cancer: Acute Toxicity Results

    SciTech Connect

    Lim, Tee S.; Cheung, Patrick Loblaw, D. Andrew; Morton, Gerard; Sixel, Katharina E.; Pang, Geordi; Basran, Parminder; Zhang Liying; Tirona, Romeo; Szumacher, Ewa; Danjoux, Cyril; Choo, Richard; Thomas, Gillian

    2008-09-01

    Purpose: To evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer. Methods and Materials: This report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score {>=}8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT. Results: The median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence (n = 1), urinary frequency/urgency (n = 3), and urinary retention (n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity. Conclusion: The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity.

  9. Brachytherapy or Conformal External Radiotherapy for Prostate Cancer: A Single-Institution Matched-Pair Analysis

    SciTech Connect

    Pickles, Tom; Keyes, Mira; Morris, W. James

    2010-01-15

    Purpose: In the absence of randomized study data, institutional case series have shown brachytherapy (BT) to produce excellent biochemical control (bNED) in patients with localized prostate cancer compared with alternative curative treatments. This study was designed to overcome some of the limitations of case series studies by using a matched-pair design in patients treated contemporaneously with BT and external beam radiation therapy (EBRT) at a single institution. Methods and Materials: Six hundred one eligible patients treated between 1998 and 2001 were prospectively followed up in our institutional databases and matched on a 1:1 basis for the following known prognostic variables: prostate-specific antigen (PSA) level, Gleason score, T stage, the use and duration of neoadjuvant androgen deprivation therapy, and the percentage of positive tissue core samples. Two hundred seventy-eight perfect matches of patients (139 in each group) with low- and intermediate-risk cancer were further analyzed. bNED (Phoenix definition) was the primary endpoint. Other endpoints were toxicity, PSA kinetics, and the secondary use of androgen deprivation therapy. Results: The 5-year bNED rates were 95% (BT) and 85% (EBRT) (p < 0.001). After 7 years, the BT bNED result was unchanged, but the rate in EBRT patients had fallen to 75%. The median posttreatment PSA nadirs were 0.04 ng/mL (BT) and 0.62 ng/mL (EBRT, p < 0.001), which predicted a higher ongoing treatment failure rate in association with EBRT use than with BT use. Late urinary toxicity and rectal/bowel toxicity were worse in patients treated with BT and EBRT, respectively. Conclusions: BT for both low-risk and selected intermediate-risk cancers achieves exceptional cure rates. Even with dose escalation, it will be difficult for EBRT to match the proven track record of BT seen over the past decade.

  10. Aplastic anemia associated with severe hemorrhagic cystitis following radiotherapy for prostate cancer

    PubMed Central

    NAKANO, TAITO; IZUMI, KOUJI; MAOLAKE, AERKEN; NATSAGDORJI, ARIUNBOLD; IWAMOTO, HIROAKI; KITAGAWA, YASUHIDE; KADONO, YOSHIFUMI; KONAKA, HIROYUKI; MIZOKAMI, ATSUSHI; NAMIKI, MIKIO

    2016-01-01

    Hemorrhagic cystitis is a rare complication following radiotherapy for intrapelvic cancer types, including cervical cancer, bladder cancer and prostate cancer. The severity of hemorrhagic cystitis is different in each case, although symptoms improve spontaneously in certain cases, and often significant morbidity requiring numerous interventions occurs. Since no treatment strategy exists with high evidences for such severe hemorrhagic cystitis, urologists have difficulty in solving the bleeding and pain, which the patients suffer. Aplastic anemia is a rare blood disorder, with an incidence reported as 2/1 million individuals annually. Patients have a risk of diffuse bleeding for presentation with anemia, thrombocytopenia and neutropenia. The present report presented a case of severe hemorrhagic cystitis remitted successfully by the treatment for underlying aplastic anemia. PMID:27123281

  11. MDM2 Inhibition Sensitizes Prostate Cancer Cells to Androgen Ablation and Radiotherapy in a p53-Dependent Manner12

    PubMed Central

    Feng, Felix Y.; Zhang, Yu; Kothari, Vishal; Evans, Joseph R.; Jackson, William C.; Chen, Wei; Johnson, Skyler B.; Luczak, Connor; Wang, Shaomeng; Hamstra, Daniel A.

    2016-01-01

    PURPOSE: Increased murine double minute 2 (MDM2) expression, independent of p53 status, is associated with increased cancer-specific mortality for men with prostate cancer treated with radiotherapy. We assessed MI-219, a small molecule inhibitor of MDM2 with improved pharmacokinetics over nutlin-3, for sensitization of prostate cancer cells to radiotherapy and androgen deprivation therapy, a standard treatment option for men with high-risk prostate cancer. EXPERIMENTAL DESIGN: The effect of MDM2 inhibition by MI-219 was assessed in vitro and in vivo with mouse xenograft models across multiple prostate cancer cell lines containing varying p53 functional status. RESULTS: MDM2 inhibition by MI-219 resulted in dose- and time-dependent p53 activation and decreased clonogenic cell survival after radiation in a p53-dependent manner. Mechanistically, radiosensitization following inhibition of MDM2 was largely the result of p53-dependent increases in apoptosis and DNA damage as evidenced by Annexin V flow cytometry and γ-H2AX foci immunofluorescence. Similarly, treatment with MI-219 enhanced response to antiandrogen therapy via a p53-dependent increase in apoptotic cell death. Lastly, triple therapy with radiation, androgen deprivation therapy, and MI-219 decreased xenograft tumor growth compared with any single- or double-agent treatment. CONCLUSION: MDM2 inhibition with MI-219 results in p53-dependent sensitization of prostate cancer cells to radiation, antiandrogen therapy, and the combination. These findings support MDM2 small molecule inhibitor therapy as a therapy intensification strategy to improve clinical outcomes in high-risk localized prostate cancer. TRANSLATIONAL RELEVANCE: The combination of radiotherapy and androgen deprivation therapy is a standard treatment option for men with high-risk prostate cancer. Despite improvements in outcomes when androgen deprivation therapy is added to radiation, men with high-risk prostate cancer have significant risk for

  12. Phase II Trial of Hypofractionated Image-Guided Intensity-Modulated Radiotherapy for Localized Prostate Adenocarcinoma

    SciTech Connect

    Martin, Jarad M.; Rosewall, Tara; Bayley, Andrew; Bristow, Robert; Chung, Peter; Crook, Juanita; Gospodarowicz, Mary; McLean, Michael; Menard, Cynthia; Milosevic, Michael; Warde, Padraig; Catton, Charles

    2007-11-15

    Purpose: To assess in a prospective trial the feasibility and late toxicity of hypofractionated radiotherapy (RT) for prostate cancer. Methods and Materials: Eligible patients had clinical stage T1c-2cNXM0 disease. They received 60 Gy in 20 fractions over 4 weeks with intensity-modulated radiotherapy including daily on-line image guidance with intraprostatic fiducial markers. Results: Between June 2001 and March 2004, 92 patients were treated with hypofractionated RT. The cohort had a median prostate-specific antigen value of 7.06 ng/mL. The majority had Gleason grade 5-6 (38%) or 7 (59%) disease, and 82 patients had T1c-T2a clinical staging. Overall, 29 patients had low-risk, 56 intermediate-risk, and 7 high-risk disease. Severe acute toxicity (Grade 3-4) was rare, occurring in only 1 patient. Median follow-up was 38 months. According to the Phoenix definition for biochemical failure, the rate of biochemical control at 14 months was 97%. According to the previous American Society for Therapeutic Radiology and Oncology definition, biochemical control at 3 years was 76%. The incidence of late toxicity was low, with no severe (Grade {>=}3) toxicity at the most recent assessment. Conclusions: Hypofractionated RT using 60 Gy in 20 fractions over 4 weeks with image guidance is feasible and is associated with low rates of late bladder and rectal toxicity. At early follow-up, biochemical outcome is comparable to that reported for conventionally fractionated controls. The findings are being tested in an ongoing, multicenter, Phase III trial.

  13. Implementing intensity modulated radiotherapy to the prostate bed: Dosimetric study and early clinical results

    SciTech Connect

    Riou, Olivier; Laliberté, Benoit; Azria, David; Menkarios, Cathy; Llacer Moscardo, Carmen; Dubois, Jean-Bernard; Aillères, Norbert; Fenoglietto, Pascal

    2013-07-01

    Salvage intensity modulated radiotherapy (IMRT) to the prostate bed has hardly been studied so far. We present here a feasibility study and early clinical results for 10 patients. These patients were selected on the basis of having either a biochemical relapse or high risk histology after prostatectomy. They were treated using “sliding-window” IMRT to 68 Gy in 34 fractions. Three-dimensional conformal radiotherapy (3D-CRT) plans were generated using the same planning computed tomography data set. Dose coverage of planning target volumes (PTVs) and of organs-at-risk (OAR, namely: rectum, bladder, and femoral heads) were compared. Acute toxicity and chronic toxicity were measured using the Common Toxicity Criteria for Adverse Events version 3.0 scale. IMRT significantly reduces the dose above the prescription dose given to the PTV1 (mean dose: IMRT 67.2 Gy vs 3D-CRT 67.7 Gy (p = 0.0137)), without altering dose coverage for PTV2 (mean dose: IMRT 68.1 Gy vs 3D-CRT 68.0 Gy (p = 0.3750)). Doses to OAR were lower with IMRT and differences were statistically significant (mean dose: IMRT 51.4 Gy vs 3D-CRT 56.6 Gy for rectum (p = 0.002), IMRT 45.1 Gy vs 3D-CRT 53.1 Gy for bladder (p = 0.002), and IMRT 26.1 Gy vs 3D-CRT 28.4 Gy for femoral heads (p = 0.0059)). There was no acute or chronic genitourinary or gastrointestinal toxicity >1 with a median follow-up of 38 months. IMRT to the prostatic fossa is feasible and reduces dose to OAR, with consequential limited toxicity.

  14. Clinical Application of High-Dose, Image-Guided Intensity-Modulated Radiotherapy in High-Risk Prostate Cancer

    SciTech Connect

    Bayley, Andrew; Rosewall, Tara; Craig, Tim; Bristow, Rob; Chung, Peter; Gospodarowicz, Mary; Menard, Cynthia; Milosevic, Michael; Warde, Padraig; Catton, Charles

    2010-06-01

    Purpose: To report the feasibility and early toxicity of dose-escalated image-guided IMRT to the pelvic lymph nodes (LN), prostate (P), and seminal vesicles (SV). Methods and Materials: A total of 103 high-risk prostate cancer patients received two-phase, dose-escalated, image-guided IMRT with 3 years of androgen deprivation therapy. Clinical target volumes (CTVs) were delineated using computed tomography/magnetic resonance co-registration and included the prostate, portions of the SV, and the LN. Planning target volume margins (PTV) used were as follows: P (10 mm, 7 mm posteriorly), SV (10 mm), and LN (5 mm). Organs at risk (OaR) were the rectal and bladder walls, femoral heads, and large and small bowel. The IMRT was planned with an intended dose of 55.1 Gy in 29 fractions to all CTVs (Phase 1), with P+SV consecutive boost of 24.7 Gy in 13 fractions. Daily online image guidance was performed using bony landmarks and intraprostatic markers. Feasibility criteria included delivery of intended doses in 80% of patients, 95% of CTV displacements incorporated within PTV during Phase 1, and acute toxicity rate comparable to that of lower-dose pelvic techniques. Results: A total of 91 patients (88%) received the total prescription dose. All patients received at least 72 Gy. In Phase 1, 63 patients (61%) received the intended 55.1 Gy, whereas 87% of patients received at least 50 Gy. Dose reductions were caused by small bowel and rectal wall constraints. All CTVs received the planned dose in >95% of treatment fractions. There were no Radiation Therapy Oncology Group acute toxicities greater than Grade 3, although there were five incidences equivalent to Grade 3 within a median follow-up of 23 months. Conclusion: These results suggest that dose escalation to the PLN+P+SV using IMRT is feasible, with acceptable rates of acute toxicity.

  15. Radiotherapy Treatment Plans With RapidArc for Prostate Cancer Involving Seminal Vesicles and Lymph Nodes

    SciTech Connect

    Yoo, Sua; Wu, Q. Jackie; Lee, W. Robert; Yin Fangfang

    2010-03-01

    Purpose: Dosimetric results and treatment delivery efficiency of RapidArc plans to those of conventional intensity-modulated radiotherapy (IMRT) plans were compared using the Eclipse treatment planning system for high-risk prostate cancer. Materials and Methods: This study included 10 patients. The primary planning target volume (PTV{sub P}) contained prostate, seminal vesicles, and pelvic lymph nodes with a margin. The boost PTV (PTV{sub B}) contained prostate and seminal vesicles with a margin. The total prescription dose was 75.6 Gy (46.8 Gy to PTV{sub P} and an additional 28.8 Gy to PTV{sub B}; 1.8 Gy/fraction). Three plans were generated for each PTV: Multiple-field IMRT, one-arc RapidArc (1ARC), and two-arc RapidArc (2ARC). Results: In the primary IMRT with PTV{sub P}, average mean doses to bladder, rectum and small bowel were lower by 5.9%, 7.7% and 4.3%, respectively, than in the primary 1ARC and by 3.6%, 4.8% and 3.1%, respectively, than in the primary 2ARC. In the boost IMRT with PTV{sub B}, average mean doses to bladder and rectum were lower by 2.6% and 4.8% than with the boost 1ARC and were higher by 0.6% and 0.2% than with the boost 2ARC. Integral doses were 7% to 9% higher with RapidArc than with IMRT for both primary and boost plans. Treatment delivery time was reduced by 2-7 minutes using RapidArc. Conclusion: For PTVs including prostate, seminal vesicles, and lymph nodes, IMRT performed better in dose sparing for bladder, rectum, and small bowel than did RapidArc. For PTVs including prostate and seminal vesicles, RapidArc with two arcs provided plans comparable to those for IMRT. The treatment delivery is more efficient with RapidArc.

  16. Duration of Androgen Suppression Before Radiotherapy for Localized Prostate Cancer: Radiation Therapy Oncology Group Randomized Clinical Trial 9910

    PubMed Central

    Pisansky, Thomas M.; Hunt, Daniel; Gomella, Leonard G.; Amin, Mahul B.; Balogh, Alexander G.; Chinn, Daniel M.; Seider, Michael J.; Duclos, Marie; Rosenthal, Seth A.; Bauman, Glenn S.; Gore, Elizabeth M.; Rotman, Marvin Z.; Lukka, Himanshu R.; Shipley, William U.; Dignam, James J.; Sandler, Howard M.

    2015-01-01

    Purpose To determine whether prolonged androgen suppression (AS) duration before radiotherapy improves survival and disease control in prostate cancer. Patients and Methods One thousand five hundred seventy-nine men with intermediate-risk prostate cancer were randomly assigned to 8 weeks of AS followed by radiotherapy with an additional 8 weeks of concurrent AS (16 weeks total) or to 28 weeks of AS followed by radiotherapy with an additional 8 weeks of AS (36 weeks total). The trial sought primarily to detect a 33% reduction in the hazard of prostate cancer death in the 28-week assignment. Time-to-event end points are reported for up to 10 years of follow-up. Results There were no between-group differences in baseline characteristics of 1,489 eligible patients with follow-up. For the 8- and 28-week assignments, 10-year disease-specific survival rates were 95% (95% CI, 93.3% to 97.0%) and 96% (95% CI, 94.6% to 98.0%; hazard ratio [HR], 0.81; P = .45), respectively, and 10-year overall survival rates were 66% (95% CI, 62.0% to 69.9%) and 67% (95% CI, 63.0% to 70.8%; HR, 0.95; P = .62), respectively. For the 8- and 28-week assignments, 10-year cumulative incidences of locoregional progression were 6% (95% CI, 4.3% to 8.0%) and 4% (95% CI, 2.5% to 5.7%; HR, 0.65; P = .07), respectively; 10-year distant metastasis cumulative incidences were 6% (95% CI, 4.0% to 7.7%) and 6% (95% CI, 4.0% to 7.6%; HR, 1.07; P = .80), respectively; and 10-year prostate-specific antigen–based recurrence cumulative incidences were 27% (95% CI, 23.1% to 29.8%) and 27% (95% CI, 23.4% to 30.3%; HR, 0.97; P = .77), respectively. Conclusion Extending AS duration from 8 weeks to 28 weeks before radiotherapy did not improve outcomes. A lower than expected prostate cancer death rate reduced ability to detect a between-group difference in disease-specific survival. The schedule of 8 weeks of AS before radiotherapy plus 8 weeks of AS during radiotherapy remains a standard of care in intermediate

  17. Systematic Review of the Relationship between Acute and Late Gastrointestinal Toxicity after Radiotherapy for Prostate Cancer

    PubMed Central

    Peach, Matthew Sean; Showalter, Timothy N.; Ohri, Nitin

    2015-01-01

    A small but meaningful percentage of men who are treated with external beam radiation therapy for prostate cancer will develop late gastrointestinal toxicity. While numerous strategies to prevent gastrointestinal injury have been studied, clinical trials concentrating on late toxicity have been difficult to carry out. Identification of subjects at high risk for late gastrointestinal injury could allow toxicity prevention trials to be performed using reasonable sample sizes. Acute radiation therapy toxicity has been shown to predict late toxicity in several organ systems. Late toxicities may occur as a consequential effect of acute injury. In this systematic review of published reports, we found that late gastrointestinal toxicity following prostate radiotherapy seems to be statistically and potentially causally related to acute gastrointestinal morbidity as a consequential effect. We submit that acute gastrointestinal toxicity may be used to identify at-risk patients who may benefit from additional attention for medical interventions and close follow-up to prevent late toxicity. Acute gastrointestinal toxicity could also be explored as a surrogate endpoint for late effects in prospective trials. PMID:26697225

  18. Dosimetry verification on VMAT and IMRT radiotherapy techniques: In the case of prostate cancer

    NASA Astrophysics Data System (ADS)

    Maulana, A.; Pawiro, S. A.

    2016-03-01

    Radiotherapy treatment depends on the accuracy of the dose delivery to patients, the purpose of the study is to verify the dose in IMRT and VMAT technique in prostate cancer cases correspond to TPS dose using phantom base on ICRU No.50. The dose verification of the target and OAR was performed by placing the TLD Rod LiF100 and EBT2 Gafchromic film at slab hole of pelvic part of the Alderson RANDO phantom for prostate cancer simulation. The Exposed TLDs was evaluated using the TLD Reader Harshaw while EBT2 film was scanned using Epson scanner. The point dose measurements were compared between planned dose and measured dose at target volume and OAR. The result is the dose difference at target volume, bladder and rectum for IMRT and VMAT are less than 5%. On the other hand, the dose difference at the Femoral head is more than 5% for both techniques because the location of OAR already in low gradient dose. Furthermore, the difference dose of the target volume for IMRT technique tends to be smaller than VMAT either for TLD and EBT2 film detectors. From the measurement showed that the delivered dose on the phantom simulation match with ICRU No.50 criteria.

  19. Reducing stray radiation dose to patients receiving passively scattered proton radiotherapy for prostate cancer

    PubMed Central

    Taddei, Phillip J; Fontenot, Jonas D; Zheng, Yuanshui; Mirkovic, Dragan; Lee, Andrew K; Titt, Uwe; Newhauser, Wayne D

    2014-01-01

    Proton beam radiotherapy exposes healthy tissue to stray radiation emanating from the treatment unit and secondary radiation produced within the patient. These exposures provide no known benefit and may increase a patient's risk of developing a radiogenic second cancer. The aim of this study was to explore strategies to reduce stray radiation dose to a patient receiving a 76 Gy proton beam treatment for cancer of the prostate. The whole-body effective dose from stray radiation, E, was estimated using detailed Monte Carlo simulations of a passively scattered proton treatment unit and an anthropomorphic phantom. The predicted value of E was 567 mSv, of which 320 mSv was attributed to leakage from the treatment unit; the remainder arose from scattered radiation that originated within the patient. Modest modifications of the treatment unit reduced E by 212 mSv. Surprisingly, E from a modified passive-scattering device was only slightly higher (109 mSv) than from a nozzle with no leakage, e.g., that which may be approached with a spot-scanning technique. These results add to the body of evidence supporting the suitability of passively scattered proton beams for the treatment of prostate cancer, confirm that the effective dose from stray radiation was not excessive, and, importantly, show that it can be substantially reduced by modest enhancements to the treatment unit. PMID:18369278

  20. Time of Decline in Sexual Function After External Beam Radiotherapy for Prostate Cancer

    SciTech Connect

    Siglin, Joshua; Kubicek, Gregory J.; Leiby, Benjamin; Valicenti, Richard K.

    2010-01-15

    Purpose: Erectile dysfunction is one of the most concerning toxicities for patients in the treatment of prostate cancer. The inconsistent evaluation of sexual function (SF) and limited follow-up data have necessitated additional study to clarify the rate and timing of erectile dysfunction after external beam radiotherapy (EBRT) for prostate cancer. Methods and Materials: A total of 143 men completed baseline data on SF before treatment and at the subsequent follow-up visits. A total of 1187 validated SF inventories were analyzed from the study participants. Multiple domains of SF (sex drive, erectile function, ejaculatory function, and overall satisfaction) were analyzed for <=8 years of follow-up. Results: The median follow-up was 4.03 years. The strongest predictor of SF after EBRT was SF before treatment. For all domains of SF, the only statistically significant decrease in function occurred in the first 24 months after EBRT. SF stabilized 2 years after treatment completion, with no statistically significant change in any area of SF >2 years after the end of EBRT. Conclusion: These data suggest that SF does not have a continuous decline after EBRT. Instead, SF decreases maximally within the first 24 months after EBRT, with no significant changes thereafter.

  1. Reducing stray radiation dose to patients receiving passively scattered proton radiotherapy for prostate cancer

    NASA Astrophysics Data System (ADS)

    Taddei, Phillip J.; Fontenot, Jonas D.; Zheng, Yuanshui; Mirkovic, Dragan; Lee, Andrew K.; Titt, Uwe; Newhauser, Wayne D.

    2008-04-01

    Proton beam radiotherapy exposes healthy tissue to stray radiation emanating from the treatment unit and secondary radiation produced within the patient. These exposures provide no known benefit and may increase a patient's risk of developing a radiogenic second cancer. The aim of this study was to explore strategies to reduce stray radiation dose to a patient receiving a 76 Gy proton beam treatment for cancer of the prostate. The whole-body effective dose from stray radiation, E, was estimated using detailed Monte Carlo simulations of a passively scattered proton treatment unit and an anthropomorphic phantom. The predicted value of E was 567 mSv, of which 320 mSv was attributed to leakage from the treatment unit; the remainder arose from scattered radiation that originated within the patient. Modest modifications of the treatment unit reduced E by 212 mSv. Surprisingly, E from a modified passive-scattering device was only slightly higher (109 mSv) than from a nozzle with no leakage, e.g., that which may be approached with a spot-scanning technique. These results add to the body of evidence supporting the suitability of passively scattered proton beams for the treatment of prostate cancer, confirm that the effective dose from stray radiation was not excessive, and, importantly, show that it can be substantially reduced by modest enhancements to the treatment unit.

  2. Evaluation of volume change in rectum and bladder during application of image-guided radiotherapy for prostate carcinoma

    NASA Astrophysics Data System (ADS)

    Luna, J. A.; Rojas, J. I.

    2016-07-01

    All prostate cancer patients from Centro Médico Radioterapia Siglo XXI receive Volumetric Modulated Arc Therapy (VMAT). This therapy uses image-guided radiotherapy (IGRT) with the Cone Beam Computed Tomography (CBCT). This study compares the planned dose in the reference CT image against the delivered dose recalculate in the CBCT image. The purpose of this study is to evaluate the anatomic changes and related dosimetric effect based on weekly CBCT directly for patients with prostate cancer undergoing volumetric modulated arc therapy (VMAT) treatment. The collected data were analyzed using one-way ANOVA.

  3. [Rectal mucosa metastasis in recurrent prostate cancer : (68)Ga-PSMA-PET/CT allows targeted salvage radiotherapy].

    PubMed

    Düwel, C; Blümel, C; Westenfelder, K; Wagner-Thiessen, E; Becker, A; Gschwend, J E; Eiber, M; Maurer, T

    2016-08-01

    This article presents for the first time a case of rectal mucosa metastasis of recurrent prostate cancer that was diagnosed with (68)Ga-PSMA PET/CT. After histological confirmation, the patient was treated with salvage radiotherapy. This case report underlines the specificity and efficacy of PSMA-based PET imaging. In case of biochemical relapse, it can be used even at low PSA levels to detect prostate cancer metastases that might also be in atypical locations. Thus, (68)Ga-PSMA PET/CT may allow new options for salvage therapy. PMID:27385310

  4. Voxel-based population analysis for correlating local dose and rectal toxicity in prostate cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Acosta, Oscar; Drean, Gael; Ospina, Juan D.; Simon, Antoine; Haigron, Pascal; Lafond, Caroline; de Crevoisier, Renaud

    2013-04-01

    The majority of current models utilized for predicting toxicity in prostate cancer radiotherapy are based on dose-volume histograms. One of their main drawbacks is the lack of spatial accuracy, since they consider the organs as a whole volume and thus ignore the heterogeneous intra-organ radio-sensitivity. In this paper, we propose a dose-image-based framework to reveal the relationships between local dose and toxicity. In this approach, the three-dimensional (3D) planned dose distributions across a population are non-rigidly registered into a common coordinate system and compared at a voxel level, therefore enabling the identification of 3D anatomical patterns, which may be responsible for toxicity, at least to some extent. Additionally, different metrics were employed in order to assess the quality of the dose mapping. The value of this approach was demonstrated by prospectively analyzing rectal bleeding (⩾Grade 1 at 2 years) according to the CTCAE v3.0 classification in a series of 105 patients receiving 80 Gy to the prostate by intensity modulated radiation therapy (IMRT). Within the patients presenting bleeding, a significant dose excess (6 Gy on average, p < 0.01) was found in a region of the anterior rectal wall. This region, close to the prostate (1 cm), represented less than 10% of the rectum. This promising voxel-wise approach allowed subregions to be defined within the organ that may be involved in toxicity and, as such, must be considered during the inverse IMRT planning step.

  5. Proton Radiotherapy for Prostate Cancer Is Not Associated With Post-Treatment Testosterone Suppression

    SciTech Connect

    Nichols, R. Charles; Morris, Christopher G.; Hoppe, Bradford S.; Henderson, Randal H.; Marcus, Robert B.; Mendenhall, William M.; Li Zuofeng; Williams, Christopher R.; Costa, Joseph A.; Mendenhall, Nancy P.

    2012-03-01

    Purpose: Three independent studies of photon (x-ray) radiotherapy (RT) for prostate cancer have demonstrated evidence of testosterone suppression after treatment. The present study was undertaken to determine whether this would also be the case with conformal protons. Methods and Materials: Between August 2006 and October 2007, 171 patients with low- and intermediate-risk prostate cancer were enrolled and underwent treatment according to University of Florida Proton Therapy Institute institutional review board-approved PR01 and PR02 protocols. Of the 171 patients, 18 were excluded because they had received androgen deprivation therapy either before (n = 17) or after (n = 1) RT. The pretreatment serum testosterone level was available for 150 of the remaining 153 patients. These 150 patients were included in the present study. The post-treatment levels were compared with the pretreatment levels. Results: The median baseline pretreatment serum testosterone level was 357.9 ng/dL. The median post-treatment testosterone value was 375.5 ng/dL at treatment completion (p = .1935) and 369.9 ng/dL (p = .1336), 348.7 ng/dL (p = .7317), 353.4 ng/dL (p = .6996), and 340.9 ng/dL (p = .1669) at 6, 12, 18, and 24 months after proton therapy, respectively. Conclusions: Conformal proton therapy to the prostate, as delivered using University of Florida Proton Therapy Institute PR01 and PR02 protocols, did not appear to significantly affect the serum testosterone levels within 24 months after RT.

  6. Postoperative Prostate-Specific Antigen Velocity Independently Predicts for Failure of Salvage Radiotherapy After Prostatectomy

    SciTech Connect

    King, Christopher R. Presti, Joseph C.; Brooks, James D.; Gill, Harcharan; Spiotto, Michael T.

    2008-04-01

    Purpose: Identification of patients most likely to benefit from salvage radiotherapy (RT) using postoperative (postop) prostate-specific antigen (PSA) kinetics. Methods and Materials: From 1984 to 2004, 81 patients who fit the following criteria formed the study population: undetectable PSA after radical prostatectomy (RP); pathologically negative nodes; biochemical relapse defined as a persistently detectable PSA; salvage RT; and two or more postop PSAs available before salvage RT. Salvage RT included the whole pelvic nodes in 55 patients and 4 months of total androgen suppression in 56 patients. The median follow-up was >5 years. All relapses were defined as a persistently detectable PSA. Kaplan-Meier and Cox proportional hazards multivariable analysis were performed for all clinical, pathological, and treatment factors predicting for biochemical relapse-free survival (bRFS). Results: There were 37 biochemical relapses observed after salvage RT. The 5-year bRFS after salvage RT for patients with postop prostate-specific antigen velocity {<=}1 vs. >1 ng/ml/yr was 59% vs. 29%, p = 0.002. In multivariate analysis, only postop PSAV (p = 0.0036), pre-RT PSA level {<=}1 (p = 0.037) and interval-to-relapse >10 months (p = 0.012) remained significant, whereas pelvic RT, hormone therapy, and RT dose showed a trend (p = {approx}0.06). PSAV, but not prostate-specific antigen doubling time, predicted successful salvage RT, suggesting an association of zero-order kinetics with locally recurrent disease. Conclusions: Postoperative PSA velocity independently predicts for the failure of salvage RT and can be considered in addition to high-risk features when selecting patients in need of systemic therapy following biochemical failure after RP. For well-selected patients, salvage RT can achieve high cure rates.

  7. Concurrent Androgen Deprivation Therapy During Salvage Prostate Radiotherapy Improves Treatment Outcomes in High-Risk Patients

    SciTech Connect

    Soto, Daniel E.; Passarelli, Michael N.; Daignault, Stephanie; Sandler, Howard M.

    2012-03-01

    Purpose: To determine whether concurrent androgen deprivation therapy (ADT) during salvage radiotherapy (RT) improves prostate cancer treatment outcomes. Methods and Materials: A total of 630 postprostatectomy patients were retrospectively identified who were treated with three-dimensional conformal RT. Of these, 441 were found to be treated for salvage indications. Biochemical failure was defined as prostate-specific antigen (PSA) of 0.2 ng/mL or greater above nadir with another PSA increase or the initiation of salvage ADT. Progression-free survival (PFS) was defined as the absence of biochemical failure, continued PSA rise despite salvage therapy, initiation of systemic therapy, clinical progression, or distant failure. Multivariate-adjusted Cox proportional hazards modeling was performed to determine which factors predict PFS. Results: Low-, intermediate-, and high-risk patients made up 10%, 24%, and 66% of patients, respectively. The mean RT dose was 68 Gy. Twenty-four percent of patients received concurrent ADT (cADT). Regional pelvic nodes were treated in 16% of patients. With a median follow-up of 3 years, the 3-year PFS was 4.0 years for cADT vs. 3.4 years for cADT patients (p = 0.22). Multivariate analysis showed that concurrent ADT (p = 0.05), Gleason score (p < 0.001), and pre-RT PSA (p = 0.03) were independent predictors of PFS. When patients were stratified by risk group, the benefits of cADT (hazard ratio, 0.65; p = 0.046) were significant only for high-risk patients. Conclusions: This retrospective study showed a PFS benefit of concurrent ADT during salvage prostate RT. This benefit was observed only in high-risk patients.

  8. Salvage high-intensity focused ultrasound for the recurrent prostate cancer after radiotherapy in Japan

    NASA Astrophysics Data System (ADS)

    Shoji, S.; Nakano, M.; Nagata, Y.; Uchida, T.

    2012-10-01

    Aim: to investigate the use of minimally invasive high-intensity focused ultrasound (HIFU) as a salvage therapy in men with localized prostate cancer recurrence following external beam radiotherapy (EBRT), brachytherapy or proton therapy. A review of 22 cases treated using the Sonablate® 500 HIFU device, between August 28, 2002 and April 1, 2010, was carried out. All men had presumed organ-confined, histologically confirmed recurrent prostate adenocarcinoma following radiation therapy. The mean (range) age was 65 (52-80) years with a mean PSA level before radiation therapy of 14.3 (5.7-118) ng/mL. The mean (range) period after radiation therapy to HIFU was 36 (4-96) months. All men with presumed, organ-confined, recurrent disease following EBRT in 14 patients, brachytherapy in 5 patients (4 patients with high-dose brachytherapy with In192 and 1 with low-dose brachytherapy with Au98) or proton therapy in 3 patients treated with salvage HIFU were included. The patients were followed for a mean (range) of 24 months. Biochemical disease-free survival (bDFS) rates in patients with low-, intermediate-and high risk groups were 100%, 86%, and 14%, respectively. All nine patients who received a post HIFU prostate biopsy showed no malignancy. Side-effects included urethral stricture in 4 of the 25 patients (16%) and urinary incontinence in 4 of the 25 patients (16%). Recto-urethral fistula occurred in one patient (4%). Salvage HIFU is a minimally invasive for patients with low-and intermediate risk group with comparable morbidity to other forms of salvage treatment.

  9. Salvage High-intensity Focused Ultrasound for the Recurrent Prostate Cancer after Radiotherapy in Japan

    NASA Astrophysics Data System (ADS)

    Shoji, S.; Nakano, M.; Nagata, Y.; Uchida, T.

    2011-09-01

    To investigate the use of minimally invasive high-intensity focused ultrasound (HIFU) as a salvage therapy in men with localized prostate cancer recurrence following external beam radiotherapy (EBRT), brachytherapy or proton therapy. A review of 20 cases treated using the Sonablate® 500 HIFU device, between August 28, 2002 and June 1, 2010, was carried out. All men had presumed organ-confined, histologically confirmed recurrent prostate adenocarcinoma following radiation therapy. The mean (range) age was 65 (52-80) years with a mean PSA level before radiation therapy of 26.6 (4.8-118) ng/mL. The mean (range) period after radiation therapy to HIFU was 41 (4-96) months. All men with presumed, organ-confined, recurrent disease following EBRT in 13 patients, brachytherapy in 5 patients (4 patients with high-dose brachytherapy with In192 and 1 with low-dose brachytherapy with Au98) or proton therapy in 4 patients treated with salvage HIFU were included. The patients were followed for a mean (range) of 21 months. Biochemical disease-free survival (bDFS) rates in patients with low-, intermediate- and high risk groups were 100%, 85.7%, and 18.2%, respectively. All nine patients who received a post HIFU prostate biopsy showed no malignancy. Side-effects included urethral stricture in 4 of the 22 patients (18%) and urinary incontinence in 4 of the 22 patients (18%). Recto-urethral fistula occurred in one patient (5%). Salvage HIFU is a minimally invasive for patients with low-and intermediate risk group with comparable morbidity to other forms of salvage treatment.

  10. Voxel-based population analysis for correlating local dose and rectal toxicity in prostate cancer radiotherapy.

    PubMed

    Acosta, Oscar; Drean, Gael; Ospina, Juan D; Simon, Antoine; Haigron, Pascal; Lafond, Caroline; de Crevoisier, Renaud

    2013-04-21

    The majority of current models utilized for predicting toxicity in prostate cancer radiotherapy are based on dose-volume histograms. One of their main drawbacks is the lack of spatial accuracy, since they consider the organs as a whole volume and thus ignore the heterogeneous intra-organ radio-sensitivity. In this paper, we propose a dose-image-based framework to reveal the relationships between local dose and toxicity. In this approach, the three-dimensional (3D) planned dose distributions across a population are non-rigidly registered into a common coordinate system and compared at a voxel level, therefore enabling the identification of 3D anatomical patterns, which may be responsible for toxicity, at least to some extent. Additionally, different metrics were employed in order to assess the quality of the dose mapping. The value of this approach was demonstrated by prospectively analyzing rectal bleeding (≥Grade 1 at 2 years) according to the CTCAE v3.0 classification in a series of 105 patients receiving 80 Gy to the prostate by intensity modulated radiation therapy (IMRT). Within the patients presenting bleeding, a significant dose excess (6 Gy on average, p < 0.01) was found in a region of the anterior rectal wall. This region, close to the prostate (1 cm), represented less than 10% of the rectum. This promising voxel-wise approach allowed subregions to be defined within the organ that may be involved in toxicity and, as such, must be considered during the inverse IMRT planning step. PMID:23528429

  11. Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients

    PubMed Central

    EL-SAGHIRE, HOUSSEIN; VANDEVOORDE, CHARLOT; OST, PIET; MONSIEURS, PIETER; MICHAUX, ARLETTE; DE MEERLEER, GERT; BAATOUT, SARAH; THIERENS, HUBERT

    2014-01-01

    Intensity modulated radiotherapy (IMRT) is one of the modern conformal radiotherapies that is widely used within the context of cancer patient treatment. It uses multiple radiation beams targeted to the tumor, however, large volumes of the body receive low doses of irradiation. Using γ-H2AX and global genome expression analysis, we studied the biological responses induced by low doses of ionizing radiation in prostate cancer patients following IMRT. By means of different bioinformatics analyses, we report that IMRT induced an inflammatory response via the induction of viral, adaptive, and innate immune signaling. In response to growth factors and immune-stimulatory signaling, positive regulation in the progression of cell cycle and DNA replication were induced. This denotes pro-inflammatory and pro-survival responses. Furthermore, double strand DNA breaks were induced in every patient 30 min after the treatment and remaining DNA repair and damage signaling continued after 18–24 h. Nine genes belonging to inflammatory responses (TLR3, SH2D1A and IL18), cell cycle progression (ORC4, SMC2 and CCDC99) and DNA damage and repair (RAD17, SMC6 and MRE11A) were confirmed by quantitative RT-PCR. This study emphasizes that the risk assessment of health effects from the out-of-field low doses during IMRT should be of concern, as these may increase the risk of secondary cancers and/or systemic inflammation. PMID:24435511

  12. Early Proctoscopy is a Surrogate Endpoint of Late Rectal Toxicity in Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Ippolito, Edy; Massaccesi, Mariangela; Digesu, Cinzia; Deodato, Francesco; Macchia, Gabriella; Pirozzi, Giuseppe Antonio; Cilla, Savino; Cuscuna, Daniele; Di Lallo, Alessandra; Mattiucci, Gian Carlo; Mantini, Giovanna; Pacelli, Fabio; Valentini, Vincenzo; Cellini, Numa; Ingrosso, Marcello; Morganti, Alessio Giuseppe

    2012-06-01

    Purpose: To predict the grade and incidence of late clinical rectal toxicity through short-term (1 year) mucosal alterations. Methods and Materials: Patients with prostate adenocarcinoma treated with curative or adjuvant radiotherapy underwent proctoscopy a year after the course of radiotherapy. Mucosal changes were classified by the Vienna Rectoscopy Score (VRS). Late toxicity data were analyzed according to the Kaplan-Meier method. Comparison between prognosis groups was performed by log-rank analysis. Results: After a median follow-up time of 45 months (range, 18-99), the 3-year incidence of grade {>=}2 rectal late toxicity according to the criteria of the European Organization for Research and Treatment of Cancer and the Radiation Therapy Oncology Group was 24%, with all patients (24/24; 100%) experiencing rectal bleeding. The occurrence of grade {>=}2 clinical rectal late toxicity was higher in patients with grade {>=}2 (32% vs. 15 %, p = 0.02) or grade {>=}3 VRS telangiectasia (47% vs. 17%, p {<=} 0.01) and an overall VRS score of {>=}2 (31% vs. 16 %, p = 0.04) or {>=}3 (48% vs. 17%, p = 0.01) at the 1-year proctoscopy. Conclusions: Early proctoscopy (1 year) predicts late rectal bleeding and therefore can be used as a surrogate endpoint for late rectal toxicity in studies aimed at reducing this frequent complication.

