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ABSTRACT: Report of clinical cancer control outcomes on Radiation Therapy Oncology Group (RTOG) 9406, a three-dimensional conformal radiation therapy (3D-CRT) dose escalation trial for localized adenocarcinoma of the prostate.
RTOG 9406 is a Phase I/II multi-institutional dose escalation study of 3D-CRT for men with localized prostate cancer. Patients were registered on five sequential dose levels: 68.4 Gy, 73.8 Gy, 79.2 Gy, 74 Gy, and 78 Gy with 1.8 Gy/day (levels I-III) or 2.0 Gy/day (levels IV and V). Neoadjuvant hormone therapy (NHT) from 2 to 6 months was allowed. Protocol-specific, American Society for Therapeutic Radiation Oncology (ASTRO), and Phoenix biochemical failure definitions are reported.
Thirty-four institutions enrolled 1,084 patients and 1,051 patients are analyzable. Median follow-up for levels I, II, III, IV, and V was 11.7, 10.4, 11.8, 10.4, and 9.2 years, respectively. Thirty-six percent of patients received NHT. The 5-year overall survival was 90%, 87%, 88%, 89%, and 88% for dose levels I-V, respectively. The 5-year clinical disease-free survival (excluding protocol prostate-specific antigen definition) for levels I-V is 84%, 78%, 81%, 82%, and 82%, respectively. By ASTRO definition, the 5-year disease-free survivals were 57%, 59%, 52%, 64% and 75% (low risk); 46%, 52%, 54%, 56%, and 63% (intermediate risk); and 50%, 34%, 46%, 34%, and 61% (high risk) for levels I-V, respectively. By the Phoenix definition, the 5-year disease-free survivals were 68%, 73%, 67%, 84%, and 80% (low risk); 70%, 62%, 70%, 74%, and 69% (intermediate risk); and 42%, 62%, 68%, 54%, and 67% (high risk) for levels I-V, respectively.
Dose-escalated 3D-CRT yields favorable outcomes for localized prostate cancer. This multi-institutional experience allows comparison to other experiences with modern radiation therapy.
International journal of radiation oncology, biology, physics 07/2012; 83(3):e363-70. · 4.59 Impact Factor
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Julian R Perks,
Sinisa Stanic,
Robin L Stern,
Barbara Henk,
Marsha S Nelson,
Rick D Harse,
Mathew Mathai,
James A Purdy, Richard K Valicenti,
Allan D Siefkin,
Allen M Chen
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ABSTRACT: To improve the quality and safety of our practice of stereotactic body radiation therapy (SBRT), we analyzed the process following the failure mode and effects analysis (FMEA) method.
The FMEA was performed by a multidisciplinary team. For each step in the SBRT delivery process, a potential failure occurrence was derived and three factors were assessed: the probability of each occurrence, the severity if the event occurs, and the probability of detection by the treatment team. A rank of 1 to 10 was assigned to each factor, and then the multiplied ranks yielded the relative risks (risk priority numbers). The failure modes with the highest risk priority numbers were then considered to implement process improvement measures.
A total of 28 occurrences were derived, of which nine events scored with significantly high risk priority numbers. The risk priority numbers of the highest ranked events ranged from 20 to 80. These included transcription errors of the stereotactic coordinates and machine failures.
Several areas of our SBRT delivery were reconsidered in terms of process improvement, and safety measures, including treatment checklists and a surgical time-out, were added for our practice of gantry-based image-guided SBRT. This study serves as a guide for other users of SBRT to perform FMEA of their own practice.
International journal of radiation oncology, biology, physics 12/2011; 83(4):1324-9. · 4.59 Impact Factor
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ABSTRACT: To investigate dose-volume consequences of inclusion of the seminal vesicle (SV) bed in the clinical target volume (CTV) for the rectum and bladder using biological response indices in postprostatectomy patients receiving intensity-modulated radiotherapy (IMRT).
