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Radiation Oncology/Prostate/Brachytherapy

Prostate Brachytherapy

Guidelines

 * Please see Prostate Guidelines page

Isotope

 * Seattle (1999 - 2006) -- I-125 vs. Pd-103
 * Randomized. 602 patients, Stage T1c-T2a, GS 2-6, PSA 4-10 ng/ml. Arm 1) I-125 at 144 Gy vs. Arm 2) Pd-103 at 125 Gy. Modified peripheral loading pattern. Postimplant CT 2-4 hours later
 * Preliminary toxicity; 2002 PMID 11895205 -- "I-125 versus Pd-103 for low-risk prostate cancer: morbidity outcomes from a prospective randomized multicenter trial." (Wallner K, Cancer J. 2002 Jan-Feb;8(1):67-73.) Min F/U 1 year
 * 110 of planned 380 patients
 * Outcome: 6-month AUA score I-125 16 vs. Pd-103 11; 1-year AUA score 13 vs. 12; benefit dependent on baseline AUA score but not on volume or age
 * Toxicity: Generally, trend to higher morbidity with I-125
 * Conclusion: Patients treated with Pd-103 recovered from radiation induced prostatitis faster; patients with minimal pretreatment urinary symptoms benefit most
 * Preliminary PSA; 2003 PMID 14630265 -- "125I versus 103Pd for low-risk prostate cancer: preliminary PSA outcomes from a prospective randomized multicenter trial." (Wallner K, Int J Radiat Oncol Biol Phys. 2003 Dec 1;57(5):1297-303.)
 * 115 of planned 600 patients. Short neoadjuvant ADT in 20 patients. bPFS defined PSA <= 0.5 ng/ml. Median F/U 2.9 years
 * Outcome: 3-year bPFS I-125 89% vs. Pd-103 91% (NS). If D90 <100% 82% vs. >= 100% 97% (SS). If V100 <90% 87% vs. >=90% 97% (SS). Dosimetric parameters more pronounced for I-125
 * Conclusion: No difference at 3 years
 * Morbidity; 2005 PMID 16259869 -- "I-125 versus Pd-103 for low-risk prostate cancer: long-term morbidity outcomes from a prospective randomized multicenter controlled trial." (Herstein A, Cancer J. 2005 Sep-Oct;11(5):385-9.)
 * 352 of planned 600 patients. Use of alpha-blockers at discretion. Minimum F/U 2 years
 * GU: AUA peak at 1 month postimplant. 1-month AUA score I-125 15 vs. Pd-103 19 (SS); 6-months 12 vs. 10 (SS). Use of alpha-blockers similar.
 * GI: Radiation proctitis (persistent bleeding) in 9%, no difference between arms. If R100 <1.0 cc, bleeding in 2%
 * Conclusion: Pd-103 results in more intense symptoms, but faster recovery than I-125
 * Dosimetry; 2008 PMID 18376221 -- "There is a wide range of predictive dosimetric factors for I-125 and pd-103 prostate brachytherapy." (Herstein A, Am J Clin Oncol. 2008 Feb;31(1):6-10.)
 * 265 of 602 patients with CT-dosimetry. V50, V75, V100, V150, V200, V300; D50, D75, D90, D200 evaluated
 * Outcome: bPFS I-125 85% vs. Pd-103 89%. Almost all parameters (not just D90 and V100) showed improvement with higher values.
 * D90 and V100 dosimetry: Highly correlated (r=0.7-0.8). V100 (I-125) 3-year bPFS >90% 91% vs. <90% 86% (NS); V100 (Pd-103) 100% vs. 89% (SS); D90 (I-125) >100% 91% vs. <100% 85% (NS); D90 (Pd-103) 100% vs. 87% (SS)
 * Conclusion: Most dosimetric parameters have predictive value, in addition to D90 and V100

Strand vs loose seeds

 * Seattle (2003-2004) -- Stranded seeds vs loose seeds
 * Randomized. 62 patients with cT1c-T2a. Brachytherapy, 144 Gy, treatment plan devised prior to randomization. Arm 1) Strand seeds via Mick needles (however, 1/3 of seeds were lose to accommodate standard implant pattern) vs. Arm 2) Loose seeds via Mick applicator. Post-implant dosimetry at day 0 and day 30. Primary outcome seed loss and dosimetric parameters
 * 2007 PMID 17434106 -- "A prospective randomized comparison of stranded vs. loose 125I seeds for prostate brachytherapy." (Reed DR, Brachytherapy. 2007 Apr-Jun;6(2):129-34.)
 * Outcome: Seed loss strand 23% vs. loose 47% (p=0.053). Mean seeds lost 0.4 vs. 1.1 (p=0.06). Multiple seed loss in 10% vs. 25% patients. Strand seeds trend to worse V100 and D90
 * Conclusion: Strong trend to lower seed loss with stranded seeds

Critera for implant

 * Volume of the prostate: should be > 20 cc and < 60 cc. Can use androgen ablation to shrink the prostate if it is too large.
 * Men with large prostates have significant voiding problems.

Timing of NSAIDs

 * Toronto (2004-2008) -- Meloxicam 1 week prior to implant vs day of implant
 * Randomized. 300 patients, treated with brachytherapy. Arm 1) meloxicam 7.5 mg BID started 1 weeks prior to implant x4 weeks vs Arm 2) started day of implant x4 weeks. Primary outcome: MRI prostate volume at 1 month, IPSS at 1 and 3 months, catheterization
 * 2010 PMID 20350785 -- "A Phase III Randomized Trial of the Timing of Meloxicam with Iodine-125 Prostate Brachytherapy." (Crook J, Int J Radiat Oncol Biol Phys. 2010 Mar 27. [Epub ahead of print])
 * Outcome: No difference in edema, catheterization (8% vs 6%, NS), or IPSS
 * Conclusion: Starting meloxicam 1 week prior to BT did not impact edema and urinary symptoms

Erectile function

 * PMID 15890585, 2004 - Merrick GS et al.
 * Most were Pd-103, 16% were I-125. 37% had implant only; the remainder had EBRT to prostate + seminal vesicles. Hormones used in 23%.
 * 3-yr potency preservation of 50.5%. The preimplant erectile score was 29 for those with adequate postimplant function and 25 for those without.  Median time to ED was 5.4 months. After brachy, erectile score was 20 in potent patients and 3 in those with ED.  On multivariate analysis, the preimplant erectile score and D50 to the proximal crura predicted for ED.

Comparison to Radical Prostatectomy

 * ACOSOG Z0070 - Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial (SPIRIT)
 * See information at Radiation_Oncology/Prostate/Localized Prostate Cancer
 * A randomized trial of radical prostatectomy versus brachytherapy for patients with T1c or T2a N0 M0, PSA < 10, G <= 6 prostate cancer.
 * Closed early due to non-accrual.

EBRT and Implant Combinations

 * RTOG 00-19 (2000-01) - phase II. Intermediate risk: PSA 10-20 and GS <7, or PSA <20 and GS 7. 45 Gy EBRT followed by 108 Gy I-125 brachytherapy.
 * Median f/u 20 mos. Acute grade 3 genitourinary toxicity in 7.6%. No grade 4 or 5. Late grade 3 GU and GI toxicity was 3.3% at 18 mos. No grade 4 or 5.

Supplemental EBRT dose

 * Seattle (2000-2004) -- (EBRT 44 Gy + BT 90 Gy) vs. (EBRT 20 Gy + BT 115 Gy)
 * Randomized. Closed prematurely due to slowing accrual. 568 of planned 600 patients, clinical T1c-T2a, Glease 7-10 and/or PSA 10-20 ng/ml. Arm 1) EBRT 44 Gy + Pd-103 implant 90 Gy vs. Arm 2) EBRT 20 Gy + Pd-103 implant 115 Gy
 * 2005 PMID 16086912 -- "20 Gy versus 44 Gy supplemental beam radiation with Pd-103 prostate brachytherapy: preliminary biochemical outcomes from a prospective randomized multi-center trial." (Wallner K, Radiother Oncol. 2005 Jun;75(3):307-10.)
 * 165 patients reported
 * Outcome: 3-year bPFS 44 Gy 88% vs. 20 Gy 83% (NS)
 * Conclusion: Likelihood of cure similar with standard or lower dose, in the setting of high prostate coverage by brachytherapy
 * Treatment gap; 2008 PMID 18525300 -- "The time gap between Pd-103 prostate brachytherapy and supplemental beam radiation does not impact on rectal morbidity or likelihood of cure." (Bittner N, Am J Clin Oncol. 2008 Jun;31(3):231-6.)
 * Median gap time between completion of EBRT and implant was 3 days (-6 to 40 days). Median F/U 3.2 years
 * Outcome: 3-year bPFS 84%, no significant difference based on gap. Predictors of failure GS, PSA, and D90
 * Rectal toxicity: Overall 7%. Predictors high R100 and EBRT 44 Gy, but not treatment gap
 * Conclusion: Shorter gap between EBRT and BT safe; doesn't improve bPFS but allows timely treatment

EBRT + Implant Boost vs. EBRT alone

 * ASCENDE-RT
 * Randomized. 398 men. Median age 68. High risk disease 69%. Arm 1) ADT + pelvic RT 46 Gy + EBRT boost to 78 Gy, vs Arm 2) ADT + pelvic RT 46 Gy + LDR BT boost.
 * 2016 PMID 28262473 -- "Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer" (Morris WJ, Int J Radiat Oncol Biol Phys. 2017 Jun 1;98(2):275-285. doi: 10.1016/j.ijrobp.2016.11.026. Epub 2016 Nov 24.) Median F/U 6.5 years
 * Outcome: EBRT boost 2x more likely to have biochemical failure. 5-year bPFS EBRT 84% vs 89%; 9-year 83% vs 62% (SS). Benefit in both intermediate- and high-risk groups. No OS difference at 6.5 years
 * Conclusion: LDR brachy boost lower biochemical failure rate