  13. NBN gain is predictive for adverse outcome following image-guided radiotherapy for localized prostate cancer.

    PubMed

    Berlin, Alejandro; Lalonde, Emilie; Sykes, Jenna; Zafarana, Gaetano; Chu, Kenneth C; Ramnarine, Varune R; Ishkanian, Adrian; Sendorek, Dorota H S; Pasic, Ivan; Lam, Wan L; Jurisica, Igor; van der Kwast, Theo; Milosevic, Michael; Boutros, Paul C; Bristow, Robert G

    2014-11-30

    Despite the use of clinical prognostic factors (PSA, T-category and Gleason score), 20-60% of localized prostate cancers (PCa) fail primary local treatment. Herein, we determined the prognostic importance of main sensors of the DNA damage response (DDR): MRE11A, RAD50, NBN, ATM, ATR and PRKDC. We studied copy number alterations in DDR genes in localized PCa treated with image-guided radiotherapy (IGRT; n=139) versus radical prostatectomy (RadP; n=154). In both cohorts, NBN gains were the most frequent genomic alteration (14.4 and 11% of cases, respectively), and were associated with overall tumour genomic instability (p<0.0001). NBN gains were the only significant predictor of 5yrs biochemical relapse-free rate (bRFR) following IGRT (46% versus 77%; p=0.00067). On multivariate analysis, NBN gain remained a significant independent predictor of bRFR after adjusting for known clinical prognostic variables (HR=3.28, 95% CI 1.56-6.89, Wald p-value=0.0017). No DDR-sensing gene was prognostic in the RadP cohort. In vitro studies correlated NBN gene overexpression with PCa cells radioresistance. In conclusion, NBN gain predicts for decreased bRFR in IGRT, but not in RadP patients. If validated independently, Nibrin gains may be the first PCa predictive biomarker to facilitate local treatment decisions using precision medicine approaches with surgery or radiotherapy. PMID:25415046

  14. Outcome After Conformal Salvage Radiotherapy in Patients With Rising Prostate-Specific Antigen Levels After Radical Prostatectomy

    SciTech Connect

    Geinitz, Hans; Riegel, Martina G.; Thamm, Reinhard; Astner, Sabrina T.; Lewerenz, Carolin; Zimmermann, Frank; Molls, Michael; Nieder, Carsten

    2012-04-01

    Purpose: This study attempts to improve our understanding of the role of salvage radiotherapy (SRT) in patients with prostate-specific antigen (PSA) relapse after radical prostatectomy with regard to biochemical control, rate of distant metastasis, and survival. Methods and Materials: We performed a retrospective analysis of 96 men treated with conformal prostate bed SRT (median, 64.8 Gy) at a single institution (median follow-up, 70 months). The majority had intermediate- or high-risk prostate cancer. Fifty-four percent underwent a resection with positive margins (R1 resection). The median time interval between surgery and SRT was 22 months. Results: After SRT, 66% of patients reached a PSA nadir of less than 0.2 ng/mL. However, the 5-year biochemical no evidence of disease rate was 35%. Seminal vesicle involvement was predictive for a significantly lower biochemical no evidence of disease rate. All patients with a preoperative PSA level greater than 50 ng/mL relapsed biochemically within 2 years. The 5-year distant metastasis rate was 18%, the 5-year prostate cancer-specific survival rate was 90%, and the 5-year overall survival rate was 88%. Significantly more distant metastases developed in patients with a PSA nadir greater than 0.05 ng/mL after SRT, and they had significantly inferior prostate cancer-specific and overall survival rates. Resection status (R1 vs. R0) was not predictive for any of the endpoints. Conclusions: Men with postoperative PSA relapse can undergo salvage treatment by prostate bed radiotherapy, but durable PSA control is maintained only in about one-third of the patients. Despite a high biochemical failure rate after SRT, prostate cancer-specific survival does not decrease rapidly.

  15. Improving Positioning in High-Dose Radiotherapy for Prostate Cancer: Safety and Visibility of Frequently Used Gold Fiducial Markers

    SciTech Connect

    Fonteyne, Valerie; Ost, Piet; Villeirs, Geert; Oosterlinck, Willem; Impens, Aline; De Gersem, Werner; De Wagter, Carlos; De Meerleer, Gert

    2012-05-01

    Purpose: The use of gold fiducial markers (GFMs) for prostate positioning in high-dose radiotherapy is gaining interest. The purpose of this study was to compare five GFMs regarding feasibility of ultrasound-based implantation in the prostate and intraprostatic lesion (IPL); toxicity; visibility on transabdominal ultrasound (TU) and cone-beam CT (CBCT); reliability of automatic, soft tissue, and GFM-based CBCT patient positioning by comparing manual and automatic fusion CBCT. Methods and Materials: Twenty-five patients were included. Pain and toxicity were scored after implantation and high-dose radiotherapy. Fisher exact test was used to evaluate the correlation of patients' characteristics and prostatitis. Positioning was evaluated on TU and kilovoltage CBCT images. CBCT fusion was performed automatically (Elekta XVI technology, release 3.5.1 b27, based on grey values) and manually on soft tissue and GFMs. Pearson correlation statistics and Bland-Altman evaluation were used. Five GFMs were compared. Results: Twenty percent of the patients developed prostatitis despite antibiotic prophylaxis. Cigarette smoking was significantly correlated with prostatitis. The visualization of all GFMs on TU was disappointing. Consequently we cannot recommend the use of these GFMs for TU-based prostate positioning. For all GFMs, there was only fair to poor linear correlation between automatic and manual CBCT images, indicating that even when GFMs are used, an operator evaluation is imperative. However, when GFMs were analyzed individually, a moderate to very strong correlation between automatic and manual positioning was found for larger GFMs in all directions. Conclusion: The incidence of prostatitis in our series was high. Further research is imperative to define the ideal preparation protocol preimplantation and to select patients. Automatic fusion is more reliable with larger GFMs at the cost of more scatter. The stability of all GFMs was proven.

  16. Customizable radiotherapy enhancement (CuRE) for prostate cancer using platinum based nanoparticles

    NASA Astrophysics Data System (ADS)

    Cifter, Gizem

    New approach to prostate cancer (PCa) therapy titled "Customizable Radiotherapy Enhancement (CuRE)" employs cisplatin (C), carboplatin (Ca) and oxaliplatin (O) nanoparticles (CNPs, CaNPs and ONPs) as adjuvants to brachytherapy and external beam radiation therapy (EBRT), with the CNPs/CaNPs/ONPs released in situ from either brachytherapy spacers or fudicials loaded with the nanoparticles. The chemotherapy dose from the nanoparticles released in situ from within the prostate capsule, is enhanced by the physical dose due to photon interactions with the nanoparticles. The physical dose enhancement is due to low energy photons from the brachytherapy and EBRT sources interacting with the high-Z platinum component of the nanoparticles, causing emission of short-range photoelectrons to boost dose to the tumor. By varying the nanoparticle parameters, such as size, initial concentration, functionalization, location of spacer or fiducial, and intra-tumor biodistribution, the dose enhancement can be customized to maximize dose to tumor cells while minimizing toxicity to healthy cells. The hypothesis is that the CuRE approach will be a more efficacious method for concomitant cisplatin/carboplatin/oxaliplatin and radiotherapy treatment of localized prostate cancer due to significant dose boost to the PCa cells with minimal toxicity to healthy tissue. To investigate this hypothesis, microdosimetry calculations employing the energy loss formula of Cole were used to calculate the dose enhancement to the PCa cells from the CNPs/CaNPs/OPNs. The dose enhancement ratio (DEF) representing the ratio of the overall dose in the presence of CNPs/CaNPs/ONPs to the dose without CNPs/CaNPs/ONPs was determined for a range of CNP/CaNP/OPN concentrations up to their FDA approved limits. The dose enhancement to endothelial cells with (EDEF) with single concentration of cisplatin (42.8 mg/g) was found 2.6 with Pd-103. When EBRT source was used with single concentration of cisplatin, with 10cm x 10

  17. Acute and late gastrointestinal toxicity after radiotherapy in prostate cancer patients: Consequential late damage

    SciTech Connect

    Heemsbergen, Wilma D. . E-mail: w.heemsbergen@nki.nl; Peeters, Stephanie T.H.; Koper, Peter; Hoogeman, Mischa S.; Lebesque, Joos V.

    2006-09-01

    Purpose: Late gastrointestinal (GI) toxicity after radiotherapy can be partly explained by late effects of acute toxicity (consequential late damage). We studied whether there is a direct relationship between acute and late GI toxicity. Patients and Methods: A total of 553 evaluable patients from the Dutch dose escalation trial (68 Gy vs. 78 Gy) were included. We defined three outcomes for acute reactions: 1) maximum Radiation Therapy Oncology Group acute toxicity, 2) maximum acute mucous discharge (AMD), and 3) maximum acute proctitis. Within a multivariable model, late endpoints (overall toxicity and five toxicity indicators) were studied as a function of acute toxicity, pretreatment symptoms, and relevant dose parameters. Results: At multivariable analysis, AMD and acute proctitis were strong predictors for overall toxicity, 'intermittent bleeding,' and 'incontinence pads' (p {<=} 0.01). For 'stools {>=}6/day' all three were strong predictors. No significant associations were found for 'severe bleeding' and 'use of steroids.' The predictive power of the dose parameters remained at the same level or became weaker for most late endpoints. Conclusions: Acute GI toxicity is an independent significant predictor of late GI toxicity. This suggests a significant consequential component in the development of late GI toxicity.

  18. Health-Related Quality of Life 2 Years After Treatment With Radical Prostatectomy, Prostate Brachytherapy, or External Beam Radiotherapy in Patients With Clinically Localized Prostate Cancer

    SciTech Connect

    Ferrer, Montserrat Suarez, Jose Francisco; Guedea, Ferran; Fernandez, Pablo; Macias, Victor; Marino, Alfonso; Hervas, Asuncion; Herruzo, Ismael; Ortiz, Maria Jose; Villavicencio, Humberto; Craven-Bratle, Jordi; Garin, Olatz; Aguilo, Ferran

    2008-10-01

    Purpose: To compare treatment impact on health-related quality of life (HRQL) in patients with localized prostate cancer, from before treatment to 2 years after the intervention. Methods and Materials: This was a longitudinal, prospective study of 614 patients with localized prostate cancer treated with radical prostatectomy (134), three-dimensional external conformal radiotherapy (205), and brachytherapy (275). The HRQL questionnaires administered before and after treatment (months 1, 3, 6, 12, and 24) were the Medical Outcomes Study 36-Item Short Form, the Functional Assessment of Cancer Therapy (General and Prostate Specific), the Expanded Prostate Cancer Index Composite (EPIC), and the American Urological Association Symptom Index. Differences between groups were tested by analysis of variance and within-group changes by univariate repeated-measures analysis of variance. Generalized estimating equations (GEE) models were constructed to assess between-group differences in HRQL at 2 years of follow-up after adjusting for clinical variables. Results: In each treatment group, HRQL initially deteriorated after treatment with subsequent partial recovery. However, some dimension scores were still significantly lower after 2 years of treatment. The GEE models showed that, compared with the brachytherapy group, radical prostatectomy patients had worse EPIC sexual summary and urinary incontinence scores (-20.4 and -14.1; p < 0.001), and external radiotherapy patients had worse EPIC bowel, sexual, and hormonal summary scores (-3.55, -5.24, and -1.94; p < 0.05). Prostatectomy patients had significantly better EPIC urinary irritation scores than brachytherapy patients (+4.16; p < 0.001). Conclusions: Relevant differences between treatment groups persisted after 2 years of follow-up. Radical prostatectomy had a considerable negative effect on sexual functioning and urinary continence. Three-dimensional conformal radiotherapy had a moderate negative impact on bowel

  19. Quality of Life After Hypofractionated Concomitant Intensity-Modulated Radiotherapy Boost for High-Risk Prostate Cancer

    SciTech Connect

    Quon, Harvey; Cheung, Patrick C.F.; Loblaw, D. Andrew; Morton, Gerard; Pang, Geordi; Szumacher, Ewa; Danjoux, Cyril; Choo, Richard; Kiss, Alex; Mamedov, Alexandre; Deabreu, Andrea

    2012-06-01

    Purpose: To evaluate the change in health-related quality of life (QOL) of patients with high-risk prostate cancer treated using hypofractionated radiotherapy combined with long-term androgen deprivation therapy. Methods and Materials: A prospective Phase I-II study enrolled patients with any of the following: clinical Stage T3 disease, prostate-specific antigen level {>=}20 ng/mL, or Gleason score 8-10. Radiotherapy consisted of 45 Gy (1.8 Gy per fraction) to the pelvic lymph nodes with a concomitant 22.5 Gy intensity-modulated radiotherapy boost to the prostate, for a total of 67.5 Gy (2.7 Gy per fraction) in 25 fractions over 5 weeks. Daily image guidance was performed using three gold seed fiducials. Quality of life was measured using the Expanded Prostate Cancer Index Composite (EPIC), a validated tool that assesses four primary domains (urinary, bowel, sexual, and hormonal). Results: From 2004 to 2007, 97 patients were treated. Median follow-up was 39 months. Compared with baseline, at 24 months there was no statistically significant change in the mean urinary domain score (p = 0.99), whereas there were decreases in the bowel (p < 0.01), sexual (p < 0.01), and hormonal (p < 0.01) domains. The proportion of patients reporting a clinically significant difference in EPIC urinary, bowel, sexual, and hormonal scores at 24 months was 27%, 31%, 55%, and 60%, respectively. However, moderate and severe distress related to these symptoms was minimal, with increases of only 3% and 5% in the urinary and bowel domains, respectively. Conclusions: Hypofractionated radiotherapy combined with long-term androgen deprivation therapy was well tolerated. Although there were modest rates of clinically significant patient-reported urinary and bowel toxicity, most of this caused only mild distress, and moderate and severe effects on QOL were limited. Additional follow-up is ongoing to characterize long-term QOL.

  20. TGFB1 Single Nucleotide Polymorphisms Are Associated With Adverse Quality of Life in Prostate Cancer Patients Treated With Radiotherapy

    SciTech Connect

    Peters, Christopher A. Stock, Richard G.; Cesaretti, Jamie A.; Atencio, David P.; Peters, Sheila B.A.; Burri, Ryan J.; Stone, Nelson N.; Ostrer, Harry; Rosenstein, Barry S.

    2008-03-01

    Purpose: To investigate whether the presence of single nucleotide polymorphisms (SNPs) located within TGFB1 might be predictive for the development of adverse quality-of-life outcomes in prostate cancer patients treated with radiotherapy. Methods and Materials: A total of 141 prostate cancer patients treated with radiotherapy were screened for SNPs in TGFB1 using DNA sequencing. Three quality-of-life outcomes were investigated: (1) prospective decline in erectile function, (2) urinary quality of life, and (3) rectal bleeding. Median follow-up was 51.3 months (range, 12-138 months; SD, 24.4 months). Results: Those patients who possessed either the T/T genotype at position -509, the C/C genotype at position 869 (pro/pro, codon 10) or the G/C genotype at position 915 (arg/pro, codon 25) were significantly associated with the development of a decline in erectile function compared with those who did not have these genotypes: 56% (9 of 16) vs. 24% (11 of 45) (p = 0.02). In addition, patients with the -509 T/T genotype had a significantly increased risk of developing late rectal bleeding compared with those who had either the C/T or C/C genotype at this position: 55% (6 of 11) vs. 26% (34 of 130) (p = 0.05). Conclusions: Possession of certain TGFB1 genotypes is associated with the development of both erectile dysfunction and late rectal bleeding in patients treated with radiotherapy for prostate cancer. Therefore, identification of patients harboring these genotypes may represent a means to predict which men are most likely to suffer from poor quality-of-life outcomes after radiotherapy for prostate cancer.

  1. Automatic Segmentation of Pelvic Structures From Magnetic Resonance Images for Prostate Cancer Radiotherapy

    SciTech Connect

    Pasquier, David . E-mail: d-pasquier@o-lambret.fr; Lacornerie, Thomas; Vermandel, Maximilien; Rousseau, Jean; Lartigau, Eric; Betrouni, Nacim

    2007-06-01

    Purpose: Target-volume and organ-at-risk delineation is a time-consuming task in radiotherapy planning. The development of automated segmentation tools remains problematic, because of pelvic organ shape variability. We evaluate a three-dimensional (3D), deformable-model approach and a seeded region-growing algorithm for automatic delineation of the prostate and organs-at-risk on magnetic resonance images. Methods and Materials: Manual and automatic delineation were compared in 24 patients using a sagittal T2-weighted (T2-w) turbo spin echo (TSE) sequence and an axial T1-weighted (T1-w) 3D fast-field echo (FFE) or TSE sequence. For automatic prostate delineation, an organ model-based method was used. Prostates without seminal vesicles were delineated as the clinical target volume (CTV). For automatic bladder and rectum delineation, a seeded region-growing method was used. Manual contouring was considered the reference method. The following parameters were measured: volume ratio (Vr) (automatic/manual), volume overlap (Vo) (ratio of the volume of intersection to the volume of union; optimal value = 1), and correctly delineated volume (Vc) (percent ratio of the volume of intersection to the manually defined volume; optimal value 100). Results: For the CTV, the Vr, Vo, and Vc were 1.13 ({+-}0.1 SD), 0.78 ({+-}0.05 SD), and 94.75 ({+-}3.3 SD), respectively. For the rectum, the Vr, Vo, and Vc were 0.97 ({+-}0.1 SD), 0.78 ({+-}0.06 SD), and 86.52 ({+-}5 SD), respectively. For the bladder, the Vr, Vo, and Vc were 0.95 ({+-}0.03 SD), 0.88 ({+-}0.03 SD), and 91.29 ({+-}3.1 SD), respectively. Conclusions: Our results show that the organ-model method is robust, and results in reproducible prostate segmentation with minor interactive corrections. For automatic bladder and rectum delineation, magnetic resonance imaging soft-tissue contrast enables the use of region-growing methods.

  2. Long-Term Outcomes From a Prospective Trial of Stereotactic Body Radiotherapy for Low-Risk Prostate Cancer

    SciTech Connect

    King, Christopher R.; Brooks, James D.; Gill, Harcharan; Presti, Joseph C.

    2012-02-01

    Purpose: Hypofractionated radiotherapy has an intrinsically different normal tissue and tumor radiobiology. The results of a prospective trial of stereotactic body radiotherapy (SBRT) for prostate cancer with long-term patient-reported toxicity and tumor control rates are presented. Methods and Materials: From 2003 through 2009, 67 patients with clinically localized low-risk prostate cancer were enrolled. Treatment consisted of 36.25 Gy in 5 fractions using SBRT with the CyberKnife as the delivery technology. No patient received hormone therapy. Patient self-reported bladder and rectal toxicities were graded on the Radiation Therapy Oncology Group scale (RTOG). Results: Median follow-up was 2.7 years. There were no grade 4 toxicities. Radiation Therapy Oncology Group Grade 3, 2, and 1 bladder toxicities were seen in 3% (2 patients), 5% (3 patients), and 23% (13 patients) respectively. Dysuria exacerbated by urologic instrumentation accounted for both patients with Grade 3 toxicity. Urinary incontinence, complete obstruction, or persistent hematuria was not observed. Rectal Grade 3, 2, and 1 toxicities were seen in 0, 2% (1 patient), and 12.5% (7 patients), respectively. Persistent rectal bleeding was not observed. Low-grade toxicities were substantially less frequent with QOD vs. QD dose regimen (p = 0.001 for gastrointestinal and p = 0.007 for genitourinary). There were two prostate-specific antigen (PSA), biopsy-proven failures with negative metastatic workup. Median PSA at follow-up was 0.5 {+-} 0.72 ng/mL. The 4-year Kaplan-Meier PSA relapse-free survival was 94% (95% confidence interval, 85%-102%). Conclusion: Significant late bladder and rectal toxicities from SBRT for prostate cancer are infrequent. PSA relapse-free survival compares favorably with other definitive treatments. The current evidence supports consideration of stereotactic body radiotherapy among the therapeutic options for localized prostate cancer.

  3. Dose-distance metric that predicts late rectal bleeding in patients receiving radical prostate external-beam radiotherapy

    NASA Astrophysics Data System (ADS)

    Lee, Richard; Chan, Elisa K.; Kosztyla, Robert; Liu, Mitchell; Moiseenko, Vitali

    2012-12-01

    The relationship between rectal dose distribution and the incidence of late rectal complications following external-beam radiotherapy has been previously studied using dose-volume histograms or dose-surface histograms. However, they do not account for the spatial dose distribution. This study proposes a metric based on both surface dose and distance that can predict the incidence of rectal bleeding in prostate cancer patients treated with radical radiotherapy. One hundred and forty-four patients treated with radical radiotherapy for prostate cancer were prospectively followed to record the incidence of grade ≥2 rectal bleeding. Radiotherapy plans were used to evaluate a dose-distance metric that accounts for the dose and its spatial distribution on the rectal surface, characterized by a logistic weighting function with slope a and inflection point d0. This was compared to the effective dose obtained from dose-surface histograms, characterized by the parameter n which describes sensitivity to hot spots. The log-rank test was used to determine statistically significant (p < 0.05) cut-off values for the dose-distance metric and effective dose that predict for the occurrence of rectal bleeding. For the dose-distance metric, only d0 = 25 and 30 mm combined with a > 5 led to statistical significant cut-offs. For the effective dose metric, only values of n in the range 0.07-0.35 led to statistically significant cut-offs. The proposed dose-distance metric is a predictor of rectal bleeding in prostate cancer patients treated with radiotherapy. Both the dose-distance metric and the effective dose metric indicate that the incidence of grade ≥2 rectal bleeding is sensitive to localized damage to the rectal surface.

  4. Moderate dose escalation for advanced stage Hodgkin's disease using the bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone scheme and adjuvant radiotherapy: a study of the German Hodgkin's Lymphoma Study Group.

    PubMed

    Tesch, H; Diehl, V; Lathan, B; Hasenclever, D; Sieber, M; Rüffer, U; Engert, A; Franklin, J; Pfreundschuh, M; Schalk, K P; Schwieder, G; Wulf, G; Dölken, G; Worst, P; Koch, P; Schmitz, N; Bruntsch, U; Tirier, C; Müller, U; Loeffler, M

    1998-12-15

    The BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen, a rearranged and accelerated version of the standard COPP/adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, has been shown to be effective and safe in a previous pilot study for advanced stage Hodgkin's disease (HD). The present study aimed to determine a maximum practicable dose of three drugs, ie, etoposide, adriamycin, and cyclophosphamide, for which acute toxicities were acceptable and to assess the feasibility of the escalated scheme. Sixty untreated patients with advanced stage HD were enrolled in this study. Radiotherapy was given in 44 patients (73%) after chemotherapy to initial bulk lesions and residual disease. Granulocyte-colony stimulating factor (G-CSF) was given from day 8 to prevent prolonged neutrocytopenia and severe infections. The intended doses of adriamycin, etoposide, and cyclophosphamide in the BEACOPP schedule could be substantially escalated: adriamycin from 25 to 35, cyclophosphamide from 650 to 1,200, and etoposide from 100 to 200 mg/m2. The major toxicities were leukocytopenia and thrombocytopenia with considerable heterogeneity between individual patients. Of 60 patients, 56 (93%) achieved a complete remission (CR). At a median observation of 32 months, the rates of survival and freedom from treatment failure (FFTF) were estimated to be 91% (95% confidence interval 83% to 99%) and 90% (82% to 98%). These results show that a moderate dose escalation of adriamycin, cyclophosphamide, and etoposide of the baseline BEACOPP regimen is feasible. The escalated BEACOPP regimen shows very encouraging results in advanced stage HD and is now being compared in a randomized phase III study with BEACOPP at baseline dose level. PMID:9845521

  5. [Prostate-rectum spacers: optimization of prostate cancer irradiation].

    PubMed

    Zilli, T; Benz, E; Miralbell, R

    2014-06-01

    In the curative radiotherapy of localized prostate cancer, improvements in biochemical control observed with dose escalation have been counterbalanced by an increase in radiation-induced toxicity. The injection of biodegradable spacers between prostate and rectum represents a new frontier in the optimization of radiotherapy treatments for patients with localized disease. Transperineal injection of different types of spacers under transrectal ultrasound guidance allows creating a 7-to-20 mm additional space between the prostate and the anterior rectal wall lasting 3 to 12 months. Dosimetrically, a relative reduction in the rectal volume receiving at least 70 Gy (V70) in the order of 43% to 84% is observed with all types of spacers, regardless of the radiotherapy technique used. Preliminary clinical results show for all spacers a good tolerance and a possible reduction in the acute side effects rate. The aim of the present systematic review of the literature is to report on indications as well as dosimetric and clinical advantages of the different types of prostate-rectum spacers commercially available (hydrogel, hyaluronic acid, collagen, biodegradable balloon). PMID:24746454

  6. Expression of vascular endothelial growth factor (VEGF) in locally invasive prostate cancer is prognostic for radiotherapy outcome

    SciTech Connect

    Green, Melanie M.L.; Hiley, Crispin T.; Shanks, Jonathan H.; Bottomley, Ian C.; West, Catharine; Cowan, Richard A.; Stratford, Ian J. . E-mail: ian.j.stratford@manchester.ac.uk

    2007-01-01

    Purpose: Vascular endothelial growth factor (VEGF) is an important hypoxia-inducible pro-angiogenic protein that has been linked with an adverse survival outcome after radiotherapy in other cancer types: we hypothesized that this may also occur in prostate cancer. A retrospective study was, therefore, carried out to evaluate the potential of tumor VEGF expression to predict radiotherapy outcome in patients with high-risk prostate cancer. Methods and Materials: Fifty patients with locally advanced (T3 N0 M0) tumors of Gleason score {>=}6, and who received radiotherapy alone as primary treatment for their disease, were studied. Vascular endothelial growth factor expression was assessed on pretreatment diagnostic tumor biopsies using a semiquantitative immunohistochemical scoring system. The results were analyzed in relation to clinicopathologic factors and patient outcome including biochemical failure and disease-specific mortality. Results: High VEGF expression was associated with a poor prognosis: in univariate log rank analysis, VEGF was the only significant prognostic factor for disease-specific survival (p = 0.035). High VEGF expression also associated with increased Gleason score (p = 0.02), but not posttreatment biochemical failure. Conclusion: High tumor expression of VEGF identified patients at high risk of failure of treatment with radiotherapy. These patients might benefit from additional treatment approaches incorporating anti-angiogenic or hypoxia-specific agents.

  7. A survival model for fractionated radiotherapy with an application to prostate cancer

    NASA Astrophysics Data System (ADS)

    Zaider, Marco; Zelefsky, Michael J.; Hanin, Leonid G.; Tsodikov, Alexander D.; Yakovlev, Andrei Y.; Leibel, Steven A.

    2001-10-01

    time decreases (41, 28.5, 26.2 and 14.7 months for dose groups 1-4, respectively). This analysis confirms that, in terms of cure rate, dose escalation has a significant positive effect only in the intermediate and unfavourable groups. It was found that progression time is inversely proportional to dose, which means that patients recurring in higher dose groups have shorter recurrence times, yet these groups have better survival, particularly long-term. The explanation for this seemingly illogical observation lies in the fact that less aggressive tumours, potentially recurring after a long period of time, are cured by higher doses and do not contribute to the recurrence pattern. As a result, patients in higher dose groups are less likely to recur; however, if they do, they tend to recur earlier. The estimated hazard rates for prostate cancer pass through a clear-cut maximum, thus revealing a time period with especially high values of instantaneous cancer-specific risk; the estimates appear to be nonproportional across dose strata.

  8. Failure-Free Survival and Radiotherapy in Patients With Newly Diagnosed Nonmetastatic Prostate Cancer

    PubMed Central

    James, Nicholas D.; Spears, Melissa R.; Clarke, Noel W.; Dearnaley, David P.; Mason, Malcolm D.; Parker, Christopher C.; Ritchie, Alastair W. S.; Russell, J. Martin; Schiavone, Francesca; Attard, Gerhardt; de Bono, Johann S.; Birtle, Alison; Engeler, Daniel S.; Elliott, Tony; Matheson, David; O’Sullivan, Joe; Pudney, Delia; Srihari, Narayanan; Wallace, Jan; Barber, Jim; Syndikus, Isabel; Parmar, Mahesh K. B.; Sydes, Matthew R.

    2016-01-01

    IMPORTANCE The natural history of patients with newly diagnosed high-risk nonmetastatic (M0) prostate cancer receiving hormone therapy (HT) either alone or with standard-of-care radiotherapy (RT) is not well documented. Furthermore, no clinical trial has assessed the role of RT in patients with node-positive (N+) M0 disease. The STAMPEDE Trial includes such individuals, allowing an exploratory multivariate analysis of the impact of radical RT. OBJECTIVE To describe survival and the impact on failure-free survival of RT by nodal involvement in these patients. DESIGN, SETTING, AND PARTICIPANTS Cohort study using data collected for patients allocated to the control arm (standard-of-care only) of the STAMPEDE Trial between October 5, 2005, and May 1, 2014. Outcomes are presented as hazard ratios (HRs) with 95% CIs derived from adjusted Cox models; survival estimates are reported at 2 and 5 years. Participants were high-risk, hormone-naive patients with newly diagnosed M0 prostate cancer starting long-term HT for the first time. Radiotherapy is encouraged in this group, but mandated for patients with node-negative (N0) M0 disease only since November 2011. EXPOSURES Long-term HT either alone or with RT, as per local standard. Planned RT use was recorded at entry. MAIN OUTCOMES AND MEASURES Failure-free survival (FFS) and overall survival. RESULTS A total of 721 men with newly diagnosed M0 disease were included: median age at entry, 66 (interquartile range [IQR], 61-72) years, median (IQR) prostate-specific antigen level of 43 (18-88) ng/mL. There were 40 deaths (31 owing to prostate cancer) with 17 months’ median follow-up. Two-year survival was 96% (95% CI, 93%-97%) and 2-year FFS, 77% (95% CI, 73%-81%). Median (IQR) FFS was 63 (26 to not reached) months. Time to FFS was worse in patients with N+ disease (HR, 2.02 [95% CI, 1.46-2.81]) than in those with N0 disease. Failure-free survival outcomes favored planned use of RT for patients with both N0M0 (HR, 0.33 [95% CI

  9. Defining Molecular Signature of Pro-Immunogenic Radiotherapy Targets in Human Prostate Cancer Cells

    PubMed Central

    Aryankalayil, Molykutty J.; Makinde, Adeola Y.; Gameiro, Sofia R.; Hodge, James W.; Rivera-Solis, Patricia P.; Palayoor, Sanjeewani T.; Ahmed, Mansoor M.; Coleman, C. Norman

    2014-01-01

    To understand the impact of clinically relevant radiation therapy (RT) on tumor immune gene expression and to utilize the changes that occur during treatment to improve cancer treatment outcome, we examined how immune response genes are modulated in prostate cancer cells of varying p53 status. LNCaP (p53 wild-type), PC3 (p53 null) and DU145 (p53 mutant) cells received a 10 Gy single dose or 1 Gy × 10 multifractionated radiation dose to simulate hypofractionated and conventionally fractionated prostate radiotherapy. Total RNA was isolated 24 h after multi-fractionated radiation treatment and single-dose treatments and subjected to microarray analysis and later validated by RT-PCR. RT-PCR was utilized to identify total-dose inflection points for significantly upregulated genes in response to multifractionated radiation therapy. Radiation-induced damage-associated molecular pattern molecules (DAMPs) and cytokine analyses were performed using bioluminescence and ELISA. Multifractionated doses activated immune response genes more robustly than single-dose treatment, with a relatively larger number of immune genes upregulated in PC3 compared to DU145 and LNCaP cells. The inflection point of multifractionated radiation-induced immune genes in PC3 cells was observed in the range of 8–10 Gy total radiation dose. Although both multifractionated and single-dose radiation-induced proinflammatory DAMPs and positively modulated the cytokine environment, the changes were of higher magnitude with multifractionated therapy. The findings of this study together with the gene expression data suggest that cells subjected to multifractionated radiation treatment would promote productive immune cell–tumor cell interactions. PMID:25003313

  10. Comparison of biochemical recurrence in prostate cancer patients treated with radical prostatectomy or radiotherapy

    PubMed Central

    Kim, Dong Soo; Jeon, Seung Hyun; Chang, Sung-Goo

    2015-01-01

    Purpose We evaluated the biochemical recurrence (BCR) of prostate cancer patients treated by radical prostatectomy (RP) or radiotherapy (RT). Materials and Methods Patients who underwent RP or RT as primary definitive treatment from 2007 were enrolled for this study. They were divided into two groups; the low-intermediate risk group and the high risk group according to the National Comprehensive Cancer Network guidelines. We compared differences such as age, prostate specific antigen, Gleason score, follow-up duration, clinical T staging, and BCR. Their BCR-free survival rates were analyzed. Results A total of 165 patients were enrolled. There were 115 patients in the low-intermediate risk. Among them, 88 received RP and 27 underwent RT. BCR occurred in 9 of the RP patients (10.2%) and 3 of the RT patients (11.1%). For the high risk group, 50 patients were included. RP was performed in 25 patients and RT in 25 patients. BCR was observed in 4 of the RP patients (16%) and 12 of the RT patients (48%). There were no differences in BCR-free survival for the low-intermediate group (p=0.765). For the high risk group, the RP group had a higher BCR free survival rate (p=0.032). Conclusions No difference of BCR and BCR-free survival was seen in the low-intermediate risk group but lower BCR and better BCR-free survival were observed for patients that received RP in the high risk group. RP should be a more strongly considered option when deciding the treatment method for selected high risk patients. PMID:26495071

  11. Pathological Predictors for Site of Local Recurrence After Radiotherapy for Prostate Cancer

    SciTech Connect

    Chopra, Supriya; Toi, Ants; Taback, Nathan; Evans, Andrew; Haider, Masoom A.; Milosevic, Michael; Bristow, Robert G.; Chung, Peter; Bayley, Andrew; Morton, Gerard; Vesprini, Danny; Warde, Padraig; Catton, Charles; Menard, Cynthia

    2012-03-01

    Purpose: Rational design of targeted radiotherapy (RT) in prostate cancer (Pca) hinges on a better understanding of spatial patterns of recurrence. We sought to identify pathological factors predictive for site of local recurrence (LR) after external beam RT. Methods and Materials: Prospective databases were reviewed to identify men with LR after RT from 1997 through 2009. Patients with biochemical failure and biopsy-confirmed Pca more than 2 years after RT were evaluated. Prediction for site of recurrence based on the following pretreatment factors was determined on independent and cluster-sextant basis: presence of malignancy, dominant vs. nondominant percentage core length (PCL) involvement, PCL {>=} or <40%, and Gleason score. Sites of dominant PCL were defined as sextants with peak PCL involvement minus 10%, and >5% for each patient. Results: Forty-one patients with low-intermediate risk Pca constituted the study cohort. Median time to biopsy after RT was 51 months (range, 24-145). Of 246 sextants, 74 were involved with tumor at baseline. When sextants are treated as independent observations the presence of malignancy (77% vs. 22%, p = 0.0001), dominant PCL (90% vs. 46%, p = 0.0001), and PCL {>=}40% (89% vs. 68 %, p = 0.04) were found to be significant predictors for LR, although PCL {>=}40% did not retain statistical significance if sextants were considered correlated. The vast majority of patients (95%) recurred at the original site of dominant PCL or PCL {>=}40%, and 44% also recurred in regions of nondominant PCL <40% (n = 8) and/or benign sampling (n = 14) at baseline. Conclusions: LR after RT predominantly occurs in regions bearing higher histological tumor burden but are not isolated to these sites. Our data highlights the value of spatially resolved baseline pathological sampling and may assist in the design of clinical trials tailoring RT dose prescriptions to subregions of the prostate gland.

  12. Variation in Adherence to External Beam Radiotherapy Quality Measures Among Elderly Men With Localized Prostate Cancer

    SciTech Connect

    Bekelman, Justin E. Zelefsky, Michael J.; Jang, Thomas L.; Basch, Ethan M.; Schrag, Deborah

    2007-12-01

    Purpose: To characterize the variation in adherence to quality measures of external beam radiotherapy (EBRT) for localized prostate cancer and its relation to patient and provider characteristics in a population-based, representative sample of U.S. men. Methods and Materials: We evaluated EBRT quality measures proposed by a RAND expert panel of physicians among men aged {>=}65 years diagnosed between 2000 and 2002 with localized prostate cancer and treated with primary EBRT using data from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare program. We assessed the adherence to five EBRT quality measures that were amenable to analysis using SEER-Medicare data: (1) use of conformal RT planning; (2) use of high-energy (>10-MV) photons; (3) use of custom immobilization; (4) completion of two follow-up visits with a radiation oncologist in the year after therapy; and (5) radiation oncologist board certification. Results: Of the 11,674 patients, 85% had received conformal RT planning, 75% had received high-energy photons, and 97% had received custom immobilization. One-third of patients had completed two follow-up visits with a radiation oncologist, although 91% had at least one visit with a urologist or radiation oncologist. Most patients (85%) had been treated by a board-certified radiation oncologist. Conclusions: The overall high adherence to EBRT quality measures masked substantial variation in geography, socioeconomic status in the area of residence, and teaching affiliation of the RT facility. Future research should examine the reasons for the variations in these measures and whether the variation is associated with important clinical outcomes.

  13. Celastrol Potentiates Radiotherapy by Impairment of DNA Damage Processing in Human Prostate Cancer

    SciTech Connect

    Dai Yao; DeSano, Jeffrey T.; Meng Yang; J, Qing; Ljungman, Mats; Lawrence, Theodore S.; Xu Liang

    2009-07-15

    Purpose: Celastrol is an active ingredient of traditional herbal medicine and has recently been identified as a potent natural proteasome inhibitor. In the present study, we evaluated the radiosensitizing potential of celastrol in the human prostate cancer PC-3 model. Methods and Materials: Clonogenic assays were performed to determine the radiosensitizing effect of celastrol. Apoptosis was examined by flow cytometry using Annexin V and propidium iodide staining and by a caspase-3 activation assay. DNA damage processing was examined by immunofluorescent staining and Western blot for phosphorylated H2AX ({gamma}H2AX). The PC-3 xenograft model in the athymic nude mouse was used for the determination of the in vivo efficacy of celastrol combined with radiotherapy. The tumor samples were also analyzed for apoptosis and angiogenesis. Results: Celastrol sensitized PC-3 cells to ionizing radiation (IR) in a dose- and schedule-dependent manner, in which pretreatment with celastrol for 1 h followed by IR achieved maximal radiosensitization. Celastrol significantly prolonged the presence of IR-induced {gamma}H2AX and increased IR-induced apoptosis. Celastrol, combined with fractionated radiation, significantly inhibited PC-3 tumor growth in vivo without obvious systemic toxicity. The combination treatment increased {gamma}H2AX levels and apoptosis, induced cleavage of poly(adenosine diphosphate-ribose)polymerase and Mcl-1, and reduced angiogenesis in vivo compared with either treatment alone. Conclusion: Celastrol sensitized PC-3 cells to radiation both in vitro and in vivo by impairing DNA damage processing and augmenting apoptosis. Celastrol might represent a promising new adjuvant regimen for the treatment of hormone-refractory prostate cancer.