We studied 10 consecutive patients who underwent prostatectomy for prostate cancer and subsequently received adjuvant or salvage RT to the prostate fossa. The CTV to planning target volume (PTV) expansion was 7 mm, except posterior expansion, which was 5 mm. Two IMRT plans were generated for each patient, including either the prostate fossa alone or the prostate fossa with the SV bed, but identical in all other aspects. Prescription dose was 68.4 Gy in 1.8-Gy fractions prescribed to ≥95% PTV.
With inclusion of the SV bed in the treatment volume, PTV increased and correlated with PTV-bladder and PTV-rectum volume overlap (Spearman ρ 0.91 and 0.86, respectively; p < 0.05). As a result, the dose delivered to the bladder and rectum was higher (p < 0.05): mean bladder dose increased from 11.3 ± 3.5 Gy to 21.2 ± 6.6 Gy, whereas mean rectal dose increased from 25.8 ± 5.5 Gy to 32.3 ± 5.5 Gy. Bladder and rectal equivalent uniform dose correlated with mean bladder and rectal dose. Inclusion of the SV bed in the treatment volume increased rectal normal tissue complication probability from 2.4% to 4.8% (p < 0.01).
Inclusion of the SV bed in the CTV in postprostatectomy patients receiving IMRT increases bladder and rectal dose, as well as rectal normal tissue complication probability. The magnitude of PTV-bladder and PTV-rectal volume overlap and subsequent bladder and rectum dose increase will be higher if larger PTV expansion margins are used.
International journal of radiation oncology, biology, physics 04/2011; 82(5):1897-902. · 4.59 Impact Factor
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ABSTRACT: 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).
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.
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.
International journal of radiation oncology, biology, physics 04/2011; 79(5):1323-9. · 4.59 Impact Factor
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ABSTRACT: We completed a Phase I trial to determine the maximum tolerated dose of samarium-153 EDTMP (153Sm) with hormonal therapy (HT) and radiation therapy (RT) in high-risk clinically nonmetastatic prostate cancer.
High-risk M0 prostate cancer patients (prostate-specific antigen>20 ng/mL, Gleason score>7, or>T3) were eligible for this prospective trial of dose-escalated radioactive 153Sm-EDTMP (.25-2.0 mCi/kg) as primary or postoperative therapy. After 1 month of HT, we administered 153Sm-EDTMP followed by 4 more months of HT, 46.8 Gy to the pelvic region and 23.4 Gy to the prostate target (TD=70.2 Gy). The primary endpoint was Grade III toxicity or higher by the National Cancer Institute Common Toxicity Criteria.
Twenty-nine patients enrolled (median prostate-specific antigen=8.2 ng/mL, 27/29 (93%) T stage≥T2b, 24/29 (83%) had Gleason>7) and received 153Sm-EDTMP (.25 mCi/kg, 4 patients; 0.5 mCi/kg, 4 patients; 0.75 mCi/kg, 6 patients; 1.0 mCi/kg, 6 patients; 1.5 mCi/kg, 5 patients; 2.0 mCi/kg, 4 patients). Twenty-eight patients underwent all planned therapy without delays (1 patient required surgery before the start of RT). With a median follow-up time of 23 months, there were 2 patients (7%) experiencing Grade III hematologic toxicity. There were no other Grade III or IV side effects.
Our trial demonstrates that 2 mCi/kg 153Sm -EDTMP with HT and RT was safe and feasible in men with high-risk M0 prostate cancer. A Phase II study to test this treatment is currently underway by the Radiation Therapy Oncology Group.
