text:
Radiation Oncology/Prostate/Localized Prostate Cancer

Localized Prostate Cancer

Definitions

 * Historically, clinically localized prostate cancer was primarily determined by stage. Patients with T1-T2 could be offered watchful waiting, surgery, or radiation therapy. Patients with T3-T4 disease were not considered surgical candidates
 * Localized: T1-T2
 * Locally advanced: T3-T4
 * More recently, urologists have been treating some T3a patients using the robotic surgery. Also, NCCN (www.nccn.org) risk stratification includes T3a patients in the localized disease
 * Low risk: T1-T2a and PSA <10 and GS 2-6
 * Intermediate risk: T2b-T2c or PSA 10-20 or GS 7
 * High risk: T3a or PSA >20 or GS 8-10
 * Locally advanced: T3b-T4

Prospective Comparisons

 * There are no conclusive randomized trials comparing the 3 primary modalities (EBRT, permanent brachytherapy, radical prostatectomy)
 * There have been a number of failed trials in the past, but more recently both the PIVOT trial and the ProtecT trial completed accrual. START trial is ongoing

 * Also see:
 * Radiation_Oncology/Prostate/Prostatectomy

Systematic Reviews

 * Italy; 2014 (1965-2007) PMID 24589471 -- "Radical Prostatectomy or Radiotherapy in High-Risk Prostate Cancer: A Systematic Review and Metaanalysis." (Petrelli F, Clin Genitourin Cancer. 2014 Aug;12(4):215-224.)
 * Meta-analysis; high risk pts, treated with RT vs RP (w/ or w/o ADT), no brachy. 17 studies (16 retrospective, 1 randomized); 13,704 pts.
 * RP associated with improved OS (OR 0.51), PCSM (OR 0.56), and non-PCSM (OR 0.53). bRFS similar to RT.
 * Conclusion: "Overall and cancer-specific mortality rates appear to be better with RP compared with RT in localized, high-risk PC. Surgery is also associated with a 50% decreased risk of non-PCSM compared with RT."

 * Amsterdam; 2009 (1980-2007) PMID 19748692 -- "Comparison of three radiotherapy modalities on biochemical control and overall survival for the treatment of prostate cancer: a systematic review." (Pieters BR, Radiother Oncol. 2009 Nov;93(2):168-73. Epub 2009 Sep 11.)
 * Systematic review; EBRT vs EBRT + seed brachytherapy vs EBRT + HDR. 40 studies.
 * Outcome: HR for biochemical recurrence EBRT 1.40 vs EB+Seeds 1.37 vs EB+HDR 1.0 (SS); HR for OS EBRT 1.5 vs EB+Seed 2.33 vs EB+HDR 1.0 (SS)
 * Conclusion: EBRT with HDR boost results in superior biochemical control and overall survival

 * Minnesota; 2008 PMID 18252677 -- "Systematic Review: The Comparative Effectiveness and Harms of Treatments for Clinically Localized Prostate Cancer." (Wilt TJ, Ann Intern Med. 2008 Feb 4 [Epub ahead of print])
 * 18 RCTs and 473 observational studies reviewed
 * Conclusion: Assessment of comparative effectiveness and harms is difficult because of limitations in the evidence

 * Karolinska; 2004 PMID 15303499 -- "A systematic overview of radiation therapy effects in prostate cancer." (Nilsson S, Acta Oncol. 2004;43(4):316-81.)
 * 30 RCTs, 55 prospective trials, 210 retrospective studies. Total of 152,614 patients
 * Conclusions: There is lack of randomized studies comparing surgery with EBRT or brachytherapy. With advent of prognostic markers (T-stage, PSA, GS), comparisons between modalities can be made in absence of randomized trials and some conclusions can be drawn

 * Toronto; 2004 PMID 15003149 -- "A systematic review of randomized trials in localized prostate cancer." (Alibhai SM, Can J Urol. 2004 Feb;11(1):2110-7.)
 * 9 publications dealing with 4 RCTs identified (RP vs WW x2, RP vs EBRT x2)
 * Conclusion: Further randomized trials are needed