 * UK (Mount Vernon), 2007 (1997-2005)
 * 220 pts. Stage T1-T3, localized, PSA < 50. Randomized to: 1) EBRT alone: 55 Gy / 20 fx (2.75 Gy/fx), or 2) EBRT + HDR brachy: EBRT 35.75 Gy / 13 fx (2.75/fx) then 8.5 Gy HDR x 2 over 2 days. Majority (76%) received neoadjuvant hormonal therapy (6 months for low/int risk; up to 3 yrs for high risk)
 * Low risk 4%, Int risk 42%, High risk 54%.
 * PMID 17531335 — "High dose rate brachytherapy in combination with external beam radiotherapy in the radical treatment of prostate cancer: initial results of a randomised phase three trial." Hoskin PJ et al. Radiother Oncol. 2007 Aug;84(2):114-20.
 * Median f/u 30 mo. Mean PSA relapse-free survival (using 1997 ASTRO definition): 5.1 yrs (combined) vs 4.3 yrs (EBRT alone)
 * 2012: PMID 22341794 -- "Randomised trial of external beam radiotherapy alone or combined with high-dose-rate brachytherapy boost for localised prostate cancer." (Hoskin PJ, Radiother Oncol. 2012 May;103(2):217-22.)
 * Median f/u 7 yrs. Improved RFS: Median time to relapse 74 mo (EBRT) vs 116 mo (EBRT+Brachy). 5-, 7-, and 10-yr RFS 61%, 48% and 39% (EBRT) vs 75%, 66% and 46% (EBRT+Brachy). On multivariate analysis, treatment arm, risk category, and ADT use were significate for risk of relapse. No significant difference in OS
 * Similar rate of severe late urinary and bowel morbidity
 * Conclusion: "EBRT+HDR-BTb resulted in a significant improvement in RFS compared to EBRT alone with a 31% reduction in the risk of recurrence (p=0.01) and similar incidence of severe late urinary and rectal morbidity."
 * Comment: relatively low EBRT dose

 * McMaster University (Ontario), 2005 (1992-97)
 * PMID 15718316 — "Randomized trial comparing iridium implant plus external-beam radiation therapy with external-beam radiation therapy alone in node-negative locally advanced cancer of the prostate." Sathya JR et al. J Clin Oncol. 2005 Feb 20;23(6):1192-9.
 * 138 pts. Clinical stage T2-T3,N0, surgically-staged node negative. Randomized to: 1) EBRT alone: 66 Gy four-field box to the prostate + SV + 2cm margin, or 2) EBRT + implant boost: Iridium seed placed at time of lymphadenectomy if frozen section negative. Used Syed's template to guide needle placement of 18 needles; TRUS was not done. Prescribed 35 Gy to entire prostate, 40 Gy to >80%. Two weeks after implant, 40 Gy of EBRT to prostate + SV + 2 cm.
 * Median f/u 8.2 yrs. 61% biochemical failure (EBRT) vs 29% (EBRT+brachy)
 * Comment: suboptimal EBRT dose

EBRT Field Size

 * Wheeling (WV) (1995-2005)
 * Retrospective. 186 pts w/ high risk, treated with 45 Gy EBRT (Whole Pelvis or Mini-Pelvis) and brachytherapy (93% with Pd-103). >75% received hormonal therapy.
 * 2010 PMID 19553031 -- "Whole-pelvis radiotherapy in combination with interstitial brachytherapy: does coverage of the pelvic lymph nodes improve treatment outcome in high-risk prostate cancer?" (Bittner N, Int J Radiat Oncol Biol Phys. 2010 Mar 15;76(4):1078-84.)
 * Median f/u 6.7 yrs. 10-yr bPFS 91.7% (WP) vs 84.4% (MP). Nonsignificant trend toward improved bPFS, CSS, and OS with WPRT. Improved OS for WPRT for pts who did not receive hormones.
 * Limited by retrospective nature. Pts treated with WP had higher risk features and were more likely to be treated with a longer course of hormonal therapy (69% receiving >6 months vs 38%).

Optimal dose

 * BED equation for low dose-rate implants:
 * BED = (R0/λ)*{1+(R0/(μ+λ)*(α/β))}
 * R0 = initial dose rate of implant = D90 * λ
 * λ = radioactive decay constant = ln2/T1/2
 * T1/2 = isotope half-life
 * μ = repair rate constant = 0.693/t1/2
 * t1/2 = tissue repair half time
 * Based on PMID 16242258: t1/2 = 1h, T1/2 = 60 days for I-125 or 17 days for Pd-103

 * Stock and Stone, Mount Sinai, 1998 - PMID 9588923 — "A dose-response study for I-125 prostate implants." Stock RG, Stone NN et al. Int J Radiat Oncol Biol Phys. 1998 Apr 1;41(1):101-8.
 * Retrospective. 134 pts, T1-T2, G <= 6. I-125 seeds. No EBRT or hormonal therapy. CT scan for post implant dosimetry performed at one month on all pts. Used TG43 guidelines. Biochemical failure defined as two consecutive PSA rises or nadir > 1. Biopsies routinely performed at 2 yrs.
 * Median f/u 32 months. Improved freedom from biochemical failure (FFBF) with increasing D90. 4-yr FFBF 68% (D90 < 140 Gy) vs 92% (>= 140 Gy). Negative prostate biopsies at 2 yr in 70% vs 83%.
 * Conclusions: Dose was most significant predictor of biochemical failure. Dose response is more pronounced in pts with PSA > 10, with 51% vs 100% FFBF.

Outcomes
Disease-specific survival:
 * Mount Sinai, 2006 (1990-2004) - PMID 16309852 — "Disease-specific survival following the brachytherapy management of prostate cancer." Stock RG et al.
 * Retrospective. 1561 pts. Treated with various techniques including brachy alone, brachy + hormones, or brachy + EBRT. Death from prostate cancer was counted if a pt died with the presence of metastatic disease. Pts who had rising PSA at the time of death or who were receiving systemic treatment at the time of death were not necessarily counted as prostate cancer related deaths.
 * 10-yr DSS 96% and OS 74%. Gleason score significantly affected DSS, 98% (6 or less), 91% (7), 92% (8+). PSA after treatment had most significant effect on DSS: 100% for no PSA failure, 52% for doubling time < 10 m, and 98% for doubling time > 10 m.
 * Comment: first brachytherapy series to report DSS>

Implant Quality Assessment
HDR + EBRT Combination:

 *  Hospital A C Camargo (Brazil) (1997-2005)
 * 2008 PMID 18566673 -- "The relationship between the biochemical control outcomes and the quality of planning of high-dose rate brachytherapy as a boost to external beam radiotherapy for locally and locally advanced prostate cancer using the RTOG-ASTRO Phoenix definition. "(Pellizzon AC, Int J Med Sci. 2008 Jun 4;5(3):113-20.)
 * Retrospective. 209 patients, low/intermediate/high risk. HDR 16-24Gy/4 + EBRT 45 Gy. Median F/U 5.3 years
 * Outcome:Overall survival (OS) and disease specific survival rates at 3.3 years were 97.8% and 98.4%, respectively. On univariate analysis the prognostic factors related bC were GR (p= 0.040), GS ≤ 6 (p= 0.002), total dose of HDR-BT ≥ 20 Gy (p< 0.001), 3DHDR (p< 0.001), BED-HDR ≥ 99 Gy1.5 (p<0.001) and BED-TT ≥ 185 (p<0.001). On multivariate analysis the statistical significant predictive factors related to bC were RG (p< 0.001), HDR-BT ≥ 20 Gy (p=0.008) and 3DHDR (p<0.001).
 * 2008 PMID 18601759 -- "Updated results of high-dose rate brachytherapy and external beam radiotherapy for locally and locally advanced prostate cancer using the RTOG-ASTRO Phoenix definition." (Pellizzon AC, Int Braz J Urol. 2008 May-Jun;34(3):293-301.)
 * On multivariate analysis the only statistical significant predictive factor for biochemical control (bNED) was the risk group.
 * Conclusion: "Although the radiation dose administered to the prostate is an important factor related to bNED, this could not be established with statistical significance in this group of patients. "

PSA kinetics
Brachytherapy alone:
 * Princess Margaret, 2007 (1999-2003) PMID 17869662 — "PSA kinetics and PSA bounce following permanent seed prostate brachytherapy." (Crook J, Int J Radiat Oncol Biol Phys. 2007 Oct 1;69(2):426-33.)
 * 292 pts treated with I-125 brachytherapy without EBRT or hormones. All have >30 months of PSA followup.
 * Resolved PSA bounces (>=0.2) seen in 40%, median onset 15 months with median magnitude 0.76. Magnitude >2 (i.e. biochemical failure by Phoenix definition) seen in 15%. Younger age is predictive of bounce.
 * Conclusions: The PSA bounce does not predict subsequent failure. Caution is advised in interpreting an early increasing PSA level in the first 30 months after 125I brachytherapy in favorable-risk patients.

With hormonal thearpy:
 * Germany, 2007 PMID 17270634 — "Prostate-specific antigen kinetics after brachytherapy or external beam radiotherapy and neoadjuvant hormonal therapy." (Pinkawa M, Urology. 2007 Jan;69(1):129-33.)
 * 75 pts treated with neoadj hormones (median 4 mo). RT was implant alone (29 pts), EBRT + implant boost (21), or EBRT only (25). Minimum 24 mo f/u.
 * Trend: initial nadir - PSA 0.1 at 3 months after RT. Rising PSA levels noted in 83%. Subsequent PSA rises/bounces noted (one time-23%, two-21%, or more-17%) to median 0.6 at 16 months. New nadir of 0.1 reached by 35 mo.
 * Conclusion: Temporarily rising PSA levels can be expected for most patients after primary RT and NHT following a first nadir.

Mixed (pts with and without hormones)
 * Cleveland Clinic, 2007 PMID 16213667 — "PSA kinetics after prostate brachytherapy: PSA bounce phenomenon and its implications for PSA doubling time." (Ciezki JP, Int J Radiat Oncol Biol Phys. 2006 Feb 1;64(2):512-7.)
 * 162 pts, brachytherapy +/- hormones (in 38%).
 * PSA bounce (>=0.2) in 46%.
 * Conclusions: "Patients experiencing a PSA bounce are more likely to be younger and will have a better bRFS. The PSADT cannot differentiate a PSA bounce from bF. The time to the initial PSA rise after nadir is an excellent discriminator of bF from PSA bounce. The time of the PSA rise after nadir occurs far sooner for a PSA bounce than for bF. This factor should be considered when assessing a patient with a rising PSA level after PI before a patient is administered salvage therapy."