International journal of radiation oncology, biology, physics 03/2011; 79(3):732-7. · 4.59 Impact Factor
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Leonard G Gomella,
Jianqing Lin,
Jean Hoffman-Censits,
Patricia Dugan,
Fran Guiles,
Costas D Lallas,
Jaspreet Singh,
Peter McCue,
Timothy Showalter, Richard K Valicenti,
Adam Dicker,
Edouard J Trabulsi
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ABSTRACT: To report on the 15-year prostate cancer experience of our multidisciplinary genitourinary cancer clinic established in 1996 at the National Cancer Institute (NCI) -designated Jefferson Kimmel Cancer Center. Patients with genitourinary cancers were evaluated weekly by multiple specialists at a single site, and we focus on the 83% of patients with prostate cancer. To our knowledge, our multidisciplinary genitourinary cancer clinic is the longest continuously operating center of its kind at an NCI Cancer Center in the United States.
Data from Jefferson's Oncology Data Services were compared to SEER prostate cancer outcomes. Data on treatment changes in localized disease, patient satisfaction, and related parameters were also assessed.
Ten-year survival data approach 100% in stage I and II prostate cancer. Ten-year data for stage III (T3 N0M0) and stage IV (T4 N0M0) disease show that our institutional survival rate exceeds SEER. There is a shift toward robotically assisted laparoscopic radical prostatectomy and a slight decrease in brachytherapy relative to external beam radiation therapy in localized disease. Patient satisfaction is high as measured by survey instruments.
Our long-term experience suggests a benefit of the multidisciplinary clinic approach to prostate cancer, most pronounced for high-risk, locally advanced disease. A high level of satisfaction with this patient-centered model is seen. The multidisciplinary clinic approach to prostate cancer may enhance outcomes and possibly reduce treatment regret through a coordinated presentation of all therapeutic options. This clinic model serves as an interdisciplinary educational tool for patients, their families, and our trainees and supports clinical trial participation.
Journal of Oncology Practice 11/2010; 6(6):e5-e10.
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Urology 09/2010; 76(3):768-9. · 2.43 Impact Factor
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ABSTRACT: To update the incidence of late toxicity of RTOG 9406, a three-dimensional conformal radiation therapy (3DCRT) dose escalation trial for prostate cancer.
A total of 1,084 men were registered to this Phase I/II trial of 3DCRT (eligible patients, 1,055). The dose for level I was 68.4 Gy; 73.8 Gy for level II; 79.2 Gy for level III; 74 Gy for level IV; and 78 Gy for level V. Patients in levels I to III received 1.8 Gy/fraction, and those in levels IV to V received 2.0 Gy/fraction. Disease group I patients were treated at the prostate only, group 2 patients were treated at the prostate and at the seminal vesicles with a prostate boost, and group 3 patients were treated at the prostate and seminal vesicles. The median follow-up period for surviving patients was 6.1 y (level V) to 12.1 y (level I).
The incidence rates of RTOG grade 3 or less gastrointestinal or genitourinary toxicity were 3%, 4%, 6%, 7%, and 9% in group 1 and 6%, 2%, 6%, 9%, and 12% in group 2 at dose levels of I, II, III, IV, and V, respectively. In group 1, level V patients had a higher probability of grade 2 late or greater gastrointestinal or genitourinary toxicity than those in levels I, II, and III (hazard ratio [HR] = 1.93, p = 0.0101; HR = 2.29, p = 0.0007; HR = 2.52, p = 0.0002, respectively). In group 2, dose level V patients had a higher probability of grade 2 or greater late gastrointestinal or genitourinary toxicity than those in dose levels II, III, and IV (HR = 2.61, p = 0.0002; HR = 2.22, p = 0.0051; HR = 1.60, p = 0.0276, respectively).
Tolerance to high-dose 3DCRT remains excellent. There is significantly more grade 2 or greater toxicity with a dose of 78 Gy at 2 Gy/fraction than with 68.4 Gy to 79.2 Gy at 1.8 Gy/fraction and with 74 Gy at 2 Gy/fraction.