  14. First-year PSA kinetics and minima after prostate cancer radiotherapy are predictive of overall survival

    SciTech Connect

    Cheung, Rex . E-mail: mrcheung@mdanderson.org; Tucker, Susan L.; Kuban, Deborah A.

    2006-09-01

    Purpose: We analyzed whether first-year prostate-specific antigen (PSA) kinetics and minima are predictive of overall survival (OS). Methods and Materials: The data set contained 1,174 patients treated with external beam radiotherapy (RT) from 1987 to 2001. The relative rate of change ({lambda}) in post-RT PSA values during the first year (13.5 months) was computed using regression analysis of ln(PSA) vs. time. We also computed the PSA minimum (mPSA) reached during the same period. Recursive partitioning analysis was used to identify the relevant cutpoints for the factors being investigated for its association with survival: age, pretreatment PSA, radiation dose, relative rate of change in PSA post-RT, and 1-year PSA minimum. For each of the other factors stage, Gleason score and risk group, all possible cutpoints were considered in the multivariate analyses. Significant factors were considered in the multivariate analyses to identify independent predictors for overall survival. Results: The median value of {lambda} was -1.0 years{sup -1} (range, -11.0-5.1 years{sup -1}). The 1-year minimum had a median of 0.8 ng/mL (range, 0.01-30.9 ng/mL). Recursive partitioning analysis and Cox proportional hazards analyses identified the following pretreatment or treatment factors adversely related to OS: age, Gleason score, stage, and dose. First-year mPSA {>=} 4 ng/mL and {lambda} > 0 were post-RT independent prognostic factors for worse OS. Conclusion: First-year post-RT PSA kinetics and minima are early response parameters predictive of overall survival for prostate cancer patients. These factors may be useful in selecting patients for early salvage therapy.

  15. Dose-Effect Relationships for Individual Pelvic Floor Muscles and Anorectal Complaints After Prostate Radiotherapy

    SciTech Connect

    Smeenk, Robert Jan; Hoffmann, Aswin L.; Hopman, Wim P.M.; Lin, Emile N.J. Th. van; Kaanders, Johannes H.A.M.

    2012-06-01

    Purpose: To delineate the individual pelvic floor muscles considered to be involved in anorectal toxicity and to investigate dose-effect relationships for fecal incontinence-related complaints after prostate radiotherapy (RT). Methods and Materials: In 48 patients treated for localized prostate cancer, the internal anal sphincter (IAS) muscle, the external anal sphincter (EAS) muscle, the puborectalis muscle (PRM), and the levator ani muscles (LAM) in addition to the anal wall (Awall) and rectal wall (Rwall) were retrospectively delineated on planning computed tomography scans. Dose parameters were obtained and compared between patients with and without fecal urgency, incontinence, and frequency. Dose-effect curves were constructed. Finally, the effect of an endorectal balloon, which was applied in 28 patients, was investigated. Results: The total volume of the pelvic floor muscles together was about three times that of the Awall. The PRM was exposed to the highest RT dose, whereas the EAS received the lowest dose. Several anal and rectal dose parameters, as well as doses to all separate pelvic floor muscles, were associated with urgency, while incontinence was associated mainly with doses to the EAS and PRM. Based on the dose-effect curves, the following constraints regarding mean doses could be deduced to reduce the risk of urgency: {<=}30 Gy to the IAS; {<=}10 Gy to the EAS; {<=}50 Gy to the PRM; and {<=}40 Gy to the LAM. No dose-effect relationships for frequency were observed. Patients treated with an endorectal balloon reported significantly less urgency and incontinence, while their treatment plans showed significantly lower doses to the Awall, Rwall, and all pelvic floor muscles. Conclusions: Incontinence-related complaints show specific dose-effect relationships to individual pelvic floor muscles. Dose constraints for each muscle can be identified for RT planning. When only the Awall is delineated, substantial components of the continence apparatus are

  16. On feature extraction and classification in prostate cancer radiotherapy using tensor decompositions.

    PubMed

    Fargeas, Auréline; Albera, Laurent; Kachenoura, Amar; Dréan, Gaël; Ospina, Juan-David; Coloigner, Julie; Lafond, Caroline; Delobel, Jean-Bernard; De Crevoisier, Renaud; Acosta, Oscar

    2015-01-01

    External beam radiotherapy is commonly prescribed for prostate cancer. Although new radiation techniques allow high doses to be delivered to the target, the surrounding healthy organs (rectum and bladder) may suffer from irradiation, which might produce undesirable side-effects. Hence, the understanding of the complex toxicity dose-volume effect relationships is crucial to adapt the treatment, thereby decreasing the risk of toxicity. In this paper, we introduce a novel method to classify patients at risk of presenting rectal bleeding based on a Deterministic Multi-way Analysis (DMA) of three-dimensional planned dose distributions across a population. After a non-rigid spatial alignment of the anatomies applied to the dose distributions, the proposed method seeks for two bases of vectors representing bleeding and non bleeding patients by using the Canonical Polyadic (CP) decomposition of two fourth order arrays of the planned doses. A patient is then classified according to its distance to the subspaces spanned by both bases. A total of 99 patients treated for prostate cancer were used to analyze and test the performance of the proposed approach, named CP-DMA, in a leave-one-out cross validation scheme. Results were compared with supervised (linear discriminant analysis, support vector machine, K-means, K-nearest neighbor) and unsupervised (recent principal component analysis-based algorithm, and multidimensional classification method) approaches based on the registered dose distribution. Moreover, CP-DMA was also compared with the Normal Tissue Complication Probability (NTCP) model. The CP-DMA method allowed rectal bleeding patients to be classified with good specificity and sensitivity values, outperforming the classical approaches. PMID:25443534

  17. SU-E-J-83: CBCT Based Rectum and Bladder Dose Tracking in the Prostate Radiotherapy

    SciTech Connect

    Chen, Z; Wang, J; Yang, Z; Hu, W

    2015-06-15

    Purpose: The aim of this study is to monitor the volume changes of bladder and rectum and evaluate the dosimetric changes of bladder and rectum using daily cone-beam CT for prostate radiotherapy. Methods: The data of this study were obtained from 12 patients, totally 222 CBCTs. All the volume of the bladder and the rectum on the CBCT were normalized to the bladder and the rectum on their own original CT to monitory the volume changes. To evaluate dose delivered to the OARs, volumes that receive 70Gy (V70Gy), 60Gy, 50Gy, 40Gy and 30Gy are calculated for the bladder and the rectum, V20Gy and V10Gy for rectum additionally. And the deviation of the mean dose to the bladder and the rectum are also chosen as the evaluation parameter. Linear regression analysis was performed to identify the mean dose change of the volume change using SPSS 19. Results: The results show that the variances of the normalize volume of the bladder and the rectum are 0.15–0.58 and 0.13–0.50. The variances of V70Gy, V60Gy, V50Gy, V40Gy and V30Gy of bladder are bigger than rectum for 11 patients. The linear regression analysis indicated a negative correlation between the volume and the mean dose of the bladder (p < 0.05). A 10% increase in bladder volume will cause 5.1% (±4.3%) reduction in mean dose. Conclusion: The bladder volume change is more significant than that for rectum for the prostate cancer patient. The volume changes of rectum are not significant except air gap in the rectum. Bladder volume varies will cause significant dose change. The bladder volume monitoring before fractional treatment delivery would be crucial for accuracy dose delivery.

  18. Technical Note: MRI only prostate radiotherapy planning using the statistical decomposition algorithm

    SciTech Connect

    Siversson, Carl; Nordström, Fredrik; Nilsson, Terese; Nyholm, Tufve; Jonsson, Joakim; Gunnlaugsson, Adalsteinn; Olsson, Lars E.

    2015-10-15

    Purpose: In order to enable a magnetic resonance imaging (MRI) only workflow in radiotherapy treatment planning, methods are required for generating Hounsfield unit (HU) maps (i.e., synthetic computed tomography, sCT) for dose calculations, directly from MRI. The Statistical Decomposition Algorithm (SDA) is a method for automatically generating sCT images from a single MR image volume, based on automatic tissue classification in combination with a model trained using a multimodal template material. This study compares dose calculations between sCT generated by the SDA and conventional CT in the male pelvic region. Methods: The study comprised ten prostate cancer patients, for whom a 3D T2 weighted MRI and a conventional planning CT were acquired. For each patient, sCT images were generated from the acquired MRI using the SDA. In order to decouple the effect of variations in patient geometry between imaging modalities from the effect of uncertainties in the SDA, the conventional CT was nonrigidly registered to the MRI to assure that their geometries were well aligned. For each patient, a volumetric modulated arc therapy plan was created for the registered CT (rCT) and recalculated for both the sCT and the conventional CT. The results were evaluated using several methods, including mean average error (MAE), a set of dose-volume histogram parameters, and a restrictive gamma criterion (2% local dose/1 mm). Results: The MAE within the body contour was 36.5 ± 4.1 (1 s.d.) HU between sCT and rCT. Average mean absorbed dose difference to target was 0.0% ± 0.2% (1 s.d.) between sCT and rCT, whereas it was −0.3% ± 0.3% (1 s.d.) between CT and rCT. The average gamma pass rate was 99.9% for sCT vs rCT, whereas it was 90.3% for CT vs rCT. Conclusions: The SDA enables a highly accurate MRI only workflow in prostate radiotherapy planning. The dosimetric uncertainties originating from the SDA appear negligible and are notably lower than the uncertainties

  19. Effectiveness of Educational Intervention on the Congruence of Prostate and Rectal Contouring as Compared With a Gold Standard in Three-Dimensional Radiotherapy for Prostate

    SciTech Connect

    Szumacher, Ewa; Harnett, Nicole; Warner, Saar; Kelly, Valerie; Danjoux, Cyril; Barker, Ruth; Woo, Milton; Mah, Kathy; Ackerman, Ida; Dubrowski, Adam; Rose, Stuart; Crook, Juanita

    2010-02-01

    Purpose: To examine effects of a teaching intervention on precise delineation of the prostate and rectum during planning of three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. Methods and Materials: A pretest, posttest, randomized controlled group design was used. During pretest all participants contoured prostate and rectum on planning CT. Afterward, they participated in two types of workshops. The experimental group engaged in an interactive teaching session focused on prostate and rectum MR anatomy compared with CT anatomy. The control group focused on 3D-CRT planning without mention of prostate or rectal contouring. The experimental group practiced on fused MR-CT images, whereas the control group practiced on CT images. All participants completed the posttest. Results: Thirty-one trainees (12 male, 19 female) were randomly assigned to two groups, 17 in the experimental arm, and 14 in the control group. Seventeen felt familiar or very familiar with pelvic organ contouring, 12 somewhat, and 2 had never done it. Thirteen felt confident with organ contouring, 13 somewhat, and 5 not confident. The demographics and composition of groups were analyzed with chi{sup 2} and repeated-measures analysis of variance with the two groups (experimental or control) and two tests (pre- or posttest) as factors. Satisfaction with the course and long-term effects of the course on practice were assessed with immediate and delayed surveys. All performance variables showed a similar pattern of results. Conclusions: The training sessions improved the technical performance similarly in both groups. Participants were satisfied with the course content, and the delayed survey reflected that cognitively participants felt more confident with prostate and rectum contouring and would investigate opportunities to learn more about organ contouring.

  20. The proportion of prostate biopsy tissue with Gleason pattern 4 or 5 predicts for biochemical and clinical outcome after radiotherapy for prostate cancer

    SciTech Connect

    D'Ambrosio, David J.; Hanlon, Alexandra L.; Al-Saleem, Tahseen; Feigenberg, Steven J.; Horwitz, Eric M.; Uzzo, Robert G.; Pollack, Alan; Buyyounouski, Mark K. . E-mail: mark.buyyounouski@fccc.edu

    2007-03-15

    Purpose: To investigate the prognostic utility of the proportion of prostate biopsy tissue containing Gleason pattern 4 or 5 (GP4/5) after definitive radiotherapy (RT) for prostate cancer. Methods and Materials: A total of 568 patients with T1c-3 Nx/0 prostate cancer who received three-dimensional conformal RT alone between May 1989 and August 2001 were studied. There were 161 men with Gleason score 7-10 disease. The GP4/5 was defined as the percentage of biopsy tissue containing Gleason pattern 4 or 5. A Cox proportional hazards model was used for univariate and multivariate analyses (MVA) for biochemical failure (BF) (American Society of Therapeutic Radiology and Oncology definition) and distant metastasis (DM). A recursive partitioning analysis was done using the results of the MVA to identify a cutpoint for GP4/5. Results: The median follow-up was 46 (range, 13-114) months and median RT dose was 76 (range, 65-82) Gy. On MVA, increasing initial prostate-specific antigen (p = 0.0248) decreasing RT dose (continuous, p = 0.0022), T stage (T1/2 vs. T3) (p = 0.0136) and GP4/5 (continuous, p < 0.0001) were significant predictors of BF in a model also containing GS. GP4/5 was the only significant predictor of DM in the same model (p < 0.0001). Conclusion: The GP4/5 in prostate biopsy specimens is a predictor of BF and DM after RT independent of Gleason score. This parameter should be reported by the pathologist when reviewing prostatic biopsy specimens.

  1. Effect of Whole Pelvic Radiotherapy for Patients With Locally Advanced Prostate Cancer Treated With Radiotherapy and Long-Term Androgen Deprivation Therapy

    SciTech Connect

    Mantini, Giovanna; Tagliaferri, Luca; Mattiucci, Gian Carlo; Balducci, Mario; Frascino, Vincenzo; Dinapoli, Nicola; Di Gesu, Cinzia; Ippolito, Edy; Morganti, Alessio G.; Cellini, Numa

    2011-12-01

    Purpose: To evaluate the effect of whole pelvic radiotherapy (WPRT) in prostate cancer patients treated with RT and long-term (>1 year) androgen deprivation therapy (ADT). Methods and materials: Prostate cancer patients with high-risk features (Stage T3-T4 and/or Gleason score {>=}7 and/or prostate-specific antigen level {>=}20 ng/mL) who had undergone RT and long-term ADT were included in the present analysis. Patients with bowel inflammatory disease, colon diverticula, and colon diverticulitis were excluded from WPRT and treated with prostate-only radiotherapy (PORT). Patients were grouped according to nodal risk involvement as assessed by the Roach formula using different cutoff levels (15%, 20%, 25%, and 30%). Biochemical disease-free survival (bDFS) was analyzed in each group according to the RT type (WPRT or PORT). Results: A total of 358 patients treated between 1994 and 2007 were included in the analysis (46.9% with WPRT and 53.1% with PORT). The median duration of ADT was 24 months (range, 12-38). With a median follow-up of 52 months (range, 20-150), the overall 4-year bDFS rate was 90.5%. The 4-year bDFS rate was similar between the patients who had undergone WPRT or PORT (90.4% vs. 90.5%; p = NS). However, in the group of patients with the greatest nodal risk (>30%), a significant bDFS improvement was recorded for the patients who had undergone WPRT (p = .03). No differences were seen in acute toxicity among the patients treated with WPRT or PORT. The late gastrointestinal toxicity was similar in patients treated with PORT or WPRT (p = NS). Conclusions: Our analysis has supported the use of WPRT in association with long-term ADT for patients with high-risk nodal involvement (>30%), although a definitive recommendation should be confirmed by a randomized trial.

  2. A monte carlo comparison of three different media for contrast enhanced radiotherapy of the prostate.

    PubMed

    Garnica-Garza, H M

    2010-06-01

    Contrast-enhanced radiotherapy makes use of a kilovoltage X-ray beam, either from a diagnostic X-ray tube or modified megavoltage linear accelerator, in conjunction with a high-Z contrast medium deposited into the target volume to enhance the absorption of radiation. In this work, using the Monte Carlo code PENELOPE and the voxelized Zubal phantom to model a prostate radiotherapy treatment, a comparison between the physical absorbed dose distributions rendered by three different enhancing agents namely bismuth, gadolinium, and iodine is performed. It is assumed that there exists a concentration of 10 mg of enhancing agent per 1 g of tissue in the target volume while in the background a concentration of 1.5 mg per 1 g of tissue is present. The X-ray beam energy spectrum was obtained by means of Monte Carlo simulation of a tungsten target upon which a 220 keV mono-energetic electron pencil beam is made to impinge, and the resultant photon beam is heavily filtrated by 0.2 cm of copper. The treatment delivery is simulated as a 3608 arc collimated to conform to the target from every direction. Cumulative dose-volume histograms and isodose curves are presented for the target as well as five organs-at-risk, namely rectal wall, bladder, femoral heads, skin, and bone marrow. It is shown that under these conditions clinically acceptable treatment plans are obtained for all three contrast agents. A 72 Gy dose to 100% of the target volume results in maximum absorbed doses to the above mentioned organs-at-risk of 65, 56, 44, 32 and 65 Gy respectively when bismuth is used as the contrast agent, but the results obtained with gadolinium follow closely. PMID:20441237

  3. Quality assessment for VMAT prostate radiotherapy planning based on data envelopment analysis

    NASA Astrophysics Data System (ADS)

    Lin, Kuan-Min; Simpson, John; Sasso, Giuseppe; Raith, Andrea; Ehrgott, Matthias

    2013-08-01

    The majority of commercial radiotherapy treatment planning systems requires planners to iteratively adjust the plan parameters in order to find a satisfactory plan. This iterative trial-and-error nature of radiotherapy treatment planning results in an inefficient planning process and in order to reduce such inefficiency, plans can be accepted without achieving the best attainable quality. We propose a quality assessment method based on data envelopment analysis (DEA) to address this inefficiency. This method compares a plan of interest to a set of past delivered plans and searches for evidence of potential further improvement. With the assistance of DEA, planners will be able to make informed decisions on whether further planning is required and ensure that a plan is only accepted when the plan quality is close to the best attainable one. We apply the DEA method to 37 prostate plans using two assessment parameters: rectal generalized equivalent uniform dose (gEUD) as the input and D95 (the minimum dose that is received by 95% volume of a structure) of the planning target volume (PTV) as the output. The percentage volume of rectum overlapping PTV is used to account for anatomical variations between patients and is included in the model as a non-discretionary output variable. Five plans that are considered of lesser quality by DEA are re-optimized with the goal to further improve rectal sparing. After re-optimization, all five plans improve in rectal gEUD without clinically considerable deterioration of the PTV D95 value. For the five re-optimized plans, the rectal gEUD is reduced by an average of 1.84 Gray (Gy) with only an average reduction of 0.07 Gy in PTV D95. The results demonstrate that DEA can correctly identify plans with potential improvements in terms of the chosen input and outputs.

  4. Toxicity Assessment of Pelvic Intensity-Modulated Radiotherapy With Hypofractionated Simultaneous Integrated Boost to Prostate for Intermediate- and High-Risk Prostate Cancer

    SciTech Connect

    McCammon, Robert; Rusthoven, Kyle E.; Kavanagh, Brian; Newell, Sherri B.S.; Newman, Francis M.S.; Raben, David

    2009-10-01

    Purpose: To evaluate the toxicity of pelvic intensity-modulated radiotherapy (IMRT) with hypofractionated simultaneous integrated boost (SIB) to the prostate for patients with intermediate- to high-risk prostate cancer. Methods and Materials: A retrospective toxicity analysis was performed in 30 consecutive patients treated definitively with pelvic SIB-IMRT, all of whom also received androgen suppression. The IMRT plans were designed to deliver 70 Gy in 28 fractions (2.5 Gy/fraction) to the prostate while simultaneously delivering 50.4 Gy in 28 fractions (1.8 Gy/fraction) to the pelvic lymph nodes. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, was used to score toxicity. Results: The most common acute Grade 2 events were cystitis (36.7%) and urinary frequency/urgency (26.7%). At a median follow-up of 24 months, late toxicity exceeding Grade 2 in severity was uncommon, with two Grade 3 events and one Grade 4 event. Grade 2 or greater acute bowel toxicity was associated with signficantly greater bowel volume receiving {>=}25 Gy (p = .04); Grade 2 or greater late bowel toxicity was associated with a higher bowel maximal dose (p = .04) and volume receiving {>=}50 Gy (p = .02). Acute or late bladder and rectal toxicity did not correlate with any of the dosimetric parameters examined. Conclusion: Pelvic IMRT with SIB to the prostate was well tolerated in this series, with low rates of Grade 3 or greater acute and late toxicity. SIB-IMRT combines pelvic radiotherapy and hypofractionation to the primary site and offers an accelerated approach to treating intermediate- to high-risk disease. Additional follow-up is necessary to fully define the long-term toxicity after hypofractionated, whole pelvic treatment combined with androgen suppression.

  5. Concurrent segmentation of the prostate on MRI and CT via linked statistical shape models for radiotherapy planning

    SciTech Connect

    Chowdhury, Najeeb; Toth, Robert; Chappelow, Jonathan; Kim, Sung; Motwani, Sabin; Punekar, Salman; Lin Haibo; Both, Stefan; Vapiwala, Neha; Hahn, Stephen; Madabhushi, Anant

    2012-04-15

    Purpose: Prostate gland segmentation is a critical step in prostate radiotherapy planning, where dose plans are typically formulated on CT. Pretreatment MRI is now beginning to be acquired at several medical centers. Delineation of the prostate on MRI is acknowledged as being significantly simpler to perform, compared to delineation on CT. In this work, the authors present a novel framework for building a linked statistical shape model (LSSM), a statistical shape model (SSM) that links the shape variation of a structure of interest (SOI) across multiple imaging modalities. This framework is particularly relevant in scenarios where accurate boundary delineations of the SOI on one of the modalities may not be readily available, or difficult to obtain, for training a SSM. In this work the authors apply the LSSM in the context of multimodal prostate segmentation for radiotherapy planning, where the prostate is concurrently segmented on MRI and CT. Methods: The framework comprises a number of logically connected steps. The first step utilizes multimodal registration of MRI and CT to map 2D boundary delineations of the prostate from MRI onto corresponding CT images, for a set of training studies. Hence, the scheme obviates the need for expert delineations of the gland on CT for explicitly constructing a SSM for prostate segmentation on CT. The delineations of the prostate gland on MRI and CT allows for 3D reconstruction of the prostate shape which facilitates the building of the LSSM. In order to perform concurrent prostate MRI and CT segmentation using the LSSM, the authors employ a region-based level set approach where the authors deform the evolving prostate boundary to simultaneously fit to MRI and CT images in which voxels are classified to be either part of the prostate or outside the prostate. The classification is facilitated by using a combination of MRI-CT probabilistic spatial atlases and a random forest classifier, driven by gradient and Haar features

  6. Treatment outcome of localized prostate cancer by 70 Gy hypofractionated intensity-modulated radiotherapy with a customized rectal balloon

    PubMed Central

    Kim, Hyunjung; Kim, Jun Won; Hong, Sung Joon; Rha, Koon Ho; Lee, Chang-Geol; Yang, Seung Choul; Choi, Young Deuk; Suh, Chang-Ok

    2014-01-01

    Purpose We aimed to analyze the treatment outcome and long-term toxicity of 70 Gy hypofractionated intensity-modulated radiotherapy (IMRT) for localized prostate cancer using a customized rectal balloon. Materials and Methods We reviewed medical records of 86 prostate cancer patients who received curative radiotherapy between January 2004 and December 2011 at our institution. Patients were designated as low (12.8%), intermediate (20.9%), or high risk (66.3%). Thirty patients received a total dose of 70 Gy in 28 fractions over 5 weeks via IMRT (the Hypo-IMRT group); 56 received 70.2 Gy in 39 fractions over 7 weeks via 3-dimensional conformal radiotherapy (the CF-3DRT group, which served as a reference for comparison). A customized rectal balloon was placed in Hypo-IMRT group throughout the entire radiotherapy course. Androgen deprivation therapy was administered to 47 patients (Hypo-IMRT group, 17; CF-3DRT group, 30). Late genitourinary (GU) and gastrointestinal (GI) toxicity were evaluated according to the Radiation Therapy Oncology Group criteria. Results The median follow-up period was 74.4 months (range, 18.8 to 125.9 months). The 5-year actuarial biochemical relapse-free survival rates for low-, intermediate-, and high-risk patients were 100%, 100%, and 88.5%, respectively, for the Hypo-IMRT group and 80%, 77.8%, and 63.6%, respectively, for the CF-3DRT group (p < 0.046). No patient presented with acute or late GU toxicity ≥grade 3. Late grade 3 GI toxicity occurred in 2 patients (3.6%) in the CF-3DRT group and 1 patient (3.3%) in the Hypo-IMRT group. Conclusion Hypo-IMRT with a customized rectal balloon resulted in excellent biochemical control rates with minimal toxicity in localized prostate cancer patients. PMID:25324991

  7. Radiotherapy Doses of 80 Gy and Higher Are Associated With Lower Mortality in Men With Gleason Score 8 to 10 Prostate Cancer

    SciTech Connect

    Pahlajani, Niraj; Ruth, Karen J.; Buyyounouski, Mark K.; Chen, David Y.T.; Horwitz, Eric M.; Hanks, Gerald E.; Price, Robert A.; Pollack, Alan

    2012-04-01

    Purpose: Men with Gleason score (GS) 8-10 prostate cancer (PCa) are assumed to have a high risk of micrometastatic disease at presentation. However, local failure is also a major problem. We sought to establish the importance of more aggressive local radiotherapy (RT) to {>=}80 Gy. Methods and Materials: There were 226 men treated consecutively with RT {+-} ADT from 1988 to 2002 for GS 8-10 PCa. Conventional, three-dimensional conformal or intensity-modulated (IM) RT was used. Radiation dose was divided into three groups: (1) <75 Gy (n = 50); (2) 75-79.9 Gy (n = 60); or (3) {>=}80 Gy (n = 116). The endpoints examined included biochemical failure (BF; nadir + 2 definition), distant metastasis (DM), cause-specific mortality, and overall mortality (OM). Results: Median follow-up was 66, 71, and 58 months for Groups 1, 2, and 3. On Fine and Gray's competing risk regression analysis, significant predictors of reduced BF were RT dose {>=}80 Gy (p = 0.011) and androgen deprivation therapy duration {>=}24 months (p = 0.033). In a similar model of DM, only RT dose {>=}80 Gy was significant (p = 0.007). On Cox regression analysis, significant predictors of reduced OM were RT dose {>=}80 Gy (p = 0.035) and T category (T3/4 vs. T1, p = 0.041). Dose was not a significant determinant of cause-specific mortality. Results for RT dose were similar in a model with RT dose and ADT duration as continuous variables. Conclusion: The results indicate that RT dose escalation to {>=}80 Gy is associated with lower risks of BF, DM, and OM in men with GS 8-10 PCa, independently of androgen deprivation therapy.

  8. Long-Term Outcome and Toxicity of Salvage Brachytherapy for Local Failure After Initial Radiotherapy for Prostate Cancer

    SciTech Connect

    Burri, Ryan J.; Stone, Nelson N.; Unger, Pam; Stock, Richard G.

    2010-08-01

    Purpose: To describe long-term outcomes and toxicity after salvage brachytherapy (BT) for local failure after initial radiotherapy for prostate cancer. Methods and Materials: Between 1994 and 2008, 37 men with local failure after initial prostate radiotherapy (32 external-beam radiation therapy [EBRT] and 5 BT) underwent salvage BT with {sup 103}Pd or {sup 125}I. Estimates of freedom from biochemical failure (FFbF, Phoenix definition) and cause-specific survival (CSS) were calculated using the Kaplan-Meier method. Toxicities were graded using CTCv3.0. Results: Median follow-up was 86 months (range, 2-156). The median dose to 90% of the prostate volume was 122 Gy (range, 67-166). The 10-year FFbF and CSS were 54% and 96%, respectively. On univariate analysis, prostate-specific antigen (PSA) >10 ng/mL at initial diagnosis was significantly associated with FFbF (p = 0.01), and there were trends for both age <70 years (p = 0.08) and PSA <6 ng/mL (p = 0.08) at the time of salvage BT. On multivariate analysis, only presalvage PSA <6 ng/mL (p = 0.046) was significantly associated with improved FFbF. There were three Grade 3 toxicities and one Grade 4 toxicity. Pelvic lymph node dissection before salvage BT was the only variable significantly associated with Grade {>=}2 toxicity (p = 0.03). Conclusion: With a median follow-up of 86 months, salvage prostate BT was associated with a 10-year FFbF of 54% and CSS of 96%. Improved FFbF was associated with a presalvage PSA <6 ng/mL. Toxicity was worse in patients who had undergone pelvic lymph node dissection before salvage BT. Careful patient selection for salvage BT may result in improved outcomes and reduced toxicity.

  9. Radical External Beam Radiotherapy for Clinically Localized Prostate Cancer in Japan: Changing Trends in the Patterns of Care Process Survey

    SciTech Connect

    Ogawa, Kazuhiko; Nakamura, Katsumasa; Sasaki, Tomonari; Onishi, Hiroshi; Koizumi, Masahiko; Araya, Masayuki; Mukumoto, Nobutaka; Teshima, Teruki; Mitsumori, Michihide

    2011-12-01

    Purpose: To delineate changing trends in radical external beam radiotherapy (EBRT) for prostate cancer in Japan. Methods and Materials: Data from 841 patients with clinically localized prostate cancer treated with EBRT in the Japanese Patterns of Care Study (PCS) from 1996 to 2005 were analyzed. Results: Significant increases in the proportions of patients with stage T1 to T2 disease and decrease in prostate-specific antigen values were observed. Also, there were significant increases in the percentages of patients treated with radiotherapy by their own choice. Median radiation doses were 65.0 Gy and 68.4 Gy from 1996 to 1998 and from 1999 to 2001, respectively, increasing to 70 Gy from 2003 to 2005. Moreover, conformal therapy was more frequently used from 2003 to 2005 (84.9%) than from 1996 to 1998 (49.1%) and from 1999 to 2001 (50.2%). On the other hand, the percentage of patients receiving hormone therapy from 2003 to 2005 (81.1%) was almost the same as that from 1996 to 1998 (86.3%) and from 1999 to 2001 (89.7%). Compared with the PCS in the United States, patient characteristics and patterns of treatments from 2003 to 2005 have become more similar to those in the United States than those from 1996 to 1998 and those from 1999 to 2001. Conclusions: This study indicates a trend toward increasing numbers of patients with early-stage disease and increasing proportions of patients treated with higher radiation doses with advanced equipment among Japanese prostate cancer patients treated with EBRT during 1996 to 2005 survey periods. Patterns of care for prostate cancer in Japan are becoming more similar to those in the United States.

  10. Pelvic Radiotherapy versus Radical Prostatectomy with Limited Lymph Node Sampling for High-Grade Prostate Adenocarcinoma

    PubMed Central

    McDonald, Andrew M.; Yang, Eddy S.; Jacob, Rojymon; Rais-Bahrami, Soroush; Nix, Jeffrey W.; Fiveash, John B.

    2016-01-01

    Purpose. To compare oncologic outcomes for patients with Gleason score (GS) ≥ 8 prostate adenocarcinoma treated with radical prostatectomy (RP) versus external beam radiotherapy combined with androgen deprivation (RT + ADT). Methods. Between 2001 and 2014, 121 patients with GS ≥ 8 were treated at our institution via RT + ADT (n = 71) or RP (n = 50) with ≥ 1 year of biochemical follow-up. Endpoints included biochemical failure (BF), distant metastasis, and initiation of salvage ADT. Results. The RT + ADT group was older, had higher biopsy GS, and had greater risk of lymph node involvement. All other pretreatment characteristics were similar between groups. Mean number of lymph nodes (LNs) sampled for patients undergoing RP was 8.2 (±6.18). Mean biochemical follow-up for all patients was 61 months. Five-year estimates of BF for the RT + ADT and RP groups were 7.2% versus 42.3%, (p < 0.001). The RT + ADT group also had lower rates of distant metastasis (2% versus 7.8%) and salvage ADT (8% versus 33.8%). Conclusion. In this analysis, RT + ADT was associated with improved biochemical and metastatic control when compared to RP with limited LN sampling. How RT + ADT compares with more aggressive lymphadenectomy, as is currently our institutional standard, remains an important unanswered question. PMID:27051534

  11. Investigation of MR image distortion for radiotherapy treatment planning of prostate cancer

    NASA Astrophysics Data System (ADS)

    Chen, Z.; Ma, C.-M.; Paskalev, K.; Li, J.; Yang, J.; Richardson, T.; Palacio, L.; Xu, X.; Chen, L.

    2006-03-01

    MR imaging based treatment planning for radiotherapy of prostate cancer is limited due to MR imaging system related geometrical distortions, especially for patients with large body sizes. On our 0.23 T open scanner equipped with the gradient distortion correction (GDC) software, the residual image distortions after the GDC were <5 mm within the central 36 cm × 36 cm area for a standard 48 cm field of view (FOV). In order to use MR imaging alone for treatment planning the effect of residual MR distortions on external patient contour determination, especially for the peripheral regions outside the 36 cm × 36 cm area, must be investigated and corrected. In this work, we performed phantom measurements to quantify MR system related residual geometric distortions after the GDC and the effective FOV. Our results show that for patients with larger lateral dimensions (>36 cm), the differences in patient external contours between distortion-free CT images and GDC-corrected MR images were 1-2 cm because of the combination of greater gradient distortion and loss of field homogeneity away from the isocentre and the uncertainties in patient setup during CT and MRI scans. The measured distortion maps were used to perform point-by-point corrections for patients with large dimensions inside the effective FOV. Using the point-by-point method, the geometrical distortion after the GDC were reduced to <3 mm for external contour determination and the effective FOV was expanded from 36 cm to 42 cm.

  12. The Role of Radiotherapy After Radical Prostatectomy in Patients with Prostate Cancer.

    PubMed

    Gandaglia, Giorgio; Cozzarini, Cesare; Mottrie, Alexandre; Bossi, Alberto; Fossati, Nicola; Montorsi, Francesco; Briganti, Alberto

    2015-12-01

    A non-negligible proportion of prostate cancer (PCa) patients undergoing radical prostatectomy (RP) harbors aggressive disease. These individuals are at higher risk of experiencing recurrence after surgery. Results from prospective, randomized trials support the efficacy of adjuvant radiotherapy (aRT) on cancer control in selected patients with adverse disease features at RP. However, only one of these randomized trials found a significant benefit of aRT on survival. Although such a level of evidence is not currently available for salvage RT, retrospective studies demonstrated that this approach leads to excellent outcomes if administered at the earliest sign of PSA recurrence. Prognostic models might help clinicians in identifying patients who would benefit the most from adjuvant and/or salvage RT. This individualized approach would allow sparing the risk of short- and long-term toxicity in a substantial proportion of patients. Nonetheless, results from randomized trials are still awaited to compare the efficacy of (early) salvage and aRT. PMID:26449841

  13. Volumetric-modulated arc therapy (RapidArc) vs. conventional fixed-field intensity-modulated radiotherapy for {sup 18}F-FDG-PET-guided dose escalation in oropharyngeal cancer: A planning study

    SciTech Connect

    Teoh, May; Beveridge, Sabeena; Wood, Katie; Whitaker, Stephen; Adams, Elizabeth; Rickard, Donna; Jordan, Tom; Nisbet, Andrew; Clark, Catharine H.

    2013-04-01

    Fluorine-18-fluorodeoxyglucose-positron emission tomography ({sup 18}F-FDG-PET)–guided focal dose escalation in oropharyngeal cancer may potentially improve local control. We evaluated the feasibility of this approach using volumetric-modulated arc therapy (RapidArc) and compared these plans with fixed-field intensity-modulated radiotherapy (IMRT) focal dose escalation plans. Materials and methods: An initial study of 20 patients compared RapidArc with fixed-field IMRT using standard dose prescriptions. From this cohort, 10 were included in a dose escalation planning study. Dose escalation was applied to {sup 18}F-FDG-PET–positive regions in the primary tumor at dose levels of 5% (DL1), 10% (DL2), and 15% (DL3) above standard radical dose (65 Gy in 30 fractions). Fixed-field IMRT and double-arc RapidArc plans were generated for each dataset. Dose-volume histograms were used for plan evaluation and comparison. The Paddick conformity index (CI{sub Paddick}) and monitor units (MU) for each plan were recorded and compared. Both IMRT and RapidArc produced clinically acceptable plans and achieved planning objectives for target volumes. Dose conformity was significantly better in the RapidArc plans, with lower CI{sub Paddick} scores in both primary (PTV1) and elective (PTV2) planning target volumes (largest difference in PTV1 at DL3; 0.81 ± 0.03 [RapidArc] vs. 0.77 ± 0.07 [IMRT], p = 0.04). Maximum dose constraints for spinal cord and brainstem were not exceeded in both RapidArc and IMRT plans, but mean doses were higher with RapidArc (by 2.7 ± 1 Gy for spinal cord and 1.9 ± 1 Gy for brainstem). Contralateral parotid mean dose was lower with RapidArc, which was statistically significant at DL1 (29.0 vs. 29.9 Gy, p = 0.01) and DL2 (29.3 vs. 30.3 Gy, p = 0.03). MU were reduced by 39.8–49.2% with RapidArc (largest difference at DL3, 641 ± 94 vs. 1261 ± 118, p < 0.01). {sup 18}F-FDG-PET–guided focal dose escalation in oropharyngeal cancer is feasible with Rapid

  14. Prostate cancer

    SciTech Connect

    Murphy, G.P.; Kuss, R., Khoury, S.; Chatelain, C.; Denis, L.

    1987-01-01

    This book contains over 70 selections. Some of the titles are: Place of the Computed Tomography in the Staging of Prostatic Cancer; Magnetic Resonance Imaging (MRI) in Staging of the Prostatic Cancer; Magnetic Resonance Imaging of the Prostate; Long-Term Results in Radiotherapy of Prostatic Cancer; Interstitial Irradiation Using I-125 Seeds; and Treatment of Cancer of the Prostate by Use of Physiotherapy: Long-Term Results.