PSA bounce

 * Cleveland Clinic (1996-2005)
 * 1261 pts, predominantly low-int risk, T1-T2, treated with I-125 brachy alone. 3 yrs minimum follow-up. Androgen deprivation given in 22%.
 * 2011 PMID 20646846 -- "PSA Bounce and Biochemical Failure After Brachytherapy for Prostate Cancer: A Study of 820 Patients With a Minimum of 3 Years of Follow-Up." (Caloglu M, Int J Radiat Oncol Biol Phys. 2011 Jul 1;80(3):735-41.)
 * Median f/u 58 m. PSA bounce ≥0.2 above nadir in 30%. Median time to first PSA rise was 17.4 months vs 34.35 months for bF.
 * The use of PSA bounce definitions other than 0.2 did not provide additional prognostic benefit. Patients with PSA bounce had superior bRFS rates to those without PSA bounce. The time to first rise in PSA is an important discriminator between a PSA bounce and bF; a bounce usually occurs much earlier than a rise that corresponds to bF.
 * Conclusion: A bounce definition of a rise ≥0.2 ng/mL is a reliable definition among several other definitions. The time to first PSA rise is the most valuable factor for distinguishing between a bounce and biochemical failure.

 * Institut Curie, 2006 (1999-2001) - PMID 16644467 — "PSA bounce after permanent implant prostate brachytherapy may mimic a biochemical failure: a study of 295 patients with a minimum 3-year followup." (Toledano A, Brachytherapy. 2006 Apr-Jun;5(2):122-6.)
 * 295 pts. I-125.
 * 55% showed a bounce of at least 0.1 ng/ml. Mean bounce 0.8 at mean time to bounce 19 months. 11% of pts had 3 consecutive rises (met ASTRO criteria for biochemical failure), among which 56% had complete normalization of PSA. D90 > 200 Gy predicted PSA bounce of > 0.4.

HDR Boost

 * RTOG 0321; 2010 PMID 20207506 -- "Phase II Trial of Combined High-Dose-Rate Brachytherapy and External Beam Radiotherapy for Adenocarcinoma of the Prostate: Preliminary Results of RTOG 0321." (Hsu IC, Int J Radiat Oncol Biol Phys. 2010 Mar 5. [Epub ahead of print])
 * Phase II. 112/125 patients, T1c-T3b (T3 9%) prostate cancer. EBRT 45/25 + HDR 19/2. Median F/U 2.5 years
 * Toxicity: Acute G3 GU/GI 3%, Late G3+ GU/GI 3%
 * Conclusion: Acceptable level of adverse events

 * Geneva; 2009 (2000-2004) PMID 19250768 -- "Hypofractionated boost with high-dose-rate brachytherapy and open magnetic resonance imaging-guided implants for locally aggressive prostate cancer: a sequential dose-escalation pilot study." (Ares C, Int J Radiat Oncol Biol Phys. 2009 Nov 1;75(3):656-63. Epub 2009 Feb 26.)
 * Phase I. 77 patients with locally aggressive PCA (perineural invasion, GS 8-10). Conventional 3D-CRT 64-64.4, followed by MRI-guided HDR boost Ir-192 given 12/2 -> 14/2 -> 16/2. ADT 81%
 * Outcome: 3-year bDFS 87%, DSS 100%
 * Toxicity: 3-year late GI Grade 2+ 6%, GU Grade 2+ 9%
 * Conclusion: Boosting partial volume with HDR brachytherapy is feasible, preliminary control is encouraging
 * Comment: See PMID 19910135 for SBRT boost from same group

 * William Beaumont/Kiel
 * 2006 PMID 16520907 -- "Hypofractionated conformal HDR brachytherapy in hormone naive men with localized prostate cancer. Is escalation to very high biologically equivalent dose beneficial in all prognostic risk groups?" (Galalae RM, Strahlenther Onkol. 2006 Mar;182(3):135-41.)
 * Retrospective. 378 patients at WBH, 201 patients at Kiel. Localized PCA, hormone-naive, high risk features (>=T2b or GS >=7 or PSA >=10). Mean F/U 5.3 years
 * bNED: 80%, dose >94Gy 85% vs. <94Gy 59% (SS)
 * By risk group: no difference if only 1 risk factor, benefit with 2 RFs (p=0.02) and 3 RFs (p<0.001)
 * Conclusion: Dose escalation >94 Gy results in improved long-term outcomes, especially if 2-3 risk factors

 * William Beaumont
 * 2002 PMID 12023135 -- "Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer." (Martinez AA, Int J Radiat Oncol Biol Phys. 2002 Jun 1;53(2):316-27.)
 * Dose escalation. 207 patients (PSA>10, or GS>=7, or >=cT2b) treated with pelvic EBRT 46 Gy + HDR (5.5 - 11.5 Gy/fx x2-3). 58 patients low-dose (<93 Gy), 149 patients high-dose (>93 Gy). Mean F/U 4.4 years
 * 5-year bNED: 74% (low-dose 52% vs. high-dose 87%)
 * Toxicity: GI/GU Grade III 0.5%-9%
 * Conclusion: Effective for unfavorable PCA. Incremental benefit for bNED and CSS

Primary HDR

 * William Beaumont/California Endocurietherapy; 2009 (1993-2004) PMID 19952715 -- "High-Dose-Rate Prostate Brachytherapy: An Excellent Accelerated-Hypofractionated Treatment for Favorable Prostate Cancer (Martinez AA, Am J Clin Oncol. 2009 Nov 30. [Epub ahead of print])
 * Retrospective. 454 patients (HDR 55%, LDR-Pd 45%). WBH-HDR dose 38/4 BID, CET-HDR dose 42/6 in 2 implants one week apart, WBH-LDR 120 Gy. Median F/U 4.8 years
 * Outcome: 5-year bPFS WBH-HDR 91% vs. CET-HDR 88% vs WBH-LDR 89%
 * Toxicity: HDR better Grade 1-3 dysuria, urinary frequency/urgency, and rectal pain (SS). No difference in impotence rate
 * Conclusion: Comparable control, better toxicity with HDR monotherapy

 * Mount Vernon, UK; 2008 (2003-2006) PMID 18249501 -- "A Phase II study of high-dose-rate afterloading brachytherapy as monotherapy for the treatment of localized prostate cancer." (Corner C, Int J Radiat Oncol Biol Phys. 2008 Oct 1;72(2):441-6. Epub 2008 Feb 4.)
 * Phase II. 110 patients, locally advanced PCA. Dose escalation: 34/4 (n=30), 36/4 (n=25), 31.5/3 (n=55). Mean F/U (30, 18, 12 months)
 * Outcome: No PSA failures
 * Toxicity: No difference between groups; urethral cath rate 6%. Late G3 GU toxicity 2%; Late G3 GI toxicity 0%
 * Conclusion: Excellent biochemical response with no difference in toxicity

 * University of Bern
 * Gold markers; 2009 (2003-2006) PMID 19899006 -- "Use of gold markers for setup in image-guided fractionated high-dose-rate brachytherapy as a monotherapy for prostate cancer." (Ghadjar P, Strahlenther Onkol. 2009 Nov;185(11):731-5. Epub 2009 Nov 10.)
 * Retrospective. 35 patients. HDR monotherapy 38/4. Review of gold markers for position verification. Median F/U 3 years
 * Outcome: Change of applicator position compared to plan: fraction #1 1.4 mm, fraction #2 13.1 mm, fraction #3 4.1 mm, and fraction #4 2.6 mm. Readjustment required in 51% patients
 * Toxicity: No difference between patients who required readjustment vs none
 * Conclusion: Shifts up to 36 mm were observed; gold markers ensure setup accuracy
 * Initial; 2009 (2003-2005) PMID 19038584 --- "Toxicity and early treatment outcomes in low- and intermediate-risk prostate cancer managed by high-dose-rate brachytherapy as a monotherapy." (Ghadjar P, Brachytherapy. 2009 Jan-Mar;8(1):45-51. Epub 2008 Nov 26.)
 * Retrospective. 36 patients (low risk 78%, intermediate risk 22%). HDR 38/4 BID. ADT 13%. Median F/U 3 years
 * Outcome: 3-year bPFS 100%
 * Toxicity: Acute G3 GU toxicity 3%; late G3 GU toxicity 11%. No G3 GI toxicity. Sexual preservation 75%. Late G3 GU toxicity associated with urethral and PTV doses
 * Conclusion: Decrease of irradiated urethral volume may reduce GU toxicity and improve therapeutic ratio