International journal of radiation oncology, biology, physics 08/2009; 76(1):14-22. · 4.59 Impact Factor
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ABSTRACT: To investigate the significance of the percentage of positive biopsy cores (PPBCs) in predicting the biochemical outcome in patients with low-risk prostate cancer undergoing brachytherapy or three-dimensional conformal external beam radiotherapy (3D-CRT).
We retrospectively reviewed 360 patients with low-risk prostate cancer who had undergone low dose-rate brachytherapy ((125)I) or 3D-CRT from 1993 to 2006. Of the 360 patients, 189 had undergone 3D-CRT and 171 had undergone brachytherapy. The patients were stratified according to treatment modality and PPBCs (<34%, 34%-50%, >50%). Biochemical failure was defined by the 2006 Radiation Therapy Oncology Group-American Society for Therapeutic Radiology and Oncology, Phoenix Consensus Conference definition.
The median follow-up in the 3D-CRT and brachytherapy groups was 51 and 37 months, respectively. The number of patients who had a PPBCs of <34%, 34%-50%, and >50% in the 3D-CRT and brachytherapy cohorts was 154, 26, and 9 and 133, 25, and 15, respectively. The 5-year freedom from biochemical failure rate for 3D-CRT and brachytherapy was 95% and 96%, respectively; the corresponding median prostate-specific antigen nadirs were 0.7 and 0.3 ng/mL (P < .001). No significant differences were found in age, stage, Gleason score, or PPBCs between the 2 cohorts. Cox regression analysis showed that the pretreatment prostate-specific antigen level, stage, PPBCs, and treatment modality did not predict for the time to biochemical failure. When stratified by PPBCs, no significant difference in FFBF for either modality was seen.
In patients with low-risk prostate cancer, brachytherapy and 3D-CRT remain excellent treatment choices, regardless of the tumor volume as estimated by the PPBCs. Longer follow-up and the recruitment of men with a greater volume of disease (>50% PPBCs) are needed to confirm these preliminary findings.
Urology 04/2009; 73(6):1328-34. · 2.43 Impact Factor
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ABSTRACT: 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.
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 < or =8 years of follow-up.
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.
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.
International journal of radiation oncology, biology, physics 04/2009; 76(1):31-5. · 4.59 Impact Factor
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Jeff M Michalski,
Colleen Lawton,
Issam El Naqa,
Mark Ritter,
Elizabeth O'Meara,
Michael J Seider,
W Robert Lee,
Seth A Rosenthal,
Thomas Pisansky,
Charles Catton, Richard K Valicenti,
Anthony L Zietman,
Walter R Bosch,
Howard Sandler,
Mark K Buyyounouski,
Cynthia Ménard
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ABSTRACT: To define a prostate fossa clinical target volume (PF-CTV) for Radiation Therapy Oncology Group (RTOG) trials using postoperative radiotherapy for prostate cancer.
An RTOG-sponsored meeting was held to define an appropriate PF-CTV after radical prostatectomy. Data were presented describing radiographic failure patterns after surgery. Target volumes used in previous trials were reviewed. Using contours independently submitted by 13 radiation oncologists, a statistical imputation method derived a preliminary "consensus" PF-CTV.
Starting from the model-derived CTV, consensus was reached for a CT image-based PF-CTV. The PF-CTV should extend superiorly from the level of the caudal vas deferens remnant to >8-12 mm inferior to vesicourethral anastomosis (VUA). Below the superior border of the pubic symphysis, the anterior border extends to the posterior aspect of the pubis and posteriorly to the rectum, where it may be concave at the level of the VUA. At this level, the lateral border extends to the levator ani. Above the pubic symphysis, the anterior border should encompass the posterior 1-2 cm of the bladder wall; posteriorly, it is bounded by the mesorectal fascia. At this level, the lateral border is the sacrorectogenitopubic fascia. Seminal vesicle remnants, if present, should be included in the CTV if there is pathologic evidence of their involvement.
Consensus on postoperative PF-CTV for RT after prostatectomy was reached and is available as a CT image atlas on the RTOG website. This will allow uniformity in defining PF-CTV for clinical trials that include postprostatectomy RT.