 * Oregon; 1993 PMID 8487449 -- "A decision analysis of alternative treatment strategies for clinically localized prostate cancer. Prostate Patient Outcomes Research Team." (Fleming C, JAMA. 1993 May 26;269(20):2650-8.)
 * Decision analysis on RP, EBRT or WW using data from review of literature and Medicare claims data
 * Outcome: In well-differentiated tumors, treatment offers at best limited benefit in terms of QALY and may result in harm. In moderately/poorly differentiated tumors and age 60-65, RP or EBRT may benefit over WW, but typically <1 QALY. In patients >70, treatment generally appears harmful
 * Conclusion: RP and EBRT may benefit select groups, however, in most cases potential benefits are small and choice of therapy is sensitive to patient's preference

Observation vs Radical Prostatectomy
Please see the natural history page

 * VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT) (1994-2002) -- radical prostatectomy vs observation
 * Randomized. 731 men. clinicaltrials.gov entry
 * 2017 PMID 28700844 -- "Follow-up of Prostatectomy versus Observation for Early Prostate Cancer." (Wilt TJ, N Engl J Med. 2017 Jul 13;377(2):132-142.)
 * Median f/u 12.7 years. Death in 61.3% (surgery) vs 66.8% (obs)(p=0.06). PC-related mortality in 7.4% vs 11.4% (p=0.06).
 * Disease progression in 40.9% vs 68.4%. Most progression local; regional in 9.1%/14.2%; distant in 10.2%/14.7%. Treatment for disease progression in 33.5% vs 59.7%. Definitive treatment in 20.4% (obs). Use of ADT in 21.7% vs 44.4%.
 * Conclusion: After nearly 20 years of follow-up among men with localized prostate cancer, surgery was not associated with significantly lower all-cause or prostate-cancer mortality than observation. Surgery was associated with a higher frequency of adverse events than observation but a lower frequency of treatment for disease progression, mostly for asymptomatic, local, or biochemical progression.
 * 2012 PMID 22808955 -- "Radical prostatectomy versus observation for localized prostate cancer" (Wilt TJ, N Engl J Med. 2012 Jul 19;367(3):203-13)
 * Median F/U 10.0 years, 171 of 364 men (47.0%) assigned to radical prostatectomy died, as compared with 183 of 367 (49.9%) assigned to observation NS. Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter (SS). Adverse events within 30 days after surgery occurred in 21.4% of men, including one death.
 * 2009 PMID 18783735 -- "The Prostate cancer Intervention Versus Observation Trial:VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy to watchful waiting for men with clinically localized prostate cancer." (Wilt TJ, Contemp Clin Trials. 2009 Jan;30(1):81-7. Epub 2008 Aug 23.)
 * Study overview. 13,022 men screened; 5,023 met eligibility criteria; 731 agreed to participate and were randomized.
 * Description: Mean age 67 years. Median PSA 7.8 ng/ml. Low risk 43%, intermediate risk 36%, high risk 20%. Predominately detected by rising PSA
 * Conclusion: Diverse population representative of men diagnosed with PCA in United States
 * 1994 PMID 7523736 -- "The Prostate Cancer Intervention Versus Observation Trial: a randomized trial comparing radical prostatectomy versus expectant management for the treatment of clinically localized prostate cancer" (Wilt TJ, J Urol. 1994 Nov;152(5 Pt 2):1910-4.)
 * Description of the trial