 * William Beaumont
 * 2004 (1999-2001) PMID 14767279 -- "High dose rate brachytherapy as prostate cancer monotherapy reduces toxicity compared to low dose rate palladium seeds." (Grills IS, J Urol. 2004 Mar;171(3):1098-104.)
 * Retrospective. 149 patients with early stage low-risk PCA, treated with HDR (44%) or LDR (56%) Pd-103 implant. HDR 38/4 BID; LDR 120 Gy. Neoadjuvant ADT in 36% for gland volume optimization. Median F/U 2.9 years
 * Outcome: bPFS (ASTRO) HDR 98% vs LDR 97%
 * Toxicity: Acute dysuria HDR 36% vs LDR 67% (SS), acute urinary frequency/urgency 54% vs 92% (SS), acute rectal pain 6% vs 20% (SS). Late urinary frequency/urgency 23% vs 56% (SS), urethral stricture (NS). 3-year impotence HDR 16% vs LDR 45%
 * Conclusion: HDR and LDR have comparable control, but HDR better toxicity profile
 * 2001 (1999-2000) PMID 11163498 -- "Phase II prospective study of the use of conformal high-dose-rate brachytherapy as monotherapy for the treatment of favorable stage prostate cancer: a feasibility report." (Martinez AA, Int J Radiat Oncol Biol Phys. 2001 Jan 1;49(1):61-9.)
 * Phase II. 41 patients, favorable risk PCA, prostate 15-60cc (mean 31 cc). HDR monotherapy 38/4 BID (estimated equivalent to 76.4 Gy)
 * Outcome: Dosimetric outcomes reported
 * Conclusion: HDR protocol feasible
 * Osaka University
 * Initial; 2000 (1995-1998) PMID 11020563 -- "High-dose-rate interstitial brachytherapy as a monotherapy for localized prostate cancer: treatment description and preliminary results of a phase I/II clinical trial." (Yoshioka Y, Int J Radiat Oncol Biol Phys. 2000 Oct 1;48(3):675-81.)
 * Prospective. 22 patients with localized PCA (T1-T4). HDR 48/8 BID or 54/9 BID. ADT in 86%. Median F/U 2.6 years
 * Outcome: 4-year bPFS 55%, 4-year cPFS 95%.
 * Toxicity: No acute G3+ toxicity
 * Conclusion: Acute toxicity acceptable; continued patient accrual
 * Toxicity; 2003 (1995-2001) PMID 12694841 -- "High-dose-rate brachytherapy as monotherapy for localized prostate cancer: a retrospective analysis with special focus on tolerance and chronic toxicity." (Yoshioka Y, Int J Radiat Oncol Biol Phys. 2003 May 1;56(1):213-20.)
 * Retrospective. 43 patients, localized PCA (T1-T4). Median PSA 19.3. HDR 54/9 BID (except first 7 cases 48/8 BID). ADT in 88%. Median F/U 2 years
 * Outcome: 3-year bPFS 55%, local control 100%, OS 94%. Low risk 100% (5/5), intermediate risk 80% (8/10), high risk 61% (17/28)
 * Toxicity: Acute G4 in 2%, no Grade 3. No Late G3-4 toxicity; late G1-2 toxicity in 12% (rectal bleeding and rectal ulcer)
 * Conclusion: HDR as monotherapy feasible and well tolerated
 * Technique; 2006 PMID 17041799 -- "New ambulatory implant technique of high-dose-rate interstitial brachytherapy for prostate cancer." (Yoshida K, Radiat Med. 2006 Oct;24(8):595-9.)
 * Technique. New removable template described, to allow ambulatory implant
 * ADT; 2006 (1995-2002) PMID 16715663 -- "High-dose-rate brachytherapy combined with long-term hormonal therapy for high-risk prostate cancer: results of a retrospective analysis." (Oh RJ, Radiat Med. 2006 Jan;24(1):58-64.)
 * Retrospective. 35 patients, high risk PCA (>=T2b or Grade 3 or PSA >= 20). HDR 54/9. Median neoadjuvant ADT 7 months, median adjuvant ADT 3.3 years. Median F/U 4.7 years
 * Outcome: 5-year bPFS 62%, local control 96%, DFS 76%, CSS 89%, OS 87%
 * Conclusion: HDR plus long-term ADT is at least as effective as EBRT plus ADT
 * Outcomes; 2006 (1995-2004) PMID 16870289 -- "High-dose-rate brachytherapy without external beam irradiation for locally advanced prostate cancer." (Yoshioka Y, Radiother Oncol. 2006 Jul;80(1):62-8. Epub 2006 Jul 25.)
 * Retrospective. 111 patients, localized PCA (low risk 13%, intermediate 25%, high risk 61%). HDR dose 48/8 BID or 54/9 BID. Median F/U 2.2 years
 * Outcome: 3-year bPFS 83%; 5-year bPFS 70%. Local control 100% and 97%.
 * Toxicity: Late G3 toxicity 1%
 * Conclusion: Feasible and acceptable toxicity
 *  Late toxicity; 2009 (2001-2005) PMID 19345517 -- "Correlation between dosimetric parameters and late rectal and urinary toxicities in patients treated with high-dose-rate brachytherapy used as monotherapy for prostate cancer." (Konishi K, Int J Radiat Oncol Biol Phys. 2009 Nov 15;75(4):1003-7. Epub 2009 Apr 3.)
 * Retrospective. 83 patients, T1-T4 (low risk 17%, intermediate risk 23%, high risk 59%). HDR 54/9 BID. Median F/U 3 years
 * Toxicity: Grade 3 toxicity 1/83 patients (urethrorectal fistula). Grade 2 GI toxicity 5%, Grade 2 GU toxicity 6%
 * Predictors for rectal bleeding: Rectal V40 <8cc, D5cc <27 Gy
 * Conclusion: Dosimetric parameters predicting for rectal bleeding identified

 * Offenbach, Germany; 2004 (2002-2003) PMID 15057433 -- "3-D conformal HDR brachytherapy as monotherapy for localized prostate cancer. A pilot study." (Martin T, Strahlenther Onkol. 2004 Apr;180(4):225-32.)
 * Retrospective. 52 patients, low/intermediate risk. HDR 38/4. Median F/U 8 months
 * Outcome: Acute G3 GU toxicity 4%; no G2+ GI toxicity
 * Conclusion: HDR as monotherapy is feasible, with minimal acute toxicity

Dose Comparisons
 * Ohio State; 2000 PMID 10661360 -- "A simple method of obtaining equivalent doses for use in HDR brachytherapy." (Nag S, Int J Radiat Oncol Biol Phys. 2000 Jan 15;46(2):507-13.)
 * Microsoft Excel based program that applies the LQ formula to calculate BED for various fractionation schemes, and reconverts it to "standard" (2 Gy/fx) fractionation
 * Comment (PMID 11183737): impact of a/b on prostate hypofractionated regimens. Consider 5 x 6.7 Gy equivalent to 78 Gy as a good dose vs. 5 x 8.0 Gy proposed equivalent to 60 Gy proposed by Nag


text:
Radiation Oncology/Prostate/Hormones

Androgen Deprivation Therapy
 * Medications
 * Primary Androgen Deprivation
 * Combined Androgen Deprivation and RT
 * Metastatic Disease

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Radiation Oncology/Prostate/Hormones


text:
Radiation Oncology/Prostate/Prostatectomy

Prostatectomy vs. Watchful waiting
''Please see the Watchful waiting chapter

Role of surgical staging

 * Rate of lymphedema is 25-30% in pts undergoing limited dissection, 66% if complete (therapeutic) dissection in pts receiving XRT.
 * Abstract Pilepich, from RTOG 75-06 and 77-06

 * Abstract — "Impact of surgical staging in evaluating the radiotherapeutic outcome in RTOG #77-06, a phase III study for T1BN0M0 (A2) and T2N0M0 (B) prostate carcinoma." Asbell et al.
 * Not randomized. 12-year OS 48% (staging laparotomy) vs 38% (lymphangiogram), DFS 38% vs 26%, decreased bone mets. Indicates that lymphangiogram group was understaged compared with surgical group.

Natural history after RP

 * Multi-Institutional; 2009 (1987-2005) PMID 19636023 -- "Prostate cancer-specific mortality after radical prostatectomy for patients treated in the prostate-specific antigen era." (Stephenson AJ, J Clin Oncol. 2009 Sep 10;27(26):4300-5. Epub 2009 Jul 27.)
 * Retrospective; Memorial Sloan Kettering and Baylor patients to develop a nomogram, validation on Cleveland Clinic and University of Michigan data. 12,677 patients treated with RP. Primary outcome PCA-specific mortality. Median F/U 4 years
 * Outcome: 15-year PCSM 12%, all-cause mortality 38%. Only 4% of contemporary patients had predicted 15-year PCSM >5%. Using D'Amico risk groups, 15-year PCSM good risk 2% vs. intermediate risk 10% vs. high risk 19% (good risk comprised 46% of patients)
 * Conclusion: Few patients will die from prostate cancer within 15 years after radical prostatectomy, despite presence of adverse clinical features

Natural history of biochemical failure:
 * Pound, 1999 - PMID 10235151 — "Natural history of progression after PSA elevation following radical prostatectomy." Pound CR et al. JAMA. 1999 May 5;281(17):1591-7.
 * 315 of 1997 men developed biochemical failure. 34% developed mets in median time to mets 8 years after PSA elevation. Median time to death 5 years after mets. Predictive of mets: Gleason 8-10, PSA recurrence < 2 yrs after surgery, PSA doubling time < 10 months.

Factors predicting local recurrence:
 * See section: Clinical and Pathologic Factors predicting recurrence at Adjuvant RT after Prostatectomy.

Factors predicting biochemical failure:
 * Harvard 2005 (1989-2002) - PMID 16051949 — "Identifying patients at risk for significant versus clinically insignificant postoperative prostate-specific antigen failure." D'Amico AV et al. J Clin Oncol. 2005 Aug 1;23(22):4975-9.
 * 1011 pts. Looked for factors identifying post-op PSA doubling time < 3 months ("clinically significant") or PSA DT > 12 months or no failure ("clinically insignificant")
 * Predictive of clinically significant failure: 1) preoperative PSA velocity > 2 ng/mL/yr, and 2) Gleason 7 or above.
 * Predictive of clinically insignificant or no failure: 1) PSA < 10, 2) nonpalpable cancer with Gleason 6 or less, and 3)preoperative PSA velocity < 2

Factors predicting metastatic disease:

 * PSA doubling time < 10 months (from Pound)
 * Extracapsular extension, SV invasion, Gleason 8-10, higher PSA at time of biochemical failure — (Dotan ZA et al - Abstract 162, 2005 Multidisciplinary Prostate Cancer Symposium) - nomogram

Factors predicting survival:
 * Post-Prostatectomy PSA Velocity Linked to Increased Mortality
 * Anthony D'Amico. NEJM, 8 July 2004, 351:125-135

 * D'Amico - (Abstract) American Urological Association, 2005, Abstract 1678
 * 1011 pts. Evaluated factors predictive of mortality - included 1-year PSA velocity prior to diagnosis, baseline PSA, Gleason score, clinical stage. Correlated with post-operative PSA doubling time, and correlated PSA doubling time with mortality.
 * Short postoperative PSA doubling time (<3 months) predicted death due to cancer and overall deaths. Short PSA DT more likely in pts with preoperative PSA velocity > 2 per year and a Gleason of 7 or higher.  Factors predictive of long PSA doubling time (>12 months) or no PSA failure were baseline PSA < 10, clinical stage T1c or less, Gleason 6 or less, and PSA velocity < 0.5 / yr.
 * Conclusion: pts with protracted PSA after surgery may not need salvage treatment.