  15. Three-dimensional conformal external beam radiotherapy compared with permanent prostate implantation in low-risk prostate cancer based on endorectal magnetic resonance spectroscopy imaging and prostate-specific antigen level

    SciTech Connect

    Pickett, Barby . E-mail: pickett@radonc17.ucsf.edu; Kurhanewicz, John; Pouliot, Jean; Weinberg, Vivian; Shinohara, Katsuto; Coakley, Fergus; Roach, Mack

    2006-05-01

    Purpose: To evaluate the metabolic response by comparing the time to resolution of spectroscopic abnormalities (TRSA) and the time to prostate-specific antigen level in low-risk prostate cancer patients after treatment with three-dimensional conformal external beam radiotherapy (3D-CRT) compared with permanent prostate implantation (PPI). Recent studies have suggested that the treatment of low-risk prostate cancer yields similar results for patients treated with 3D-CRT or PPI. Methods and Materials: A total of 50 patients, 25 in each group, who had been treated with 3D-CRT or PPI, had undergone endorectal magnetic resonance spectroscopy imaging before and/or at varying times after therapy. The 3D-CRT patients had received radiation doses of {>=}72 Gy compared with 144 Gy for the PPI patients. The spectra from all usable voxels were examined for detectable levels of metabolic signal, and the percentages of atrophic and cancerous voxels were tabulated. Results: The median time to resolution of the spectroscopic abnormalities was 32.2 and 24.8 months and the time to the nadir prostate-specific antigen level was 52.4 and 38.0 months for the 3D-CRT and PPI patients, respectively. Of the 3D-CRT patients, 92% achieved negative endorectal magnetic resonance spectroscopy imaging findings, with 40% having complete metabolic atrophy. All 25 PPI patients had negative endorectal magnetic resonance spectroscopy imaging findings, with 60% achieving complete metabolic atrophy. Conclusion: The results of this study suggest that metabolic and biochemical responses of the prostate are more pronounced after PPI. Our results have not proved PPI is more effective at curing prostate cancer, but they have demonstrated that it may be more effective at destroying prostate metabolism.

  16. Monte Carlo Simulations for Dosimetry in Prostate Radiotherapy with Different Intravesical Volumes and Planning Target Volume Margins

    PubMed Central

    Lv, Wei; Yu, Dong; He, Hengda; Liu, Qian

    2016-01-01

    In prostate radiotherapy, the influence of bladder volume variation on the dose absorbed by the target volume and organs at risk is significant and difficult to predict. In addition, the resolution of a typical medical image is insufficient for visualizing the bladder wall, which makes it more difficult to precisely evaluate the dose to the bladder wall. This simulation study aimed to quantitatively investigate the relationship between the dose received by organs at risk and the intravesical volume in prostate radiotherapy. The high-resolution Visible Chinese Human phantom and the finite element method were used to construct 10 pelvic models with specific intravesical volumes ranging from 100 ml to 700 ml to represent bladders of patients with different bladder filling capacities during radiotherapy. This series of models was utilized in six-field coplanar 3D conformal radiotherapy simulations with different planning target volume (PTV) margins. Each organ’s absorbed dose was calculated using the Monte Carlo method. The obtained bladder wall displacements during bladder filling were consistent with reported clinical measurements. The radiotherapy simulation revealed a linear relationship between the dose to non-targeted organs and the intravesical volume and indicated that a 10-mm PTV margin for a large bladder and a 5-mm PTV margin for a small bladder reduce the effective dose to the bladder wall to similar degrees. However, larger bladders were associated with evident protection of the intestines. Detailed dosimetry results can be used by radiation oncologists to create more accurate, individual water preload protocols according to the patient’s anatomy and bladder capacity. PMID:27441944

  17. Intensity-Modulated Radiotherapy Causes Fewer Side Effects than Three-Dimensional Conformal Radiotherapy When Used in Combination With Brachytherapy for the Treatment of Prostate Cancer

    SciTech Connect

    Forsythe, Kevin; Blacksburg, Seth; Stone, Nelson; Stock, Richard G.

    2012-06-01

    Purpose: To measure the benefits of intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3D-CRT) when used in combination with brachytherapy for the treatment of prostate cancer. Methods and Materials: We conducted a retrospective review of all patients with localized prostate cancer who received external-beam radiotherapy (EBRT) in combination with brachytherapy with at least 1 year follow-up (n = 812). Combination therapy consisted of {sup 103}Pd or {sup 125}I implant, followed by a course of EBRT. From 1993 to March 2003 521 patients were treated with 3D-CRT, and from April 2003 to March 2009 291 patients were treated with IMRT. Urinary symptoms were prospectively measured with the International Prostate Symptom Score questionnaire with a single quality of life (QOL) question; rectal bleeding was assessed per the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Schema. The Pearson {chi}{sup 2} test was used to compare toxicities experienced by patients who were treated with either IMRT or 3D-CRT. Logistic regression analyses were also performed to rule out possible confounding factors. Results: Within the first 3 months after treatment, patients treated with 3D-CRT scored their urinary symptoms as follows: 19% mild, 44% moderate, and 37% severe; patients treated with IMRT scored their urinary symptoms as follows: 36% mild, 47% moderate, and 17% severe (p < 0.001). The 3D-CRT patients rated their QOL as follows: 35% positive, 20% neutral, and 45% negative; IMRT patients rated their QOL as follows: 51% positive, 18% neutral, and 31% negative (p < 0.001). After 1 year of follow-up there was no longer any difference in urinary morbidity between the two groups. Logistic regression confirmed the differences in International Prostate Symptom Score and QOL in the acute setting (p < 0.001 for both). Grade {>=}2 rectal bleeding was reported by 11% of 3D

  18. Dosimetric correlation of acute and late toxicities in high-risk prostate cancer patients treated with three-dimensional conformal radiotherapy followed by intensity modulated radiotherapy boost

    PubMed Central

    Kapoor, Rakesh; Bansal, Anshuma; Kumar, Narendra; Oinam, Arun S.

    2016-01-01

    Introduction: In prostate cancer, higher radiation doses are often related to higher local control rates. However, the clinical effect of these higher doses on normal tissue toxicities is generally overlooked. We dosimetrically analyze sequential intensity modulated radiotherapy (IMRT) plans in high-risk prostate cancer patients and correlate them with acute and late normal tissue toxicities. Materials and Methods: Twenty-five high-risk prostate cancer patients were planned with three-dimensional conformal radiotherapy to a dose of 50 Gy delivered in 25 fractions in 5 weeks, followed by seven-field IMRT boost, to a dose of 24 Gy delivered in 12 fractions in 2.5 weeks, along with hormonal therapy. Acute and late toxicities were analyzed using Radiation Therapy Oncology Group toxicity criteria. Student's t-test was used for correlating doses received by normal tissues with toxicity grade. Five-year disease-free survival (DFS) and biochemical relapse-free survival (RFS) were evaluated using Kaplan–Meier analysis. Results: Median follow-up of patients was 65 months. Of 25 patients, two developed acute Grade 2 rectal toxicity. Only 1 patient developed acute Grade 2 bladder toxicity. Late Grade 2 and 3 rectal toxicity was seen in 2 and 1 patient, respectively. Late Grade 2 and 3 bladder toxicity was seen in 1 patient each. Grade 2 or more acute rectal toxicity correlated significantly with rectal volume receiving >70 Gy (P = 0.04). The 5-year DFS and biochemical RFS was 70.2% and 79.2%, respectively. One patient failed locally and seven failed at distant sites. Conclusion: Sequential IMRT with a dose of 74 Gy and maximum androgen blockade is well tolerated in high-risk patients in Indian setup with adequate control rates. PMID:27555679

  19. SU-E-J-79: Evaluation of Prostate Volume Changes During Radiotherapy Using Implanted Markers and On-Board Imaging

    SciTech Connect

    Ispir, B; Akdeniz, Y; Ugurluer, G; Eken, A; Arpaci, T; Serin, M

    2015-06-15

    Purpose: To evaluate prostate volume changes during radiation therapy using implanted gold markers and on-board imaging. Methods: Twenty-five patients were included who underwent an implantation of three gold markers. Cartesian coordinates of markers were assessed in kV-images. The coordinates of centers of two markers were measured on kV-images from the center of the marker at the apex which was reference. The distances between the markers were extrapolated from the coordinates using the Euclid formula. The radius of the sphere through markers was calculated using sinus theorem. The prostate volume for the first and last fraction was substituted with a sphere model and was calculated for each patient. The t-test was used for analysis. Results: The mean prostate volume for first and last fraction was 24.65 and 20.87 cc, respectively (p≤0.05). The prostate volume was smaller for 23 patients, whereas there was an expansion for 2 patients. Fifteen patients had androgen deprivation during radiotherapy (H group) and ten did not (NH group). The mean prostate volume for the first and last fraction for the NH group was 30.73 cc and 24.89 cc and for the H group 20.84 cc and 18.19 cc, respectively. There was a 15.8% volume change during treatment for the NH group and 12.2% for the H group, but the difference was not statistically significant. The radius difference of the theoretical sphere for the first and last fraction was 0.98 mm (range, 0.09–2.95 mm) and remained below 2 mm in 88% of measurements. Conclusion: There was a significant volume change during prostate radiotherapy. The difference between H group and NH group was not significant. The radius changes did not exceed 3 mm and it was below adaptive treatment requirements. Our results indicate that prostate volume changes during treatment should be taken into account during contouring and treatment planning.

  20. Poster — Thur Eve — 59: Atlas Selection for Automated Segmentation of Pelvic CT for Prostate Radiotherapy

    SciTech Connect

    Mallawi, A; Farrell, T; Diamond, K; Wierzbicki, M

    2014-08-15

    Automated atlas-based segmentation has recently been evaluated for use in planning prostate cancer radiotherapy. In the typical approach, the essential step is the selection of an atlas from a database that best matches the target image. This work proposes an atlas selection strategy and evaluates its impact on the final segmentation accuracy. Prostate length (PL), right femoral head diameter (RFHD), and left femoral head diameter (LFHD) were measured in CT images of 20 patients. Each subject was then taken as the target image to which all remaining 19 images were affinely registered. For each pair of registered images, the overlap between prostate and femoral head contours was quantified using the Dice Similarity Coefficient (DSC). Finally, we designed an atlas selection strategy that computed the ratio of PL (prostate segmentation), RFHD (right femur segmentation), and LFHD (left femur segmentation) between the target subject and each subject in the atlas database. Five atlas subjects yielding ratios nearest to one were then selected for further analysis. RFHD and LFHD were excellent parameters for atlas selection, achieving a mean femoral head DSC of 0.82 ± 0.06. PL had a moderate ability to select the most similar prostate, with a mean DSC of 0.63 ± 0.18. The DSC obtained with the proposed selection method were slightly lower than the maximums established using brute force, but this does not include potential improvements expected with deformable registration. Atlas selection based on PL for prostate and femoral diameter for femoral heads provides reasonable segmentation accuracy.

  1. Matched Cohort Analysis of Outcomes of Definitive Radiotherapy for Prostate Cancer in Human Immunodeficiency Virus-Positive Patients

    SciTech Connect

    Kahn, Shannon; Jani, Ashesh; Edelman, Scott; Rossi, Peter; Godette, Karen; Landry, Jerome; Anderson, Cynthia

    2012-05-01

    Purpose: To compare the biochemical outcome and toxicity scores of men with human immunodeficiency virus (HIV) and prostate cancer with a matched control population with negative or unknown HIV status when treated with external-beam radiotherapy (EBRT). Methods and Materials: A single-institution database of men with prostate cancer treated with EBRT from 1999 to 2009 was reviewed. Thirteen men with HIV were identified and matched to 2 control patients according to age, race, T stage, prostate-specific antigen level, Gleason score, RT dose, intensity-modulated RT vs. three-dimensional conformal RT, and whole-pelvis vs. prostate-only RT, for a total of 39 cases. The median follow-up time was 39 months (range, 3-110 months). Results: The 4-year biochemical failure (BF)-free survival rate was 87% in the HIV-positive group vs. 89% in the controls (p = 0.94). Pre- and post-RT viral loads were found to be predictive of BF (p = 0.04 and p = 0.04, respectively). No men with HIV died, whereas 2 in the control group died of causes unrelated to prostate cancer. Acute and chronic genitourinary and gastrointestinal toxicity were less in the HIV-positive patients than in controls (p < 0.001, p < 0.001, p = 0.003, and p < 0.001, respectively). The HIV-positive men experienced an average decline in CD4 count of 193 cells/mm{sup 3}. Conclusions: Our findings suggest that men with HIV treated with EBRT have a similar risk of BF; however, high viral loads may contribute to an increased risk. This analysis supports that HIV-positive men with prostate cancer can be treated with definitive EBRT with similar disease control and toxicity outcomes as in the general population.

  2. RapidArc radiotherapy planning for prostate cancer: Single-arc and double-arc techniques vs. intensity-modulated radiotherapy

    SciTech Connect

    Sze, Henry C.K.; Lee, Michael C.H.; Hung, Wai-Man; Yau, Tsz-Kok; Lee, Anne W.M.

    2012-04-01

    RapidArc is a novel technique using arc radiotherapy aiming to achieve intensity-modulated radiotherapy (IMRT)-quality radiotherapy plans with shorter treatment time. This study compared the dosimetric quality and treatment efficiency of single-arc (SA) vs. double-arc (DA) and IMRT in the treatment of prostate cancer. Fourteen patients were included in the analysis. The planning target volume (PTV), which contained the prostate gland and proximal seminal vesicles, received 76 Gy in 38 fractions. Seven-field IMRT, SA, and DA plans were generated for each patient. Dosimetric quality in terms of the minimum PTV dose, PTV hotspot, inhomogeneity, and conformity index; and sparing of rectum, bladder, and femoral heads as measured by V70, V-40, and V20 (% of volume receiving >70 Gy, 40 Gy, and 20 Gy, respectively), treatment efficiency as assessed by monitor units (MU) and treatment time were compared. All plan objectives were met satisfactorily by all techniques. DA achieved the best dosimetric quality with the highest minimum PTV dose, lowest hotspot, and the best homogeneity and conformity. It was also more efficient than IMRT. SA achieved the highest treatment efficiency with the lowest MU and shortest treatment time. The mean treatment time for a 2-Gy fraction was 4.80 min, 2.78 min, and 1.30 min for IMRT, DA, and SA, respectively. However, SA also resulted in the highest rectal dose. DA could improve target volume coverage and reduce treatment time and MU while maintaining equivalent normal tissue sparing when compared with IMRT. SA achieved the greatest treatment efficiency but with the highest rectal dose, which was nonetheless within tolerable limits. For busy units with high patient throughput, SA could be an acceptable option.

  3. An assessment of PTV margin based on actual accumulated dose for prostate cancer radiotherapy

    PubMed Central

    Wen, Ning; Kumarasiri, Akila; Nurushev, Teamour; Burmeister, Jay; Xing, Lei; Liu, Dezhi; Glide-Hurst, Carri; Kim, Jinkoo; Zhong, Hualiang; Movsas, Benjamin; Chetty, Indrin J

    2014-01-01

    The purpose of this work is to present the results of a margin reduction study involving dosimetric and radiobiologic assessment of cumulative dose distributions, computed using an image guided adaptive radiotherapy based framework. Eight prostate cancer patients, treated with 7–9, 6 MV, intensity modulated radiation therapy (IMRT) fields, were included in this study. The workflow consists of cone beam CT (CBCT) based localization, deformable image registration of the CBCT to simulation CT image datasets (SIMCT), dose reconstruction and dose accumulation on the SIM-CT, and plan evaluation using radiobiological models. For each patient, three IMRT plans were generated with different margins applied to the CTV. The PTV margin for the original plan was 10 mm and 6 mm at the prostate/anterior rectal wall interface (10/6 mm) and was reduced to: (a) 5/3 mm, and (b) 3 mm uniformly. The average percent reductions in predicted tumor control probability (TCP) in the accumulated (actual) plans in comparison to the original plans over eight patients were 0.4%, 0.7% and 11.0% with 10/6 mm, 5/3 mm and 3 mm uniform margin respectively. The mean increase in predicted normal tissue complication probability (NTCP) for grades 2/3 rectal bleeding for the actual plans in comparison to the static plans with margins of 10/6, 5/3 and 3 mm uniformly was 3.5%, 2.8% and 2.4% respectively. For the actual dose distributions, predicted NTCP for late rectal bleeding was reduced by 3.6% on average when the margin was reduced from 10/6 mm to 5/3 mm, and further reduced by 1.0% on average when the margin was reduced to 3 mm. The average reduction in complication free tumor control probability (P+) in the actual plans in comparison to the original plans with margins of 10/6, 5/3 and 3 mm was 3.7%, 2.4% and 13.6% correspondingly. The significant reduction of TCP and P+ in the actual plan with 3 mm margin came from one outlier, where individualizing patient treatment plans through margin adaptation

  4. An assessment of PTV margin based on actual accumulated dose for prostate cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Wen, Ning; Kumarasiri, Akila; Nurushev, Teamour; Burmeister, Jay; Xing, Lei; Liu, Dezhi; Glide-Hurst, Carri; Kim, Jinkoo; Zhong, Hualiang; Movsas, Benjamin; Chetty, Indrin J.

    2013-11-01

    The purpose of this work is to present the results of a margin reduction study involving dosimetric and radiobiologic assessment of cumulative dose distributions, computed using an image guided adaptive radiotherapy based framework. Eight prostate cancer patients, treated with 7-9, 6 MV, intensity modulated radiation therapy (IMRT) fields, were included in this study. The workflow consists of cone beam CT (CBCT) based localization, deformable image registration of the CBCT to simulation CT image datasets (SIM-CT), dose reconstruction and dose accumulation on the SIM-CT, and plan evaluation using radiobiological models. For each patient, three IMRT plans were generated with different margins applied to the CTV. The PTV margin for the original plan was 10 mm and 6 mm at the prostate/anterior rectal wall interface (10/6 mm) and was reduced to: (a) 5/3 mm, and (b) 3 mm uniformly. The average percent reductions in predicted tumor control probability (TCP) in the accumulated (actual) plans in comparison to the original plans over eight patients were 0.4%, 0.7% and 11.0% with 10/6 mm, 5/3 mm and 3 mm uniform margin respectively. The mean increase in predicted normal tissue complication probability (NTCP) for grades 2/3 rectal bleeding for the actual plans in comparison to the static plans with margins of 10/6, 5/3 and 3 mm uniformly was 3.5%, 2.8% and 2.4% respectively. For the actual dose distributions, predicted NTCP for late rectal bleeding was reduced by 3.6% on average when the margin was reduced from 10/6 mm to 5/3 mm, and further reduced by 1.0% on average when the margin was reduced to 3 mm. The average reduction in complication free tumor control probability (P+) in the actual plans in comparison to the original plans with margins of 10/6, 5/3 and 3 mm was 3.7%, 2.4% and 13.6% correspondingly. The significant reduction of TCP and P+ in the actual plan with 3 mm margin came from one outlier, where individualizing patient treatment plans through margin adaptation

  5. Complete PSA Response Following Stereotactic Ablative Radiotherapy for a Bony Metastasis in the Setting of Castrate-Resistant Prostate Cancer.

    PubMed

    Lukovic, Jelena; Rodrigues, George

    2015-01-01

    A majority of patients with castrate-resistant prostate cancer ultimately develop distant metastases, with bone being the most common site of spread. Classically, systemic therapy has been considered the standard of care for patients with metastatic cancer. Emerging evidence, however, suggests that an intermediate oligometastatic state, between limited disease and widespread metastases, exists; theoretically, with locally ablative treatment, patients may be curable. We describe a complete PSA response following aggressive management, using stereotactic body radiotherapy (SBRT), of an oligometastatic spine lesion in the setting of castrate-resistant prostate cancer (CRPC). This case report supports the use of SBRT in oligometastatic CRPC and suggests that management of limited metastases may provide good long-term outcomes in well-selected patients. PMID:26623220

  6. Complete PSA Response Following Stereotactic Ablative Radiotherapy for a Bony Metastasis in the Setting of Castrate-Resistant Prostate Cancer

    PubMed Central

    Rodrigues, George

    2015-01-01

    A majority of patients with castrate-resistant prostate cancer ultimately develop distant metastases, with bone being the most common site of spread. Classically, systemic therapy has been considered the standard of care for patients with metastatic cancer. Emerging evidence, however, suggests that an intermediate oligometastatic state, between limited disease and widespread metastases, exists; theoretically, with locally ablative treatment, patients may be curable. We describe a complete PSA response following aggressive management, using stereotactic body radiotherapy (SBRT), of an oligometastatic spine lesion in the setting of castrate-resistant prostate cancer (CRPC). This case report supports the use of SBRT in oligometastatic CRPC and suggests that management of limited metastases may provide good long-term outcomes in well-selected patients. PMID:26623220

  7. Influence of image slice thickness on rectal dose-response relationships following radiotherapy of prostate cancer

    NASA Astrophysics Data System (ADS)

    Olsson, C.; Thor, M.; Liu, M.; Moissenko, V.; Petersen, S. E.; Høyer, M.; Apte, A.; Deasy, J. O.

    2014-07-01

    When pooling retrospective data from different cohorts, slice thicknesses of acquired computed tomography (CT) images used for treatment planning may vary between cohorts. It is, however, not known if varying slice thickness influences derived dose-response relationships. We investigated this for rectal bleeding using dose-volume histograms (DVHs) of the rectum and rectal wall for dose distributions superimposed on images with varying CT slice thicknesses. We used dose and endpoint data from two prostate cancer cohorts treated with three-dimensional conformal radiotherapy to either 74 Gy (N = 159) or 78 Gy (N = 159) at 2 Gy per fraction. The rectum was defined as the whole organ with content, and the morbidity cut-off was Grade ≥2 late rectal bleeding. Rectal walls were defined as 3 mm inner margins added to the rectum. DVHs for simulated slice thicknesses from 3 to 13 mm were compared to DVHs for the originally acquired slice thicknesses at 3 and 5 mm. Volumes, mean, and maximum doses were assessed from the DVHs, and generalized equivalent uniform dose (gEUD) values were calculated. For each organ and each of the simulated slice thicknesses, we performed predictive modeling of late rectal bleeding using the Lyman-Kutcher-Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased (≤18%), whereas maximum and mean doses decreased (≤0.8 and ≤4.2 Gy, respectively). For all a values, the gEUD for the simulated DVHs were ≤1.9 Gy different than the gEUD for the original DVHs. The best-fitting LKB model parameter values with 95% CIs were consistent between all DVHs. In conclusion, we found that the investigated slice thickness variations had minimal impact on rectal dose-response estimations. From the perspective of predictive modeling, our results suggest that variations within 10 mm in slice thickness between cohorts are unlikely to be a limiting factor when pooling multi-institutional rectal dose data that include slice thickness

  8. Intensity-Modulated Radiotherapy of Pelvic Lymph Nodes in Locally Advanced Prostate Cancer: Planning Procedures and Early Experiences

    SciTech Connect

    Muren, Ludvig Paul Wasbo, Ellen; Helle, Svein Inge; Hysing, Liv Bolstad; Karlsdottir, Asa; Odland, Odd Harald; Valen, Harald; Ekerold, Randi; Johannessen, Dag Clement

    2008-07-15

    Purpose: We present planning and early clinical outcomes of a study of intensity-modulated radiotherapy (IMRT) for locally advanced prostate cancer. Methods and Materials: A total of 43 patients initially treated with an IMRT plan delivering 50 Gy to the prostate, seminal vesicles, and pelvic lymph nodes, followed by a conformal radiotherapy (CRT) plan delivering 20 Gy to the prostate and seminal vesicles, were studied. Dose-volume histogram (DVH) data for the added plans were compared with dose-volume histogram data for the sum of two CRT plans for 15 cases. Gastrointestinal (GI) and genitourinary (GU) toxicity, based on the Radiation Therapy Oncology Group scoring system, was recorded weekly throughout treatment as well as 3 to 18 months after treatment and are presented. Results: Treatment with IMRT both reduced normal tissue doses and increased the minimum target doses. Intestine volumes receiving more than 40 and 50 Gy were significantly reduced (e.g., at 50 Gy, from 81 to 19 cm{sup 3}; p = 0.026), as were bladder volumes above 40, 50, and 60 Gy, rectum volumes above 30, 50, and 60 Gy, and hip joint muscle volumes above 20, 30, and 40 Gy. During treatment, Grade 2 GI toxicity was reported by 12 of 43 patients (28%), and Grade 2 to 4 GU toxicity was also observed among 12 patients (28%). With 6 to 18 months of follow-up, 2 patients (5%) experienced Grade 2 GI effects and 7 patients (16%) experienced Grade 2 GU effects. Conclusions: Use of IMRT for pelvic irradiation in prostate cancer reduces normal tissue doses, improves target coverage, and has a promising toxicity profile.

  9. Prognostic Significance of Neuroendocrine Differentiation in Patients With Gleason Score 8-10 Prostate Cancer Treated With Primary Radiotherapy

    SciTech Connect

    Krauss, Daniel J.; Hayek, Sylvia; Amin, Mitual; Ye Hong; Kestin, Larry L.; Zadora, Steven; Vicini, Frank A.; Cotant, Matthew; Brabbins, Donald S.; Ghilezan, Michel I.; Gustafson, Gary S.; Martinez, Alvaro A.

    2011-11-01

    Purpose: To determine the prognostic significance of neuroendocrine differentiation (NED) in Gleason score 8-10 prostate cancer treated with primary radiotherapy (RT). Methods and Materials: Chromogranin A (CgA) staining was performed and overseen by a single pathologist on core biopsies from 176 patients from the William Beaumont prostate cancer database. A total of 143 had evaluable biopsy material. Staining was quantified as 0%, <1%, 1-10%, or >10% of tumor cells. Patients received external beam RT alone or together with high-dose-rate brachytherapy. Cox regression and Kaplan-Meier estimates determined if the presence/frequency of neuroendocrine cells correlated with clinical endpoints. Results: Median follow-up was 5.5 years. Forty patients (28%) had at least focal positive CgA staining (<1% n = 21, 1-10% n = 11, >10% n = 8). No significant differences existed between patients with or without staining in terms of age, pretreatment prostate-specific antigen, tumor stage, hormone therapy administration, % biopsy core involvement, mean Gleason score, or RT dose/modality. CgA staining concentration independently predicted for biochemical and clinical failure, distant metastases (DM), and cause-specific survival (CSS). For patients with <1% vs. >1% staining, 10-year DM rates were 13.4% vs. 55.3%, respectively (p = 0.001), and CSS was 91.7% vs. 58.9% (p < 0.001). As a continuous variable, increasing CgA staining concentration predicted for inferior rates of DM, CSS, biochemical control, and any clinical failure. No differences in outcomes were appreciated for patients with 0% vs. <1% NED. Conclusions: For Gleason score 8-10 prostate cancer, >1% NED is associated with inferior clinical outcomes for patients treated with radiotherapy. This relates most directly to an increase in distant disease failure.

  10. Secondary external-beam radiotherapy and hyperthermia for local recurrence after 125-iodine implantation in adenocarcinoma of the prostate

    SciTech Connect

    Kaplan, I.; Kapp, D.S.; Bagshaw, M.A. )

    1991-03-01

    At Standford, six patients underwent a course of external radiotherapy after local recurrence following 125-iodine implantation. Four of the six patients also received concomitant hyperthermia. Four patients were initially managed with hormonal manipulation at time of local relapse and subsequently received external beam radiotherapy with or without hyperthermia. The hyperthermia was non-invasively induced using an annular phased array radiative electromagnetic system. Treatment was well tolerated, and none of the patients experienced severe rectal or bladder complications. Three patients are free from disease; one patient experience local-regional recurrence based on biopsy; one recurred in the bladder, was treated with cystoprostatectomy and subsequently succumbed to metastatic disease; and one patient died of presumed metastatic disease. External-beam irradiation with concurrent hyperthermia can be safely delivered to treat locally recurrent prostatic carcinoma after 125-iodine implantation.

  11. The Effect of Registration Surrogate and Patient Factors on the Interobserver Variability of Electronic Portal Image Guidance During Prostate Radiotherapy

    SciTech Connect

    Kong, Vickie Lockwood, Gina; Yan Jing; Catton, Charles; Chung, Peter; Bayley, Andrew; Rosewall, Tara

    2011-01-01

    Intraprostatic fiducial markers (IPM) and electronic portal imaging (EPI) are commonly used to identify and correct for prostate motion during radiotherapy. However, little data is available on the precision of this image-guidance technique. This study quantified impact of different registration surrogates and patient factors on the interobserver variability of manual EPI alignment during prostate radiotherapy. For 50 prostate radiotherapy patients previously implanted with 3 IPM, five observers manually aligned 150 pairs of orthogonal EPI to the reference digital reconstructed radiograph using Varian Vision EPI analysis software. Images were aligned using: Bony anatomy (BA), single mid-prostate IPM (SM); and 2 strategies using 3 IPM: center of mass (COM) and rotate and translate (R and T). Intraclass correlation coefficients (ICCs) were calculated to quantify interobserver variability. The absolute displacements measured using SM and R and T were compared with those using COM. The impact of patients' pelvic diameter and adjuvant hormone therapy on interobserver variability were also evaluated. Twelve thousand displacement values were collected for analysis. The maximum discrepancy between the 5 observers was >2 mm in 47% of measurements using BA, 5% using SM, 4% using R and T, and 3% using COM. Both of the 3 IPM alignment strategies demonstrated lower interobserver variability than the single IPM strategy (ICC 0.94-0.97 vs. 0.82-0.94). BA had the highest interobserver variability (ICC = 0.43-0.90). Pelvic diameter and hormone therapy had no discernible impact on interobserver variability. Compared with COM, the absolute displacements measured using the other IPM strategies were statistically different (p < 0.001), but 95% of the absolute magnitude of differences between the strategies were {<=}1 mm. The high reproducibility among the observers demonstrated the precision of prostate localization using multiple IPM and EPI, which was not influenced by the patient

  12. Hypofractionated helical intensity-modulated radiotherapy of the prostate bed after prostatectomy with or without the pelvic lymph nodes - the PRIAMOS trial

    PubMed Central

    2012-01-01

    Background While evidence on safety and efficacy of primary hypofractionated radiotherapy in prostate cancer is accumulating, data on postoperative hypofractionated treatment of the prostate bed and of the pelvic lymph nodes is still scarce. This phase II trial was initiated to investigate safety and feasibility of hypofractionated treatment of the prostate bed alone or with the pelvic lymph nodes. Methods/design A total of 80 prostate cancer patients with the indication for adjuvant radiotherapy will be enrolled, where 40 patients with a low risk of lymph node involvement (arm 1) and another 40 patients with a high risk of lymph node involvement (arm 2) will each receive 54 Gy in 18 fractions to the prostate bed. Arm 2 will be given 45 Gy to the pelvic lymph nodes additionally. Helical Tomotherapy and daily image guidance will be used. Discussion This trial was initiated to substantiate data on hypofractionated treatment of the prostate bed and generate first data on adjuvant hypofractionated radiotherapy of the pelvic lymph nodes. Trial registration ClinicalTrials.gov; NCT01620710 PMID:23114055

  13. Improved biochemical outcome with adjuvant radiotherapy after radical prostatectomy for prostate cancer with poor pathologic features

    SciTech Connect

    Vargas, Carlos; Kestin, Larry L. . E-mail: lkestin@beaumont.edu; Weed, Dan W.; Krauss, Daniel; Vicini, Frank A.; Martinez, Alvaro A.

    2005-03-01

    Purpose: The indications for adjuvant external beam radiotherapy (EBRT) after radical prostatectomy (RP) are poorly defined. We performed a retrospective comparison of our institution's experience treating prostate cancer with RP vs. RP followed by adjuvant EBRT. Methods and materials: Between 1987 and 1998, 617 patients with clinical Stage T1-T2N0M0 prostate cancer underwent RP. Patients who underwent preoperative androgen deprivation and those with positive lymph nodes were excluded. Of the 617 patients, 34 (5.5%) with an undetectable postoperative prostate-specific antigen (PSA) level underwent adjuvant prostatic fossa RT at a median of 0.25 year (range, 0.1-0.6) postoperatively because of poor pathologic features. The median total dose was 59.4 Gy (range, 50.4-66.6 Gy) in 1.8-2.0-Gy fractions. These 34 RP+RT patients were compared with the remaining 583 RP patients. Biochemical failure was defined as any postoperative PSA level {>=}0.1 ng/mL and any postoperative PSA level {>=}0.3 ng/mL (at least 30 days after surgery). Administration of androgen deprivation was also scored as biochemical failure when applying either definition. The median clinical follow-up was 8.2 years (range, 0.1-11.2 years) for RP and 8.4 years (range, 0.3-13.8 years) for RP+RT. Results: Radical prostatectomy + radiation therapy patients had a greater pathologic Gleason score (mean, 7.3 vs. 6.5; p < 0.01) and pathologic T stage (median, T3a vs. T2c; p < 0.01). Age (median, 65.7 years) and pretreatment PSA level (median, 7.9 ng/mL) were similar between the treatment groups. Extracapsular extension was present in 72% of RP+RT patients vs. 27% of RP patients (p < 0.01). The RP+RT patients were more likely to have seminal vesicle invasion (29% vs. 9%, p < 0.01) and positive margins (73% vs. 36%, p < 0.01). Despite these poor pathologic features, the 5-year biochemical control (BC) rate (PSA < 0.1 ng/mL) was 57% for RP+RT and 47% for RP (p = 0.28). For patients with extracapsular extension, the

  14. Correlation Between Acute and Late Toxicity in 973 Prostate Cancer Patients Treated With Three-Dimensional Conformal External Beam Radiotherapy

    SciTech Connect

    Jereczek-Fossa, Barbara A.; Zerini, Dario; Fodor, Cristiana

    2010-09-01

    Purpose: To analyze the correlation between acute and late injury in 973 prostate cancer patients treated with radiotherapy and to evaluate the effect of patient-, tumor-, and treatment-related variables on toxicity. Methods and Materials: Of the 973 patients, 542 and 431 received definitive or postprostatectomy radiotherapy, respectively. Three-dimensional conformal radiotherapy included a six-field technique and two-dynamic arc therapy. Toxicity was classified according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. The correlation between acute and late toxicity (incidence and severity) was assessed. Results: Multivariate analysis showed that age {<=}65 years (p = .06) and use of the three-dimensional, six-field technique (p <.0001) correlated significantly with greater acute rectal toxicity. The three-dimensional, six-field technique (p = .0002), dose >70 Gy (p = .014), and radiotherapy duration (p = .05) correlated with greater acute urinary toxicity. Acute rectal toxicity (p <.0001) was the only factor that correlated with late rectal injury on multivariate analysis. Late urinary toxicity correlated with acute urinary events (p <.0001) and was inversely related to the use of salvage radiotherapy (p = .018). A highly significant correlation was found between the incidence of acute and late events for both rectal (p <.001) and urinary (p <.001) reactions. The severity of acute toxicity (Grade 2 or greater) was predictive for the severity of late toxicity for both rectal and urinary events (p <.001). Conclusion: The results of our study have shown that the risk of acute reactions depends on both patient-related (age) and treatment-related (dose, technique) factors. Acute toxicity was an independent significant predictor of late toxicity. These findings might help to predict and prevent late radiotherapy-induced complications.

  15. Meta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer.

    PubMed

    Kerns, Sarah L; Dorling, Leila; Fachal, Laura; Bentzen, Søren; Pharoah, Paul D P; Barnes, Daniel R; Gómez-Caamaño, Antonio; Carballo, Ana M; Dearnaley, David P; Peleteiro, Paula; Gulliford, Sarah L; Hall, Emma; Michailidou, Kyriaki; Carracedo, Ángel; Sia, Michael; Stock, Richard; Stone, Nelson N; Sydes, Matthew R; Tyrer, Jonathan P; Ahmed, Shahana; Parliament, Matthew; Ostrer, Harry; Rosenstein, Barry S; Vega, Ana; Burnet, Neil G; Dunning, Alison M; Barnett, Gillian C; West, Catharine M L

    2016-08-01

    Nearly 50% of cancer patients undergo radiotherapy. Late radiotherapy toxicity affects quality-of-life in long-term cancer survivors and risk of side-effects in a minority limits doses prescribed to the majority of patients. Development of a test predicting risk of toxicity could benefit many cancer patients. We aimed to meta-analyze individual level data from four genome-wide association studies from prostate cancer radiotherapy cohorts including 1564 men to identify genetic markers of toxicity. Prospectively assessed two-year toxicity endpoints (urinary frequency, decreased urine stream, rectal bleeding, overall toxicity) and single nucleotide polymorphism (SNP) associations were tested using multivariable regression, adjusting for clinical and patient-related risk factors. A fixed-effects meta-analysis identified two SNPs: rs17599026 on 5q31.2 with urinary frequency (odds ratio [OR] 3.12, 95% confidence interval [CI] 2.08-4.69, p-value 4.16×10(-8)) and rs7720298 on 5p15.2 with decreased urine stream (OR 2.71, 95% CI 1.90-3.86, p-value=3.21×10(-8)). These SNPs lie within genes that are expressed in tissues adversely affected by pelvic radiotherapy including bladder, kidney, rectum and small intestine. The results show that heterogeneous radiotherapy cohorts can be combined to identify new moderate-penetrance genetic variants associated with radiotherapy toxicity. The work provides a basis for larger collaborative efforts to identify enough variants for a future test involving polygenic risk profiling. PMID:27515689

  16. Localized volume effects for late rectal and anal toxicity after radiotherapy for prostate cancer

    SciTech Connect

    Peeters, Stephanie T.H.; Lebesque, Joos V. . E-mail: j.lebesque@nki.nl; Heemsbergen, Wilma D.; Putten, Wim L.J. van; Slot, Annerie; Dielwart, Michel F.H.; Koper, Peter C.M.

    2006-03-15

    Purpose: To identify dosimetric parameters derived from anorectal, rectal, and anal wall dose distributions that correlate with different late gastrointestinal (GI) complications after three-dimensional conformal radiotherapy for prostate cancer. Methods and Materials: In this analysis, 641 patients from a randomized trial (68 Gy vs. 78 Gy) were included. Toxicity was scored with adapted Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer (RTOG/EORTC) criteria and five specific complications. The variables derived from dose-volume histogram of anorectal, rectal, and anal wall were as follows: % receiving {>=}5-70 Gy (V5-V70), maximum dose (D{sub max}), and mean dose (D{sub mean}). The anus was defined as the most caudal 3 cm of the anorectum. Statistics were done with multivariate Cox regression models. Median follow-up was 44 months. Results: Anal dosimetric variables were associated with RTOG/EORTC Grade {>=}2 (V5-V40, D{sub mean}) and incontinence (V5-V70, D{sub mean}). Bleeding correlated most strongly with anorectal V55-V65, and stool frequency with anorectal V40 and D{sub mean}. Use of steroids was weakly related to anal variables. No volume effect was seen for RTOG/EORTC Grade {>=}3 and pain/cramps/tenesmus. Conclusion: Different volume effects were found for various late GI complications. Therefore, to evaluate the risk of late GI toxicity, not only intermediate and high doses to the anorectal wall volume should be taken into account, but also the dose to the anal wall.

  17. Radiotherapy and Survival in Prostate Cancer Patients: A Population-Based Study

    SciTech Connect

    Zhou, Esther H. Ellis, Rodney J.; Cherullo, Edward; Colussi, Valdir; Xu Fang; Chen Weidong; Gupta, Sanjay; Whalen, Christopher C.; Bodner, Donald; Resnick, Martin I.; Rimm, Alfred A.