 * Scandinavian SPCG-4 (1989-99) - prostatectomy vs watchful waiting
 * Randomized. 695 men, early prostate cancer (T1-T2), biopsy proven. No adjuvant treatment. If symptomatic local progression, treated with orchidectomy or GnRH analog. Clinical follow-up with PSA, exam. Cause of death scored as due to prostate cancer (if progressive distant mets) or due to other causes. 75% had T2 tumors.
 * 11-years; 2008 PMID 18695132 -- "Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial." (Bill-Axelson A, J Natl Cancer Inst. 2008 Aug 20;100(16):1144-54. Epub 2008 Aug 11.) Median F/U 10.8 years (3 weeks - 17.2 years)
 * Outcome: 12-year death due to PCA surgery 12% vs. observation 18% (SS); 12-year DM rate 19% vs. 26% (SS). For surgery, if ECE+ PCA death rate 14x higher than if ECE-
 * Conclusion: RP reduces PCA mortality, with little or no further increase in benefit 10+ years after surgery
 * Median FU 12.8-years; 2011 PMID 21542742 -- "Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial." (N Engl J Med. 2011 May 5;364(18):1708-17) Median F/U 12.8 years
 * Outcome: 12-year death with surgery 48% vs. observation 57% (SS); Survival benefit confined to <65-years of age ; death from prostate cancer that was 7 times that of men without extracapsular tumor growth -
 * Conclusion: RP reduces mortality
 * VACURG (1967-1975) -- prostatectomy vs. watchful waiting
 * Randomized. 111/142 patients, prostate cancer Tis-T2, no palpable tumor, no pelvic staging prior to randomization. Arm 1) Radical prostatectomy vs. Arm 2) Placebo
 * 1988 PMID 3187435 -- "Treatment of localized prostatic cancer. Radical prostatectomy versus placebo. A 15-year follow-up." (Madsen PO, Scand J Urol Nephrol Suppl. 1988;110:95-100.)
 * Outcome:
 * Stage I: 5-year OS RP 87% vs. placebo 67%, 10-years 48% vs. 43%, 15-years 23% vs. 13%
 * Stage II: 5-year RP 92% vs. placebo 90%, 10-years 37% vs 55%, 15-years 17% vs. 20%
 * Conclusion: No significant difference in cummulative survival, either by Stage or overall

Active Surveillance vs Radical Intervention
Please see the natural history page

 * Surveillance Therapy Against Radical Treatment (START) -- radical intervention (RP or RT) vs. active surveillance
 * See also: Active Surveillance
 * Terminated. January 10, 2013 (Not meeting accrual target) Randomized. . NCIC coordinated, enrolling in Canada, US and UK

 * Prostate testing for cancer and treatment (ProtecT) -- surgery vs RT vs active surveillance
 * Randomized, nested. First ask to randomize to 3 arm trial (surgery vs RT vs active surveillance), if refused, asked to randomize to 2 arm trial (surgery vs RT).
 * Active surveillance: consider definitive treatment if PSA increase by 50% in one year. RT: neoadj hormones 3-6 months, 74 Gy. Surgery: post-op RT allowed.
 * 2016 PMID 27626136 -- "10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer." (Hamdy FC, N Engl J Med. 2016 Oct 13;375(15):1415-1424.)
 * No difference in PC-related deaths or overall deaths. Higher rate of metastases and disease progression in AS group vs surgery or RT.
 * AS: 54.8% received radical intervention (1/4 of these within 9 months).
 * RP: 18 of 391 (4.6%) with primary treatment failure, including 9 with detectable PSA at 3 months and 9 who received adjuvant RT.
 * RT: 14% had PSA failure (nadir+2)
 * Clinical progression (Met dz, T3 or T4, long term ADT, obstruction, need for catheter): 22.9% per 10 yr (AS) vs 8.9% (RP) vs 9.0% (RT). [i.e. 22.9 per 1000 person-yr = 22.9% of men per 10 yrs]
 * Conclusion: At a median of 10 years, prostate-cancer-specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring.
 * 2002 PMID 12364308 -- "Quality improvement report: Improving design and conduct of randomised trials by embedding them in qualitative research: ProtecT (prostate testing for cancer and treatment) study. Commentary: presenting unbiased information to patients can be difficult." (Donovan J, BMJ. 2002 Oct 5;325(7367):766-70.)
 * Lessons learned. After changes, all treatments became acceptable, the three arm trial became the preferred design, and randomisation rate increased from 40% to 70%
 * Conclusion: Embedding trial within qualitative research improved recruitment

Surgery vs RT

 * CaPSURE -- radical prostatectomy vs RT vs hormonal therapy
 * Prospective, non-randomized. 7538 pts. Pts followed uniformly
 * 2010 PMID 20690197 -- "Comparative risk-adjusted mortality outcomes after primary surgery, radiotherapy, or androgen-deprivation therapy for localized prostate cancer." (Cooperberg MR, Cancer. 2010 Aug 5. [Epub ahead of print])
 * Hazard ratio for cancer-specific mortality 2.21 for RT and 3.22 for ADT (relative to prostatectomy). Absolute differences between RP and RT were small for low risk prostate cancer but increased for intermediate and high risk disease.