 * Johns Hopkins (1982-2000)
 * 379 pts with biochemical recurrences after RP. PSA-DT groups of <3 (6%), 3-9 (31%), 9-15 (21%), >15 (42%) months
 * 2005 PMID 16046649 — "Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy." Freedland SJ et al. JAMA. 2005 Jul 27;294(4):433-9. Median f/u 10 yrs after surgery.
 * Prostate-cancer specific survival is predicted by: PSA doubling time, Gleason score, and interval from surgery to biochemical failure.
 * 2007 PMID 17470867 -- "Death in patients with recurrent prostate cancer after radical prostatectomy: prostate-specific antigen doubling time subgroups and their associated contributions to all-cause mortality." (Freedland SJ, J Clin Oncol. 2007 May 1;25(13):1765-71.) Median F/U 11.4 years
 * Outcome: PSA-DT <3 deaths account for only 13% due to low number; they die quickly, but with longer follow-up, slower PSA-DT patients start to die too. Intermediate PSA-DT 3-9 months account for 60% of PCA-related deaths
 * In PSA-DT <15 months, 90% will die *of* prostate cancer, not *with* prostate cancer at 15 years. Only if PSA-DT >15 months, competing-cause mortality greater
 * Conclusion: Even intermediate PSA-DT leads to prostate-cancer death

Prostatectomy vs RT

 * Also see: Radiation Oncology/Prostate/Localized Prostate Cancer (for comparisons of treatment modalities)

 * Cleveland Clinic, 2002 (1990-98) - PMID 12177097 — "Comparison of the efficacy of local therapies for localized prostate cancer in the prostate-specific antigen era: a large single-institution experience with radical prostatectomy and external-beam radiotherapy." Kupelian PA et al. J Clin Oncol. 2002 Aug 15;20(16):3376-85.
 * Retrospective, single-institution. 1682 pts with clinical stage T1-T2, treated during the PSA era. Treated with prostatectomy or RT to 68-78 Gy (median 70.2 Gy). Excluded pts with adjuvant androgen deprivation. Allowed neoadjuvant androgen deprivation if less than 6 months (19%). End-point was biochemical relapse free survival. Used ASTRO definition for PSA failure after RT. For RP failure was two consecutive PSA > 0.2; defined failure at time of first detectable level.
 * bRFS increased for prostatectomy arm 80% vs 73% at 5-years and 72% vs 70% at 8-years. On multivariate analysis, treatment modality was not an independent predictor of relapse. For favorable tumors, no difference between RP and RT: 8-year bRFS 86% vs 90%. For unfavorable tumors, 8-year bRFS 62% vs 59% (N.S.). For unfavorable pts treated with RT to >= 72 Gy, there was an improved bRFS 82% vs 70% at 5 years compared to RP. For dose < 72 Gy, it was worse compared to RP: 50% vs 70%.
 * Conclusion: "Eight-year biochemical failure rates were identical between RT and RP in any subgroup. Outcome is determined mainly by pretreatment PSA levels, bGS, clinical T stage, and, for RT patients, radiation dose."

 * M. D. Anderson Cancer Center Orlando, 2004 (1990-98) - PMID 14697417 — "Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy > or =72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer." Int J Radiat Oncol Biol Phys. 2004 Jan 1;58(1):25-33 Kupelian et al.
 * Retrospective. Comparison of biochemical relapse-free survival (bRFS) for various methods.
 * CONCLUSION: The biochemical failure rates were similar among PI, high-dose (> or =72 Gy) EBRT, COMB, and RP for localized prostate cancer. The outcomes were significantly worse for low-dose (<72 Gy) EBRT.

 * Memorial Sloan Kettering Cancer Center at Mercy Medical Center, 2004 (1992-98) - PMID 15066293 — "Monotherapy for stage T1-T2 prostate cancer: radical prostatectomy, external beam radiotherapy, or permanent seed implantation" Radiother Oncol. 2004 Apr;71(1):29-33 Potters L et Al.
 * Retrospective. 1819 pts, clinical stage T1-T2 (AJCC 1997). Compared freedom from biochemical recurrence (FBR) for various methods. EBRT dose was >= 70 Gy. All received monotherapy without adjuvant therapy.
 * 7-year FBR for PPB vs EBRT vs RP were 74, 77, and 79%, respectively. Multivariate analysis identified iPSA and bGS as prognostic factors of relapse. Treatment modality, age, clinical T-stage, and race were not independent predictors of failure.
 * CONCLUSIONS: Pretreatment PSA levels, and biopsy Gleason score determined outcome in this study cohort. Biochemical failure rates in this study cohort are similar between PPB, RT, and RP as monotherapy for clinically localized prostate cancer.

Prostatectomy vs RT and Expected Patient survival
Although treatment outcomes after radical prostatectomy seem to be independent of the age of the patient, at least one study has found a higher PSA failure rate in patients younger than 60 years treated with conventional dose levels external-beam radiotherapy. Men with prostate cancer 60 years or younger treated with high dose conformal external beam radiotherapy seem to have an excellent biochemical outcome and to fare as well as older patients.

 * PMID 12131302, 2002 - "Competing risk analysis after radical prostatectomy for clinically nonmetastatic prostate adenocarcinoma according to clinical Gleason score and patient age." Sweat et Al. J Urol 2002; 168: 525–29.
 * Conclusions: This study shows that for any given Gleason score the prostate cancer death rate is similar in older and younger patients with few to no co-morbidities. Men with a score of 7 to 10 were at 29% to 43% risk of death from prostate cancer even when cancer was diagnosed as late as age 74 years and treated surgically.

 * PMID 12131304 - "Biochemical disease-free survival in men younger than 60 years with prostate cancer treated with external beam radiation." Rosser CJ et al. J Urol. 2002 Aug;168(2):536-41
 * 964 pts treated with RT alone. Biochemical failure defined per ASTRO consensus statement.
 * Median f/u 48 months. Of the 98 men < 60 y.o. 46 (47%) had biochemical failure, whereas 261 (30%) of the 866 older men had biochemical failure. 5 and 7-year bDFS was 55% and 47% in younger men and 65% and 59% in older men (S.S.) In men > 60 yo, PSA, Gleason score, and lower radiation doses were predictive of biochemical failure.
 * CONCLUSIONS: Men with prostate cancer who are 60 years or younger and treated with radiotherapy may be at significant risk for long-term biochemical failure.

 * PMID 14532785 - "Improved biochemical disease-free survival of men younger than 60 years with prostate cancer treated with high dose conformal external beam radiotherapy." Zelefsky MJ et Al. J Urol. 2003 Nov;170(5):1828-32.
 * Retrospective. 740 pts treated with 3D-CRT or IMRT to median dose of 75.6 Gy. Biochemical failure per ASTRo consensus statement.
 * Median f/u 88 months. Biochemical failure in 21%-22%; 5 and 7 year bDFS in 79-82% and 78-79%. No difference between young men (< age 60) and older men. For young men who received >= 81 Gy, 7-year relapse free survival 96%, 87% and 50^ for favorable, intermediate, and unfavorable risk pts. For young pts, most important predictor of biochemical relapse was dose < 75.6 Gy followed by Gleason score > 7.
 * Conclusions: Men < 60 yrs old treated with high dose XRT have excellent outcome and do as well as older pts. Treating younger pts with conventional RT doses led to 8-fold increase in relapse rate.

Prostatectomy after neoadjuvant hormones
Hormones decrease the incidence of extracapsular extension and positive surgical margins. However, this does not lead to improved freedom from biochemical failure or survival (unlike hormones combined with RT).
 * PMID 11743286 (Soloway), PMID 12230618 (Aus)

 * SWOG 9109 - PMID 12394698 — "Neoadjuvant therapy before radical prostatectomy for clinical T3/T4 carcinoma of the prostate: 5-year followup, Phase II Southwest Oncology Group Study 9109." Powell IJ et al.
 * 61 pts. Phase II. T3-4N0
 * PFS 70%. OS 90%.

Adjuvant Chemotherapy

 * For adjuvant hormonal therapy after RP, See also: Radiation_Oncology/Prostate/Hormones/Adjuvant_ADT

 * SWOG 9921 / Intergroup (2000-2007) -- ADT vs. ADT + mitoxantrone
 * Randomized. Closed prematurely after AML toxicity. 983 patients, radical prostatectomy, high risk features (GS >=8, or pT3b-T4, or N1, or GS 7 and SM+, or PSA >15 ng/ml. Had to have undetectable post-op PSA). Arm 1) ADT x2 years (bicalutamide 50mg QD + goserelin 10.8 mg SC q3 months) vs. Arm 2) ADT x2 years + mitoxantrone 12 mg/m2 q3W x6 cycles
 * 2008 PMID 18349405 -- "Randomization reveals unexpected acute leukemias in Southwest Oncology Group prostate cancer trial." (Flaig TW, J Clin Oncol. 2008 Mar 20;26(9):1532-6.)
 * Outcome: 3 cases of AML reported in 487 patients in mitoxantrone arm. Time-to-detection 13, 48, and 72 months. Trial stopped
 * Conclusion: Highlights importantce of controlled trials to define safety and efficacy
 * 2011 PMID 21502546 -- "Adjuvant Androgen Deprivation for High-Risk Prostate Cancer After Radical Prostatectomy: SWOG S9921 Study." (Dorff TB, J Clin Oncol. 2011 May 20;29(15):2040-5.)
 * Final endpoints not yet available. In the ADT-alone control arm, 5-yr bFFS 92.5% and OS 95.9%.
 * Conclusion: consider use of adjuvant ADT in men with high risk prostate cancer


text:
Radiation Oncology/Prostate/Chemotherapy

RT + Brachy + TAS + Docetaxel
Phase II Trial Preliminary
 * Protocol: 45 Gy pelvic EBRT + prostate brachytherapy + Docetaxel x 3 months + TAS x 2 years
 * Eligibility: T3/T4, or (GS 7 and PSA >10) or (GS 8-10 and PSA >7) without extrapelvic disease
 * Results: 36 patients, 20 months follow-up. No failures. Well tolerated.