International journal of radiation oncology, biology, physics 04/2009; 76(2):361-8. · 4.59 Impact Factor
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ABSTRACT: To describe our technique and preliminary toxicity profile for ultrasound-guided outpatient placement of intraprostatic fiducial markers before intensity-modulated radiotherapy (IMRT) for prostate cancer.
A total of 98 men with prostate cancer who underwent IMRT from August 2003 through September 2006 were included in the present study. All subjects underwent ultrasound-guided transrectal placement of 3 gold intraprostatic fiducial markers under local anesthesia using our standard technique. Daily on-line image guidance adjustments were made according to the location of the fiducial markers. The charts were reviewed to evaluate the acute toxicity profile of IMRT with fiducial markers during the treatment course using the Common Toxicity Criteria, version 3.0. The International Prostate Symptom Score, clinical stage, and Gleason score were tabulated.
Fiducial marker placement proceeded without complications. The median radiation dose administered was 75.6 Gy (range 50-79.2). Grade 1 or 2 enteritis was observed in 30 of 98 patients (31%), with no cases of rectal bleeding. Grade 1 or 2 perineal dermatitis occurred in 9 patients (9.2%). Genitourinary toxicity manifested in 75 patients (77%) as grade 1 or 2 cystitis. Four patients (4%) developed urinary retention, requiring catheterization. One patient (1%) had an episode of gross hematuria. No grade 3 toxicities were observed. No significant change in the International Prostate Symptom Score at 3 months in patients with available follow-up was found (P = .34).
The placement of intraprostatic fiducial markers before prostate IMRT is a safe and efficacious method for prostate localization that produces an excellent toxicity profile.
Urology 03/2009; 73(4):881-6. · 2.43 Impact Factor
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Urology 01/2009; 72(6):1304. · 2.43 Impact Factor
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Edouard J Trabulsi, Richard K Valicenti,
Alexandra L Hanlon,
Thomas M Pisansky,
Howard M Sandler,
Deborah A Kuban,
Charles N Catton,
Jeff M Michalski,
Michael J Zelefsky,
Patrick A Kupelian, [......],
Mitchell S Anscher,
Kevin M Slawin,
Claus G Roehrborn,
Jeffrey D Forman,
Stanley L Liauw,
Larry L Kestin,
Theodore L DeWeese,
Peter T Scardino,
Andrew J Stephenson,
Alan Pollack
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ABSTRACT: It is unclear whether postoperative salvage radiation therapy (SRT) and early adjuvant radiotherapy (ART) after radical prostatectomy lead to equivalent long-term tumor control. We studied a group of patients undergoing ART by comparing them with a matched control group undergoing SRT after biochemical failure.
Using a multi-institutional database of 2299 patients, 449 patients with pT3-4N0 disease were eligible for inclusion, including 211 patients receiving ART and 238 patients receiving SRT. Patients were matched in a 1:1 ratio according to preoperative prostate-specific antigen Gleason score, seminal vesicle invasion, surgical margin status, and follow-up from date of surgery.
A total of 192 patients were matched (96:96). The median follow-up was 94 months from surgery and 73 months from RT completion. There was a significant reduction in biochemical failure with ART compared with SRT. The 5-year freedom from biochemical failure (FFBF) from surgery was 75% after ART, compared with 66% for SRT (hazard ratio [HR] = 1.6, P = .049). The 5-year FFBF from the end of RT was 73% after ART, compared with 50% after SRT (HR = 2.3, log rank [LR] P = .0007). From the end of RT, SRT and Gleason score >or=8 were independent predictors of diminished FFBF. From the date of surgery, Gleason score >or=8 was a significant predictor of FFBF.
Early ART for pT3-4N0 prostate cancer significantly reduces the risk of long-term biochemical progression after radical prostatectomy compared with SRT. Gleason score >or=8 was the only factor on multivariate analysis associated with metastasic progression.