    2009-01-01

    Purpose: To investigate the association of overall and disease-specific survival with the five standard treatment modalities for prostate cancer (CaP): radical prostatectomy (RP), brachytherapy (BT), external beam radiotherapy, androgen deprivation therapy, and no treatment (NT) within 6 months after CaP diagnosis. Methods and Materials: The study population included 10,179 men aged 65 years and older with incident CaP diagnosed between 1999 and 2001. Using the linked Ohio Cancer Incidence Surveillance System, Medicare, and death certificate files, overall and disease-specific survival through 2005 among the five clinically accepted therapies were analyzed. Results: Disease-specific survival rates were 92.3% and 23.9% for patients with localized vs. distant disease at 7 years, respectively. Controlling for age, race, comorbidities, stage, and Gleason score, results from the Cox multiple regression models indicated that the risk of CaP-specific death was significantly reduced in patients receiving RP or BT, compared with NT. For localized disease, compared with NT, in the monotherapy cohort, RP and BT were associated with reduced hazard ratios (HR) of 0.25 and 0.45 (95% confidence intervals 0.13-0.48 and 0.23-0.87, respectively), whereas in the combination therapy cohort, HR were 0.40 (0.17-0.94) and 0.46 (0.27-0.80), respectively. Conclusions: The present population-based study indicates that RP and BT are associated with improved survival outcomes. Further studies are warranted to improve clinical determinates in the selection of appropriate management of CaP and to improve predictive modeling for which patient subsets may benefit most from definitive therapy vs. conservative management and/or observation.

  18. Retrospective evaluation of dosimetric quality for prostate carcinomas treated with 3D conformal, intensity modulated and volumetric modulated arc radiotherapy

    SciTech Connect

    Crowe, Scott B; Kairn, Tanya; Middlebrook, Nigel; Hill, Brendan; Christie, David R H; Knight, Richard T; Kenny, John; Langton, Christian M; Trapp, Jamie V

    2013-12-15

    This study examines and compares the dosimetric quality of radiotherapy treatment plans for prostate carcinoma across a cohort of 163 patients treated across five centres: 83 treated with three-dimensional conformal radiotherapy (3DCRT), 33 treated with intensity modulated radiotherapy (IMRT) and 47 treated with volumetric modulated arc therapy (VMAT). Treatment plan quality was evaluated in terms of target dose homogeneity and organs at risk (OAR), through the use of a set of dose metrics. These included the mean, maximum and minimum doses; the homogeneity and conformity indices for the target volumes; and a selection of dose coverage values that were relevant to each OAR. Statistical significance was evaluated using two-tailed Welch's T-tests. The Monte Carlo DICOM ToolKit software was adapted to permit the evaluation of dose metrics from DICOM data exported from a commercial radiotherapy treatment planning system. The 3DCRT treatment plans offered greater planning target volume dose homogeneity than the other two treatment modalities. The IMRT and VMAT plans offered greater dose reduction in the OAR: with increased compliance with recommended OAR dose constraints, compared to conventional 3DCRT treatments. When compared to each other, IMRT and VMAT did not provide significantly different treatment plan quality for like-sized tumour volumes. This study indicates that IMRT and VMAT have provided similar dosimetric quality, which is superior to the dosimetric quality achieved with 3DCRT.

  19. Retrospective evaluation of dosimetric quality for prostate carcinomas treated with 3D conformal, intensity modulated and volumetric modulated arc radiotherapy

    PubMed Central

    Crowe, Scott B; Kairn, Tanya; Middlebrook, Nigel; Hill, Brendan; Christie, David R H; Knight, Richard T; Kenny, John; Langton, Christian M; Trapp, Jamie V

    2013-01-01

    Introduction This study examines and compares the dosimetric quality of radiotherapy treatment plans for prostate carcinoma across a cohort of 163 patients treated across five centres: 83 treated with three-dimensional conformal radiotherapy (3DCRT), 33 treated with intensity modulated radiotherapy (IMRT) and 47 treated with volumetric modulated arc therapy (VMAT). Methods Treatment plan quality was evaluated in terms of target dose homogeneity and organs at risk (OAR), through the use of a set of dose metrics. These included the mean, maximum and minimum doses; the homogeneity and conformity indices for the target volumes; and a selection of dose coverage values that were relevant to each OAR. Statistical significance was evaluated using two-tailed Welch's T-tests. The Monte Carlo DICOM ToolKit software was adapted to permit the evaluation of dose metrics from DICOM data exported from a commercial radiotherapy treatment planning system. Results The 3DCRT treatment plans offered greater planning target volume dose homogeneity than the other two treatment modalities. The IMRT and VMAT plans offered greater dose reduction in the OAR: with increased compliance with recommended OAR dose constraints, compared to conventional 3DCRT treatments. When compared to each other, IMRT and VMAT did not provide significantly different treatment plan quality for like-sized tumour volumes. Conclusions This study indicates that IMRT and VMAT have provided similar dosimetric quality, which is superior to the dosimetric quality achieved with 3DCRT. PMID:26229621

  20. Increased risk of biochemical and local failure in patients with distended rectum on the planning CT for prostate cancer radiotherapy

    SciTech Connect

    Crevoisier, Renaud de; Tucker, Susan L. . E-mail: sltucker@mdanderson.org; Dong Lei; Mohan, Radhe; Cheung, Rex; Cox, James D.; Kuban, Deborah A.

    2005-07-15

    Purpose: To retrospectively test the hypothesis that rectal distension on the planning computed tomography (CT) scan is associated with an increased risk of biochemical and local failure among patients irradiated for prostate carcinoma when a daily repositioning technique based on direct prostate-organ localization is not used. Methods and Materials: This study included 127 patients who received definitive three-dimensional conformal radiotherapy for prostate cancer to a total dose of 78 Gy at University of Texas M.D. Anderson Cancer Center. Rectal distension was assessed by calculation of the average cross-sectional rectal area (CSA; defined as the rectal volume divided by length) and measuring three rectal diameters on the planning CT. The impact of rectal distension on biochemical control, 2-year prostate biopsy results, and incidence of Grade 2 or greater late rectal bleeding was assessed. Results: The incidence of biochemical failure was significantly higher among patients with distended rectums (CSA >11.2 cm{sup 2}) on the planning CT scan (p 0.0009, log-rank test). Multivariate analysis indicates that rectal distension and high-risk disease are independent risk factors for biochemical failure, with hazard ratios of 3.89 (95% C.I. 1.58 to 9.56, p = 0.003) and 2.45 (95% C.I. 1.18 to 5.08, p = 0.016), respectively. The probability of residual tumor without evidence of radiation treatment (as scored by the pathologist) increased significantly with rectal distension (p = 0.010, logistic analysis), and a lower incidence of Grade 2 or greater late rectal bleeding within 2 years was simultaneously observed with higher CSA values (p = 0.031, logistic analysis). Conclusions: We found strong evidence that rectal distension on the treatment-planning CT scan decreased the probability of biochemical control, local control, and rectal toxicity in patients who were treated without daily image-guided prostate localization, presumably because of geographic misses. Therefore

  1. SU-E-J-39: Dosimetric Benefit of Implanted Marker-Based CBCT Setup for Definitive Prostatic Radiotherapy

    SciTech Connect

    Zhen, H; Wu, Z; Bluemenfeld, P; Chu, J; Wang, D

    2015-06-15

    Purpose Daily setup for definitive prostatic radiotherapy is challenged by suboptimal visibility of the prostate boundary and daily variation of rectum shape and position. For patients with improved bowel preparation, we conducted a dosimetric comparison between prostate implanted marker (IM)-based daily setup and anterior rectal wall (ARW)-based setup, with the hypothesis that the former leads to adequate target coverage with better rectal sparing. Methods Five IMRT/VMAT prostate cases with implanted markers were selected for analysis. Daily CBCT showed improvement of the rectal volume compared to planning CT. For each patient, the prostate and rectum were contoured on three CBCT images (fraction 5/15/25) with subsequent physician review. The CBCTs were then registered to a planning CT using IM-based registration. The deviation of ARW positions from planning CT to CBCT were analyzed at various sup-inf levels (−1.8 cm to 1.8 cm from level of prostate center). To estimate the potential dosimetric impact from ARW-based setup, the treatment plans were recalculated using A-P shifts ranging from −1mm to +6mm. Clinically important rectum DVH values including Dmax, D3cc and Dmean were computed. Results For the studied patients, we observed on average 32% rectum volume reduction from planning CT to CBCT. As a Results, the ARW on average shifts posteriorly by −1mm to +5mm, depending on the sup-inf level of observation, with larger shifts observed at more superior levels. Recalculation shows that when ARW shifts 1mm posteriorly, ARW-based CBCT setup leads to a 1.0%, 4.2%, and 3.2% increase in rectum Dmax, D3cc, and Dmean, respectively, compared to IM-based setup. The dosimetric deviations increase to 4.7%, 25.8% and 24.7% when ARW shifts 6mm posteriorly. No significant prostate-only dose difference was observed. Conclusion For patients with improved bowel preparation, IM-based CBCT setup leads to accurate prostate coverage along with significantly lower rectal dose

  2. A Phase I/II Trial of Gefitinib Given Concurrently With Radiotherapy in Patients With Nonmetastatic Prostate Cancer

    SciTech Connect

    Joensuu, Greetta; Joensuu, Timo; Nokisalmi, Petri

    2010-09-01

    Purpose: To estimate the safety and tolerability of daily administration of 250 mg of gefitinib given concurrently with three-dimensional conformal radiotherapy for patients with nonmetastatic prostate cancer. Methods and Materials: A total of 42 patients with T2-T3N0M0 tumors were treated in a nonrandomized single-center study. A prostate-specific antigen (PSA) level of <20 and a good performance status (WHO, 0-1) were required. Adjuvant or neoadjuvant hormone treatments were not allowed. A daily regimen of 250 mg of gefitinib was started 1 week before radiation therapy began and lasted for the duration of radiation therapy. A dose of 50.4 Gy (1.8 Gy/day) was administered to the tumor, prostate, and seminal vesicles, followed by a 22-Gy booster (2 Gy/day) for a total dose of 72.4 Gy. Correlative studies included analysis of epidermal growth factor receptor (EGFR), EGFRvIII, and phosphorylated EGFR in tumors and tumor necrosis factor, interleukin-1{alpha} (IL-1{alpha}), and IL-6 in serum. Results: Maximum tolerated dose was not reached in phase I (12 patients), and 30 additional patients were treated in phase II. Thirty (71.4%) patients completed trial medication. Dose-limiting toxicities were recorded for 16 (38.1%) patients, the most common of which was a grade 3 to 4 increase in transaminase (6 patients). After a median follow-up of 38 months, there were no deaths due to prostate cancer. The estimated PSA relapse-free survival rate at 4 years (Kaplan-Meier) was 97%, the salvage therapy-free survival rate was 91%, and the overall survival rate was 87%. These figures compared favorably with those of matched patients treated with radiation only at higher doses. Conclusions: The combination of gefitinib and radiation is reasonably well tolerated and has promising activity against nonmetastatic prostate cancer.

  3. Retrospective Comparison of External Beam Radiotherapy and Radical Prostatectomy in High-Risk, Clinically Localized Prostate Cancer

    SciTech Connect

    Arcangeli, Giorgio; Strigari, Lidia; Arcangeli, Stefano; Petrongari, Maria Grazia; Saracino, Biancamaria; Gomellini, Sara; Papalia, Rocco; Simone, Giuseppe; De Carli, Piero; Gallucci, Michele

    2009-11-15

    Purpose: Because of the lack of conclusive and well-conducted randomized studies, the optimal therapy for prostate tumors remains controversial. The aim of this study was to retrospectively compare the results of radical surgery vs. a conservative approach such as external beam radiotherapy (EBRT) plus androgen deprivation therapy using an intent-to-treat analysis on two pretreatment defined, concurrently treated, high-risk patient populations. Methods and Materials: Between January 2003 and December 2007, 162 patients with high-risk prostate cancer underwent an EBRT plus androgen deprivation therapy program at the RT department of our institute. In the same period, 122 patients with the same high-risk disease underwent radical prostatectomy (RP) at the urologic department of our institute. Patients with adverse pathologic factors also underwent adjuvant EBRT with or without androgen deprivation therapy. The primary endpoint was freedom from biochemical failure. Results: The two groups of high-risk patients were homogeneous in terms of freedom from biochemical failure on the basis of the clinical T stage, biopsy Gleason score, and initial prostate-specific antigen level. The median follow-up was 38.6 and 33.8 months in the EBRT and RP groups, respectively. The actuarial analysis of the freedom from biochemical failure showed a 3-year rate of 86.8% and 69.8% in the EBRT and RP group, respectively (p = .001). Multivariate analysis of the whole group revealed the initial prostate-specific antigen level and treatment type (EBRT vs. RP) as significant covariates. Conclusion: This retrospective intention-to-treat analysis showed a significantly better outcome after EBRT than after RP in patients with high-risk prostate cancer, although a well-conducted randomized comparison would be the best procedure to confirm these results.

  4. Accuracy of dose planning for prostate radiotherapy in the presence of metallic implants evaluated by electron spin resonance dosimetry

    PubMed Central

    Alves, G.G.; Kinoshita, A.; de Oliveira, H.F.; Guimarães, F.S.; Amaral, L.L.; Baffa, O.

    2015-01-01

    Radiotherapy is one of the main approaches to cure prostate cancer, and its success depends on the accuracy of dose planning. A complicating factor is the presence of a metallic prosthesis in the femur and pelvis, which is becoming more common in elderly populations. The goal of this work was to perform dose measurements to check the accuracy of radiotherapy treatment planning under these complicated conditions. To accomplish this, a scale phantom of an adult pelvic region was used with alanine dosimeters inserted in the prostate region. This phantom was irradiated according to the planned treatment under the following three conditions: with two metallic prostheses in the region of the femur head, with only one prosthesis, and without any prostheses. The combined relative standard uncertainty of dose measurement by electron spin resonance (ESR)/alanine was 5.05%, whereas the combined relative standard uncertainty of the applied dose was 3.35%, resulting in a combined relative standard uncertainty of the whole process of 6.06%. The ESR dosimetry indicated that there was no difference (P>0.05, ANOVA) in dosage between the planned dose and treatments. The results are in the range of the planned dose, within the combined relative uncertainty, demonstrating that the treatment-planning system compensates for the effects caused by the presence of femur and hip metal prostheses. PMID:26017344

  5. Phase II Study of Vinorelbine and Estramustine in Combination With Conformational Radiotherapy for Patients With High-Risk Prostate Cancer

    SciTech Connect

    Carles, Joan; Nogue, Miguel; Sole, Josep M.; Foro, Palmira; Domenech, Montserrat; Suarez, Marta; Gallardo, Enrique; Garcia, Dario; Ferrer, Ferran; Gelabert-Mas, Antoni; Gayo, Javier; Fabregat, Xavier

    2010-03-15

    Purpose: To evaluate the efficacy and safety profile of vinorelbine and estramustine in combination with three-dimensional conformational radiotherapy (3D-CRT) in patients with localized high-risk prostate cancer. Methods and Materials: Fifty patients received estramustine, 600 mg/m{sup 2} daily, and vinorelbine, 25 mg/m{sup 2}, on days 1 and 8 of a 21-day cycle for three cycles in combination with 8 weeks of 3D-CRT (total dose of 70.2 gray [Gy] at 1.8-Gy fractions or 70 Gy at 2.0-Gy fractions). Additionally, patients received luteinizing hormone-releasing hormone analogs for 3 years. Results: All patients were evaluated for response and toxicity. Progression-free survival at 5 years was 72% (95% confidence interval [CI]: 52-86). All patients who relapsed had only biochemical relapse. The most frequent severe toxicities were cystitis (16% of patients), leucopenia (10% of patients), diarrhea (10% of patients), neutropenia (8% of patients), and proctitis (8% of patients). Six patients (12%) did not complete study treatment due to the patient's decision (n = 1) and to adverse events such as hepatotoxicity, proctitis, paralytic ileus, and acute myocardial infarction. Conclusions: Vinorelbine and estramustine in combination with 3D-CRT is a safe and effective regimen for patients with localized high-risk prostate cancer. A randomized trial is needed to determine whether the results of this regimen are an improvement over the results obtained with radiotherapy and androgen ablation.

  6. Acute and Late Toxicity in a Randomized Trial of Conventional Versus Hypofractionated Three-Dimensional Conformal Radiotherapy for Prostate Cancer

    SciTech Connect

    Arcangeli, Giorgio; Fowler, Jack; Gomellini, Sara; Arcangeli, Stefano; Saracino, Biancamaria; Petrongari, Maria Grazia; Benassi, Marcello; Strigari, Lidia

    2011-03-15

    Purpose: To compare the toxicity between hypofractionation vs. conventional fractionation schedules in patients with high-risk prostate cancer. Methods and Materials: Between January 2003 and December 2007, 168 patients were randomized to receive either hypofractionated (62 Gy in 20 fractions within 5 weeks, 4 fractions/wk) or conventionally fractionated (80 Gy in 40 fractions within 8 weeks) three-dimensional conformal radiotherapy to the prostate and seminal vesicles. All patients had undergone a 9-month course of total androgen deprivation, with radiotherapy starting 2 months after initiation of the total androgen deprivation. Results: The median follow-up was 32 and 35 months in the hypofractionation and conventional fractionation arms, respectively. For the patients developing acute toxicity, no difference between the two fractionation groups was found in either severity or duration of gastrointestinal or genitourinary toxicity. Also, no difference was found in the incidence and severity of late gastrointestinal and genitourinary toxicity between the two treatment schedules, with a 3-year rate of Grade 2 or greater toxicity of 17% and 16% for the hypofractionation arm and 14% and 11% for the conventional fractionation arm, respectively. A statistically significant correlation between acute and late gastrointestinal toxicity was found only in the conventional fractionation group. Conclusion: Our findings suggest that the hypofractionation regimen used in our study is safe, with only a slight, nonsignificant increase in tolerable and temporary acute toxicity compared with the conventional fractionation schedule. The severity and frequency of late complications was equivalent between the two treatment groups.

  7. Monte Carlo simulations of the dosimetric impact of radiopaque fiducial markers for proton radiotherapy of the prostate

    NASA Astrophysics Data System (ADS)

    Newhauser, Wayne; Fontenot, Jonas; Koch, Nicholas; Dong, Lei; Lee, Andrew; Zheng, Yuanshui; Waters, Laurie; Mohan, Radhe

    2007-06-01

    Many clinical studies have demonstrated that implanted radiopaque fiducial markers improve targeting accuracy in external-beam radiotherapy, but little is known about the dose perturbations these markers may cause in patients receiving proton radiotherapy. The objective of this study was to determine what types of implantable markers are visible in setup radiographs and, at the same time, perturb the therapeutic proton dose to the prostate by less than 10%. The radiographic visibility of the markers was assessed by visual inspection of lateral setup radiographs of a pelvic phantom using a kilovoltage x-ray imaging system. The fiducial-induced perturbations in the proton dose were estimated with Monte Carlo simulations. The influence of marker material, size, placement depth and orientation within the pelvis was examined. The radiographic tests confirmed that gold and stainless steel markers were clearly visible and that titanium markers were not. The Monte Carlo simulations revealed that titanium and stainless steel markers minimally perturbed the proton beam, but gold markers cast unacceptably large dose shadows. A 0.9 mm diameter, 3.1 mm long cylindrical stainless steel marker provides good radiographic visibility yet perturbs the proton dose distribution in the prostate by less than 8% when using a parallel opposed lateral beam arrangement.

  8. A prospective comparison of acute intestinal toxicity following whole pelvic versus small field intensity-modulated radiotherapy for prostate cancer

    PubMed Central

    Kim, Yeon Joo; Park, Jin-hong; Yun, In-Ha; Kim, Young Seok

    2016-01-01

    Purpose To compare the acute intestinal toxicity of whole pelvic (WP) and small field (SF) intensity-modulated radiotherapy (IMRT) for prostate cancer using dosimetric and metabolic parameters as well as clinical findings. Methods Patients who received IMRT in either a definitive or postoperative setting were prospectively enrolled. Target volume and organs at risk including intestinal cavity (IC) were delineated in every patient by a single physician. The IC volume that received a 10–50 Gy dose at 5-Gy intervals (V10–V50) and the percentage of irradiated volume as a fraction of total IC volume were calculated. Plasma citrulline levels, as an objective biological marker, were checked at three time points: baseline and after exposure to 30 Gy and 60 Gy. Results Of the 41 patients, only six experienced grade 1 acute intestinal toxicity. Although all dose–volume parameters were significantly worse following WP than SF IMRT, there was no statistically significant relationship between these dosimetric parameters and clinical symptoms. Plasma citrulline levels did not show a serial decrease by radiotherapy volume difference (WP versus SF) and were not relevant to the irradiated doses. Conclusion Given that WP had comparable acute intestinal toxicities to those associated with SF, WP IMRT appears to be a feasible approach for the treatment of prostate cancer despite dosimetric disadvantages. PMID:27022287

  9. Competing-Risks Mortality After Radiotherapy vs. Observation for Localized Prostate Cancer: A Population-based Study

    SciTech Connect

    Abdollah, Firas; Sun, Maxine; Schmitges, Jan; Thuret, Rodolphe; Tian, Zhe; Shariat, Shahrokh F.; Briganti, Alberto; Jeldres, Claudio; Perrotte, Paul; Montorsi, Francesco; Karakiewicz, Pierre I.

    2012-09-01

    Purpose: Contemporary patients with localized prostate cancer (PCa) are more frequently treated with radiotherapy. However, there are limited data on the effect of this treatment on cancer-specific mortality (CSM). Our objective was to test the relationship between radiotherapy and survival in men with localized PCa and compare it with those treated with observation. Methods: A population-based cohort identified 68,797 men with cT1-T2 PCa treated with radiotherapy or observation between the years 1992 and 2005. Propensity-score matching was used to minimize potential bias related to treatment assignment. Competing-risks analyses tested the effect of treatment type (radiotherapy vs. observation) on CSM, after accounting to other-cause mortality. All analyses were carried out within PCa risk, baseline comorbidity status, and age groups. Results: Radiotherapy was associated with more favorable 10-year CSM rates than observation in patients with high-risk PCa (8.8 vs. 14.4%, hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.50-0.68). Conversely, the beneficial effect of radiotherapy on CSM was not evident in patients with low-intermediate risk PCa (3.7 vs. 4.1%, HR: 0.91, 95% CI: 0.80-1.04). Radiotherapy was beneficial in elderly patients (5.6 vs. 7.3%, HR: 0.70, 95% CI: 0.59-0.80). Moreover, it was associated with improved CSM rates among patients with no comorbidities (5.7 vs. 6.5%, HR: 0.81, 95% CI: 0.67-0.98), one comorbidity (4.6 vs. 6.0%, HR: 0.87, 95% CI: 0.75-0.99), and more than two comorbidities (4.2 vs. 5.0%, HR: 0.79, 95% CI: 0.65-0.96). Conclusions: Radiotherapy substantially improves CSM in patients with high-risk PCa, with little or no benefit in patients with low-/intermediate-risk PCa relative to observation. These findings must be interpreted within the context of the limitations of observational data.

  10. SU-D-9A-06: 3D Localization of Neurovascular Bundles Through MR-TRUS Registration in Prostate Radiotherapy

    SciTech Connect

    Yang, X; Rossi, P; Ogunleye, T; Jani, A; Curran, W; Liu, T

    2014-06-01

    Purpose: Erectile dysfunction (ED) is the most common complication of prostate-cancer radiotherapy (RT) and the major mechanism is radiation-induced neurovascular bundle (NVB) damage. However, the localization of the NVB remains challenging. This study's purpose is to accurately localize 3D NVB by integrating MR and transrectal ultrasound (TRUS) images through MR-TRUS fusion. Methods: T1 and T2-weighted MR prostate images were acquired using a Philips 1.5T MR scanner and a pelvic phase-array coil. The 3D TRUS images were captured with a clinical scanner and a 7.5 MHz biplane probe. The TRUS probe was attached to a stepper; the B-mode images were captured from the prostate base to apex at a 1-mm step and the Doppler images were acquired in a 5-mm step. The registration method modeled the prostate tissue as an elastic material, and jointly estimated the boundary condition (surface deformation) and the volumetric deformations under elastic constraint. This technique was validated with a clinical study of 7 patients undergoing RT treatment for prostate cancer. The accuracy of our approach was assessed through the locations of landmarks, as well as previous ultrasound Doppler images of patients. Results: MR-TRUS registration was successfully performed for all patients. The mean displacement of the landmarks between the post-registration MR and TRUS images was 1.37±0.42 mm, which demonstrated the precision of the registration based on the biomechanical model; and the NVB volume Dice Overlap Coefficient was 92.1±3.2%, which demonstrated the accuracy of the NVB localization. Conclusion: We have developed a novel approach to improve 3D NVB localization through MR-TRUS fusion for prostate RT, demonstrated its clinical feasibility, and validated its accuracy with ultrasound Doppler data. This technique could be a useful tool as we try to spare the NVB in prostate RT, monitor NBV response to RT, and potentially improve post-RT potency outcomes.

  11. Hormone therapy and radiotherapy for early prostate cancer: A utility-adjusted number needed to treat (NNT) analysis

    SciTech Connect

    Jani, Ashesh B.; Kao, Johnny; Heimann, Ruth; Hellman, Samuel . E-mail: s-hellman@uchicago.edu

    2005-03-01

    Purpose: To quantify, using the number needed to treat (NNT) methodology, the benefit of short-term ({<=}6 months) hormone therapy adjuvant to radiotherapy in the group of patients with early (clinical stage T1-T2c) prostate cancer. Methods and materials: The absolute biochemical control benefit for the use of hormones adjuvant to radiotherapy in early-stage disease was determined by literature review. A model was developed to estimate the utility-adjusted survival detriment due to the side effects of hormone therapy. The NNTs before and after the incorporation of hormone sequelae were computed; the sign and magnitude of the NNTs were used to gauge the effect of the hormones. Results: The absolute NNT analysis, based on summarizing the results of 8 reports including a total of 3652 patients, demonstrated an advantage to the addition of hormones for the general early-stage prostate cancer population as well as for all prognostic groups. After adjustment for hormone-induced functional loss, the advantage of hormones remained considerable in the high- and intermediate-risk groups, with the utility-adjusted NNT becoming weakened in the low-risk group when the utility compromise from complications of hormones was assumed to be considerable. Conclusions: Short-term hormone therapy seems to be beneficial for selected early-stage prostate cancer patients. The advantage seems to be greatest in the intermediate- and high-risk groups; with current follow-up, the side effects of hormones may outweigh their benefit in certain clinical situations in the favorable group. The present investigation demonstrates the significant role of the NNT technique for oncologic and radiotherapeutic management decisions when treatment complications need to be considered and balanced with the beneficial effects of the treatment.

  12. Investigation of bladder dose and volume factors influencing late urinary toxicity after external beam radiotherapy for prostate cancer

    SciTech Connect

    Cheung, M. Rex . E-mail: mrcheung@mdanderson.org; Tucker, Susan L.; Dong Lei; Crevoisier, Renaud de; Lee, Andrew K.; Frank, Steven; Kudchadker, Rajat J.; Thames, Howard; Mohan, Radhe; Kuban, Deborah

    2007-03-15

    Background: We sought to identify the bladder dose-volume factors associated with an increased risk of late urinary toxicity among prostate cancer patients treated with radiotherapy. Methods and Materials: This retrospective analysis included data from 128 prostate cancer patients treated on protocol with 2 Gy/fraction to 46 Gy followed by a boost to 78 Gy. The endpoint for this analysis was Grade 1 or greater late genitourinary (GU) toxicity occurring within two years of treatment. The Lyman-Kutcher-Burman, mean dose, threshold dose, and hottest volume models were fitted to the toxicity data using the maximum likelihood method. Results: Model fits based on dose-volume histograms tended to fit the toxicity data better than models based on dose-wall histograms. The hottest volume (hotspot) model was found to be the best-fitting model investigated. The best fit was for the hottest 2.9% of bladder (95% CI, 1.1-6.8%). This model has an area under the receiver operating characteristic curve of 0.74. The hotspot model separated the patients into clinically meaningful subgroups with {approx}25% of the patients who received <78 Gy to the hottest 2.9% of bladder had GU toxicity at eight years compared with {approx}50% when the dose was {>=}78 Gy (p = 0.002). Conclusion: This provides the first evidence supporting that bladder 'hotspots' are related to GU toxicity within two years after external beam radiotherapy for prostate cancer. Confirming data are needed from other investigators. Particular attention should be given to hotspots higher than 78 Gy in bladder in radiation treatment planning.

  13. MR-guided pulsed high intensity focused ultrasound enhancement of docetaxel combined with radiotherapy for prostate cancer treatment

    NASA Astrophysics Data System (ADS)

    Mu, Zhaomei; Ma, C.-M.; Chen, Xiaoming; Cvetkovic, Dusica; Pollack, Alan; Chen, Lili

    2012-01-01

    The purpose of this study is to evaluate the efficacy of the enhancement of docetaxel by pulsed focused ultrasound (pFUS) in combination with radiotherapy (RT) for treatment of prostate cancer in vivo. LNCaP cells were grown in the prostates of male nude mice. When the tumors reached a designated volume by MRI, tumor bearing mice were randomly divided into seven groups (n = 5): (1) pFUS alone; (2) RT alone; (3) docetaxel alone; (4) docetaxel + pFUS (5) docetaxel + RT (6) docetaxel + pFUS + RT, and (7) control. MR-guided pFUS treatment was performed using a focused ultrasound treatment system (InSightec ExAblate 2000) with a 1.5T GE MR scanner. Animals were treated once with pFUS, docetaxel, RT or their combinations. Docetaxel was given by i.v. injection at 5 mg kg-1 before pFUS. RT was given 2 Gy after pFUS. Animals were euthanized 4 weeks after treatment. Tumor volumes were measured on MRI at 1 and 4 weeks post-treatment. Results showed that triple combination therapies of docetaxel, pFUS and RT provided the most significant tumor growth inhibition among all groups, which may have potential for the treatment of prostate cancer due to an improved therapeutic ratio.

  14. Ultrasound-Guided Transrectal Implantation of Gold Markers for Prostate Localization During External Beam Radiotherapy: Complication Rate and Risk Factors

    SciTech Connect

    Langenhuijsen, Johan F.; Lin, Emile N.J.T. van Kiemeney, Lambertus A.; Vight, Lisette P. van der; McColl, Gill; Visser, Andries G.; Witjes, J. Alfred

    2007-11-01

    Purpose: To report the complication rate and risk factors of transrectally implanted gold markers, used for prostate position verification and correction procedures. Methods and Materials: In 209 consecutive men with localized prostate cancer, four gold markers (1 x 7 mm) were inserted under ultrasound guidance in an outpatient setting, and the toxicity was analyzed. All patients received a questionnaire regarding complications after marker implantation. The complications and risk factors were further evaluated by reviewing the medical charts. Results: Of the 209 men, 13 (6.2%) had a moderate complication, consisting of pain and fever that resolved after treatment with oral medication. In 1.9% of the men, minor voiding complaints were observed. Other minor transient complications, defined as hematuria lasting >3 days, hematospermia, and rectal bleeding, occurred in 3.8%, 18.5%, and 9.1% of the patients, respectively. These complications were seen more often in patients with advanced tumor stage, younger age, and shorter duration of hormonal therapy. Conclusion: Transrectal gold marker implantation for high-precision prostate radiotherapy is a safe and well-tolerated procedure.

  15. Magnitude of speed of sound aberration corrections for ultrasound image guided radiotherapy for prostate and other anatomical sites

    SciTech Connect

    Fontanarosa, Davide; Meer, Skadi van der; Bloemen-van Gurp, Esther; Stroian, Gabriela; Verhaegen, Frank

    2012-08-15

    Purpose: The purpose of this work is to assess the magnitude of speed of sound (SOS) aberrations in three-dimensional ultrasound (US) imaging systems in image guided radiotherapy. The discrepancy between the fixed SOS value of 1540 m/s assumed by US systems in human soft tissues and its actual nonhomogeneous distribution in patients produces small but systematic errors of up to a few millimeters in the positions of scanned structures. Methods: A correction, provided by a previously published density-based algorithm, was applied to a set of five prostate, five liver, and five breast cancer patients. The shifts of the centroids of target structures and the change in shape were evaluated. Results: After the correction the prostate cases showed shifts up to 3.6 mm toward the US probe, which may explain largely the reported positioning discrepancies in the literature on US systems versus other imaging modalities. Liver cases showed the largest changes in volume of the organ, up to almost 9%, and shifts of the centroids up to more than 6 mm either away or toward the US probe. Breast images showed systematic small shifts of the centroids toward the US probe with a maximum magnitude of 1.3 mm. Conclusions: The applied correction in prostate and liver cancer patients shows positioning errors of several mm due to SOS aberration; the errors are smaller in breast cancer cases, but possibly becoming more important when breast tissue thickness increases.

  16. Mathematical Model for Evaluating Incidence of Acute Rectal Toxicity During Conventional or Hypofractionated Radiotherapy Courses for Prostate Cancer

    SciTech Connect

    Strigari, Lidia Arcangeli, Giorgio; Arcangeli, Stefano; Benassi, Marcello

    2009-04-01

    Purpose: To describe the radiation-induced acute rectal toxicity (ART) using a modified Lyman-Kutcher-Burman normal tissue complication probability model and parameters set, taking into account the overall treatment time. Methods and Materials: A total of 160 patients underwent three-dimensional conformal radiotherapy to the prostate and seminal vesicles and were randomized to receive 80 Gy in 40 fractions within 8 weeks (Group A) or 62 Gy in 20 fractions within 5 weeks, 4 d/wk (Group B). An additional 52 patients (Group C) underwent intensity-modulated radiotherapy with a hypofractionation schedule consisting of 56 Gy, delivered in 16 fractions (4/wk) of 3.5 Gy. Patients were followed for ART weekly during treatment. The overall treatment time, rectal dose-volume histograms, and ART status, defined as Radiation Therapy Oncology Group Grade 2 or greater gastrointestinal toxicity, were used to determine the modified Lyman-Kutcher-Burman model parameters. The m and n values were obtained from the cohort, and the tolerance doses for 50% complication probability for uniform irradiation [TD{sub 50}(1){sub k}] were obtained for each fractionation schedule indicated with k. Results: Of 212 patients treated with localized prostate radiotherapy, 65 developed Grade for {>=}1 week during treatment. The m and n value was 0.17 and 0.08, respectively. The TD{sub 50}(1){sub k} parameter was 79, 62.5, and 53 Gy, respectively for Group A, B, and C. Conclusion: The optimized modified Lyman-Kutcher-Burman normal tissue complication probability model allowed us to describe the ART data from conventional and hypofractionated regimens, using the dose-volume histograms and overall treatment time. This model could prove useful in designing hypofractionation schedules to reduce the incidence of ART.

  17. Interval to Biochemical Failure Highly Prognostic for Distant Metastasis and Prostate Cancer-Specific Mortality After Radiotherapy

    SciTech Connect

    Buyyounouski, Mark K. Hanlon, Alexandra L.; Horwitz, Eric M.; Pollack, Alan

    2008-01-01

    Purpose: Few biochemical parameters have been related to mortality. The present study examined the clinical utility of the interval to biochemical failure (IBF) as a prognostic factor for distant metastasis (DM) and prostate cancer-specific mortality (PCSM) after radiotherapy. Methods and Materials: The study group consisted of 211 T1c-T3Nx-N0M0 patients who had experienced BF among 1,174 men treated with three-dimensional conformal radiotherapy alone. Biochemical failure was defined as a post-treatment prostate-specific antigen (PSA) level of at, or greater than, the PSA nadir plus 2 ng/mL. Cox proportional hazards modeling was used to identify independent predictors of DM and PCSM on multivariate analysis. Results: An IBF of <18 months was independently predictive for DM (p = 0.008), as was a Gleason score of 7-10 (p = 0.0005), PSA nadir {>=}2 ng/mL (p = 0.04), and decreasing radiation dose (p = 0.02) on multivariate analysis, including increasing pretreatment PSA level, PSA nadir {>=}2.5 ng/mL, PSA doubling time of <3 months, and Stage T3 disease. An IBF of <18 months was the only predictor of PCSM (p = 0.0003) in the same model. The actuarial 5-year DM rate for an IBF of <18 vs. {>=}18 months was 52% vs. 20% (p < 0.0001), and the actuarial PCSM rate was 36% vs. 6%, respectively (p = 0.0001). Conclusions: The IBF is an important descriptor of the PSA kinetics after radiotherapy to identify men at high risk of clinical failure and death. A IBF of <18 months could aid in selecting men for early, aggressive salvage therapy or participation in a clinical trial.

  18. Late Fecal Incontinence After High-Dose Radiotherapy for Prostate Cancer: Better Prediction Using Longitudinal Definitions

    SciTech Connect

    Fiorino, Claudio; Rancati, Tiziana; Fellin, Gianni; Vavassori, Vittorio; Cagna, Emanuela; Casanova Borca, Valeria; Girelli, Giuseppe; Menegotti, Loris; Monti, Angelo Filippo; Tortoreto, Francesca; Delle Canne, Stefania; Valdagni, Riccardo

    2012-05-01

    Purpose: To model late fecal incontinence after high-dose prostate cancer radiotherapy (RT) in patients accrued in the AIROPROS (prostate working group of the Italian Association of Radiation Oncology) 0102 trial using different endpoint definitions. Methods and Materials: The self-reported questionnaires (before RT, 1 month after RT, and every 6 months for {<=}3 years after RT) of 586 patients were available. The peak incontinence (P{sub I}NC) and two longitudinal definitions (chronic incontinence [C{sub I}NC], defined as the persistence of Grade 1 or greater incontinence after any Grade 2-3 event; and mean incontinence score [M{sub I}NC], defined as the average score during the 3-year period after RT) were considered. The correlation between the clinical/dosimetric parameters (including rectal dose-volume histograms) and P{sub I}NC (Grade 2 or greater), C{sub I}NC, and M{sub I}NC of {>=}1 were investigated using multivariate logistic analyses. Receiver operating characteristic curves and the area under the curve were used to assess the predictive value of the different multivariate models. Results: Of the 586 patients, 36 with a Grade 1 or greater incontinence score before RT were not included in the present analysis. Of the 550 included patients, 197 (35.8%) had at least one control with a Grade 1 or greater incontinence score (M{sub I}NC >0). Of these 197 patients, 37 (6.7%), 22 (4.0%), and 17 (3.1%) were scored as having P{sub I}NC, M{sub I}NC {>=}1, and C{sub I}NC, respectively. On multivariate analysis, Grade 2 or greater acute incontinence was the only predictor of P{sub I}NC (odds ratio [OR], 5.9; p = .0009). Grade 3 acute incontinence was predictive of C{sub I}NC (OR, 9.4; p = .02), and percentage of the rectal volume receiving >40 Gy of {>=}80% was predictive of a M{sub I}NC of {>=}1 (OR, 3.8; p = .008) and of C{sub I}NC (OR, 3.6; p = .03). Previous bowel disease, previous abdominal/pelvic surgery, and the use of antihypertensive (protective factor

  19. Dose Escalation to the Dominant Intraprostatic Lesion Defined by Sextant Biopsy in a Permanent Prostate I-125 Implant: A Prospective Comparative Toxicity Analysis

    SciTech Connect

    Gaudet, Marc; Vigneault, Eric; Aubin, Sylviane; Varfalvy, Nicolas; Harel, Francois; Beaulieu, L.; Martin, Andre-Guy

    2010-05-01

    Purpose: Using real-time intraoperative inverse-planned permanent seed prostate implant (RTIOP/PSI), multiple core biopsy maps, and three-dimensional ultrasound guidance, we planned a boost volume (BV) within the prostate to which hyperdosage was delivered selectively. The aim of this study was to investigate the potential negative effects of such a procedure. Methods and Materials: Patients treated with RTIOP/PSI for localized prostate cancer with topographic biopsy results received an intraprostatic boost (boost group [BG]). They were compared with patients treated with a standard plan (reference group [RG]). Plans were generated using a simulated annealing inverse planning algorithm. Prospectively recorded urinary, rectal, and sexual toxicities and dosimetric parameters were compared between groups. Results: The study included 120 patients treated with boost technique who were compared with 70 patients treated with a standard plan. Boost technique did not significantly change the number of seeds (55.1/RG vs. 53.6/BG). The intraoperative prostate V150 was slightly higher in BG (75.2/RG vs. 77.2/BG, p = 0.039). Urethra V100, urethra D90, and rectal D50 were significantly lower in the BG. No significant differences were seen in acute or late urinary, rectal, or sexual toxicities. Conclusions: Because there were no differences between the groups in acute and late toxicities, we believe that BV can be planned and delivered to the dominant intraprostatic lesion without increasing toxicity. It is too soon to say whether a boost technique will ultimately increase local control.