RT + ADT +/- Chemotherapy

 * RTOG 05-21 -- RT + ADT +/- docetaxel
 * "A Phase III Protocol of Androgen Suppression (AS) and 3DCRT/IMRT Vs AS and 3DCRT/IMRT Followed by Chemotherapy With Docetaxel and Prednisone for Localized, High-Risk Prostate Cancer
 * Pts: 1) Gleason >=9 and PSA <= 150, Any T stage, 2) Gleason 8, PSA <20, T2 or higher, 3) Gleason 7-8, PSA 20-150, Any T stage. Clinically negative LN.
 * Arm 1: AS (LHRH agonist + oral antiandrogen) x 8 weeks, followed by RT to 72-75.6 Gy with concurrent AS. Continue LHRH for total of 24 months. Arm 2: Arm 1 plus 6 cycles of docetaxel (q3w) and daily prednisone 28 days after completion of RT.
 * 2019 PMID 30860948 -- "Effect of Chemotherapy with Docetaxel with Androgen Suppression and Radiotherapy for Localized High-risk Prostate Cancer: The Randomized Phase III NRG Oncology RTOG 0521 Trial." (Rosenthal SA et al, J Clin Oncol. 2019 May 10;37(14):1159-1168)
 * 612 patients, median follow up 5.7 years
 * 4yr OS 89% AS+RT vs. 93% AS+RT+CT (HR 0.69, p=0.03)
 * 6yr DFS 55% AS+RT vs. 65% AS+RT+CT (HR 0.76, p=0.04)
 * 6yr DM 14% AS+RT vs.  9% AS+RT+CT (HR 0.60, p=0.04)
 * Fewer deaths due to prostate cancer/treatment and other causes in AS+RT+CT arm

 * Nihon University, Japan (2003-2006) -- RT + ADT +/- estramustine
 * Randomized. 39 patients, intermediate/high risk PCA by NCCN guidelines. Arm 1) Neoadjuvant/concurrent LHRH agonist + estramustine x6 months vs Arm 2) NCAHT x 6 months. Both groups 3D-CRT 70/35
 * 2010 PMID 19449118 -- "Neoadjuvant LHRH analog plus estramustine phosphate combined with three-dimensional conformal radiotherapy for intermediate- to high-risk prostate cancer: a randomized study." (Hirano D, Int Urol Nephrol. 2010 Mar;42(1):81-8. Epub 2009 May 16.) Median F/U 2.3 years
 * Outcome: 4-year bRFS ADT+EMP 61% vs ADT alone 49% (SS)
 * Toxicity: No severe toxicities
 * Conclusion: ADT + EMP better than ADT alone, but either arm insufficient and dose escalation or adjuvant ADT needed

 * RTOG 99-02 (2000-2004) -- RT + ADT +/- TEE (taxol, estramustine, etoposide)
 * Randomized. Closed early due to thromobembolic events. 397 patients. High risk CaP (PSA 20-100 and GS >=7, or T2+, GS8, PSA <100). Neoadjuvant/concurrent and adjuvant AS + RT (2/2/2 TAA) +/- TEE Chemotherapy (taxol, estramustine, etoposide) x 4 cycles.
 * 2009 PMID 18990504 -- "Phase III multi-institutional trial of adjuvant chemotherapy with paclitaxel, estramustine, and oral etoposide combined with long-term androgen suppression therapy and radiotherapy versus long-term androgen suppression plus radiotherapy alone for high-risk prostate cancer: preliminary toxicity analysis of RTOG 99-02." (Rosenthal SA, Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):672-8. Epub 2008 Nov 5.)
 * Toxicity: AS 37% vs. AS + TEE 715 (SS), for hematological (SS), GI (SS), and trend GU (p=0.07). Three cases of MDS/AML in TEE arm
 * Conclusion: TEE associated with significantly increased toxicity during treatment

Celecoxib

 * University of North Carolina - PMID 16609031 - "A phase II trial of celecoxib in prostate-specific antigen recurrent prostate cancer after definitive radiation therapy or radical prostatectomy" (Pruthi RS, Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2172-7.)
 * 40 pts. Celecoxib (Celebrex) 400 mg/day. 36 of 40 (90%) had a slowing of PSA; 11 of 40 with decline in PSA, 8 with stable disease.


text:
Wikibooks talk:How-tos bookshelf

Inclusion of Public Domain material
How should we include public domain how to material? For example, "Popular Mechanics ShopNotes" available on Google Books is in the public domain and well worth inclusion here given the large number of topics covered. Likewise, Popular Mechanics in the public domain contains many how to articles.

Adapted from Wikipedia:How-to
A how-to on Wikibooks should include:
 * A brief overview of the project being built or end result of the instructions.
 * A list of materials, tools or prerequisites (if needed).
 * Time needed.
 * Appropriate safety warnings (if needed).
 * Instructions for the project.
 * What to do after the project is finished (cleanup).
 * How to use the result or object constructed.

If there are multiple ways to do something, consider including more than one.

How-tos in Science
Often it is appropriate for Wikipedia to include details of a particular scientific experiment that are of interest. For example, if they are the first of their kind, or if they are commonly performed, or if they are just generally well known. It is important that scientific how-tos explain why they are of interest.

Some questions that you should consider in articles on scientific experiments:
 * Who first performed this experiment? When? Where? With whom?
 * What technical inventions allowed this experiment to be performed?
 * Where and when were the results published? Under what title?
 * What was the scientific reaction to this experiment?
 * What was the public reaction?
 * What theories did this experiment confirm or disprove?
 * How has this experiment been simplified or made redundant by later innovations?
 * What scientific principles were used in the design of this experiment?
 * Is this experiment commonly performed in schools or universities? At what age range is it typically performed?
 * What conclusions can be drawn from the experiment?

Merging Savoir-faire
Transwiki:Savoir-faire should be incorporated here somehow. Uncle G 11:16, 20 July 2005 (UTC)
 * I think that Savoir-faire ("know-how-to-make") should become a book called Savoir-faire or Basic human needs. That book would be an instructional resource listed on the How-tos bookshelf. The red links on Transwiki:Savoir-faire would become links to chapters of that book. --Kernigh 19:27, 15 October 2005 (UTC)

Move from Wikipedia
Hi,

I know this is ancient history by now, but I really didn't quite get the move in the first place (except for very long how-tos meriting their own "book". The association with the name "book" I think may turn people off who just want to get a simple how-to answered. If procedural knowledge is really so offensive to Wikipedia, how about a dedicated wiki (at least Wikicities wiki) for short how-tos? thanks... User:Brettz9

Create Separate Wikihowto Site (updated)
I really like the en.howto.wikia.com page you've built. What's the next steps for it? 208.54.15.1 18:00, 21 April 2006 (UTC)penchina

I have been working on a WikiHowTo demo/proposal for a new Wiki Project.

 * Demo site: http://en.howto.wikicities.com/
 * Scope: WikiHowTo would offer tutorials in any numbers of subjects, and unlike most on line tutorials these will stay up to date, as long as they are popular enough to be viewed.
 * Comments:
 * I believe my demo site has a long way to go before making a formal proposal, I would appreciate any help or suggestions anyone can give., thanks ZyMOS 02:16, 15 January 2006 (UTC)

 * to read old discussions on this visit http://en.howto.wikicities.com/wiki/Wikihowto/old

 * WikiHowTo, Wikisolutions, and wikicities have joined as one site
 * http://en.howto.wikicities.com/
 * We are currently working on finalizing policy and creating good examples of Howto's and Guides.
 * We could use help if anyone is interested.

 * The are now over 100 howtos on WikiHowTo. Most are small, some are stubs.

Opinions?

 * Adding a point to this thread: You are welcome to fork and grab any Wikibooks content in any form, provided you do so according to the terms of the GFDL.  While I like Wikia for a number of reasons, this is not a Wikimedia project and any forked how-to content on the how-to Wikia (formerly Wikicities) should not be construed as moving content to that other web server.  As far as I'm concerned, How-to books need to remain on Wikibooks, even though perhaps the standards for keeping them here on Wikibooks should be raised in terms of content quality and editorial standards.
 * Consider this above announcement as an advertisement for a competing (even if sympathetic) project. We are working for the same overall goals, but this is a different community.  --Rob Horning 14:10, 25 June 2006 (UTC)

List of topically arranged how-tos
Note: Someone please move the code from here to here (the last version before it was migrated to How-tos bookshelf and the listing was alphabetized. (I am in a country now where I can't reach Wikipedia for editing. The old wiki code has the advantage of being language independent (not alphabetical) and to allow one to intuitively find items by their general subject, without having to know ahead of time which exact alphabetical listing they are looking for)...Please allow this alternative categorization!!! Thank you... —The preceding unsigned comment was added by Anonymous User (talk • contribs) comment moved from deleted page.

Link word order
I feel that the change of all the link titles by Kernigh to the format XXXXX, how to make a makes the page very difficult to read through. The English-speaking brain is not accustomed to reading that way, and any benefit to alphabetizing is lost in the extra effort needed to read each line.

For example, these:

 * Novel writing
 * How to write a novel
 * Write a novel

are much easier to read than these:

 * Novel, How to go about writing a
 * Novel, How to write
 * Novel writing, How to

We usually read groups of words at a time, not individual words, so the reordering breaks up the groups we would normally pick out easily, and the line must be read one word at a time and "translated" into something sensible. If there were hundreds of links in each category, then maybe this would be worth it, but with so few I don't think it is. Jonathan Kovaciny 15:37, 14 February 2006 (UTC)

 * I tried to make each bookshelf link match the title of the book. The book is called How to go about writing a novel, so I do not like bookshelf links such as Novel writing . I introduced the "XXX, How to" format so I could continue the existing convention of alphabetical sorting.

 * However, if you think that the bookshelf is now confusing, feel free to edit this bookshelf and fix it. --Kernigh 16:00, 14 February 2006 (UTC)

Proposal to convert the bookshelf into a book
Most of the how-to books linked here are one-pagers - not exactly what you'd term a book. Where we've had a significant number of short one-pagers in the areas of cooking and cocktails we've turned them into a coherent book (Cookbook and Bartending]). To my mind, all the how-tos would look better if organised as a (more or less complete, but readily expandable) book. We can also give it a fun name The Great Wikibook of How-Tos or something of that ilk. Comments? Jguk 08:05, 25 March 2006 (UTC)
 * That seems like a very sensible suggestion. Thryduulf 21:40, 27 March 2006 (UTC)
 * I think that → DIY ← might have been an effort like that. --Kernigh 23:52, 8 June 2006 (UTC)

external how to sites
I found a new how to site that I tried to list in the external how to site links but, the page is locked. How can I add to this list?

I too would like to add to the external sites links list. Is that possible? --John Stumbles 00:37, 10 March 2007 (UTC)
 * Answered on your talk page - thanks -- Herby talk thyme 12:48, 17 March 2007 (UTC)

Wait, really?
There's a how-to guide in the listing, under "Other Guides". It's a red link, and I'm going to assume it NEVER existed. It's "How to Understand a Teenage Female". Probably vandalism, but still humorous. Could someone verify this and remove it?