 * ACOSOG Z0070 (SPIRIT) (2002-2004) -- radical prostatectomy vs brachytherapy
 * Randomized, North American, patients with T1c or T2a N0 M0 prostate cancer. Permanently closed in 2004 due to non-accrual. 56 patients randomized.
 * Princess Margaret; 2006 PMID 16943531 -- "Impact of a multi-disciplinary patient education session on accrual to a difficult clinical trial: the Toronto experience with the surgical prostatectomy versus interstitial radiation intervention trial." (Wallace K, J Clin Oncol. 2006 Sep 1;24(25):4158-62.)
 * Development and success of multidisciplinary education session described
 * Conclusion: Men who understand their treatment options are more likely to consent to random assignment
 * 2011; HRQOL (Princess Margaret) PMID 21149658 -- "Comparison of Health-Related Quality of Life 5 Years After SPIRIT: Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial." (Crook JM, J Clin Oncol. 2011 Feb 1;29(4):362-8.)
 * 190 men eligible for trial seen at Princess Margaret. 34 consented to randomization, 62 chose RP, 94 chose BT. At 5 years after treatment, HRQOL evaluation.
 * Of 168 responders, 102 had BT, 66 had RP. Men treated with BT had better urinary and sexual scores as well as better patient satisfaction; no difference in bowel or hormonal scores.
 * Conclusion: Advantage to BT for urinary and sexual domains and patient satisfaction. (Caution: only 19% were randomized; the others were by choice)

 * Scandinavian SPCG-10 -- randomized RT vs. prostatectomy
 * Trial abandoned

 * Multicenter; 2008 (2003-2006) - radical prostatectomy, brachytherapy, or EBRT.
 * Prospective, non-randomized. 1201 pts. Multicenter, 9 hospitals. Treatment with RP, BT, EBRT, +/- hormones. Outcomes surveyed at 2-24 months from the start of treatment.
 * 2008 PMID 18354103 -- "Quality of life and satisfaction with outcome among prostate-cancer survivors." (Sanda MG, N Engl J Med. 2008 Mar 20;358(12):1250-61.) -- Median f/u 30 mo
 * Erectile dysfunction: distress related to erectile dysfunction in 44% (RP), 22% (EBRT), 13% (BT).
 * Urinary: moderate or worse distress in 18% (BT), 11% (EBRT), 7% (RP). EBRT: resolved at 12 months and improved over baseline at 24 months. RP: incontinence worst by 2 months and then improved in most; urinary irritative and obstructive symptoms improved over baseline. BT: worse irritation, obstruction, and incontinence compared to baseline; incontinence 4-6% at 1-2 yrs. Large prostate size and hormonal therapy exacerbated urinary irritation after EBRT or BT.
 * GI: bothersome symptoms in 9% of patients (BT or EBRT) at 1 yr. No symptoms in RP patients. BT and EBRT pts had reduced GI QOL early after treatment, lasting 1 yr or more.

 * Christie Hospital, UK -- radical prostatectomy vs radical RT
 * Randomized. Patients with Stage T1b-T2bN0, GS <=7, PSA <20. Trial closed due to lack of accrual and was converted to a patient-preference study
 * 1999 PMID 10356027 -- "Few patients with prostate cancer are willing to be randomised to treatment." (O'Reilly P, BMJ. 1999 Jun 5;318(7197):1556.)
 * Letter to editor. 20 patients evaluated over 12 months, but only 1 agreed to randomization
 * 2000 Abstract -- "Trial of Randomisation Between Radical Prostatectomy and Radiotherapy in Early Prostate Cancer" (Livessey JE, Clin Oncol. 2000;12:63)
 * 41 patients counselled, only 1 agreed to be randomized. Reminder chose surgery (55%), RT (42%), or watchful waiting (3%)
 * 2002 PMID 12133061 -- "A preliminary report on a patient-preference study to compare treatment options in early prostate cancer." (North West Uro-Oncology Group, BJU Int. 2002 Aug;90(3):253-6.)
 * Prospective. 196 patients recruited (surgery 41%, conformal RT 41%, brachytherapy 15%, watchful waiting #). Similar patient characteristics across groups
 * Conclusion: It should be possible to answer underlying question with this study design