  20. Residual Prostate Cancer in Patients Treated With Endocrine Therapy With or Without Radical Radiotherapy: A Side Study of the SPCG-7 Randomized Trial

    SciTech Connect

    Solberg, Arne; Haugen, Olav A.; Viset, Trond; Bergh, Anders; Ahlgren, Goeran; Widmark, Anders; Angelsen, Anders

    2011-05-01

    Purpose: The Scandinavian Prostate Cancer Group-7 randomized trial demonstrated a survival benefit of combined endocrine therapy and external-beam radiotherapy over endocrine therapy alone in patients with high-risk prostate cancer. In a subset of the study population, the incidence and clinical implications of residual prostate cancer in posttreatment prostate biopsy specimens was evaluated. Methods and Materials: Biopsy specimens were obtained from 120 of 875 men in the Scandinavian Prostate Cancer Group-7 study. Results: Biopsies were performed at median of 45 months follow-up. In 63 patients receiving endocrine treatment only and 57 patients receiving combined treatment, residual cancer was found in 66% (n = 41) and 22% (n = 12), respectively (p < 0.0001). The vast majority of residual tumors were poorly differentiated (Gleason score {>=}8). Endocrine therapy alone was predictive of residual prostate cancer: odds ratio 7.49 (3.18-17.7), p < 0.0001. In patients with positive vs. negative biopsy the incidences of clinical events were as follows: biochemical recurrence 74% vs. 27% (p < 0.0001), local progression 26% vs. 4.7% (p = 0.002), distant recurrence 17% vs. 9.4% (p = 0.27), clinical recurrence 36% vs. 13% (p = 0.006), cancer-specific death 19% vs. 9.7% (p = 0.025). In multivariable analysis, biochemical recurrence was significantly associated with residual cancer: hazard ratio 2.69 (1.45-4.99), p = 0.002, and endocrine therapy alone hazard ratio 3.45 (1.80-6.62), p < 0.0001. Conclusions: Radiotherapy combined with hormones improved local tumor control in comparison with endocrine therapy alone. Residual prostate cancer was significantly associated with serum prostate-specific antigen recurrence, local tumor progression, clinical recurrence, and cancer-specific death in univariable analysis. Residual cancer was predictive of prostate-specific antigen recurrence in multivariable analysis.

  1. Interfractional Prostate Shifts: Review of 1870 Computed Tomography (CT) Scans Obtained During Image-Guided Radiotherapy Using CT-on-Rails for the Treatment of Prostate Cancer

    SciTech Connect

    Wong, James R. Gao Zhanrong; Uematsu, Minoru; Merrick, Scott; Machernis, Nolan P.; Chen, Timothy; Cheng, C.W.

    2008-12-01

    Purpose: To review 1870 CT scans of interfractional prostate shift obtained during image-guided radiotherapy. Methods and Materials: A total of 1870 pretreatment CT scans were acquired with CT-on-rails, and the corresponding shift data for 329 patients with prostate cancer were analyzed. Results: Of the 1870 scans reviewed, 44% required no setup adjustments in the anterior-posterior (AP) direction, 14% had shifts of 3-5 mm, 29% had shifts of 6-10 mm, and 13% had shifts of >10 mm. In the superior-inferior direction, 81% had no adjustments, 2% had shifts of 3-5 mm, 15% had shifts of 6-10 mm, and 2% had shifts of >10 mm. In the left-right direction, 65% had no adjustment, 13% had shifts of 3-5 mm, 17% had shifts of 6-10 mm, and 5% had shifts of >10 mm. Further analysis of the first 66 consecutive patients divided into three groups according to body mass index indicates that the shift in the AP direction for the overweight subgroup was statistically larger than those for the control and obese subgroups (p < 0.05). The interfractional shift in the lateral direction for the obese group (1 SD, 5.5 mm) was significantly larger than those for the overweight and control groups (4.1 and 2.9 mm, respectively) (p < 0.001). Conclusions: These data demonstrate that there is a significantly greater shift in the AP direction than in the lateral and superior-inferior directions for the entire patient group. Overweight and obese patient groups show a significant difference from the control group in terms of prostate shift.

  2. Effect of Gold Nanoparticles on Prostate Dose Distribution under Ir-192 Internal and 18 MV External Radiotherapy Procedures Using Gel Dosimetry and Monte Carlo Method

    PubMed Central

    Khosravi, H.; Hashemi, B.; Mahdavi, S. R.; Hejazi, P.

    2015-01-01

    Background Gel polymers are considered as new dosimeters for determining radiotherapy dose distribution in three dimensions. Objective The ability of a new formulation of MAGIC-f polymer gel was assessed by experimental measurement and Monte Carlo (MC) method for studying the effect of gold nanoparticles (GNPs) in prostate dose distributions under the internal Ir-192 and external 18MV radiotherapy practices. Method A Plexiglas phantom was made representing human pelvis. The GNP shaving 15 nm in diameter and 0.1 mM concentration were synthesized using chemical reduction method. Then, a new formulation of MAGIC-f gel was synthesized. The fabricated gel was poured in the tubes located at the prostate (with and without the GNPs) and bladder locations of the phantom. The phantom was irradiated to an Ir-192 source and 18 MV beam of a Varian linac separately based on common radiotherapy procedures used for prostate cancer. After 24 hours, the irradiated gels were read using a Siemens 1.5 Tesla MRI scanner. The absolute doses at the reference points and isodose curves resulted from the experimental measurement of the gels and MC simulations following the internal and external radiotherapy practices were compared. Results The mean absorbed doses measured with the gel in the presence of the GNPs in prostate were 15% and 8 % higher than the corresponding values without the GNPs under the internal and external radiation therapies, respectively. MC simulations also indicated a dose increase of 14 % and 7 % due to presence of the GNPs, for the same experimental internal and external radiotherapy practices, respectively. Conclusion There was a good agreement between the dose enhancement factors (DEFs) estimated with MC simulations and experiment gel measurements due to the GNPs. The results indicated that the polymer gel dosimetry method as developed and used in this study, can be recommended as a reliable method for investigating the DEF of GNPs in internal and external

  3. Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Localization of Recurrent Prostate Cancer After External Beam Radiotherapy

    SciTech Connect

    Haider, Masoom A. Chung, Peter; Sweet, Joan; Toi, Ants; Jhaveri, Kartik; Menard, Cynthia; Warde, Padraig; Trachtenberg, John; Lockwood, Gina M.Math.; Milosevic, Michael

    2008-02-01

    Purpose: To compare the performance of T2-weighted (T2w) imaging and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) of the prostate gland in the localization of recurrent prostate cancer in patients with biochemical failure after external beam radiotherapy (EBRT). Methods and Materials: T2-weighted imaging and DCE MRI were performed in 33 patients with suspected relapse after EBRT. Dynamic contrast-enhanced MRI was performed with a temporal resolution of 95 s. Voxels enhancing at 46 s after injection to a greater degree than the mean signal intensity of the prostate at 618 s were considered malignant. Results from MRI were correlated with biopsies from six regions in the peripheral zone (PZ) (base, mid, and apex). The percentage of biopsy core positive for malignancy from each region was correlated with the maximum diameter of the tumor on DCE MRI with a linear regression model. Results: On a sextant basis, DCE MRI had significantly better sensitivity (72% [21of 29] vs. 38% [11 of 29]), positive predictive value (46% [21 of 46] vs. 24% [11 of 45]) and negative predictive value (95% [144 of 152] vs. 88% [135 of 153] than T2w imaging. Specificities were high for both DCE MRI and T2w imaging (85% [144 of 169] vs. 80% [135 of 169]). There was a linear relationship between tumor diameters on DCE MRI and the percentage of cancer tissue in the corresponding biopsy core (r = 0.9, p < 0.001), with a slope of 1.2. Conclusions: Dynamic contrast-enhanced MRI performs better than T2w imaging in the detection and localization of prostate cancer in the peripheral zone after EBRT. This may be helpful in the planning of salvage therapy.

  4. Improved Biochemical Outcomes With Statin Use in Patients With High-Risk Localized Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Kollmeier, Marisa A.; Katz, Matthew S.; Mak, Kimberley; Yamada, Yoshiya; Feder, David J.; Zhang Zhigang; Jia Xiaoyu; Shi Weiji; Zelefsky, Michael J.

    2011-03-01

    Purpose: To investigate the association between 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and biochemical and survival outcomes after high-dose radiotherapy (RT) for prostate cancer. Methods and Materials: A total of 1711 men with clinical stage T1-T3 prostate cancer were treated with conformal RT to a median dose of 81 Gy during 1995-2007. Preradiotherapy medication data were available for 1681 patients. Three hundred eighty-two patients (23%) were taking a statin medication at diagnosis and throughout RT. Nine hundred forty-seven patients received a short-course of neoadjuvant and concurrent androgen-deprivation therapy (ADT) with RT. The median follow-up was 5.9 years. Results: The 5- and 8-year PSA relapse-free survival (PRFS) rates for statin patients were 89% and 80%, compared with 83% and 74% for those not taking statins (p = 0.002). In a multivariate analysis, statin use (hazard ratio [HR]0.69, p = 0.03), National Comprehensive Cancer Network (NCCN) low-risk group, and ADT use were associated with improved PRFS. Only high-risk patients in the statin group demonstrated improvement in PRFS (HR 0.52, p = 0.02). Across all groups, statin use was not associated with improved distant metastasis-free survival (DMFS) (p = 0.51). On multivariate analysis, lower NCCN risk group (p = 0.01) and ADT use (p = 0.005) predicted improved DMFS. Conclusions: Statin use during high-dose RT for clinically localized prostate cancer was associated with a significant improvement in PRFS in high-risk patients. These data suggest that statins have anticancer activity and possibly provide radiosensitization when used in conjunction with RT in the treatment of prostate cancer.

  5. Use of Local {sup 111}In-Capromab Pendetide Scan Results to Predict Outcome After Salvage Radiotherapy for Prostate Cancer

    SciTech Connect

    Koontz, Bridget F. Mouraviev, Vladimir; Johnson, Jeffrey L.; Mayes, Janice; Chen, Stephanie H.; Wong, Terence Z.; Anscher, Mitchell S.; Sun, Leon; Moul, Judd; Polascik, Thomas J.

    2008-06-01

    Purpose: The {sup 111}In-capromab pendetide scan (ProstaScint; Cytogen Corp., Princeton NJ) is approved by the Food and Drug Administration to evaluate increasing prostate-specific antigen (PSA) levels after radical prostatectomy. This study evaluated the role of prostate bed {sup 111}In-capromab pendetide scan findings to predict response to salvage radiotherapy (RT). Methods and Materials: Forty patients who had PSA recurrence after radical prostatectomy and a {sup 111}In-capromab pendetide scan immediately before salvage prostate bed RT (median, 66 Gy) were identified from the Duke Prostate Center database. Patients with distant uptake of capromab pendetide or long-term androgen deprivation therapy were excluded. Median follow-up after salvage RT was 2.7 years. Patient demographic, clinical, and pathologic characteristics; PSA values; and {sup 111}In-capromab pendetide scan results were retrospectively analyzed. A PSA failure after salvage RT was defined as PSA level greater than 0.2 ng/ml. Data were combined with other published results in a secondary pooled analysis of 106 patients. Results: {sup 111}In-Capromab pendetide findings included 20 patients with negative scan results and 20 with locally positive scan results. Two-year progression-free survival rates were 60% for patients with a negative scan result and 74% for those with a locally positive scan result (p = 0.49). Combined analysis did not show a difference in outcome based on local {sup 111}In-capromab pendetide scan result. Conclusion: For patients without distant signal detected by using {sup 111}In-capromab pendetide scan, patients with locally positive scan findings did not have statistically different progression-free survival than those with a negative scan result, suggesting that salvage RT may be successful in patients with either a locally positive or negative {sup 111}In-capromab pendetide scan result.

  6. [Use of gold radionuclide markers implanted into the prostate for image-guided radiotherapy in prostate cancer: side effects caused by the marker implantation].

    PubMed

    Kliton, Jorgo; Ágoston, Péter; Szabó, Zoltán; Major, Tibor; Polgár, Csaba

    2014-09-01

    The purpose of the study was to introduce the use of the gold radiopaque markers implanted into the prostate for image-guided radiotherapy of prostate cancer patients and to present the side effects caused by the marker implantation. Between November 2011 and November 2013, three radiopaque, gold-plated markers (Best Medical International, Springfield, VA, USA, 1.0 mm x 3.0 mm) were implanted transperineally into the prostate of 60 patients under transrectal ultrasound guidance. Local anaesthesia was performed in all patients. A week after the procedure the patients filled in a questionnaire regarding the pain, dysuria, urinary frequency, nycturia, rectal bleeding, haematuria, haematospermia or fever symptoms caused by the implantation. The pain caused by the intervention was scored on a 1-10 scale, where 1 was a very weak and 10 was an unbearable pain. Ten days after the implantation a treatment planning CT was performed and subsequently patients started intensity-modulated radiation therapy (IMRT) within one week. During the treatments markers were used for daily verification and correction of patient's setup. No patients experienced fever or infection. Based on the questionnaires nobody experienced dysuria or rectal bleeding after implantation. Among the 60 patients studied, five (8 %) had haematospermia, nine (15 %) haematuria, which lasted in average of 3.4 and 1.8 days, respectively. The average pain score on 1-10 scale was 4.2 (range: 0-9). After the marker implantation 18 patients (30%) reported less, 10 patients (17%) more, and 27 patients (45%) equal amount of pain compared to biopsy. Five patients, who had a biopsy performed under general anaesthesia, did not answer this question. None of the patients needed analgesics after implantation. The gold marker implantation implemented for image-guided radiotherapy was well tolerated under a local anaesthesia. The complications were limited, rate and frequency of perioperative pain was comparable to the pain

  7. Radiation-induced second primary cancer risks from modern external beam radiotherapy for early prostate cancer: impact of stereotactic ablative radiotherapy (SABR), volumetric modulated arc therapy (VMAT) and flattening filter free (FFF) radiotherapy

    NASA Astrophysics Data System (ADS)

    Murray, Louise J.; Thompson, Christopher M.; Lilley, John; Cosgrove, Vivian; Franks, Kevin; Sebag-Montefiore, David; Henry, Ann M.

    2015-02-01

    Risks of radiation-induced second primary cancer following prostate radiotherapy using 3D-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), flattening filter free (FFF) and stereotactic ablative radiotherapy (SABR) were evaluated. Prostate plans were created using 10 MV 3D-CRT (78 Gy in 39 fractions) and 6 MV 5-field IMRT (78 Gy in 39 fractions), VMAT (78 Gy in 39 fractions, with standard flattened and energy-matched FFF beams) and SABR (42.7 Gy in 7 fractions with standard flattened and energy-matched FFF beams). Dose-volume histograms from pelvic planning CT scans of three prostate patients, each planned using all 6 techniques, were used to calculate organ equivalent doses (OED) and excess absolute risks (EAR) of second rectal and bladder cancers, and pelvic bone and soft tissue sarcomas, using mechanistic, bell-shaped and plateau models. For organs distant to the treatment field, chamber measurements recorded in an anthropomorphic phantom were used to calculate OEDs and EARs using a linear model. Ratios of OED give relative radiation-induced second cancer risks. SABR resulted in lower second cancer risks at all sites relative to 3D-CRT. FFF resulted in lower second cancer risks in out-of-field tissues relative to equivalent flattened techniques, with increasing impact in organs at greater distances from the field. For example, FFF reduced second cancer risk by up to 20% in the stomach and up to 56% in the brain, relative to the equivalent flattened technique. Relative to 10 MV 3D-CRT, 6 MV IMRT or VMAT with flattening filter increased second cancer risks in several out-of-field organs, by up to 26% and 55%, respectively. For all techniques, EARs were consistently low. The observed large relative differences between techniques, in absolute terms, were very low, highlighting the importance of considering absolute risks alongside the corresponding relative risks, since when absolute

  8. Carbon-ion radiotherapy for locally advanced or unfavorably located choroidal melanoma: A Phase I/II dose-escalation study

    SciTech Connect

    Tsuji, Hiroshi . E-mail: h_tsuji@nirs.go.jp; Ishikawa, Hitoshi; Yanagi, Takeshi; Hirasawa, Naoki; Kamada, Tadashi; Mizoe, Jun-Etsu; Kanai, Tatsuaki; Tsujii, Hirohiko; Ohnishi, Yoshitaka

    2007-03-01

    Purpose: To evaluate the applicability of carbon ion beams for the treatment of choroidal melanoma with regard to normal tissue morbidity and local tumor control. Methods and Materials: Between January 2001 and February 2006, 59 patients with locally advanced or unfavorably located choroidal melanoma were enrolled in a Phase I/II clinical trial of carbon-ion radiotherapy at the National Institute of Radiologic Sciences. The primary endpoint of this study was normal tissue morbidity, and secondary endpoints were local tumor control and patient survival. Of the 59 subjects enrolled, 57 were followed >6 months and analyzed. Results: Twenty-three patients (40%) developed neovascular glaucoma, and three underwent enucleation for eye pain due to elevated intraocular pressure. Incidence of neovascular glaucoma was dependent on tumor size and site. Five patients had died at analysis, three of distant metastasis and two of concurrent disease. All but one patient, who developed marginal recurrence, were controlled locally. Six patients developed distant metastasis, five in the liver and one in the lung. Three-year overall survival, disease-free survival, and local control rates were 88.2%, 84.8%, and 97.4%, respectively. No apparent dose-response relationship was observed in either tumor control or normal tissue morbidity at the dose range applied. Conclusion: Carbon-ion radiotherapy can be applied to choroidal melanoma with an acceptable morbidity and sufficient antitumor effect, even with tumors of unfavorable size or site.

  9. High-Dose Conformal Radiotherapy Reduces Prostate Cancer-Specific Mortality: Results of a Meta-analysis

    SciTech Connect

    Viani, Gustavo Arruda; Godoi Bernardes da Silva, Lucas; Stefano, Eduardo Jose

    2012-08-01

    Purpose: To determine in a meta-analysis whether prostate cancer-specific mortality (PCSM), biochemical or clinical failure (BCF), and overall mortality (OM) in men with localized prostate cancer treated with conformal high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT). Methods and Materials: The MEDLINE, Embase, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing conformal HDRT with CDRT for localized prostate cancer. Results: Five randomized, controlled trials (2508 patients) that met the study criteria were identified. Pooled results from these randomized, controlled trials showed a significant reduction in the incidence of PCSM and BCF rates at 5 years in patients treated with HDRT (p = 0.04 and p < 0.0001, respectively), with an absolute risk reduction (ARR) of PCSM and BCF at 5 years of 1.7% and 12.6%, respectively. Two trials evaluated PCSM with 10 years of follow up. The pooled results from these trials showed a statistical benefit for HDRT in terms of PCSM (p = 0.03). In the subgroup analysis, trials that used androgen deprivation therapy (ADT) showed an ARR for BCF of 12.9% (number needed to treat = 7.7, p < 0.00001), whereas trials without ADT had an ARR of 13.6% (number needed to treat = 7, p < 0.00001). There was no difference in the OM rate at 5 and 10 years (p = 0.99 and p = 0.11, respectively) between the groups receiving HDRT and CDRT. Conclusions: This meta-analysis is the first study to show that HDRT is superior to CDRT in preventing disease progression and prostate cancer-specific death in trials that used conformational technique to increase the total dose. Despite the limitations of our study in evaluating the role of ADT and HDRT, our data show no benefit for HDRT arms in terms of BCF in trials with or without ADT.

  10. An adaptive MR-CT registration method for MRI-guided prostate cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Zhong, Hualiang; Wen, Ning; Gordon, James J.; Elshaikh, Mohamed A.; Movsas, Benjamin; Chetty, Indrin J.

    2015-04-01

    Magnetic Resonance images (MRI) have superior soft tissue contrast compared with CT images. Therefore, MRI might be a better imaging modality to differentiate the prostate from surrounding normal organs. Methods to accurately register MRI to simulation CT images are essential, as we transition the use of MRI into the routine clinic setting. In this study, we present a finite element method (FEM) to improve the performance of a commercially available, B-spline-based registration algorithm in the prostate region. Specifically, prostate contours were delineated independently on ten MRI and CT images using the Eclipse treatment planning system. Each pair of MRI and CT images was registered with the B-spline-based algorithm implemented in the VelocityAI system. A bounding box that contains the prostate volume in the CT image was selected and partitioned into a tetrahedral mesh. An adaptive finite element method was then developed to adjust the displacement vector fields (DVFs) of the B-spline-based registrations within the box. The B-spline and FEM-based registrations were evaluated based on the variations of prostate volume and tumor centroid, the unbalanced energy of the generated DVFs, and the clarity of the reconstructed anatomical structures. The results showed that the volumes of the prostate contours warped with the B-spline-based DVFs changed 10.2% on average, relative to the volumes of the prostate contours on the original MR images. This discrepancy was reduced to 1.5% for the FEM-based DVFs. The average unbalanced energy was 2.65 and 0.38 mJ cm-3, and the prostate centroid deviation was 0.37 and 0.28 cm, for the B-spline and FEM-based registrations, respectively. Different from the B-spline-warped MR images, the FEM-warped MR images have clear boundaries between prostates and bladders, and their internal prostatic structures are consistent with those of the original MR images. In summary, the developed adaptive FEM method preserves the prostate volume

  11. Interfraction rotation of the prostate as evaluated by kilovoltage X-ray fiducial marker imaging in intensity-modulated radiotherapy of localized prostate cancer.

    PubMed

    Graf, Reinhold; Boehmer, Dirk; Budach, Volker; Wust, Peter

    2012-01-01

    To quantify the daily rotation of the prostate during a radiotherapy course using stereoscopic kilovoltage (kV) x-ray imaging and intraprostatic fiducials for localization and positioning correction. From 2005 to 2009, radio-opaque fiducial markers were inserted into 38 patients via perineum into the prostate. The ExacTrac/Novalis Body X-ray 6-day image acquisition system (ET/NB; BrainLab AG, Feldkirchen, Germany) was used to determine and correct the target position. During the first period in 10 patients we recorded all rotation errors but used only Y (table) for correction. For the next 28 patients we used for correction all rotational coordinates, i.e., in addition Z (superior-inferior [SI] or roll) and X (left-right [LR] or tilt/pitch) according to the fiducial marker position by use of the Robotic Tilt Module and Varian Exact Couch. Rotation correction was applied above a threshold of 1° displacement. The systematic and random errors were specified. Overall, 993 software-assisted rotational corrections were performed. The interfraction rotation errors of the prostate as assessed from the radiodense surrogate markers around the three axes Y, Z, and X were on average 0.09, -0.52, and -0.01° with standard deviations of 2.01, 2.30, and 3.95°, respectively. The systematic uncertainty per patient for prostate rotation was estimated with 2.30, 1.56, and 4.13° and the mean random components with 1.81, 2.02, and 3.09°. The largest rotational errors occurred around the X-axis (pitch), but without preferring a certain orientation. Although the error around Z (roll) can be compensated on average by a transformation with 4 coordinates, a significant error around X remains and advocates the full correction with 6 coordinates. Rotational errors as assessed via daily stereoscopic online imaging are significant and dominate around X. Rotation possibly degrades the dosimetric coverage of the target volume and may require suitable strategies for correction. PMID:22534137

  12. Interfraction rotation of the prostate as evaluated by kilovoltage X-ray fiducial marker imaging in intensity-modulated radiotherapy of localized prostate cancer

    SciTech Connect

    Graf, Reinhold; Boehmer, Dirk; Budach, Volker; Wust, Peter

    2012-01-01

    To quantify the daily rotation of the prostate during a radiotherapy course using stereoscopic kilovoltage (kV) x-ray imaging and intraprostatic fiducials for localization and positioning correction. From 2005 to 2009, radio-opaque fiducial markers were inserted into 38 patients via perineum into the prostate. The ExacTrac/Novalis Body X-ray 6-day image acquisition system (ET/NB; BrainLab AG, Feldkirchen, Germany) was used to determine and correct the target position. During the first period in 10 patients we recorded all rotation errors but used only Y (table) for correction. For the next 28 patients we used for correction all rotational coordinates, i.e., in addition Z (superior-inferior [SI] or roll) and X (left-right [LR] or tilt/pitch) according to the fiducial marker position by use of the Robotic Tilt Module and Varian Exact Couch. Rotation correction was applied above a threshold of 1 Degree-Sign displacement. The systematic and random errors were specified. Overall, 993 software-assisted rotational corrections were performed. The interfraction rotation errors of the prostate as assessed from the radiodense surrogate markers around the three axes Y, Z, and X were on average 0.09, -0.52, and -0.01 Degree-Sign with standard deviations of 2.01, 2.30, and 3.95 Degree-Sign , respectively. The systematic uncertainty per patient for prostate rotation was estimated with 2.30, 1.56, and 4.13 Degree-Sign and the mean random components with 1.81, 2.02, and 3.09 Degree-Sign . The largest rotational errors occurred around the X-axis (pitch), but without preferring a certain orientation. Although the error around Z (roll) can be compensated on average by a transformation with 4 coordinates, a significant error around X remains and advocates the full correction with 6 coordinates. Rotational errors as assessed via daily stereoscopic online imaging are significant and dominate around X. Rotation possibly degrades the dosimetric coverage of the target volume and may require

  13. Proton Radiotherapy for Pediatric Bladder/Prostate Rhabdomyosarcoma: Clinical Outcomes and Dosimetry Compared to Intensity-Modulated Radiation Therapy

    SciTech Connect

    Cotter, Shane E.; Herrup, David A.; Friedmann, Alison; Macdonald, Shannon M.; Pieretti, Raphael V.; Robinson, Gregoire; Adams, Judith; Tarbell, Nancy J.; Yock, Torunn I.

    2011-12-01

    Purpose: In this study, we report the clinical outcomes of 7 children with bladder/prostate rhabdomyosarcoma (RMS) treated with proton radiation and compare proton treatment plans with matched intensity-modulated radiation therapy (IMRT) plans, with an emphasis on dose savings to reproductive and skeletal structures. Methods and Materials: Follow-up consisted of scheduled clinic appointments at our institution or direct communication with the treating physicians for referred patients. Each proton radiotherapy plan used for treatment was directly compared to an IMRT plan generated for the study. Clinical target volumes and normal tissue volumes were held constant to facilitate dosimetric comparisons. Each plan was optimized for target coverage and normal tissue sparing. Results: Seven male patients were treated with proton radiotherapy for bladder/prostate RMS at the Massachusetts General Hospital between 2002 and 2008. Median age at treatment was 30 months (11-70 months). Median follow-up was 27 months (10-90 months). Four patients underwent a gross total resection prior to radiation, and all patients received concurrent chemotherapy. Radiation doses ranged from 36 cobalt Gray equivalent (CGE) to 50.4 CGE. Five of 7 patients were without evidence of disease and with intact bladders at study completion. Target volume dosimetry was equivalent between the two modalities for all 7 patients. Proton radiotherapy led to a significant decrease in mean organ dose to the bladder (25.1 CGE vs. 33.2 Gy; p = 0.03), testes (0.0 CGE vs. 0.6 Gy; p = 0.016), femoral heads (1.6 CGE vs. 10.6 Gy; p = 0.016), growth plates (21.7 CGE vs. 32.4 Gy; p = 0.016), and pelvic bones (8.8 CGE vs. 13.5 Gy; p = 0.016) compared to IMRT. Conclusions: This study provides evidence of significant dose savings to normal structures with proton radiotherapy compared to IMRT and is well tolerated in this patient population. The long-term impact of these reduced doses can be tested in future studies

  14. Health-Related Quality of Life in Patients With Locally Advanced Prostate Cancer After 76 Gy Intensity-Modulated Radiotherapy vs. 70 Gy Conformal Radiotherapy in a Prospective and Longitudinal Study

    SciTech Connect

    Lips, Irene Dehnad, Human; Kruger, Arto Boeken; Moorselaar, Jeroen van; Heide, Uulke van; Battermann, Jan; Vulpen, Marco van

    2007-11-01

    Purpose: To compare quality of life (QoL) after 70 Gy conformal radiotherapy with QoL after 76 Gy intensity-modulated radiotherapy (IMRT) in patients with locally advanced prostate carcinoma. Methods and Materials: Seventy-eight patients with locally advanced prostate cancer were treated with 70 Gy three-field conformal radiotherapy, and 92 patients received 76 Gy IMRT with fiducial markers for position verification. Quality of life was measured by RAND-36, the European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30(+3)), and the prostate-specific EORTC QLQ-PR25, before radiotherapy (baseline) and 1 month and 6 months after treatment. Quality of life changes in time (baseline vs. 1 month and baseline vs. 6 months) of {>=}10 points were considered clinically relevant. Results: Differences between the treatment groups for QoL changes over time occurred in several QoL domains. The 76-Gy group revealed no significant deterioration in QoL compared with the 70-Gy group. The IMRT 76-Gy group even demonstrated a significantly better change in QoL from baseline to 1 month in several domains. The conformal 70-Gy group revealed temporary deterioration in pain, role functioning, and urinary symptoms; for the IMRT 76-Gy group a better QoL in terms of change in health existed after 1 month, which persisted after 6 months. For both treatment groups temporary deterioration in physical role restriction occurred after 1 month, and an improvement in emotional role restriction occurred after 6 months. Sexual activity was reduced after treatment for both groups and remained decreased after 6 months. Conclusions: Intensity-modulated radiotherapy and accurate position verification seem to provide a possibility to increase the radiation dose for prostate cancer without deterioration in QoL.

  15. Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance

    PubMed Central

    2014-01-01

    Background Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated with daily image-guided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa). Methods A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1–2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5–7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT. Results The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p < 0.001). For GU toxicity the numbers were 41.8% and 29.7%, respectively (p = 0.011). On multivariate analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p < 0.001, HR = 11.59 [CI: 6.67-20.14]). 3DCRT was also associated with an increased risk of developing GU toxicity compared to IG-IMRT. The 3-year actuarial biochemical progression-free survival probability was 86.0% for 3DCRT and 90.3% for IG-IMRT (p = 0.386). On multivariate analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT. Conclusion The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction. PMID:24495815

  16. Coplanar intensity-modulated radiotherapy class solution for patients with prostate cancer with bilateral hip prostheses with and without nodal involvement

    SciTech Connect

    Lee, Young K.; McVey, Gerard P.; South, Chris P.; Dearnaley, David P.

    2013-07-01

    Dose distributions for prostate radiotherapy are difficult to predict in patients with bilateral hip prostheses in situ, due to image distortions and difficulty in dose calculation. The feasibility of delivering curative doses to prostate using intensity-modulated radiotherapy (IMRT) in patients with bilateral hip prostheses was evaluated. Planning target volumes for prostate only (PTV1) and pelvic nodes (PTV2) were generated from data on 5 patients. PTV1 and PTV2 dose prescriptions were 70 Gy and 60 Gy, respectively, in 35 fractions, and an additional nodal boost of 65 Gy was added for 1 plan. Rectum, bladder, and bowel were also delineated. Beam angles and segments were chosen to best avoid entering through the prostheses. Dose-volume data were assessed with respect to clinical objectives. The plans achieved the required prescription doses to the PTVs. Five-field IMRT plans were adequate for patients with relatively small prostheses (head volumes<60 cm{sup 3}) but 7-field plans were required for patients with larger prostheses. Bowel and bladder doses were clinically acceptable for all patients. Rectal doses were deemed clinically acceptable, although the V{sub 50} {sub Gy} objective was not met for 4/5 patients. We describe an IMRT solution for patients with bilateral hip prostheses of varying size and shape, requiring either localized or whole pelvic radiotherapy for prostate cancer.

  17. Escalator design features evaluation

    NASA Technical Reports Server (NTRS)

    Zimmerman, W. F.; Deshpande, G. K.

    1982-01-01

    Escalators are available with design features such as dual speed (90 and 120 fpm), mat operation and flat steps. These design features were evaluated based on the impact of each on capital and operating costs, traffic flow, and safety. A human factors engineering model was developed to analyze the need for flat steps at various speeds. Mat operation of escalators was found to be cost effective in terms of energy savings. Dual speed operation of escalators with the higher speed used during peak hours allows for efficient operation. A minimum number of flat steps required as a function of escalator speed was developed to ensure safety for the elderly.

  18. Multivariate analysis of factors predicting prostate dose in intensity-modulated radiotherapy

    SciTech Connect

    Tomita, Tsuneyuki; Nakamura, Mitsuhiro; Hirose, Yoshinori; Kitsuda, Kenji; Notogawa, Takuya; Miki, Katsuhito; Nakamura, Kiyonao; Ishigaki, Takashi

    2014-01-01

    We conducted a multivariate analysis to determine relationships between prostate radiation dose and the state of surrounding organs, including organ volumes and the internal angle of the levator ani muscle (LAM), based on cone-beam computed tomography (CBCT) images after bone matching. We analyzed 270 CBCT data sets from 30 consecutive patients receiving intensity-modulated radiation therapy for prostate cancer. With patients in the supine position on a couch with the HipFix system, data for center of mass (COM) displacement of the prostate and the state of individual organs were acquired and compared between planning CT and CBCT scans. Dose distributions were then recalculated based on CBCT images. The relative effects of factors on the variance in COM, dose covering 95% of the prostate volume (D{sub 95%}), and percentage of prostate volume covered by the 100% isodose line (V{sub 100%}) were evaluated by a backward stepwise multiple regression analysis. COM displacement in the anterior-posterior direction (COM{sub AP}) correlated significantly with the rectum volume (δVr) and the internal LAM angle (δθ; R = 0.63). Weak correlations were seen for COM in the left-right (R = 0.18) and superior-inferior directions (R = 0.31). Strong correlations between COM{sub AP} and prostate D{sub 95%} and V{sub 100%} were observed (R ≥ 0.69). Additionally, the change ratios in δVr and δθ remained as predictors of prostate D{sub 95%} and V{sub 100%}. This study shows statistically that maintaining the same rectum volume and LAM state for both the planning CT simulation and treatment is important to ensure the correct prostate dose in the supine position with bone matching.

  19. Avascular Necrosis of the Femoral Head After Palliative Radiotherapy in Metastatic Prostate Cancer: Absence of a Dose Threshold?

    PubMed

    Daoud, Alia M; Hudson, Mack; Magnus, Kenneth G; Huang, Fleur; Danielson, Brita L; Venner, Peter; Saluja, Ronak; LeGuerrier, Bronwen; Daly, Helene; Emmenegger, Urban; Fairchild, Alysa

    2016-01-01

    Avascular necrosis (AVN) is the final common pathway resulting from insufficient blood supply to bone, commonly the femoral head. There are many postulated etiologies of non-traumatic AVN, including corticosteroids, bisphosphonates, and radiotherapy (RT). However, it is unclear whether there is a dose threshold for the development of RT-induced AVN. In this case report, we describe a patient with prostate cancer metastatic to bone diagnosed with AVN after receiving single-fraction palliative RT to the left femoral head. Potential contributing factors are discussed, along with a review of other reported cases. At present, the RT dose threshold below which there is no risk for AVN is unknown, and therefore detrimental impact from the RT cannot be excluded. Given the possibility that RT-induced AVN is a stochastic effect, it is important to be aware of the possibility of this diagnosis in any patient with a painful hip who has received RT to the femoral head. PMID:27081582

  20. Image-guided radiotherapy of the prostate using daily CBCT: the feasibility and likely benefit of implementing a margin reduction

    PubMed Central

    Benson, R J; Fairfoul, J; Cook, J; Huddart, R; Poynter, A

    2014-01-01

    Objective: To investigate whether planning target volume (PTV) margins may be safely reduced in radiotherapy of localized prostate cancer incorporating daily online tube potential-cone beam CT (CBCT) image guidance and the anticipated benefit in predicted rectal toxicity. Methods: The prostate-only clinical target volume (CTV2) and rectum were delineated on 1 pre-treatment CBCT each week in 18 randomly selected patients. By transposing these contours onto the original plan, dose–volume histograms (DVHs) for CTV2 and the rectum were each calculated and combined, for each patient, to produce a single mean DVH representative of the dose delivered over the treatment course. Plans were reoptimized using reduced CTV2 to PTV2 margins and the consequent radiobiological impact modelled by the tumour control probability (TCP) and normal tissue complication probability (NTCP) of the rectum. Results: All CBCT images were deemed of sufficient quality to identify the CTV and rectum. No loss of TCP was observed when plans using the standard 5-mm CTV2 to PTV2 margin of the centre were reoptimized with a 4- or 3-mm margin. Margin reduction was associated with a significant decrease in rectal NTCP (5–4 mm; p < 0.05 and 5–3 mm; p < 0.01). Conclusion: Using daily online image guidance with CBCT, a reduction in CTV2 to PTV2 margins to 3 mm is achievable without compromising tumour control. The consequent sparing of surrounding normal tissues is associated with reduced anticipated rectal toxicity. Advances in knowledge: Margin reduction is feasible and potentially beneficial. Centres with image-guided radiotherapy capability should consider assessing whether margin reduction is possible within their institutes. PMID:25354015

  1. A Phase II Trial of Arc-Based Hypofractionated Intensity-Modulated Radiotherapy in Localized Prostate Cancer

    SciTech Connect

    Lock, Michael; Best, Lara; Wong, Eugene; Bauman, Glenn; D'Souza, David; Venkatesan, Varagur; Sexton, Tracy; Ahmad, Belal; Izawa, Jonathan; Rodrigues, George

    2011-08-01

    Purpose: To evaluate acute and late genitourinary (GU) and gastrointestinal (GI) toxicity and biochemical control of hypofractionated, image-guided (fiducial markers or ultrasound guidance), simplified intensity-modulated arc therapy for localized prostate cancer. Methods and Materials: This Phase II prospective clinical trial for T1a-2cNXM0 prostate cancer enrolled 66 patients who received 63.2 Gy in 20 fractions over 4 weeks. Fiducial markers were used for image guidance in 30 patients and daily ultrasound for the remainder. Toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Results: Median follow-up was 36 months. Acute Phase Grade 2 and 3 toxicity was 34% and 9% for GU vs. 25% and 10% for GI symptoms. One Grade 4 acute GI toxicity occurred in a patient with unrecognized Crohn's disease. Late Grade 2 and 3 toxicity for GU was 14% and 5%, and GI toxicity was 25% and 3%. One late GI Grade 4 toxicity was observed in a patient with significant comorbidities (anticoagulation, vascular disease). Acute GI toxicity {>=}Grade 2 was shown to be a predictor for late toxicity Grade {>=}2 (p < 0.001). The biochemical disease-free survival at 3 years was 95%. Conclusions: Hypofractionated simplified intensity-modulated arc therapy radiotherapy given as 63.2 Gy in 20 fractions demonstrated promising biochemical control rates; however, higher rates of acute Grade 3 GU and GI toxicity and higher late Grade 2 GU and GI toxicity were noted. Ongoing randomized controlled trials should ultimately clarify issues regarding patient selection and the true rate of severe toxicity that can be directly attributed to hypofractionated radiotherapy.