How to search only in How-tos of Wikibooks ?
How can we search in How-tos of Wikibooks, I mean to search only in books of How-tos bookshelf and in books of Category:How-tos (and his sub-categories) ? This filter is necessary when we are searching a practical and immediat solution to a problem. Without such a filter we get more books related to various aspects of our search-text than books providing a howto. I know that http://howto.wikia.com (and the french version http://fr.howto.wikia.com that I initiated) can provide this quick answer, but today howto.wikia.com does not provide all answers and we have to search also in other wikies as Wikibooks/How-tos. One thing could make this search difficult in Wikibooks : many how-tos books are not in the Category:How-tos, then how could they be filtered by a search tool? Please help! Thanks.--Jean-Baptiste Martin 19:13, 21 May 2007 (UTC)

Too Small
The list of How-Tos is too small. Uncyclopedia has a list that is ten or so times as big. 59.183.183.120 18:40, 27 May 2007 (UTC)Vader1941

Variation in Titles
I was just going through the how-to section on WikiBooks when I noticed that there is no stardard form for naming the books. Some books titles are How To Build A Computer (with the "how to" in the link), Overcoming Procrastination (in active tense), and How to make Armour (with the "how to" not in the link). I think it should be standardised one way or another. Maybe make a "how to" folder and add all the files in it (all titles in one tense), so that it would be How To/Build a Computer, How To/Overcome Procastination, and How To/Make Armour. I think this make alot more sense for organization and linking. I would be willing to spend the time to go through them and change all of the names but then I would have to change the links on the how to page would I not? And it is protected and I am not an administrator. Any thoughts or ideas as to what could be done? Mason L. 13:05, 5 September 2007 (UTC)

title: Wikibooks talk:How-tos bookshelf


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title: User:5~enwikibooks/monobook.css


text:
Blender 3D: Noob to Pro/Modeling a picture

Modeling a picture
Ever seen an awesome looking picture you wanted to turn into a 3D model? Like a logo or a symbol? Well, it's actually pretty easy... it just takes some time to do.

 * First off, you're going to need a picture to trace. I'm currently doing a project for a friend to do with devils and demons, so I chose a demonic looking face for this tutorial: Demonic Face

 * Now open Blender and start a new project. Delete the default cube. Before you start tracing the face, you need to set the face as the background image.  To do this, click 'view', then 'Background Image'.  A box should pop up with only one button in it (Use Background Image), click it.  Now some settings appear, we're only interested in one of them for this tutorial.  Click the small button with a picture of a miniature folder on it (it looks kind of like a feather pen). It's the first one under the Use Background Image button.  From there, select the picture you want to trace.  Like this: Background Selection

(user note: hitting CTRL-LMB instead of SHIFT-DKEY will add a vertex that is already connected.)
 * OK, now for the long part. Zoom in to the new background image just a little bit.  Now, add a Bézier curve, and size it down a little.  Hit F9 and, in Curve Tools, find and click the Poly button.  Now there should be a few more vertices to work with and the curve should be just a bunch of joined lines.  Select one point at a time and using the GKEY move it to a point along the background image(or face in this case).  Do the same for all of the rest of the vertices, making sure you only have one vertex selected at a time or you'll move more than just the vertex you want to.  Once this is done, select one of the end vertices of the curve (it doesn't matter which end) and use SHIFT+DKEY to copy that vertex.  Move the newly copied vertex to a point along the edge of the face a small ways away from the vertex you copied it from.  Continue doing this until you have a complete outline (of the whole face or just one part, like the ear).  Here's what it should look like (I did the left ear): Tracing.  You can't see it in the picture, but six of the points on the right side of the ear are connected, while the rest aren't.  In order to get the effect we're looking for here, we need to connect all of the points around the edge to make an outline (make sure not to connect the points across the picture or you'll have a messed up outline).

[edit: A better option would be to select a vertex on one of the ends of the whole line, hold down the CTRL and left-click on a certain point on the image. This will create a new vertex, immediately connected to the vertex you selected.]
 * To get the outline for the whole face, just do exactly the same thing around all of the edges. We still have a problem though: most of the points aren't joined by a line, so all we have is a bunch of dots.  This is easily solvable.  Using the BKEY or the right click of the mouse, we select a bunch of vertices at a time (somewhere between 5 and 10), and hit the FKEY a few times.  Every time you hit the FKEY it should connect two of the points.  Do this until all of the selected points are connected, then deselect them and select another group and use FKEY to join them.  Keep doing this until all of your points are connected.  To connect the last two points, select all the points and press the CKEY, to close the polygon.

 * Now that we've got the entire face traced (or outlined if you want to call it that), we can make it 3D. Hit F9 again and find the Ext1 and Ext2 properties, shown here: Ext1 & Ext2.  Change the values and see what happens.  They correspond to the depth of the outline.  Try changing them around until you find what looks good.  Now, you'll notice that the lines just stick out straight.  I'm still investigating how to actually model a head from the outlined face ... so if anyone has any ideas, feel free to add them to this page.

 * In order to make it have depth you should make the outline out of mesh points instead of a curve. Add a primitive mesh and delete all the vertices in edit mode, then ctrl click to all point outline. Add depth to the surface in a side view (split views so you can see what you're moving). It helps to have 2 or more reference images, but you can wing it. Usually the final result has to be subsurfed.

(USER EDIT: I accidentally started it with mesh instead of curve. You can do the same thing with extrude, but I have no idea how to go on after that) (USER EDIT LATER: If you subsurf it, it creates a relatively 3D looking image. Its really cool)

(Another user, even later: If you want to turn your curve into a mesh, hit Alt-C while in Object Mode. Note that this is NOT reversible.)

(user edit: You can delete one vertex of a plane, in order to get a line. You may find easier to outline the picture extruding and moving points of the line you created.)

(user edit: you can use this tracing technique to make solid and symmetric models, else, you would really have to use normal modelling)

Printing a Rendered Image
Render your image. Exit or minimize the "Blender:Render" window. In blender, go to File -> Save Image... Then save your image. Then you can print it as you would print any other picture, using The Gimp, Paint, Microsoft's Photo Editor, or many others.


text:
User:Triddle~enwikibooks/wip

Next page:, Previous page: , First page: Demystifying Depression

title: User:Triddle~enwikibooks/wip


text:
Cookbook:Lamington

| Australian Cuisine | New Zealander Cuisine

Lamington is a dessert of sponge cake (or more traditionally, butter cake), cut into squares, coated in a layer of chocolate or strawberry icing, and topped with coconut.

Ingredients

 * Sponge cake
 * Chocolate icing
 * Dessicated coconut

Procedure

 * 1) Cut the sponge cake into your desired shapes (commonly 5–7 cm cubes).
 * 2) Prepare a flat tray with an even layer of desiccated coconut shavings
 * 3) Dip the sponge cake cubes into chocolate icing.
 * 4) Immediately dip the coated cake into the coconut, or sprinkle the coconut on top.
 * 5) Put aside to dry and set.

title: Cookbook:Lamington


text:
File talk:Demystifying Depression-Adrenaline Response.png

This graphic would benefit from a legend on the vertical axis. I can infer that it's probably "amount of adrenaline," but that's not good enough. Units would also be good if they have any relevance.


text:
User talk:Tdvorak

Radiation Oncology wikibook
Great work on the Rad Onc book so far. It was a good idea to split up the prostate chapter. It was getting pretty big, and I knew it would have to be split up into different pages soon enough, so thanks for going ahead and doing that.

Why don't you go ahead ad add yourself to the authors' page (Radiation_Oncology:Authors) and take credit for all the work you did.

Brim 06:25, 5 Jun 2005 (UTC)

Page names
I was wondering why you were changing the page names to have directory-style levels, such as changing Radiation Oncology:Brain mets to Radiation Oncology/Palliation/Brain Metastases? To me it seems more cumbersome to have these longer names. Is there some advantage to doing this that I'm not aware of? — Brim 21:37, 12 Jun 2005 (UTC)

 * It probably wasn't necessary with the brain mets. But for prostate, all the subchapters would have to then be on the pain Radiation_Oncology page (like Breast is now), which would potentially make the main page really really long. The other problem seemed to be that I didn't see an easy way to link to part of the page (sort of like # does in HTML). So when I wanted to reference back to "palliation" from the RTOG studies, it would just load up the main Rad Onc page. It seemed to me that using directory structures allows to have a page dedicated to a particular topic. I guess with wiki you can keep all topics on the top level, including the "parent" pages and just crosslink. But then you lose the auto-navigation on top that wiki provides. And I guess the last part is just habit, I find it easy to keep track of things like this. Your preference would be to keep it a flat structure? Tdvorak 12:11, 13 Jun 2005 (UTC)
 * Now that I have thought about it, there probably isn't much difference in how you set it up. So maybe the shorter path names are easier. I will have to play around with it some more. But for now, I guess I will leave prostate hierarchical and see how it works on the other topics you have already set up. Tdvorak 13:26, 13 Jun 2005 (UTC)

The main reason I was asking is because I had set-up the wiki using : but saw that you were switching to / and wanted to keep things consistent. I now see how the path names create the auto-navigation links. I wasn't aware of that before when I first created this wiki, which is why I used the : delimiter instead of the /. I prefer to use templates (like the Radiation Oncology:TOC template) for navigation since it's more flexible and customizable. I like having the ability to link to the RTOG trials page from any page within the book since it makes it easy to keep the RTOG trials up to date.

For large topics like prostate, I think the path names make sense since there will be many subpages within the topic. For brain mets (as an example) I think it makes more sense for the page name to be Radiation_Oncology/Brain_mets rather than Radiation_Oncology/Palliation/Brain_mets since brain mets is really the main topic rather than being a subtopic of palliation. — Brim 18:18, 13 Jun 2005 (UTC)

Bile duct
Awesome job!! Brim 17:31, 27 November 2005 (UTC)
 * Thanks! Since I was doing a lit review anyway for my paper, and since it's such a rare topic, figured I might as well make it all-inclusive :) Tdvorak 14:37, 7 December 2005 (UTC)

Optin
I agree to the edit counter opt-in terms

That's a lot of edits
Thanks for adding the edit count tally to the Author List. It's pretty interesting to look at it that way. Thanks for all the outstanding work you've done on the project.

If you're a believer in "edit velocity" (akin to PSA velocity), consider that it took me two years for my 2585 edits, but you did your 1443 edits in roughly half that time (and were on hiatus for roughly 6 months of that period). In short, great job! Brim 00:46, 13 September 2006 (UTC)

Contact
Hey T, looks like you are still busy working away at the wiki. I'm not sure how to get ahold of you, but wanted to email you. Send me your email address using wiki if you don't mind. Hope to hear from you,

Shogun (rodney)

Details about your book
Hello Tdvorak! I was wondering if you could give me some details about the Radiation Oncology book that you are working on? I know that the book is relatively old, and I also know that it is impressively big and well-structured. Are you the only major contributor, or are there more? Is this book affiliated with any kinds of groups or classes? Is there any specific help that the book needs, at least from non-experts? (formatting or editing help, for instance).