Urology 07/2008; 72(6):1298-302; discussion 1302-4. · 2.43 Impact Factor
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ABSTRACT: There are no accepted guidelines for target volume definition for online image-guided radiation therapy (IGRT) after radical prostatectomy (RP). This study used cone beam CT (CBCT) imaging to generate information for use in post-RP IGRT.
The pelvic anatomy of 10 prostate cancer patients undergoing post-RP radiation therapy (RT) to 68.4 Gy was studied using CBCT images obtained immediately before treatment. Contoured bladder and rectal volumes on CBCT images were compared with planning CT (CT(ref)) volumes from seminal vesicle stump (SVS) to bladder-urethral junction. This region was chosen to approximate the prostatic fossa (PF) during a course of post-RP RT. Anterior and posterior planning target volume margins were calculated using ICRU report 71 guidelines, accounting for systematic and random error based on bladder and rectal motion, respectively.
A total of 176 CBCT study sets obtained 2 to 5 times weekly were analyzed. The rectal and bladder borders were reliably identified in 166 of 176 (94%) of CBCT images. Relative to CT(ref), mean posterior bladder wall position was anterior by 0.1 to 1.5 mm, and mean anterior rectum wall position was posterior by 1.6 to 2.7 mm. Calculated anterior margin as derived from bladder motion ranged from 5.9 to 7.1 mm. Calculated posterior margin as derived from rectal motion ranged from 8.6 to 10.2 mm.
Normal tissue anatomy was definable by CBCT imaging throughout the course of post-RP RT, and the interfraction anteroposterior motion of the bladder and rectum was studied. This information should be considered in devising post-RP RT techniques using image guidance.
International Journal of Radiation OncologyBiologyPhysics 03/2008; 70(2):431-6. · 4.11 Impact Factor
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Mary Feng,
Alexandra L Hanlon,
Thomas M Pisansky,
Deborah Kuban,
Charles N Catton,
Jeff M Michalski,
Michael J Zelefsky,
Patrick A Kupelian,
Alan Pollack,
Larry L Kestin, Richard K Valicenti,
Theodore L DeWeese,
Howard M Sandler
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ABSTRACT: To determine the rate and magnitude of late genitourinary (GU) and gastrointestinal (GI) toxicities after salvage or adjuvant radiotherapy (RT) for prostate cancer, and to determine predictive factors for these toxicities.
A large multi-institutional database that included 959 men who received postoperative RT after radical prostatectomy (RP) was analyzed: 19% received adjuvant RT, 81% received salvage RT, 78% were treated to the prostate bed only, and 22% received radiation to the pelvis.
The median follow-up time was 55 months. At 5 years, 10% of patients had Grade 2 late GU toxicity and 1% had Grade 3 late GU toxicity, while 4% of patients had Grade 2 late GI toxicity and 0.4% had Grade 3 late GI toxicity. Multivariate analysis demonstrated that adjuvant RT (p = 0.03), androgen deprivation (p < 0.0001), and prostate bed-only RT (p = 0.007) predicted for Grade 2 or higher late GU toxicity. For GI toxicity, although adjuvant RT was significant in the univariate analysis, no significant factors were found in the multivariate analysis.
Overall, the number of high-grade toxicities for postoperative RT was low. Therefore, adjuvant and salvage RT can safely be used in the appropriate settings.