 * MRC PR06 (1994-1996) -- Radical prostatectomy vs RT vs watchful waiting
 * Randomized. Trial closed early due to non-accrual. 35 men accrued of target 1800.
 * 2004 PMID 15610132 -- "Early closure of a randomized controlled trial of three treatment approaches to early localised prostate cancer: the MRC PR06 trial." (PR06 Collaborators, BJU Int. 2004 Dec;94(9):1400-1.)

 * Japanese Study Group for Locally Advanced Prostate Cancer (1989-1993) -- RP vs EBRT
 * Randomized. 95 patients. T2b-T3N0M0. Arm 1) radical prostatectomy + pelvic LN dissection + endocrine therapy vs. Arm 2) Pelvic RT 40-50 Gy + 20 Gy prostate boost + endocrine therapy. Hormones initiated 8 wks prior to primary therapy (using DES) then continued indefinitely (LHRH agonist +/- antiandrogen, or estrogen).
 * 2006 PMID 17082219 — "A randomized trial comparing radical prostatectomy plus endocrine therapy versus external beam radiotherapy plus endocrine therapy for locally advanced prostate cancer: results at median follow-up of 102 months." (Akakura K et al. Jpn J Clin Oncol. 2006 Dec;36(12):789-93.) Median F/U 8.5 years
 * Outcome: 10-year bPFS RP 76% vs. RT 71% (NS); cPFS 83% vs. 66% (p=0.06); DSS 86% vs. 77% (SS); OS 68% vs. 61% (NS)
 * Toxicity: Incontinence worse in surgical arm; erectile dysfunction in almost all patients due to ADT
 * Conclusion: For locally advanced patients, either RP or EBRT demonstrated favorable outcomes. DSS better with surgery. RT dose 60-70 Gy may not be enough
 * Comment: low RT dose. Small study.

 * SWOG 8890 -- randomized RT vs. prostatectomy
 * Randomized. Stage A2 and B. Goal 1128 patients. Study closed due to poor accrual (referenced in PMID 7754277, PMID 16018945)

 * Uro-Oncology Research Group -- radical surgery vs. radiation
 * Randomized. 97 patients. cT1-2N0M0. Arm 1) radical prostatectomy vs. Arm 2) megavoltage RT (using Co-60 or betatron) to pelvic field 45-50 Gy + prostate 20 Gy boost. Primary outcome development of metastatic disease by prostatic acid phosphatase, bone scan, and/or pelvic lymphadenectomy
 * 1982 PMID 6811766 -- "Radical surgery versus radiotherapy for adenocarcinoma of the prostate." (Paulson DF, J Urol. 1982 Sep;128(3):502-4.)
 * Outcome: Actuarial development of mets RP 8% vs. RT 31% (SS)
 * Conclusion: Radical surgery more effective than RT
 * 1988 PMID 3360648 -- "More on the Uro-Oncology Research Group report of radical surgery vs. radiotherapy for adenocarcinoma of the prostate." (Hanks GE, Int J Radiat Oncol Biol Phys.)
 * Critique: small sample, randomization artifacts (imbalances in health, age, lymph node assessment), worse than usual RT outcomes. Results never widely accepted