  2. Prolongation of Total Treatment Time Because of Infrequently Missed Days of Treatment Is Not Associated With Inferior Biochemical Outcome After Dose-Escalated Radiation Therapy for Prostate Cancer

    SciTech Connect

    Liauw, Stanley L.; Liauw, Sun H.

    2011-11-01

    Purpose: Prolongation of treatment time with radiation therapy (RT) is associated with inferior disease control for many rapidly proliferating tumors, but it is uncertain whether the same effect is seen in prostate cancer. Methods and Materials: 596 patients underwent with curative-intent RT for adenocarcinoma of the prostate. By National Comprehensive Cancer Network criteria, men were classified as having low-risk (30%), medium-risk (40%), or high-risk (30%) disease. The median RT dose was 72 Gy. Androgen-deprivation therapy (ADT) was used in 45%. The idealized treatment time was defined as the total elapsed time (including weekends) to complete treatment if started on a Monday. Missed days of treatment, defined as the number of days beyond the idealized treatment time, was recorded for all patients. Missed days were added to the end of therapy resulting in a longer treatment time. Analysis was conducted for missed days and other standard prognostic variables against freedom from biochemical failure (FFBF). Results: The median number of missed days was 2 (range, -3 to 22). With a median follow-up of 51 months, men with 5 or more missed days had similar 4-year FFBF rates (79% vs. 83% in men with <5 missed days, p = 0.0809), especially in the subset of men receiving 74 Gy or greater (89% for both groups, p = 0.8008). Analysis of missed days was performed for the subsets of dose, ADT, and risk category. Men without ADT had a lower FFBF rate with more missed days (p = 0.0030), but this association was not seen in men treated to a dose of 74 Gy or greater (p = 0.7425). On multivariate analysis, dose (p = 0.0010), T stage (p = 0.0145), and prostate-specific antigen level (p < 0.0001) were associated with FFBF, but Gleason score (p = 0.1351) and missed days (p = 0.3767) were not. Conclusions: Slight prolongation of treatment time (e.g., {<=}7 days) was not associated with inferior FFBF, especially in men receiving an RT dose of 74 Gy or greater.

  3. Determination of action thresholds for electromagnetic tracking system-guided hypofractionated prostate radiotherapy using volumetric modulated arc therapy

    SciTech Connect

    Zhang, Pengpeng; Mah, Dennis; Happersett, Laura; Cox, Brett; Hunt, Margie; Mageras, Gig

    2011-07-15

    Purpose: Hypofractionated prostate radiotherapy may benefit from both volumetric modulated arc therapy (VMAT) due to shortened treatment time and intrafraction real-time monitoring provided by implanted radiofrequency(RF) transponders. The authors investigate dosimetrically driven action thresholds (whether treatment needs to be interrupted and patient repositioned) in VMAT treatment with electromagnetic (EM) tracking. Methods: VMAT plans for five patients are generated for prescription doses of 32.5 and 42.5 Gy in five fractions. Planning target volume (PTV) encloses the clinical target volume (CTV) with a 3 mm margin at the prostate-rectal interface and 5 mm elsewhere. The VMAT delivery is modeled using 180 equi-spaced static beams. Intrafraction prostate motion is simulated in the plan by displacing the beam isocenter at each beam assuming rigid organ motion according to a previously recorded trajectory of the transponder centroid. The cumulative dose delivered in each fraction is summed over all beams. Two sets of 57 prostate motion trajectories were randomly selected to form a learning and a testing dataset. Dosimetric end points including CTV D95%, rectum wall D1cc, bladder wall D1cc, and urethra Dmax, are analyzed against motion characteristics including the maximum amplitude of the anterior-posterior (AP), superior-inferior (SI), and left-right components. Action thresholds are triggered when intrafraction motion causes any violations of dose constraints to target and organs at risk (OAR), so that treatment is interrupted and patient is repositioned. Results: Intrafraction motion has a little effect on CTV D95%, indicating PTV margins are adequate. Tight posterior and inferior action thresholds around 1 mm need to be set in a patient specific manner to spare organs at risk, especially when the prescription dose is 42.5 Gy. Advantages of setting patient specific action thresholds are to reduce false positive alarms by 25% when prescription dose is low, and

  4. Equivalent Biochemical Control and Improved Prostate-Specific Antigen Nadir After Permanent Prostate Seed Implant Brachytherapy Versus High-Dose Three-Dimensional Conformal Radiotherapy and High-Dose Conformal Proton Beam Radiotherapy Boost

    SciTech Connect

    Jabbari, Siavash; Weinberg, Vivian K.; Shinohara, Katsuto; Speight, Joycelyn L.; Gottschalk, Alexander R.; Hsu, I.-C.; Pickett, Barby; McLaughlin, Patrick W.; Sandler, Howard M.; Roach, Mack

    2010-01-15

    Purpose: Permanent prostate implant brachytherapy (PPI), three-dimensional conformal radiotherapy (3D-CRT), and conformal proton beam radiotherapy (CPBRT) are used in the treatment of localized prostate cancer, although no head-to-head trials have compared these modalities. We studied the biochemical control (biochemical no evidence of disease [bNED]) and prostate-specific antigen (PSA) nadir achieved with contemporary PPI, and evaluated it against 3D-CRT and CPBRT. Patients and Methods: A total of 249 patients were treated with PPI at the University of California, San Francisco, and the outcomes were compared with those from a 3D-CRT cohort and the published results of a high-dose CPBRT boost (CPBRTB) trial. For each comparison, subsets of the PPI cohort were selected with patient and disease criteria similar to those of the reference group. Results: With a median follow-up of 5.3 years, the bNED rate at 5 and 7 years achieved with PPI was 92% and 86%, respectively, using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, and 93% using the PSA nadir plus 2 ng/mL definition. Using the ASTRO definition, a 5-year bNED rate of 78% was achieved for the 3D-CRT patients compared with 94% for a comparable PPI subset and 93% vs. 92%, respectively, using the PSA nadir plus 2 ng/mL definition. The median PSA nadir for patients treated with PPI and 3D-CRT was 0.10 and 0.40 ng/mL, respectively (p < .0001). For the CPBRT comparison, the 5-year bNED rate after a CPBRTB was 91% using the ASTRO definition vs. 93% for a similar group of PPI patients. A greater proportion of PPI patients achieved a lower PSA nadir compared with those achieved in the CPBRTB trial (PSA nadir <=0.5 ng/mL, 91% vs. 59%, respectively). Conclusion: We have demonstrated excellent outcomes in low- to intermediate-risk patients treated with PPI, suggesting at least equivalent 5-year bNED rates and a greater proportion of men achieving lower PSA nadirs compared with 3D-CRT or

  5. Long-Term PSA Control with Repeated Stereotactic Body Radiotherapy in a Patient with Oligometastatic Castration-Resistant Prostate Cancer.

    PubMed

    Pasqualetti, Francesco; Cocuzza, Paola; Coraggio, Gabriele; Ferrazza, Patrizia; Derosa, Lisa; Galli, Luca; Pasqualetti, Giuseppe; Locantore, Luisa; Boni, Roberto; Fabrini, Maria G; Erba, Paola A

    2016-01-01

    Prostate cancer (PCa) is one of the most common malignancies and main causes of cancer death in Western countries. In the presence of metastatic disease, systemic treatment remains the main clinical option. However, since the introduction of highly sensitive imaging techniques, a new clinical 'entity' of metastatic patients with a limited number of lesions has been defined: oligometastatic patients. In this patient group, the use of stereotactic body radiotherapy (SBRT) or other local therapies against all active sites of disease revealed by 18F-choline positron emission tomography/computed tomography (PET/CT) could achieve sufficient prostate-specific antigen (PSA) control. However, a clear benefit of this procedure in terms of significant endpoints is yet to be demonstrated. This case report describes our experience with treating a castration-resistant PCa patient with 18F-choline PET/CT-guided SBRT. Because of the occurrence of 5 metachronous lesions over 4 years, the pattern of recurrence was defined by the local multidisciplinary team as oligometastatic disease, and the patient was treated with 5 courses of SBRT which yielded good PSA control. He started systemic therapy with abiraterone acetate almost 5 years after the diagnosis of recurrent PCa. PMID:27160394

  6. Split-Course, High-Dose Palliative Pelvic Radiotherapy for Locally Progressive Hormone-Refractory Prostate Cancer

    SciTech Connect

    Gogna, Nirdosh Kumar; Baxi, Siddhartha; Hickey, Brigid; Baumann, Kathryn; Burmeister, Elizabeth; Holt, Tanya

    2012-06-01

    Purpose: Local progression, in patients with hormone-refractory prostate cancer, often causes significant morbidity. Pelvic radiotherapy (RT) provides effective palliation in this setting, with most published studies supporting the use of high-dose regimens. The aim of the present study was to examine the role of split-course hypofractionated RT used at our institution in treating this group of patients. Methods and Materials: A total of 34 men with locoregionally progressive hormone-refractory prostate cancer, treated with a split course of pelvic RT (45-60 Gy in 18-24 fractions) between 2000 and 2008 were analyzed. The primary endpoints were the response rate and actuarial locoregional progression-free survival. Secondary endpoints included overall survival, compliance, and acute and late toxicity. Results: The median age was 71 years (range, 53-88). Treatment resulted in an overall initial response rate of 91%, a median locoregional progression-free survival of 43 months, and median overall survival of 28 months. Compliance was excellent and no significant late toxicity was reported. Conclusions: The split course pelvic RT described has an acceptable toxicity profile, is effective, and compares well with other high-dose palliative regimens that have been previously reported.

  7. Radiotherapy for prostate carcinoma: the JCRT experience (1968-1978). II. Factors related to tumor control and complications

    SciTech Connect

    Rosen, E.; Cassady, J.R.; Connolly, J.; Chaffey, J.T.

    1985-04-01

    The authors have analyzed treatment failure and complications as a function of radiotherapy technique and other factors in 229 patients irradiated for prostate carcinoma from 1968-1978. Thirty-four patients (15%) developed clinical evidence of local-regional recurrence. In about one- quarter of these recurrences, there was a component of ureteral obstruction, possibly due to marginal miss in the seminal vesicles. Although different parameters of treatment technique were not significantly correlated with local failure, there was a trend toward higher failure rates for Stage B and C patients when the length and/or width of the conedown field was less than 8 cm (p = 0.27 and 0.25, respectively). As in other recent studies, patients with Stage C disease who had undergone trans-urethral resection of the prostate had a lower disease-free survival rate than patients who had only needle biopsy (39 vs. 65% at 5 years, p = 0.055). The use of larger initial fields treating the pelvic lymph nodes did not result in better local tumor control or better overall control. However, the use of larger fields did result in a higher rate of significant complications (8.7 vs. 1.6% for fields greater than or equal to 150 cm2 or less than 150 cm2, respectively, p = 0.013). In view of the higher complication rate and the absence of convincing evidence of benefit for whole pelvic treatment, irradiation of all pelvic lymph nodes can be questioned.

  8. SU-E-J-20: Adaptive Aperture Morphing for Online Correction for Prostate Cancer Radiotherapy

    SciTech Connect

    Sandhu, R; Qin, A; Yan, D

    2014-06-01

    Purpose: Online adaptive aperture morphing is desirable over translational couch shifts to accommodate not only the target position variation but also anatomic changes (rotation, deformation, and relation of target to organ-atrisks). We proposed quick and reliable method for adapting segment aperture leaves for IMRT treatment of prostate. Methods: The proposed method consists of following steps: (1) delineate the contours of prostate, SV, bladder and rectum on kV-CBCT; (2) determine prostate displacement from the rigid body registration of the contoured prostate manifested on the reference CT and the CBCT; (3) adapt the MLC segment apertures obtained from the pre-treatment IMRT planning to accommodate the shifts as well as anatomic changes. The MLC aperture adaptive algorithm involves two steps; first move the whole aperture according to prostate translational/rotational shifts, and secondly fine-tune the aperture shape to maintain the spatial relationship between the planning target contour and the MLC aperture to the daily target contour. Feasibility of this method was evaluated retrospectively on a seven-field IMRT treatment of prostate cancer patient by comparing dose volume histograms of the original plan and the aperture-adjusted plan, with/without additional segments weight optimization (SWO), on two daily treatment CBCTs selected with relative large motion and rotation. Results: For first daily treatment, the prostate rotation was significant (12degree around lateral-axis). With apertureadjusted plan, the D95 to the target was improved 25% and rectum dose (D30, D40) was reduced 20% relative to original plan on daily volumes. For second treatment-fraction, (lateral shift = 6.7mm), after adjustment target D95 improved by 3% and bladder dose (D30, maximum dose) was reduced by 1%. For both cases, extra SWO did not provide significant improvement. Conclusion: The proposed method of adapting segment apertures is promising in treatment position correction

  9. Differences in toxicity and outcome associated with circadian variations between patients undergoing daytime and evening radiotherapy for prostate adenocarcinoma.

    PubMed

    Hsu, Feng-Ming; Hou, Wei-Hsien; Huang, Chao-Yuan; Wang, Chia-Chun; Tsai, Chiao-Ling; Tsai, Yu-Chieh; Yu, Hong-Jeng; Pu, Yeong-Shiau; Cheng, Jason Chia-Hsien

    2016-01-01

    This retrospective study tested the hypothesis that disease control and treatment-related toxicity in patients undergoing high-dose radiotherapy (HDRT) for prostate cancer varies in a circadian manner. Patients with localized prostate adenocarcinoma receiving HDRT (median 78 Gy) to the prostate and involved seminal vesicle(s) without elective pelvic irradiation were divided into a daytime treatment (before 5 PM) group (n = 267) and evening treatment (after 5 PM) group (n = 142). Biochemical failure (Phoenix definition), acute and late gastrointestinal (GI) and genitourinary toxicities (Common Terminology Criteria for Adverse Events version 4), biochemical failure-free survival (BFFS) and freedom from late toxicity were assessed. Analyses were performed by binary logistic regression and Cox proportional hazard regression. The median follow-up was 68 months, and 75% of patients were ≥70 years old. Evening HDRT was significantly associated with worse freedom from ≥grade 2 late GI complications (hazard ratio = 2.96; p < 0.001). The detrimental effect of evening HDRT was significant in patients older than 70 years old (p < 0.001) but not in younger patients (p = 0.63). In a subgroup of propensity score-matched cohort with T2b-T3 disease (n = 154), the 5-year BFFS was worse in the evening group than the daytime group (72% vs. 85%, hazard ratio = 1.95, p = 0.05). Our study indicates that evening HDRT may lead to more GI complications, especially in older patients, and worse BFFS in patients with T2b-T3 disease. PMID:26818960

  10. Analysis of prostate bed motion using an endorectal balloon and cone beam computed tomography during postprostatectomy radiotherapy

    PubMed Central

    Joo, Ji Hyeon; Kim, Yeon Joo; Kim, Young Seok; Cho, Young Pil; Lee, Ho Yeon; Jeong, Chang Young; Kwak, Jungwon; Cho, Byung Chul

    2016-01-01

    Background The authors conducted this prospective study to analyze the amount of interfractional prostate bed motion (PBM) and quantify its components with the use of an endorectal balloon (ERB). Methods A total of 1,348 cone beam computed tomography images from 46 patients who underwent postprostatectomy radiotherapy were analyzed. For the pilot image, electronic portal imaging, guided by skin marks was performed to ensure proper positioning and inflation of the ERB. Then, for bone matching, manual or automatic registration of the planning and each cone beam computed tomography was performed, based on the bony anatomy of the pelvis. Shifts (bony misalignment [BM]) in three directions were recorded at each treatment session. For prostate bed matching, manual matching was conducted based on the anterior rectal wall and the shift (PBM) was recorded. Total setup error was defined as the shift from the skin mark to the prostate bed matching, based on anterior rectal wall stretched by the ERB. PBM was defined as the difference between the total setup error and BM. Results Systematic errors for the total setup error were 1.0, 1.3, and 1.0 mm in the right–left, anterior–posterior, and superior–inferior directions, with random errors of 1.9, 2.4, and 1.9 mm, respectively. Systematic errors were 1.6, 1.6, and 0.3 mm for BM and 0.8, 1.1, and 0.9 mm for PBM, with random errors of 2.4, 2.5, and 1.1 mm for BM and 1.8, 2.2, and 1.9 mm for PBM. Conclusion The BM was the main component of the total setup error, suggesting that interfractional PBM was well controlled by the ERB device. Planning target volume margins of <5 mm were needed to include 95% of the interfractional variations when using an ERB. PMID:27307750

  11. Intensity-Modulated Radiotherapy Using Implanted Fiducial Markers With Daily Portal Imaging: Assessment of Prostate Organ Motion

    SciTech Connect

    Chen Jergin . E-mail: jergin.chen@hci.utah.edu; Lee, R. Jeffrey; Handrahan, Diana; Sause, William T.

    2007-07-01

    Purpose: To assess our single institutional experience with daily localization, using fiducials for prostate radiotherapy. Methods and Materials: From January 2004 to September 2005, 33 patients were treated with 1,097 intensity-modulated radiation treatments, using three implanted fiducials. Daily portal images were obtained before treatments. Shifts were made for deviations {>=}3 mm in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) dimensions. Results: Of 1,097 treatments, 987 (90%) required shifts. Shifts were made in the LR, SI, and AP dimensions in 51%, 67%, and 58% of treatments, respectively. In the LR dimension, the median distance shifted was 5 mm. Of 739 shifts in the SI dimension, 73% were in the superior direction for a median distance of 6 mm, and 27% were shifted inferiorly for a median distance of 5 mm. The majority of shifts in the AP dimension were in the anterior direction (87%). Median distances shifted in the anterior and posterior directions were 5 mm and 4 mm, respectively. The median percentage of treatments requiring shifts per patient was 93% (range, 57-100%). Median deviations in the LR, SI, and AP dimensions were 3 mm, 4 mm, and 3 mm, respectively. Deviations in the SI and AP dimensions were more often in the superior rather than inferior (60% vs. 29%) and in the anterior rather than posterior (70% vs. 16%) directions. Conclusions: Interfraction prostate motion is significant. Daily portal imaging with implanted fiducials improves localization of the prostate, and is necessary for the reduction of treatment margins.

  12. External beam radiotherapy and abiraterone in men with localized prostate cancer: safety and effect on tissue androgens

    PubMed Central

    Cho, Eunpi; Mostaghel, Elahe A.; Russell, Kenneth J.; Liao, Jay J.; Konodi, Mark A.; Kurland, Brenda F.; Marck, Brett T.; Matsumoto, Alvin M.; Dalkin, Bruce L.; Montgomery, R. Bruce

    2015-01-01

    Purpose/Objectives Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation with definitive radiotherapy in men with locally advanced or high-grade disease. Addition of abiraterone to LHRH agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression. Materials/Methods A prospective, phase II study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at discretion of treating clinician. Prostate biopsies were obtained prior to start of therapy and prior to radiation. Serum and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. Results 22 men with intermediate (3) and high-risk PCa (19) received study therapy. 16 men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4–81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14),, fatigue (1), transaminitis (2), hypertension (2), and hypokalemia (1). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone had pre-radiation PSA nadir of <0.3. Median levels of tissue androgens downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range 3–37), only one patient (who had discontinued abiraterone at 3 months) had biochemical relapse. Conclusions Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression. Preliminary analysis of the clinical data is also promising with excellent PSA nadir and no relapse to date in this high-risk population. PMID:25772183

  13. Development of Late Toxicity and International Prostate Symptom Score Resolution After External-Beam Radiotherapy Combined With Pulsed Dose Rate Brachytherapy for Prostate Cancer

    SciTech Connect

    Pieters, Bradley R.; Rezaie, Elisa; Geijsen, Elisabeth D.; Koedooder, Kees; Grient, Johan N.B. van der; Blank, Leo E.C.M.; Reijke, Theo M. de; Koning, Caro C.E.

    2011-11-01

    Purpose: To investigate the development of gastrointestinal (GI) toxicity, genitourinary (GU) toxicity, erectile dysfunction, and International Prostate Symptom Score (IPSS) resolution in a cohort of patients treated with external-beam radiotherapy (EBRT) followed by a brachytherapy pulsed dose rate (PDR) boost. Methods and Materials: Between 2002 and 2008, 110 patients were treated with 46-Gy EBRT followed by PDR brachytherapy (24.96-28.80 Gy). The investigated outcome variables, GI toxicity, GU toxicity, erectile dysfunction, and IPSS were prospectively scored at several time points during follow-up. Association between time (as continuous and categorical variable) and the outcome variables was assessed using generalized linear models. Results: No statistically significant association was found between time (continuous) and GI toxicity (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.89-1.06), GU toxicity (OR, 0.97; 95% CI, 0.91-1.03), erectile dysfunction (OR, 1.06; 95% CI, 0.99-1.11), and IPSS (-0.11; 95% CI, -0.41-0.20). Also, no statistically significant association was found between these variables and time as a categorical variable. GU toxicity was associated with IPSS resolution (OR, 1.16; 95% CI, 1.09-1.24). Posttreatment IPSS was associated with pretreatment IPSS (0.52; 95% CI, 0.25-0.79). Conclusions: No accumulation of high-grade toxicity over time could be established for a group of patients treated with EBRT and PDR brachytherapy for prostate cancer, probably because high-grade late toxicity resolves with time. Also, differences in IPSS values among patients are smaller after treatment than before treatment.

  14. Red bone marrow dose calculations in radiotherapy of prostate cancer based on the updated VCH adult male phantom

    NASA Astrophysics Data System (ADS)

    Ai, Jinqin; Xie, Tianwu; Sun, Wenjuan; Liu, Qian

    2014-04-01

    Red bone marrow (RBM) is an important dose-limiting tissue that has high radiosensitivity but is difficult to identify on clinical medical images. In this study, we investigated dose distribution in RBM for prostate cancer radiotherapy. Four suborgans were identified in the skeleton of the visible Chinese human phantom: cortical bone (CB), trabecular bone (TB), RBM, and yellow bone marrow (YBM). Dose distributions in the phantom were evaluated by the Monte Carlo method. When the left os coxae was taken as the organ-at-risk (OAR), the difference in absorbed dose between RBM and each CB and TB was up to 20%, but was much less (≤3.1%) between RBM and YBM. When the left os coxae and entire bone were both taken as OARs, RBM dose also increased with increasing planning target volume size. The results indicate the validity of using dose to homogeneous bone marrow mixture for estimating dose to RBM when RBM is not available in computational phantoms. In addition, the human skeletal system developed in this study provides a model for considering RBM dose in radiotherapy planning.

  15. Effect of external shielding for neutrons during radiotherapy for prostate cancer, considering the 2300 CD linear accelerator and voxel phantom

    NASA Astrophysics Data System (ADS)

    Thalhofer, J. L.; Roque, H. S.; Rebello, W. F.; Correa, S. A.; Silva, A. X.; Souza, E. M.; Batita, D. V. S.; Sandrini, E. S.

    2014-02-01

    Photoneutron production occurs when high energy photons, greater than 6.7 MeV, interact with linear accelerator head structures. In Brazil, the National Cancer Institute, one of the centers of reference in cancer treatment, uses radiation at 4 angles (0°, 90°, 180° and 270°) as treatment protocol for prostate cancer. With the objective of minimizing the dose deposited in the patient due to photoneutrons, this study simulated radiotherapy treatment using MCNPX, considering the most realistic environment; simulating the radiotherapy room, the Linac 2300 head, the MAX phantom and the treatment protocol with the accelerator operating at 18 MV. In an attempt to reduce the dose deposited by photoneutrons, an external shielding was added to the Linac 2300. Results show that the equivalent dose due to photoneutrons deposited in the patient diminished. The biggest reduction was seen in bone structures, such as the tibia and fibula, and mandible, at approximately 75%. Besides that, organs such as the brain, pancreas, small intestine, lungs and thyroid revealed a reduction of approximately 60%. It can be concluded that the shielding developed by our research group is efficient in neutron shielding, reducing the dose for the patient, and thus, the risk of secondary cancer, and increasing patient survival rates.

  16. A Matched Control Analysis of Adjuvant and Salvage High-Dose Postoperative Intensity-Modulated Radiotherapy for Prostate Cancer

    SciTech Connect

    Ost, Piet; De Troyer, Bart; Fonteyne, Valerie; Oosterlinck, Willem; De Meerleer, Gert

    2011-08-01

    Purpose: It is unclear whether immediate adjuvant radiotherapy for high-risk disease at prostatectomy (capsule perforation, seminal vesicle invasion, and/or positive surgical margins) is equivalent to delayed salvage radiotherapy at biochemical recurrence. We performed a matched case analysis comparing high-dose adjuvant intensity modulated radiotherapy (A-IMRT) with salvage IMRT (S-IMRT). Methods and Materials: One hundred forty-four patients with high-risk disease at prostatectomy were referred for A-IMRT, and 134 patients with high-risk disease were referred at biochemical recurrence (rising prostate-specific antigen [PSA], following prostatectomy, above 0.2 ng/ml) for S-IMRT. Patients were matched in a 1:1 ratio according to preoperative PSA level, Gleason score, and pT stage. Median doses of 74 Gy and 76 Gy were prescribed for A-IMRT and S-IMRT, respectively. We report biochemical relapse free survival (bRFS) rates using the Kaplan-Meier method. Univariate and multivariate analyses were used to examine tumour- and treatment-related factors. Results: A total of 178 patients were matched (89:89). From the end of radiotherapy, the median follow-up was 36 months for both groups. The 3-year bRFS rate for the A-IMRT group was 90% compared to 65% for the S-IMRT group (p < 0.05). On multivariate analysis, S-IMRT, Gleason grades of {>=}4+3, perineural invasion, preoperative PSA level of {>=}10 ng/ml, and omission of androgen deprivation (AD) were independent predictors for a reduced bRFS (p < 0.05). From the date of surgery, the median follow-up was 43 and 60 months for A-IMRT and S-IMRT, respectively. The 3-year bRFS rate for A-IMRT was 91% compared to 79% for S-IMRT (p < 0.05). On multivariate analysis, Gleason grades of {>=}4+3, perineural invasion, and omission of AD were independent predictors for a reduced bRFS (p < 0.05). S-IMRT was no longer an independent prognostic factor (p = 0.08). Conclusions: High-dose A-IMRT significantly improves 3-year bRFS compared to

  17. Image-guided adaptive radiotherapy for prostate and head-and-neck cancers

    NASA Astrophysics Data System (ADS)

    O'Daniel, Jennifer C.

    In the current practice of radiation therapy, daily patient alignments have been based on external skin marks or on bone. However, internal organ variation (both motion and volumetric changes) between treatment fractions can displace the treatment target, causing target underdosage and normal tissue overdosage. In order to deliver the radiation treatment as planned, more accurate knowledge of the daily internal anatomy was needed. Additionally, treatments needed to adapt to these variations by either shifting the patient to account for the daily target position or by altering the treatment plan. In this dissertation, the question of whether inter-fractional variations in internal patient anatomy combined with external set-up uncertainties produced measurable differences between planned and delivered doses for prostate and head-and-neck cancer patients was investigated. Image-guided adaptive treatment strategies to improve tumor coverage and/or reduce normal tissue dose were examined. Treatment deliveries utilizing various alignment procedures for ten prostate cancer patients and eleven head-and-neck cancer patients, each of whom received multiple CT scans over the course of treatment, were simulated. The largest prostate dose losses between planning and delivery were correlated with anterior/posterior and superior/inferior prostate displacement. Daily bone alignment sufficiently maintained target coverage for 70% of patients, ultrasound for 90%, and CT for 100%. A no-action-level correction protocol, which corrected the daily bone alignment for the systematic internal displacement of the prostate based on a pre-determined number of CT image sets, successfully improved the prostate and seminal vesicle dosimetric coverage. Three CT image sets were sufficient to accurately correct the bone alignment scheme for the prostate internal systematic shifts. For head-and-neck cancer patient treatment, setup uncertainties and internal organ variations did not greatly affect

  18. SU-E-J-144: MRI Visualization of a Metallic Fiducial Marker Used for Image Guided Prostate Radiotherapy

    SciTech Connect

    Yee, S; Krauss, D; Yan, D

    2014-06-01

    Purpose: Unlike on the daily CBCT used for the image-guided radiation therapy, the visualization of an implantable metallic fiducial marker on the planning MRI images has been a challenge due to the inherent insensitivity of metal in MRI, and very thin (∼ 1 mm or less) diameter. Here, an MRI technique to visualize a marker used for prostate cancer radiotherapy is reported. Methods: During the MRI acquisitions, a multi-shot turbo spin echo (TSE) technique (TR=3500 ms, TE=8.6 ms, ETL=17, recon voxel=0.42x0.42x3.5 mm3) was acquired in Philips 3T Ingenia together with a T2-weighted multi-shot TSE (TR=5381 ms, TE=110 ms, ETL=17, recon voxel=0.47×0.47×3 mm3) and a balanced turbo field echo (bTFE, flip angle 60, TR=2.76 ms, TE=1.3 ms, 0.85×0.85×3 mm3, NSA=4). In acquiring the MRI to visualize the fiducial marker, a particular emphasis was made to improve the spatial resolution and visibility in the generally dark, inhomogeneous prostate area by adjusting the slice profile ordering and TE values of TSE acquisition (in general, the lower value of TE in TSE acquisition generates a brighter signal but at the cost of high spatial resolution since the k-space, responsible for high spatial resolution, is filled with noisier data). Results: While clearly visible in CT, the marker was not visible in either T2-weighted TSE or bTFE, although the image qualities of both images were superior. In the new TSE acquisition (∼ a proton-density weighted image) adjusted by changing the profile ordering and the TE value, the marker was visible as a negative (but clear) contrast in the magnitude MRI, and as a positive contrast in the imaginary image of the phase-sensitive MRI. Conclusion: A metallic fiducial marker used for image guidance before prostate cancer radiotherapy can be made visible in MRI, which may facilitate more use of MRI in planning and guiding such radiation therapy.

  19. SU-E-T-34: An in Vivo Study On Pulsed Low Dose-Rate Radiotherapy for Prostate Cancer

    SciTech Connect

    Wang, B; Cvetkovic, D; Chen, L; Ma, C; Chen, X; Zhang, P; Zhang, C

    2014-06-01

    Purpose: Re-irradiation with conventional radiotherapy techniques (CRT) may pose significant risks due to high accumulative radiation doses. Pulsed low dose-rate radiotherapy (PLDR) has been used in clinical trials for recurrent cancer treatment. In our previous studies, PLDR irradiation showed significantly lower toxicity than CRT, resulting in much longer survival of mice after PLDR total body irradiation (TBI) than conventional TBI. The purpose of this study was to investigate tumor control efficacy of PLDR treatment for prostate cancer with an animal model of prostate cancer LNCaP. Methods: We used an orthotopic murine model of LNCaP cell line for this study. LNCaP cells were implanted into immune-suppressed male nude mice via surgery. We monitored the tumor growth with MRI. The tumor-bearing mice were allocated into a PLDR(n=9), CRT(n=7), and control group(n=7) randomly. The mice in the PLDR and CRT groups were irradiated with 2Gy dose for one time. For the CRT treatment, the mice received 2Gy at a dose-rate of 300 MU/minute. For the PLDR treatment, the 2Gy dose was further divided into ten pulses of 0.2Gy at the same dose-rate with an interval of 3 minutes between the pulses. Results: Sizable tumor growth delays were observed for the PLDR and CRT groups through weekly MRI scans. The mean values of the normalized tumor volumes (± standard deviation of the mean) were 1.53±0.07, 1.53±0.14, and 1.81±0.09 at one week after treatment, 2.28±0.13, 2.19±0.16, and 3.04±0.25 at two weeks after treatment, and 3.31±0.23, 3.14±0.24 and 4.62±0.49 at three weeks after treatment, for the PLDR, CRT, and control groups, respectively. Conclusion: The PLDR and CRT treatments showed comparable tumor control rates in this study. Our in vivo results indicate that PLDR may be a viable option for treating recurrent prostate cancer due to its equivalent tumor control but low normal tissue toxocities.

  20. Early Changes in Apparent Diffusion Coefficient From Diffusion-Weighted MR Imaging During Radiotherapy for Prostate Cancer

    SciTech Connect

    Park, Sung Yoon; Kim, Chan Kyo; Park, Byung Kwan; Park, Won; Park, Hee Chul; Han, Deok Hyun; Kim, Bohyun

    2012-06-01

    Purpose: To investigate the feasibility of diffusion-weighted MRI (DWI) as an early and reproducible change indicator in patients receiving radiotherapy for prostate cancer (PC). Methods and Materials: Eight consecutive patients with biopsy-proven PC underwent DWI at 3T. All patients who received external-beam radiotherapy had four serial MR scans, as follows: before therapy (PreTx); after 1 week of therapy (PostT1); after 3 weeks of therapy (PostT2); and 1 month after the completion of therapy (PostT3). At each time, the apparent diffusion coefficient (ADC) was measured in tumors and normal tissues. For reproducibility of the ADC measurement, five patients also had two separate pretreatment DWI scans at an interval of <2 weeks. Serum prostate-specific antigen (PSA) levels were evaluated at the same time as MR scans. Results: Thirteen tumors (peripheral zone = 10; transition zone = 3) were found. The mean ADC values for the tumors from PreTx to PostT3 were 0.86, 1.03, 1.15, and 1.26 Multiplication-Sign 10{sup -3} mm{sup 2}/s in sequence, respectively. Compared with PreTx, PostT1 (p = 0.005), PostT2 (p = 0.003), and PostT3 (p < 0.001) showed a significant increase in ADC values. The mean ADC values of the benign tissues from PreTx to PostT3 were 1.60, 1.58, 1.47, and 1.46 Multiplication-Sign 10{sup -3} mm{sup 2}/s in sequence, respectively. Reproducibility of ADC measurements was confirmed with a mean difference in ADC of -0.04 in peripheral zone and -0.017 in transition zone between two separate pretreatment MR scans. The mean PSA levels from PreTx to PostT3 were 9.05, 9.18, 9.25, and 4.11 ng/mL in sequence, respectively. Conclusions: DWI, as a reproducible biomarker, has the potential to evaluate the early therapeutic changes of PC to radiotherapy.

  1. Changes in Prostate Shape and Volume and Their Implications for Radiotherapy After Introduction of Endorectal Balloon as Determined by MRI at 3T

    SciTech Connect

    Heijmink, Stijn W.T.P.J. Scheenen, Tom W.J.; Lin, Emile N.J.T. van; Visser, Andries G.; Kiemeney, Lambertus A.L.M.; Witjes, J. Alfred; Barentsz, Jelle O.

    2009-04-01

    Purpose: To determine the changes in prostate shape and volume after the introduction of an endorectal coil (ERC) by means of magnetic resonance imaging (MRI) at 3T. Methods and materials: A total of 44 consecutive patients with biopsy-proven prostate cancer underwent separate MRI examinations at 3T with a body array coil and subsequently with an ERC inflated with 50 mL of fluid. Prospectively, two experienced readers independently evaluated all data sets in random order. The maximal anteroposterior, right-to-left, and craniocaudal prostate diameters, as well as the total prostate and peripheral zone and central gland volumes were measured before and after ERC introduction. The changes in prostate shape and volume were analyzed using Wilcoxon's test for paired samples. Results: The introduction of the ERC significantly changed the prostate shape in all three directions, with mean changes in the anteroposterior, right-to-left, and craniocaudal diameters of 15.7% (5.5 mm), 7.7% (3.5 mm), and 6.3% (2.2 mm), respectively. The mean total prostate, peripheral zone, and central gland volume decreased significantly after ERC introduction by 17.9% (8.3 cm{sup 3}), 21.6% (4.8 cm{sup 3}), and 14.2% (3.4 cm{sup 3}), respectively. Conclusion: ERC introduction as observed by 3T MRI changed the prostate shape and volume significantly. The mean anteroposterior diameter was reduced by nearly one-sixth of its original diameter, and the mean total prostate volume was decreased by approximately 18%. This could cause difficulties and should be considered when using ERC-based MRI for MRI-computed tomography fusion and radiotherapy planning.

  2. Quality of Life After Whole Pelvic Versus Prostate-Only External Beam Radiotherapy for Prostate Cancer: A Matched-Pair Comparison

    SciTech Connect

    Pinkawa, Michael; Piroth, Marc D.; Holy, Richard; Fischedick, Karin; Klotz, Jens; Szekely-Orban, Dalma; Eble, Michael J.

    2011-09-01

    Purpose: Comparison of health-related quality of life after whole pelvic (WPRT) and prostate-only (PORT) external beam radiotherapy for prostate cancer. Methods and Materials: A group of 120 patients (60 in each group) was surveyed prospectively before radiation therapy (RT) (time A), at the last day of RT (time B), at a median time of 2 months (time C) and >1 year after RT (time D) using a validated questionnaire (Expanded Prostate Cancer Index Composite). All patients were treated with 1.8- to 2.0-Gy fractions up to 70.2 to 72.0 Gy with or without WPRT up to 45 to 46 Gy. Pairs were matched according to the following criteria: age {+-} 5years, planning target volume {+-} 10 cc (considering planning target volume without pelvic nodes for WPRT patients), urinary/bowel/sexual function score before RT {+-} 10, and use of antiandrogens. Results: With the exception of prognostic risk factors, both groups were well balanced with respect to baseline characteristics. No significant differences were found with regard to urinary and sexual score changes. Mean bladder function scores reached baseline levels in both patient subgroups after RT. However, bowel function scores decreased significantly more for patients after WPRT than in those receiving PORT at all times (p < 0.01, respectively). Significant differences were found for most items in the bowel domain in the acute phase. At time D, patients after WPRT reported rectal urgency (>once a day in 15% vs. 3%; p = 0.03), bloody stools ({>=}half the time in 7% vs. 0%; p = 0.04) and frequent bowel movements (>two on a typical day in 32% vs. 7%; p < 0.01) more often than did patients after PORT. Conclusion: In comparison to PORT, WPRT (larger bladder and rectum volumes in medium dose levels, but similar volumes in high dose levels) was associated with decreased bowel quality of life in the acute and chronic phases after treatment but remained without adverse long-term urinary effects.