International Journal of Radiation OncologyBiologyPhysics 08/2007; 68(5):1417-23. · 4.11 Impact Factor
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Andrew J Stephenson,
Peter T Scardino,
Michael W Kattan,
Thomas M Pisansky,
Kevin M Slawin,
Eric A Klein,
Mitchell S Anscher,
Jeff M Michalski,
Howard M Sandler,
Daniel W Lin,
Jeffrey D Forman,
Michael J Zelefsky,
Larry L Kestin,
Claus G Roehrborn,
Charles N Catton,
Theodore L DeWeese,
Stanley L Liauw, Richard K Valicenti,
Deborah A Kuban,
Alan Pollack
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ABSTRACT: An increasing serum prostate-specific antigen (PSA) level is the initial sign of recurrent prostate cancer among patients treated with radical prostatectomy. Salvage radiation therapy (SRT) may eradicate locally recurrent cancer, but studies to distinguish local from systemic recurrence lack adequate sensitivity and specificity. We developed a nomogram to predict the probability of cancer control at 6 years after SRT for PSA-defined recurrence.
Using multivariable Cox regression analysis, we constructed a model to predict the probability of disease progression after SRT in a multi-institutional cohort of 1,540 patients.
The 6-year progression-free probability was 32% (95% CI, 28% to 35%) overall. Forty-eight percent (95% CI, 40% to 56%) of patients treated with SRT alone at PSA levels of 0.50 ng/mL or lower were disease free at 6 years, including 41% (95% CI, 31% to 51%) who also had a PSA doubling time of 10 months or less or poorly differentiated (Gleason grade 8 to 10) cancer. Significant variables in the model were PSA level before SRT (P < .001), prostatectomy Gleason grade (P < .001), PSA doubling time (P < .001), surgical margins (P < .001), androgen-deprivation therapy before or during SRT (P < .001), and lymph node metastasis (P = .019). The resultant nomogram was internally validated and had a concordance index of 0.69.
Nearly half of patients with recurrent prostate cancer after radical prostatectomy have a long-term PSA response to SRT when treatment is administered at the earliest sign of recurrence. The nomogram we developed predicts the outcome of SRT and should prove valuable for medical decision making for patients with a rising PSA level.
Journal of Clinical Oncology 06/2007; 25(15):2035-41. · 18.37 Impact Factor
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JAMA The Journal of the American Medical Association 04/2007; 297(9):950-1; author reply 951. · 30.03 Impact Factor
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ABSTRACT: We evaluated whether posttreatment prostatic-specific antigen doubling time (PSADT) was predictive of prostate cancer mortality by testing the Prentice requirements for a surrogate endpoint.
We analyzed posttreatment PSA measurements in a cohort of 1,514 men with localized prostate cancer (T2c-4 and PSA level <150 ng/mL), treated and monitored prospectively on Radiation Therapy Oncology Group Protocol 92-02. From June 1992 to April 1995, men were randomized to neoadjuvant androgen deprivation and 65-70 Gy of radiation therapy (n = 761), or in combination with 24 months of adjuvant androgen deprivation (n = 753). Using an adjusted Cox proportional hazards model, we tested if PSADT was prognostic and independent of randomized treatment in this cohort. The endpoints were time to PSADT (assuming first-order kinetics for a minimum of 3 rising PSA measurements) and cancer-specific survival (CSS).
After a median follow-up time of 5.9 years, randomized treatment was a significant predictor for CSS (p(Cox) = 0.002), PSADT <6 months (p(Cox) < 0.001), PSADT <9 months (p(Cox) < 0.001), and PSADT <12 months (p(Cox) < 0.001) but not for PSADT <3 (p(Cox) = 0.4). The significant posttreatment PSADTs were also significant predictors of CSS (p(Cox)< 0.001). After adjusting for T stage, Gleason score and PSA, all of Prentice's requirements were not met, indicating that the effect of PSADT on CSS was not independent of the randomized treatment.
Prostatic specific antigen doubling time is significantly associated with CSS, but did not meet all of Prentice's requirements for a surrogate endpoint of CSS. Thus, the risk of dying of prostate cancer is not fully explained by PSADT.
International journal of radiation oncology, biology, physics 12/2006; 66(4):1064-71. · 4.59 Impact Factor
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Nature Clinical Practice Urology 06/2006; 3(5):256-7. · 4.07 Impact Factor