RT vs Cryotherapy

 * University of Calgary (1997-2003) -- EBRT vs Cryotherapy
 * Randomized. Trial closed prematurely due to slowing patient accrual. 244 patients of 240 planned, localized prostate cancer (T2-T3N0, PSA <=20 ng/ml, volume <=60 ml), PLND if GS 8+. Excluded clinically bulky patients. Neoadjuvant ADT 3 or 6 months. Arm 1) EBRT (median dose 68 Gy, max 73.5 Gy) using 4F box vs Arm 2) cryoablation using argon/helium and 2 freeze/thaw cycles. Early cryotherapy failures (within 6 months) were not scored as protocol failure, and underwent salvage cryotherapy. QoL assessment. Primary endpoing was failure rate at 3 years
 * 2009 PMID 19937954 -- "A Randomized Trial of External Beam Radiotherapy Versus Cryoablation in Patients With Localized Prostate Cancer" (Donnelly BJ, Cancer. 2010, Epublished) Median F/U of surviving patients 8.3 years
 * Outcome: 3-year failure rate (using nadir+2) cryo 17% vs. EBRT 13% (NS); 5-year rate 25% vs. 25% (NS); 7-year rate 27% vs. 32% (NS); 5-year DSS 96% vs. 96% (NS); 5-year OS 90% vs 88% (NS). Biopsy (+) cryo 8% vs EBRT 29%
 * Toxicity: GI Grade 3-4 cryo 3% vs. EBRT 7%; GU Grade 3-4 cryo 9% vs. EBRT 6%; intercourse 4% vs. 26%
 * Conclusion: Essentially no difference, but with long-term follow up, trend favors cryotherapy
 * 2009 PMID 19691092 -- "A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer: quality of life outcomes." (Robinson JW, Cancer. 2009 Oct 15;115(20):4695-704.)
 * Outcome: Cryotherapy more acute GU dysfunction (SS), no difference in late GU dysfunction. Cryotherapy worse sexual function at 3 months (SS) and 3 years (SS)
 * Conclusion: No long term QoL difference, except worse sexual function after cryoablation

 * University of Western Ontario -- EBRT vs cryotherapy
 * Randomized. Trial stopped prematurely due to slow accrual. 64 of planned 150 patients, cT2c-T3b. Neoadjuvant ADT for 6 months. Arm 1) EBRT vs. Arm 2) cryotherapy
 * 2008 PMID 17579613 -- "Randomized trial comparing cryoablation and external beam radiotherapy for T2C-T3B prostate cancer." (Chin JL, Prostate Cancer Prostatic Dis. 2008;11(1):40-5. Epub 2007 Jun 19.)
 * Outcome: Treatment failure EBRT 45% vs. cryotherapy 64%. 4-year bPFS 47% vs. 13%. Mean bPFS 41 months vs 28 months. No difference in DSS and OS
 * Toxicity: Serious complications uncommon; EBRT more frequent GI toxicity
 * Conclusion: Low numbers, but cryotherapy is suboptimal primary therapy for locally advanced prostate cancer

ADT vs RT + ADT

 * Please see the Primary ADT section for more detail

 * SPCG-7/SFUO-3 (1996-2002) -- ADT +/- RT
 * Randomized. 875 with locally advanced prostate cancer T1b-T2 G2-G3 or T3 (78%) and PSA <70 and N0 (if PSA >11, then PLND). Arm 1) ADT (total androgen blockade x3 months, then continuous flutamide 250 mg) vs. Arm 2) Same ADT + RT 70 Gy to prostate/SV. Breast RT in 80% to prevent gynecomastia
 * Outcome; 2008 PMID 19091394 -- "Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial." (Widmark A, Lancet. 2008 Dec 15. [Epub ahead of print]). Median F/U 7.6 years
 * Outcome: 10-year CSS ADT 76% vs. ADT + RT 88% (SS); 10-year OS 61% vs. 70% (SS); 10-year bPFS 25% vs. 74% (SS)
 * Toxicity: Urethral stricture ADT 0% vs. ADT + RT 2% (SS), urgency 8% vs 14% (SS), urinary incontinence 3% vs. 7% (SS), erectile dysfunction 81% vs. 89% (SS)
 * Conclusion: In patients with high risk or locally advance PCA, addition of RT to ADT improved survival, with acceptable side effects