  3. Three-dimensional conformal radiotherapy in the treatment of prostate cancer in Australia and New Zealand: Report on a survey of radiotherapy centres and the proceedings of a consensus workshop.

    PubMed

    Tai, K-H; Duchesne, G; Turner, S; Kneebone, A; See, A; Gogna, K; Berry, M

    2004-12-01

    There is an increasing use of 3-D conformal radiotherapy (3DCRT) in the radiotherapeutic management of prostate cancer. The Faculty of Radiation Oncology Genito-Urinary Group carried out a survey of Australian and New Zealand radiotherapy centres in the preparation of a consensus workshop. Of the 19 centres that were represented, there were 24 radiation oncologists, 16 radiation therapists and 12 medical physicists. The survey collected demographic information and data on the practices undertaken at those centres when delivering curative radiotherapy in the treatment of prostate cancer. There was much variation in the delivery of treatment in the areas of patient set-up, contouring of target volumes and organs of interest during computer planning, the techniques and the dose constraints used in these techniques, the use of adjuvant androgen deprivation therapy and the quality assurance processes used in monitoring effects of treatment. This variability reflects the range of data in the published literature. Emerging trends of practices were also identified. This is a first report on a multi-disciplinary approach to the development of guidelines in 3DCRT of prostate cancer. PMID:15601331

  4. Prevention of Gynecomastia and Breast Pain Caused by Androgen Deprivation Therapy in Prostate Cancer: Tamoxifen or Radiotherapy?

    SciTech Connect

    Arruda Viani, Gustavo; Bernardes da Silva, Lucas Godoi; Stefano, Eduardo Jose

    2012-07-15

    Purpose: To determine, in a meta-analysis, whether gynecomastia and breast pain rates in men with prostate cancer treated with androgen deprivation therapy (ADT) are reduced if treated with prophylactic radiotherapy (RT) or tamoxifen (TMX). Methods and Materials: The MEDLINE, EMBASE, CANCERLIT, and Cochrane Library databases, as well as proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing RT or TMX with observation for men with prostate cancer using ADT. Results: Six RCTs (three RT trials and three TMX trials, N = 777 patients total) were identified that met the study criteria. Pooled results from these RCTs comparing RT vs. observation showed a significant reduction in the incidence of gynecomastia and breast pain rates in patients treated with RT (odds ratio [OR] = 0.21, 95% confidence interval [CI] = 0.12-0.37, p < 0.0001, and OR = 0.34, 95% CI 0.20-0.57, p < 0.0001, respectively). Use of RT resulted in an absolute risk reduction (ARR) of 29.4% and 19.9%, with a number needed to treat (NNT) of 3.4 and 5 to avoid one case of gynecomastia and breast pain, respectively. Pooled results from trials comparing TMX vs. observation showed a statistical benefit for breast pain and gynecomastia in favor of TMX arms (OR = 0.04, 95% CI = 0.02-0.08, p < 0.0001 and OR = 0.07, 95% CI = 0.0-0.14, p < 0.00001). TMX resulted in an ARR = 64.1% and 47.6%, with an NNT of 1.56 and 2.1 to avoid one case of gynecomastia and breast pain, respectively. Considering adverse effects, TMX was 6 times more adverse effects than RT. Conclusions: Our data have shown that both TMX and RT prevented gynecomastia and breast pain in patients with prostate cancer receiving ADT for prostate cancer. Although TMX was two times more effective in preventing gynecomastia, RT should represent an effective and safe treatment option, to take into account mainly in patients with cardiovascular risk factors or thrombotic diathesis.

  5. Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma-long-term results of phase III RTOG 85-31

    SciTech Connect

    Pilepich, Miljenko V. . E-mail: mpilepich@mednet.ucla.edu; Winter, Kathryn; Lawton, Colleen A.; Krisch, Robert E.; Wolkov, Harvey B.; Movsas, Benjamin; Hug, Eugen B.; Asbell, Sucha O.; Grignon, David

    2005-04-01

    Purpose: Radiation Therapy Oncology Group protocol 85-31 was designed to evaluate the effectiveness of adjuvant androgen suppression, using goserelin, in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy (RT). Methods and Materials: Eligible patients were those with palpable primary tumor extending beyond the prostate (clinical Stage T3) or those with regional lymphatic involvement. Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and/or seminal vesicle involvement was documented histologically. Stratification was based on histologic differentiation, nodal status, acid phosphatase status, and prior prostatectomy. The patients were randomized to either RT and adjuvant goserelin (Arm I) or RT alone followed by observation and application of goserelin at relapse (Arm II). In Arm I, the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression. Results: Between 1987 and 1992, when the study was closed, 977 patients were entered: 488 to Arm I and 489 to Arm II. As of July 2003, the median follow-up for all patients was 7.6 years and for living patients was 11 years. At 10 years, the absolute survival rate was significantly greater for the adjuvant arm than for the control arm: 49% vs. 39%, respectively (p = 0.002). The 10-year local failure rate for the adjuvant arm was 23% vs. 38% for the control arm (p <0.0001). The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24% vs. 39% (p <0.001) and 16% vs. 22% (p = 0.0052), respectively, both in favor of the adjuvant arm. Conclusion: In a population of patients with unfavorable prognosis carcinoma of the prostate, androgen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute

  6. Total Androgen Blockade Versus a Luteinizing Hormone-Releasing Hormone Agonist Alone in Men With High-Risk Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Nanda, Akash; Moran, Brian J.; Braccioforte, Michelle H.; Dosoretz, Daniel; Salenius, Sharon; Katin, Michael; Ross, Rudi; D'Amico, Anthony V.

    2010-04-15

    Purpose: To assess whether short-course total androgen blockade vs. a luteinizing hormone-releasing hormone (LHRH) agonist alone affects the risk of prostate cancer-specific mortality (PCSM) in men with localized but high-risk disease treated with radiotherapy. Methods and Materials: The study cohort comprised 628 men with T1-T4, N0, M0 prostate cancer with high-risk disease (prostate-specific antigen level >20 ng/mL, Gleason score >=8, or clinical category >=T3) treated with 45 Gy of external beam radiotherapy followed by a brachytherapy boost in addition to receiving a median of 4.3 (interquartile range [IQR], 3.6-6.4) months of hormonal blockade with an LHRH agonist plus an antiandrogen or monotherapy with an LHRH agonist. Fine and Gray's multivariable regression analysis was used to determine whether combination androgen suppression therapy (AST) vs. monotherapy affected the risk of PCSM, adjusting for treatment year, duration of AST, age, and known prognostic factors. Results: After a median follow-up of 4.9 (IQR, 3.5-6.5) years, men receiving combination AST had a lower risk of PCSM than those treated with monotherapy (adjusted hazard ratio [AHR], 0.18; 95% confidence interval [CI], 0.04-0.90; p = 0.04). An increasing prostate-specific antigen level (AHR, 2.70; 95% CI, 1.64-4.45; p < 0.001) and clinical category T3/4 disease (AHR, 29.6; 95% CI, 2.88-303.5; p = 0.004) were also associated with an increased risk of PCSM. Conclusions: In men with localized but high-risk prostate cancer treated with external beam radiotherapy and brachytherapy, short-course AST with an LHRH agonist plus an antiandrogen is associated with a decreased risk of PCSM when compared with monotherapy with an LHRH agonist.

  7. Multi-institutional clinical experience with the Calypso System in localization and continuous, real-time monitoring of the prostate gland during external radiotherapy

    SciTech Connect

    Kupelian, Patrick . E-mail: patrick.kupelian@orhs.org; Willoughby, Twyla; Mahadevan, Arul; Djemil, Toufik; Weinstein, Geoffrey; Jani, Shirish; Enke, Charles; Solberg, Timothy; Flores, Nicholas

    2007-03-15

    Purpose: To report the clinical experience with an electromagnetic treatment target positioning and continuous monitoring system in patients with localized prostate cancer receiving external beam radiotherapy. Methods and Materials: The Calypso System is a target positioning device that continuously monitors the location of three implanted electromagnetic transponders at a rate of 10 Hz. The system was used at five centers to position 41 patients over a full course of therapy. Electromagnetic positioning was compared to setup using skin marks and to stereoscopic X-ray localization of the transponders. Continuous monitoring was performed in 35 patients. Results: The difference between skin mark vs. the Calypso System alignment was found to be >5 mm in vector length in more than 75% of fractions. Comparisons between the Calypso System and X-ray localization showed good agreement. Qualitatively, the continuous motion was unpredictable and varied from persistent drift to transient rapid movements. Displacements {>=}3 and {>=}5 mm for cumulative durations of at least 30 s were observed during 41% and 15% of sessions. In individual patients, the number of fractions with displacements {>=}3 mm ranged from 3% to 87%; whereas the number of fractions with displacements {>=}5 mm ranged from 0% to 56%. Conclusion: The Calypso System is a clinically efficient and objective localization method for positioning prostate patients undergoing radiotherapy. Initial treatment setup can be performed rapidly, accurately, and objectively before radiation delivery. The extent and frequency of prostate motion during radiotherapy delivery can be easily monitored and used for motion management.

  8. Percentage of Biopsy Cores Positive for Malignancy and Biochemical Failure Following Prostate Cancer Radiotherapy in 3,264 Men: Statistical Significance Without Predictive Performance

    SciTech Connect

    Williams, Scott G. Buyyounouski, Mark K.; Pickles, Tom; Kestin, Larry; Martinez, Alvaro; Hanlon, Alexandra L.; Duchesne, Gillian M.

    2008-03-15

    Purpose: To define and incorporate the impact of the percentage of positive biopsy cores (PPC) into a predictive model of prostate cancer radiotherapy biochemical outcome. Methods and Materials: The data of 3264 men with clinically localized prostate cancer treated with external beam radiotherapy at four institutions were retrospectively analyzed. Standard prognostic and treatment factors plus the number of biopsy cores collected and the number positive for malignancy by transrectal ultrasound-guided biopsy were available. The primary endpoint was biochemical failure (bF, Phoenix definition). Multivariate proportional hazards analyses were performed and expressed as a nomogram and the model's predictive ability assessed using the concordance index (c-index). Results: The cohort consisted of 21% low-, 51% intermediate-, and 28% high-risk cancer patients, and 30% had androgen deprivation with radiotherapy. The median PPC was 50% (interquartile range [IQR] 29-67%), and median follow-up was 51 months (IQR 29-71 months). Percentage of positive biopsy cores displayed an independent association with the risk of bF (p = 0.01), as did age, prostate-specific antigen value, Gleason score, clinical stage, androgen deprivation duration, and radiotherapy dose (p < 0.001 for all). Including PPC increased the c-index from 0.72 to 0.73 in the overall model. The influence of PPC varied significantly with radiotherapy dose and clinical stage (p = 0.02 for both interactions), with doses <66 Gy and palpable tumors showing the strongest relationship between PPC and bF. Intermediate-risk patients were poorly discriminated regardless of PPC inclusion (c-index 0.65 for both models). Conclusions: Outcome models incorporating PPC show only minor additional ability to predict biochemical failure beyond those containing standard prognostic factors.

  9. Toxicity outcome in patients treated with modulated arc radiotherapy for localized prostate cancer

    PubMed Central

    Lengua, Rafael E.; Gonzalez, Maria F.; Barahona, Kaory; Ixquiac, Milton E.; Lucero, Juan F.; Montenegro, Erick; Lopez Guerra, Jose L.; Jaén, Javier; Linares, Luis A.

    2013-01-01

    Aim This study evaluates the acute toxicity outcome in patients treated with RapidArc for localized prostate cancer. Background Modern technologies allow the delivery of high doses to the prostate while lowering the dose to the neighbouring organs at risk. Whether this dosimetric advantage translates into clinical benefit is not well known. Materials and methods Between December 2009 and May 2012, 45 patients with primary prostate adenocarcinoma were treated using RapidArc. All patients received 1.8 Gy per fraction, the median dose to the prostate gland, seminal vesicles, pelvic lymph nodes and surgical bed was 80 Gy (range, 77.4–81 Gy), 50.4 Gy, 50.4 Gy and 77.4 Gy (range, 75.6–79.2 Gy), respectively. Results The time between the last session and the last treatment follow up was a median of 10 months (range, 3–24 months). The incidence of grade 3 acute gastrointestinal (GI) and genitourinary (GU) toxicity was 2.2% and 15.5%, respectively. Grade 2 acute GI and GU toxicity occurred in 30% and 27% of patients, respectively. No grade 4 acute GI and GU toxicity were observed. Older patients (>median) or patients with V60 higher than 35% had significantly higher rates of grade ≥2 acute GI toxicity compared with the younger ones. Conclusions RapidArc in the treatment of localized prostate cancer is tolerated well with no Grade >3 GI and GU toxicities. Older patients or patients with higher V60 had significantly higher rates of grade ≥2 acute GI toxicity. Further research is necessary to assess definitive late toxicity and tumour control outcome. PMID:25061516

  10. A Randomized Trial (Irish Clinical Oncology Research Group 97-01) Comparing Short Versus Protracted Neoadjuvant Hormonal Therapy Before Radiotherapy for Localized Prostate Cancer

    SciTech Connect

    Armstrong, John G.; Gillham, Charles M.; Dunne, Mary T.; Fitzpatrick, David A.; Finn, Marie A.; Cannon, Mairin E.; Taylor, Judy C.; O'Shea, Carmel M.; Buckney, Steven J.; Thirion, Pierre G.

    2011-09-01

    Purpose: To examine the long-term outcomes of a randomized trial comparing short (4 months; Arm 1) and long (8 months; Arm 2) neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer. Methods and Materials: Between 1997 and 2001, 276 patients were enrolled and the data from 261 were analyzed. The stratification risk factors were prostate-specific antigen level >20 ng/mL, Gleason score {>=}7, and Stage T3 or more. The intermediate-risk stratum had one factor and the high-risk stratum had two or more. Staging was done from the bone scan and computed tomography findings. The primary endpoint was biochemical failure-free survival. Results: The median follow-up was 102 months. The overall survival, biochemical failure-free survival. and prostate cancer-specific survival did not differ significantly between the two treatment arms, overall or at 5 years. The cumulative probability of overall survival at 5 years was 90% (range, 87-92%) in Arm 1 and 83% (range, 80-86%) in Arm 2. The biochemical failure-free survival rate at 5 years was 66% (range, 62-71%) in Arm 1 and 63% (range, 58-67%) in Arm 2. Conclusion: No statistically significant difference was found in biochemical failure-free survival between 4 months and 8 months of neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer.

  11. Evaluations of an adaptive planning technique incorporating dose feedback in image-guided radiotherapy of prostate cancer

    SciTech Connect

    Liu Han; Wu Qiuwen

    2011-12-15

    treatment course, then 11 patients fail. If the same criteria is assessed at the end of each week (every five fractions), then 14 patients fail, with three patients failing the 1st or 2nd week but passing at the end. The average dose deficit from these 14 patients was 4.4%. They improved to 2% after the weekly compensation. Out of these 14 patients who needed dose compensation, ten passed the dose criterion after weekly dose compensation, three patients failed marginally, and one patient still failed the criterion significantly (10% deficit), representing 3.6% of the patient population. A more aggressive compensation frequency (every three fractions) could successfully reduce the dose deficit to the acceptable level for this patient. The average number of required dose compensation re-planning per patient was 0.82 (0.79) per patient for schedule A (B) delivery strategy. The doses to OARs were not significantly different from the online IG only plans without dose compensation. Conclusions: We have demonstrated the effectiveness of offline dose compensation technique in image-guided radiotherapy for prostate cancer. It can effectively account for residual uncertainties which cannot be corrected through online IG. Dose compensation allows further margin reduction and critical organs sparing.

  12. Antibiotic de-escalation.

    PubMed

    Masterton, Robert G

    2011-01-01

    Antibiotic de-escalation is a mechanism whereby the provision of effective initial antibiotic treatment is achieved while avoiding unnecessary antibiotic use that would promote the development of resistance. It is a key element within antimicrobial stewardship programs and treatment paradigms for serious sepsis. The embodiment of de-escalation is that based on microbiology results around the day 3 therapy point; the empiric antibiotic(s) that were started are stopped or reduced in number and/or narrowed in spectrum. Data are presented here which demonstrate that de-escalation is clinically effective and appropriate. However, the need for further studies, particularly in terms of realization of full benefits as well as implementation tools, is highlighted. De-escalation ought now to form a part of routine antimicrobial management, though how best to do it and the full breadth and scope of benefits remain to be identified. PMID:21144991

  13. Radiotherapy of prostatic carcinoma: long- or short-term efficacy (Stanford University experience)

    SciTech Connect

    Bagshaw, M.A.; Ray, G.R.; Cox, R.S.

    1985-02-01

    Results of a study that began at Stanford in 1956 demonstrate that long-term, disease-free survival can be achieved following appropriate irradiation in patients with prostatic carcinoma. However, the investigation has also uncovered several powerful prognostic indicators, such as the extent of anatomic involvement, histologic pattern, particularly as described by Gleason; and presence or absence of lymphnode metastases. To illustrate the importance of these parameters, the author presents data that correlate survival with the anatomic extent of the primary tumor and the Gleason pattern scores. Of the staged patients, 64 have been subjected to post-therapeutic biopsy of the prostate 18 months or more following therapy. A correlation also seems to exist among clinical stage, lymph node involvement, and subsequent biopsy status. The implication of this finding in the development of more aggressive therapeutic approaches will be discussed.

  14. Comparison of Automated Atlas-Based Segmentation Software for Postoperative Prostate Cancer Radiotherapy

    PubMed Central

    Delpon, Grégory; Escande, Alexandre; Ruef, Timothée; Darréon, Julien; Fontaine, Jimmy; Noblet, Caroline; Supiot, Stéphane; Lacornerie, Thomas; Pasquier, David

    2016-01-01

    Automated atlas-based segmentation (ABS) algorithms present the potential to reduce the variability in volume delineation. Several vendors offer software that are mainly used for cranial, head and neck, and prostate cases. The present study will compare the contours produced by a radiation oncologist to the contours computed by different automated ABS algorithms for prostate bed cases, including femoral heads, bladder, and rectum. Contour comparison was evaluated by different metrics such as volume ratio, Dice coefficient, and Hausdorff distance. Results depended on the volume of interest showed some discrepancies between the different software. Automatic contours could be a good starting point for the delineation of organs since efficient editing tools are provided by different vendors. It should become an important help in the next few years for organ at risk delineation. PMID:27536556

  15. Comparison of Automated Atlas-Based Segmentation Software for Postoperative Prostate Cancer Radiotherapy.

    PubMed

    Delpon, Grégory; Escande, Alexandre; Ruef, Timothée; Darréon, Julien; Fontaine, Jimmy; Noblet, Caroline; Supiot, Stéphane; Lacornerie, Thomas; Pasquier, David

    2016-01-01

    Automated atlas-based segmentation (ABS) algorithms present the potential to reduce the variability in volume delineation. Several vendors offer software that are mainly used for cranial, head and neck, and prostate cases. The present study will compare the contours produced by a radiation oncologist to the contours computed by different automated ABS algorithms for prostate bed cases, including femoral heads, bladder, and rectum. Contour comparison was evaluated by different metrics such as volume ratio, Dice coefficient, and Hausdorff distance. Results depended on the volume of interest showed some discrepancies between the different software. Automatic contours could be a good starting point for the delineation of organs since efficient editing tools are provided by different vendors. It should become an important help in the next few years for organ at risk delineation. PMID:27536556

  16. Improved Clinical Outcomes With High-Dose Image Guided Radiotherapy Compared With Non-IGRT for the Treatment of Clinically Localized Prostate Cancer

    SciTech Connect

    Zelefsky, Michael J.; Kollmeier, Marisa; Cox, Brett; Fidaleo, Anthony; Sperling, Dahlia; Pei, Xin; Carver, Brett; Coleman, Jonathan; Lovelock, Michael; Hunt, Margie

    2012-09-01

    Purpose: To compare toxicity profiles and biochemical tumor control outcomes between patients treated with high-dose image-guided radiotherapy (IGRT) and high-dose intensity-modulated radiotherapy (IMRT) for clinically localized prostate cancer. Materials and Methods: Between 2008 and 2009, 186 patients with prostate cancer were treated with IGRT to a dose of 86.4 Gy with daily correction of the target position based on kilovoltage imaging of implanted prostatic fiducial markers. This group of patients was retrospectively compared with a similar cohort of 190 patients who were treated between 2006 and 2007 with IMRT to the same prescription dose without, however, implanted fiducial markers in place (non-IGRT). The median follow-up time was 2.8 years (range, 2-6 years). Results: A significant reduction in late urinary toxicity was observed for IGRT patients compared with the non-IGRT patients. The 3-year likelihood of grade 2 and higher urinary toxicity for the IGRT and non-IGRT cohorts were 10.4% and 20.0%, respectively (p = 0.02). Multivariate analysis identifying predictors for grade 2 or higher late urinary toxicity demonstrated that, in addition to the baseline Internatinoal Prostate Symptom Score, IGRT was associated with significantly less late urinary toxicity compared with non-IGRT. The incidence of grade 2 and higher rectal toxicity was low for both treatment groups (1.0% and 1.6%, respectively; p = 0.81). No differences in prostate-specific antigen relapse-free survival outcomes were observed for low- and intermediate-risk patients when treated with IGRT and non-IGRT. For high-risk patients, a significant improvement was observed at 3 years for patients treated with IGRT compared with non-IGRT. Conclusions: IGRT is associated with an improvement in biochemical tumor control among high-risk patients and a lower rate of late urinary toxicity compared with high-dose IMRT. These data suggest that, for definitive radiotherapy, the placement of fiducial markers

  17. Sci—Thur AM: YIS - 02: Radiogenomic Modeling of Normal Tissue Toxicities in Prostate Cancer Patients Receiving Hypofractionated Radiotherapy

    SciTech Connect

    Coates, J; Jeyaseelan, K; Ybarra, N; David, M; Faria, S; Souhami, L; Cury, F; Duclos, M; El Naqa, I

    2014-08-15

    Inter-patient radiation sensitivity variability has recently been shown to have a genetic component. This genetic component may play a key role in explaining the fluctuating rates of radiation-induced toxicities (RITs). Single nucleotide polymorphisms (SNPs) have thus far yielded inconsistent results in delineating RITs while copy number variations (CNVs) have not yet been investigated for such purposes. We explore a radiogenomic modeling approach to investigate the association of CNVs and SNPs, along with clinical and dosimetric variables, in radiation induced rectal bleeding (RB) and erectile dysfunction (ED) in prostate cancer patients treated with curative hypofractionated irradiation. A cohort of 62 prostate cancer patients who underwent hypofractionated radiotherapy (66 Gy in 22 fractions) between 2002 to 2010 were retrospectively genotyped for CNV and SNP rs5489 in the xrcc1 DNA repair gene. Late toxicity rates for RB grade 2 and 3 and grade 3 alone were 29.0% and 12.9%, respectively. ED toxicity was found to be 62.9%. Radiogenomic model performance was evaluated using receiver operating characteristic area under the curve (AUC) and resampling by cross-validation. Binary variables were evaluated using Chi-squared contingency table analysis and multivariate models by Spearman's rank correlation coefficient (rs). Ten patients were found to have three copies of xrcc1 CNV (RB: χ{sup 2}=14.6, p<0.001 and ED: χ{sup 2}=4.88, p=0.0272) and twelve had heterozygous rs25489 SNP (RB: χ{sup 2}=0.278, p=0.599 and ED: χ{sup 2}=0.112, p=0.732). Radiogenomic modeling yielded significant, cross-validated NTCP models for RB (AUC=0.665) and ED (AUC=0.754). These results indicate that CNVs may be potential predictive biomarkers of both late ED and RB.

  18. A Comparison of In-Room Computerized Tomography Options for Detection of Fiducial Markers in Prostate Cancer Radiotherapy

    SciTech Connect

    Owen, Rebecca; Foroudi, Farshad; Kron, Tomas; Milner, Alvin; Cox, Jennifer; Cramb, Jim; Zhu Li; Duchesne, Gillian

    2010-07-15

    Purpose: To compare volumetric in-room computed tomography (CT) and kilovoltage (kV) cone-beam CT (CBCT) to planar imaging with respect to their ability to localize fiducial markers (FMs) for radiotherapy of prostate cancer. Methods and Materials: Image guidance options from two linear accelerators were compared in terms of identifying the center of gravity (COG) of FMs from the isocenter: a Siemens Primatom, where the couch is rotated 180 degrees from the treatment isocenter to the in-room CT vs. electronic portal imaging (EPI); and a Varian OBI system, where kV CBCT, EPI, and planar kV radiographs were compared. In all, 387 image pairs (CBCT = 133; CT = 254) from 18 patients were analyzed. A clinical tolerance of 3 mm was predefined as the acceptable threshold for agreement. Results: COG location on in-room CT and EPI was in agreement 96.9%, 85.8%, and 89.0% of the time in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions, respectively, vs. 99.2%, 91.7%, and 93.2% for the CBCT and EPI analysis. The CBCT vs. kV radiographs were in agreement 100% (LR), 85.4% (SI), and 88.5% (AP), and EPI vs. kV radiographs were in agreement 100% (LR), 94.6% (SI), and 91.5% (AP) of the time. Conclusion: Identification of FMs on volumetric or planar images was found to be not equivalent ({+-}3 mm) using either linear accelerator. Intrafraction prostate motion, interpretation of FM location, and spatial properties of images are contributing factors. Although in-room CT has superior image quality, the process of realigning the treatment couch to acquire a CT introduces an error, highlighting the benefits of a single isocentric system.

  19. Stereotactic Body Radiotherapy as Monotherapy or Post-External Beam Radiotherapy Boost for Prostate Cancer: Technique, Early Toxicity, and PSA Response

    SciTech Connect

    Jabbari, Siavash; Weinberg, Vivian K.; Kaprealian, Tania; Hsu, I-Chow; Ma Lijun; Chuang, Cynthia; Descovich, Martina; Shiao, Stephen; Shinohara, Katsuto; Roach, Mack; Gottschalk, Alexander R.

    2012-01-01

    Purpose: High dose rate (HDR) brachytherapy has been established as an excellent monotherapy or after external-beam radiotherapy (EBRT) boost treatment for prostate cancer (PCa). Recently, dosimetric studies have demonstrated the potential for achieving similar dosimetry with stereotactic body radiotherapy (SBRT) compared with HDR brachytherapy. Here, we report our technique, PSA nadir, and acute and late toxicity with SBRT as monotherapy and post-EBRT boost for PCa using HDR brachytherapy fractionation. Patients and Methods: To date, 38 patients have been treated with SBRT at University of California-San Francisco with a minimum follow-up of 12 months. Twenty of 38 patients were treated with SBRT monotherapy (9.5 Gy Multiplication-Sign 4 fractions), and 18 were treated with SBRT boost (9.5 Gy Multiplication-Sign 2 fractions) post-EBRT and androgen deprivation therapy. PSA nadir to date for 44 HDR brachytherapy boost patients with disease characteristics similar to the SBRT boost cohort was also analyzed as a descriptive comparison. Results: SBRT was well tolerated. With a median follow-up of 18.3 months (range, 12.6-43.5), 42% and 11% of patients had acute Grade 2 gastrourinary and gastrointestinal toxicity, respectively, with no Grade 3 or higher acute toxicity to date. Two patients experienced late Grade 3 GU toxicity. All patients are without evidence of biochemical or clinical progression to date, and favorably low PSA nadirs have been observed with a current median PSA nadir of 0.35 ng/mL (range, <0.01-2.1) for all patients (0.47 ng/mL, range, 0.2-2.1 for the monotherapy cohort; 0.10 ng/mL, range, 0.01-0.5 for the boost cohort). With a median follow-up of 48.6 months (range, 16.4-87.8), the comparable HDR brachytherapy boost cohort has achieved a median PSA nadir of 0.09 ng/mL (range, 0.0-3.3). Conclusions: Early results with SBRT monotherapy and post-EBRT boost for PCa demonstrate acceptable PSA response and minimal toxicity. PSA nadir with SBRT boost

  20. Conformal Postoperative Radiotherapy in Patients With Positive Resection Margins and/or pT3-4 Prostate Adenocarcinoma

    SciTech Connect

    Bellavita, Rita; Massetti, Michela; Abraha, Iosief; Lupattelli, Marco; Mearini, Luigi; Falcinelli, Lorenzo; Farneti, Alessia; Palumbo, Isabella; Porena, Massimo; Aristei, Cynthia

    2012-11-01

    Purpose: To evaluate outcome and toxicity of high-dose conformal radiotherapy (RT) after radical prostatectomy. Methods and Materials: Between August 1998 and December 2007, 182 consecutive patients with positive resection margins and/or pT3-4, node-negative prostate adenocarcinoma underwent postoperative conformal RT. The prescribed median dose to the prostate/seminal vesicle bed was 66.6 Gy (range 50-70). Hormone therapy (a luteinizing hormone-releasing hormone analogue and/or antiandrogen) was administered to 110/182 (60.5%) patients with high-risk features. Biochemical relapse was defined as an increase of more than 0.2 ng/mL over the lowest postoperative prostate-specific antigen (PSA) value measured on 3 occasions, each at least 2 weeks apart. Results: Median follow-up was 55.6 months (range 7.6-141.9 months). The 3- and 5-year probability of biochemical relapse-free survival were 87% and 81%, respectively. In univariate analysis, more advanced T stages, preoperative PSA values {>=}10 ng/mL, and RT doses <70 Gy were significant factors for biochemical relapse. Pre-RT PSA values >0.2 ng/mL were significant for distant metastases. In multivariate analysis, risk factors for biochemical relapse were higher preoperative and pre-RT PSA values, hormone therapy for under 402 days and RT doses of <70 Gy. Higher pre-RT PSA values were the only independent predictor of distant metastases. Acute genitourinary (GU) and gastrointestinal (GI) toxicities occurred in 72 (39.6%) and 91 (50%) patients, respectively. There were 2 cases of Grade III GI toxicity but no cases of Grade IV. Late GU and GI toxicities occurred in 28 (15.4%) and 14 (7.7%) patients, respectively: 11 cases of Grade III toxicity: 1 GI (anal stenosis) and 10 GU, all urethral strictures requiring endoscopic urethrotomy. Conclusions: Postoperative high-dose conformal RT in patients with high-risk features was associated with a low risk of biochemical relapse as well as minimal morbidity.

  1. Phase II Trial of Combined High-Dose-Rate Brachytherapy and External Beam Radiotherapy for Adenocarcinoma of the Prostate: Preliminary Results of RTOG 0321

    SciTech Connect

    Hsu, I-Chow; Bae, Kyounghwa; Shinohara, Katsuto; Pouliot, Jean; Purdy, James; Ibbott, Geoffrey; Speight, Joycelyn; Vigneault, Eric; Ivker, Robert M.D.; Sandler, Howard M.D.

    2010-11-01

    Purpose: To estimate the rate of late Grade 3 or greater genitourinary (GU) and gastrointestinal (GI) adverse events (AEs) after treatment with external beam radiotherapy and prostate high-dose-rate (HDR) brachytherapy. Methods and Materials: Each participating institution submitted computed tomography-based HDR brachytherapy dosimetry data electronically for credentialing and for each study patient. Patients with locally confined Stage T1c-T3b prostate cancer were eligible for the present study. All patients were treated with 45 Gy in 25 fractions using external beam radiotherapy and one HDR implant delivering 19 Gy in two fractions. All AEs were graded according to the Common Terminology Criteria for Adverse Events, version 3.0. Late GU/GI AEs were defined as those occurring >9 months from the start of the protocol treatment, in patients with {>=}18 months of potential follow-up. Results: A total of 129 patients from 14 institutions were enrolled in the present study. Of the 129 patients, 125 were eligible, and AE data were available for 112 patients at analysis. The pretreatment characteristics of the patients were as follows: Stage T1c-T2c, 91%; Stage T3a-T3b, 9%; prostate-specific antigen level {<=}10 ng/mL, 70%; prostate-specific antigen level >10 but {<=}20 ng/mL, 30%; and Gleason score 2-6, 10%; Gleason score 7, 72%; and Gleason score 8-10, 18%. At a median follow-up of 29.6 months, three acute and four late Grade 3 GU/GI AEs were reported. The estimated rate of late Grade 3-5 GU and GI AEs at 18 months was 2.56%. Conclusion: This is the first prospective, multi-institutional trial of computed tomography-based HDR brachytherapy and external beam radiotherapy. The technique and doses used in the present study resulted in acceptable levels of AEs.

  2. Hypofractionated radiotherapy versus conventionally fractionated radiotherapy for patients with intermediate-risk localised prostate cancer: 2-year patient-reported outcomes of the randomised, non-inferiority, phase 3 CHHiP trial

    PubMed Central

    Wilkins, Anna; Mossop, Helen; Syndikus, Isabel; Khoo, Vincent; Bloomfield, David; Parker, Chris; Logue, John; Scrase, Christopher; Patterson, Helen; Birtle, Alison; Staffurth, John; Malik, Zafar; Panades, Miguel; Eswar, Chinnamani; Graham, John; Russell, Martin; Kirkbride, Peter; O'Sullivan, Joe M; Gao, Annie; Cruickshank, Clare; Griffin, Clare; Dearnaley, David; Hall, Emma

    2015-01-01

    Summary Background Patient-reported outcomes (PROs) might detect more toxic effects of radiotherapy than do clinician-reported outcomes. We did a quality of life (QoL) substudy to assess PROs up to 24 months after conventionally fractionated or hypofractionated radiotherapy in the Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer (CHHiP) trial. Methods The CHHiP trial is a randomised, non-inferiority phase 3 trial done in 71 centres, of which 57 UK hospitals took part in the QoL substudy. Men with localised prostate cancer who were undergoing radiotherapy were eligible for trial entry if they had histologically confirmed T1b–T3aN0M0 prostate cancer, an estimated risk of seminal vesicle involvement less than 30%, prostate-specific antigen concentration less than 30 ng/mL, and a WHO performance status of 0 or 1. Participants were randomly assigned (1:1:1) to receive a standard fractionation schedule of 74 Gy in 37 fractions or one of two hypofractionated schedules: 60 Gy in 20 fractions or 57 Gy in 19 fractions. Randomisation was done with computer-generated permuted block sizes of six and nine, stratified by centre and National Comprehensive Cancer Network (NCCN) risk group. Treatment allocation was not masked. UCLA Prostate Cancer Index (UCLA-PCI), including Short Form (SF)-36 and Functional Assessment of Cancer Therapy-Prostate (FACT-P), or Expanded Prostate Cancer Index Composite (EPIC) and SF-12 quality-of-life questionnaires were completed at baseline, pre-radiotherapy, 10 weeks post-radiotherapy, and 6, 12, 18, and 24 months post-radiotherapy. The CHHiP trial completed accrual on June 16, 2011, and the QoL substudy was closed to further recruitment on Nov 1, 2009. Analysis was on an intention-to-treat basis. The primary endpoint of the QoL substudy was overall bowel bother and comparisons between fractionation groups were done at 24 months post-radiotherapy. The CHHiP trial is registered with ISRCTN registry

  3. Radiotherapy.

    PubMed

    Adamietz, Irenaus A

    2010-01-01

    The intrathoracic growth of the tumor causes several severe symptoms as cough, dyspnea, chest pain, hemoptysis, hoarseness, anorexia/nausea, and dysphagia. In patients with manifest or threatening symptoms radiotherapy (RT) as an effective measure should be implemented into the management concept. Palliative RT radiotherapy prefers short hypofractionated schemas (e.g. 10 x 3 Gy, 4 x 5 Gy, 2 x 8 Gy, 1 x 10 Gy). Careful radiation planning supports the precision of palliative RT and reduces significantly the complication rate. A good response and prolonged palliation effects (6-12 months) can be achieved in many cases. However, the minimum biologically equivalent dose should not be less than 35 Gy. RT produces a good outcome in all types of metastases of lung carcinoma. In emergencies like VCSS or spinal cord compression RT should be initiated immediately. The selection of the optimal therapy for locally advanced lung carcinoma with malignant airway obstruction is difficult. Both brachytherapy and percutaneous irradiation are effective, however published results including local a sum of response, functionality and life quality demonstrates more benefit by percutaneous RT. Due to different physical properties of these two methods the combination of brachytherapy and external beam irradiation may be advantageous. PMID:19955803

  4. Baseline Serum Testosterone in Men Treated With Androgen Deprivation Therapy and Radiotherapy for Localized Prostate Cancer

    SciTech Connect

    Roach, Mack; Bae, Kyounghwa; Lawton, Colleen; Donnelly, B.J.; Grignon, David; Hanks, Gerald E.; Porter, Arthur; Lepor, Herbert; Venketesan, Varagur; Sandler, Howard

    2010-12-01

    Introduction: It is believed that men diagnosed with prostate cancer and a low baseline serum testosterone (BST) may have more aggressive disease, and it is frequently recommended they forgo testosterone replacement therapy. We used two large Phase III trials involving androgen deprivation therapy and external beam radiation therapy to assess the significance of a BST. Methods and Materials: All patients with a BST and complete data (n = 2,478) were included in this analysis and divided into four categories: 'Very Low BST' (VLBST) {<=}16.5th percentile of BST ({<=}248 ng/dL; n = 408); 'Low BST' (LBST) >16.5th percentile and {<=}33rd percentile (>248 ng/dL but {<=}314 ng/dL; n = 415); 'Average BST' (ABST) >33rd percentile and {<=}67th percentile (314-437 ng/dL; n = 845); and 'High BST' (HBST) >67th percentile (>437 ng/dL; n = 810). Outcomes included overall survival, distant metastasis, biochemical failure, and cause-specific survival. All outcomes were adjusted for the following covariates: treatment arm, BST, age (<70 vs. {>=}70), prostate-specific antigen (PSA; <10 vs. 10 {<=} PSA <20 vs. 20 {<=}), Gleason score (2-6 vs. 7 vs. 8-10); T stage (T1-T2 vs. T3-T4), and Karnofsky Performance Status (60-90 vs. 100). Results: On multivariable analysis age, Gleason score, and PSA were independently associated with an increased risk of biochemical failure, distant metastasis and a reduced cause-specific and overall survival (p < 0.05), but BST was not. Conclusions: BST does not affect outcomes in men treated with external beam radiation therapy and androgen deprivation therapy for prostate cancer.

  5. Image-Guided Radiotherapy for Prostate Cancer: A Prospective Trial of Concomitant Boost Using Indium-111-Capromab Pendetide (ProstaScint) Imaging

    SciTech Connect

    Wong, William W.; Schild, Steven E.; Vora, Sujay A.; Ezzell, Gary A.; Nguyen, Ba D.; Ram, Panol C.; Roarke, Michael C.

    2011-11-15

    Purpose: To evaluate, in a prospective study, the use of {sup 111}In-capromab pendetid