This is an impressive book, and one that I think deserves some additional attention, both inside this project and elsewhere. If you need anything at all, please let me know. --Whiteknight (Page) (Talk) 02:30, 28 June 2007 (UTC)

 * Hello Whiteknight. Thanks for the feedback & encouragement! The Radiation Oncology book is a project that several of us (2 main authors, and couple semi-frequent contributors; also see Author List) are working on. It is not affiliated with any classes. It is meant as a quick (and eventually comprehensive) reference source for radiation oncologists, who are physicians treating cancer patients with radiotherapy. There are a number of different cancers, and they are each treated differently. This book is meant to provide a handy online reference with links to the published studies. Each PubMed link (PMID) takes one directly to the abstract of that given study, and from there it is possible to get to the actual paper. The beauty of course is that it can be as detailed as we want (and have energy!) and current (unlike print textbooks, which are immediately out of date in our specialty).

 * Thank you for your offer to help. I think we are mostly fine on formatting; we have slowly settled down on a formatting style that seems to work. There is not yet a lot of prose to edit per se, since thus far most of the content is summaries of the individual studies and clinical trials. But any help is of course appreciated, both in terms of grammar and in terms of spelling.

 * As for getting it attention elsewhere, I leave that in your hands :) We have thus far not made any active effort to disseminate its existence to our specialty, but there certainly are a number of radiation oncologists who found it via Google. We are in the process of writing a manuscript about its creation, structure, and ultimate goals.

 * Tdvorak 03:26, 28 June 2007 (UTC)

Images in Radiation Oncology
G'day, I see that you've been active in this book recently. There is a large quantity of images in this book that have been uploaded early in the project when image licensing wasn't given a priority, but are now in jeopardy of being deleted because they don't specify copyright information. A discussion has been started about these images on the Administrators' noticeboard (near the bottom), and your input could be useful. cheers, Webaware talk 03:15, 13 July 2007 (UTC)
 * Nice work so far on the graphics! Brim 22:55, 22 August 2007 (UTC)
 * Thanks! They really liven up the page, don't they :) Of course, I am putting up just about any ole' crappy image I come across for now (like PCNSL), but hopefully they will get better over time. Also, I really ought to size them more-or-less the same Tdvorak 01:21, 23 August 2007 (UTC)

Vantage Oncology
http://www.vantageoncology.com at Radiation Oncology/Corporate - This looks like advertising/spamming to me. I looked at the site and don't see any valuable resources. I meant to delete it from Talk:Radiation Oncology but Wikibooks was undergoing maintenance so I couldn't. Do you see any value to this site that I may have missed? Brim 14:22, 18 July 2007 (UTC)

 * I think it was meant as advertising. But I figured that we could set up a "corporate" page and have links to the major equipment manufacturers, planning system vendors, etc. This could also include links to the various academic departments, free-standing facilities, and places like Vantage. This was more in the spirit of providing a comprehensive radonc resource; I don't have a strong feeling about them in particular. So for now I have moved them here from the Talk page and will expand the page as I have time Tdvorak 19:42, 18 July 2007 (UTC)

 * Sounds fair enough. Brim 19:57, 10 August 2007 (UTC)

Re:Google Analytics
Installing the script is the only step you need to take, really. When the script is in your profile, every page hit you make is recorded by google and aggregated into a daily report that I can access using my google account. I am developing a bot to upload the results to a page in my user space. The records will appear there. Since the results are aggregated daily, your page hits will likely not be reflected in the list until tomorrow. I'll let you know asap. --Whiteknight (Page) (Talk) 13:19, 2 October 2007 (UTC)
 * Thanks! Do I put myself in the script (which is what I have done - import_script('User:Tdvorak/google.js');) or do I leave your username, since it's your bot that's tracking this?Tdvorak 15:46, 2 October 2007 (UTC)
 * You have to leave my username in there. I'll fix it for you. --Whiteknight (Page) (Talk) 15:59, 2 October 2007 (UTC)

WB:RIGHTS
I wonder if you'd like to help out with project maintenance. If you're interested, I'd like to nominate you for patroller rights. Feel free to ask me if you want more info. Thanks. – Mike.lifeguard  | talk 01:58, 15 March 2008 (UTC)

Please participate
Hope you wouldn't mind participating on the "vote" to restore the CheckUser (CU) function (mostly used to fight vandalism) to the Wikibooks project, a minimum of 25 expressions of support is required to grant the flag to administrator Thenub314 (this will also enable admin Adrignola to get the function active again, since there is a minimum requirement of 2 active Wikibookians with the flag). In case you do agree to participate, your vote needs to be added to administrator Thenub314 request for permission. Thanks. --Panic (talk) 14:35, 19 August 2010 (UTC)
 * You mention that the function is to be "restored". I am not familiar with the history of this tool on wikibooks; why was it removed in the first place? Thanks. Tdvorak (talk) 14:47, 19 August 2010 (UTC)
 * Former CheckUser Mike.lifeguard relinquished the use of the tools, thus bringing Wikibooks below the 2 CU minimum. – Adrignola talk 14:54, 19 August 2010 (UTC)

Global account
Hi Tdvorak! As a Steward I'm involved in the upcoming unification of all accounts organized by the Wikimedia Foundation (see m:Single User Login finalisation announcement). By looking at your account, I realized that you don't have a global account yet. In order to secure your name, I recommend you to create such account on your own by submitting your password on Special:MergeAccount and unifying your local accounts. If you have any problems with doing that or further questions, please don't hesitate to contact me on my talk page. Cheers, DerHexer (discuss • contribs) 19:13, 14 January 2015 (UTC)

title: User talk:Tdvorak


text: Template:Radiation Oncology/Prostate:TOC


text:
Wikijunior:South America/Glossary

 * The Amazon - The largest rainforest in the world, located in South America, mostly in Brazil but also in Peru, Bolivia, and other countries. The Amazon is also the name of the largest river in South America.

 * The Andes - A very long mountain range that runs North South in the western part of South America, from Colombia all the way down to Chile and Argentina.

 * Argentina - A country in South America.

 * Bolivia - A country in South America.

 * Brazil - The largest country in South America.

 * Catholic - A branch of Christianity which follows the rules set by the Vatican, particularly the Pope.

 * Carnival - A huge party in which complete cities participate with dancing, and costumes.

 * Chile - A very long and narrow country in South America

 * Colombia - A country in South America.

 * Ecuador - A country in South America. The Equator line which divides the Earth is named after Ecuador.

 * England - A country in western Europe, part of the United Kingdom.

 * Estuary - A place where a river meets the sea and water from the river and the sea mix together.

 * Falkland Islands - A group of Islands in the Southern Alantic which are claimed by both Argentina and the United Kingdom, but controlled by the UK. Argentinians call them Malvinas Islands.

 * France - A country in western Europe, South America, Africa, and several other continents.

 * French Guiana - A part of France in South America.

 * Guyana - A country in South America.

 * The Incas - A people of South America that once held an Empire based in Cuzco, Peru that included most of present day Eduador, Peru, Bolivia and half of Chile.

 * 'Iberian peninsula - A landmass in southwestern Europe which contains Portugal, Spain, a territory of the United Kingdom called Gibraltar, and a very small country called Andorra.

 * Indigenous people - People living in an area before Europeans came to settle in the area.

 * Latin - The old language spoken two thousand years ago in Rome and the Roman Empire. Many modern languages are derived from Latin, including French, Spanish and Portuguese.

 * Latin America - The part of the Americas in which Spanish or Portuguese are the main languages. It includes all of the Americas except Canada, the USA, and a few small countries. (Suriname, the Netherlands, Guyana, etc.)

 * The Netherlands - A country in western Europe and the Caribbean sea, sometimes incorrectly referred to as Holland.

 *  Paraguay - A country in South America.

 * Peru - A country in South America.

 * Portugal - A country in southwest Europe, which once conquered and ruled Brazil.

 * Simón Bolívar - One of the most important heroes in South America who liberated many countries from Spanish rule into independence. The country of Bolivia is named after him.

 * Spain - A country in southeast Europe, which once conquered and ruled most of the Americas.

 * Suriname - A country in South America.

 * UK / United Kingdom - A country in western Europe with territories all over the world, including the Falkland Islands in South America

 * Uruguay - A country in South America.

 * Venezuela - A country in South America.

Wikichicos/América del Sur/Glosario

title: Wikijunior:South America/Glossary


text:
Mambo Open Source/Getting Mambo

This explains how to get a copy of Mambo. It maybe sounds a bit strange that you need to download your website before you can use it, but it is similar to downloading any other program - Mambo is in a way a program, one that it creates, manages, and serves websites. Therefore, you will need to download it.

Mambo CMS - Download
You can use the official site, Mambo Code forge, to get a copy of mambo. This is the way most new users do it, and it is simple and easy. Here, you can also get additional information about Mambo - take a look yourself!

Mambo CMS - Forums
You can find the official Mambo CMS project forums at forum.mambo-foundation.org.

Mambo CMS - The Foundation
Every great Open Source project has great leadership. The Mambo CMS project is no different. The non-profit Mambo Foundation was established in August 2005 to provide support and protection for the development of the Mambo software system. It is modelled after similar ventures, such as the Eclipse Foundation and the GNOME Foundation.

title: Mambo Open Source/Getting Mambo


text:
Wikijunior:South America/The Incas

Part of Wikijunior South America project

The Incas were the ruling class of Peruvian Indians controlling a large empire in South America between the years 1438 and 1533 before the Spanish conquest. In Quechua, the main language of the Incas, the empire was called Tawantinsuyu which means Land of the Four Corners. The native government of the Incas was the most stable on the continent. The Peruvians were agricultural people, who irrigated their lands and built great granaries and fine roads to all parts of the empire. The Incas kept track of numerical data through a system of knotted quipu-strings. Gold was owned by them in abundance and was used in the decoration of the palaces and temple of the Incas. The capital of the empire was at Cuzco, until just before the arrival of Pizarro, when Atahualpa, heir to the throne, had moved his rule to Quito, now ../Ecuador/, to protect himself from a rebellion started by his brother. When the Spanish invaded the country in 1533, Atahualpa, the last emperor of the Incas, was executed, but it was forty years before the Incas were fully conquered. Their descendants as unmixed Indigenous people make up a large segment of the population of ../Peru/ today.

title: Wikijunior:South America/The Incas