 * MRC (1980-1985) -- orchiectomy vs RT vs orchiectomy + RT
 * Randomized, 3 arms. 277 patients, clinically localized prostate cancer (T2-T4NxM0). Arm 1) RT alone vs Arm 2) orchiectomy alone vs Arm 3) RT + orchiectomy
 * 1992 PMID 1422689 -- "Treatment of advanced localised prostatic cancer by orchiectomy, radiotherapy, or combined treatment. A Medical Research Council Study. Urological Cancer Working Party--Subgroup on Prostatic Cancer." (Fellows GJ, Br J Urol. 1992 Sep;70(3):304-9.)
 * Outcome: Orchiectomy (orchiectomy alone or orchiectomy + RT) superior to RT alone in DMFS. No difference in local control or overall survival
 * Conclusion: Orchiectomy superior to RT alone in metastatic-free survival

Retrospective Comparisons
Single institution data suggests comparable outcomes between RP and high-dose (>72 Gy) EBRT, but advantage to RP compared with low-dose (<72 Gy) EBRT. In unfavorable tumors, there appears to be some benefit to RT:

Single Institution

 * Washington U; 2012 PMID 22335870 -- "Survival among men with clinically localized prostate cancer treated with radical prostatectomy or radiation therapy in the prostate specific antigen era." (Kibel AS, J Urol. 2012 Apr;187(4):1259-65.)
 * Retrospective. 10,429 consecutive pts treated with RP, EBRT, or BT.
 * 10-yr OS: favors RP (88.9%) over EBRT (82.6%) or BT (81.7%). Adjusted PCA specific mortality favors RP (1.8%) vs EBRT (2.9%) or BT (2.3%). EBRT is associated with decreased OS and PCSM compared with RP. BT is associated with decreased OS but not PCSM compared with RP.
 * Conclusion: "After adjusting for major confounders, radical prostatectomy was associated with a small but statistically significant improvement in overall and cancer specific survival. These survival differences may arise from an imbalance of confounders, differences in treatment related mortality and/or improved cancer control when radical prostatectomy is performed as initial therapy."

 * Mayo Clinic - Scottsdale; 2009 PMID 19670452 -- "Radiation dose escalation for localized prostate cancer: intensity-modulated radiotherapy versus permanent transperineal brachytherapy." (Wong WW, Cancer. 2009 Dec 1;115(23):5596-606.)
 * Retrospective. 853 pts. Conventional dose 3D-CRT (median 68.4 Gy), high dose IMRT (75.6 Gy), brachytherapy alone (144 Gy I or 120 Gy Pd), EBRT + BT (45 + 110/90). Median f/u 58 mo.
 * 5-yr bNED 74% (3D), 87% (IMRT), 94% (BT), 94% (EBRT+BT). For int risk: improved bNED for IMRT, BT, or EBRT+BT vs 3D; no improvement noted for low risk.
 * BT caused more GU but less GI tox, EBRT + BT caused more late GU and GI tox than IMRT or 3D.

 * British Columbia Cancer Agency; 2009 (1998-2001) PMID 19570619 -- "Brachytherapy or Conformal External Radiotherapy for Prostate Cancer: A Single-Institution Matched-Pair Analysis." (Pickles T, Int J Radiat Oncol Biol Phys. 2009 Jun 29. [Epub ahead of print])
 * Retrospective, matched-pair. 601 patients, BCCA database, matched for PSA, GS, T-stage, use/duration of ADT, %positive cores. 278 perfect matches analyzed further. Median BT dose 144 Gy, EBRT dose 68 Gy. Primary endpoint bNED (Phoenix). Median F/U 5.7 years
 * Outcome: 5-year bNED BT 95% vs. EBRT 85% (SS), 7-year bNED 95% vs. 75% (SS). Median post-treatment nadir 0.04 ng/ml vs 0.62 ng/ml (SS), which predicted higher EBRT treatment failure rate. Low risk 94% vs 88% (SS); intermediate risk 100% vs. 78%
 * Toicity: Late Grade 3 GI/GU at 2 years BT 1% vs. EBRT 6%, at 5 years 5% vs. 2%. Late urinary worse with BT, late rectal/bowel worse with EBRT. Catheterization 15% (42% > 1 month) vs. 0% (SS)
 * Conclusion: Brachytherapy for low-risk and selected intermediate-risk exceptional cure rate that will be hard to match for EBRT, even with dose escalation

 * Geneva; 2007 (1989-1998) PMID 17923593 -- "Short- and Long-term Mortality With Localized Prostate Cancer." (Merglen A, Arch Intern Med. 2007 Oct 8;167(18):1944-50.)
 * Cohort study. All 844 patients with localized PCA diagnosed 1989-1998. Prostatectomy (19%), RT (24%), watchful waiting (45%), hormones (9%), other (4%). Survival curve comparison
 * Outcome: 5-year DSS no difference. 10-year DSS: surgery 83% vs. RT 75% vs. watchful waiting 72% (SS). Increased mortality primarily in patients <70 and GS >=7
 * Conclusion: Surgery offers best chance of long-term PCA-specific survival
 * Critique (PMID 18775078, Full Text): No primary end-point definition, imbalances in PSA and GS, clinical vs pathological staging, no info on RT dose which was likely low in that time period

 * University of Virginia; 2006 (1988-2000) PMID 16965872 -- "Case-matched comparison of contemporary radiation therapy to surgery in patients with locally advanced prostate cancer." (Fletcher SG, Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4):1092-9. Epub 2006 Sep 11.)
 * Retrospective, matched cohort. 409 men with high-risk PCA (Stage >= T2b or PSA >=10 or GS 7-10). Treated with RP, brachytherapy alone, or EBRT+BT boost + ADT. 208 matched
 * Outcome: 4-year bPFS EBRT+BT 72% vs. brachy 25% vs. RP 53% (SS). RR of relapse for EBRT+BT 0.56, RP 1.0, and brachy alone 0.44 (SS)
 * Conclusion: High risk PCA patients receiving multimodality therapy display superior outcome to surgery or brachytherapy alone

 * Columbia 2005 ASCO Abstract -- Intermediate-Risk Localized Prostate Cancer in the PSA Era:Radiotherapeutic Alternatives and the Effects of Biochemical Failure Definition and Year of Treatment on Outcome (Ennis RD, ASCO)
 * 347 patients with intermediate cancer treated 8/89-6/01 with standard EBRT (SD-EBRT), high dose >72 Gy EBRT (HD-EBRT), brachytherapy, or brachytherapy+EBRT. AST analyzed also. Median follow-up 36 months
 * All treatments were comparable to each other except brachytherapy-based vs. SD-EBRT (p=0.0003)
 * AS+SD-EBRT better than SD-EBRT (p=0.0001) only if failure definition PSA > 1.5 is used
 * Conclusion : "For intermediate-risk prostate cancer patients, brachytherapy-based treatment results in an excellent outcome that is significantly better than SD-EBRT. AD+SD-EBRT may also result in improve outcome compared to SD-EBRT, but this conclusion is dependent on the definition of biochemical failure. Year of treatment is an important prognostic factor in patients with intermediate-risk prostate cancer treated in the PSA era."

 * Cleveland Clinic, 2002 (1990-98) PMID 12177097 Full Article -- "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, J Clin Oncol.)
 * Retrospective, single-institution. 1682 pts with clinical stage T1-T2, treated during the PSA era. Treated with prostatectomy (n=1,054) or RT (n=628) 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. Median follow-up 51 months
 * 8-year overall PSA-DFS: RP 72% vs. RT 70% (p=0.01) but RP patients significantly more favorable profile
 * 8-year PSA-DFS for favorable tumors (T1-T2a, GS<=6, PSA<=10): RP 86% vs. RT 90% (NS)
 * 8-year PSA-DFS for unfavorable tumors: RP 62% vs. RT 59% (NS) but dose dependent:
 * 8-year PSA-DFS for unfavorable tumors at RT <72Gy: RP 70% vs. RT 50% (p<0.001)
 * 8-year PSA-DFS for unfavorable tumors at RT >72Gy: RP 70% vs. RT 82% (p=0.004)

 * Harvard/UPenn PMID 12124827 Full Article -- Biochemical outcome after radical prostatectomy or external beam radiation therapy for patients with clinically localized prostate carcinoma in the prostate specific antigen era. (2002 D'Amico, Cancer)
 * A retrospective study of 2635 men treated with RP (n = 2254) or conventional-dose RT (n = 381) between 1988-2000. ASTRO definition for both RP and RT. Median follow-up 48 months)
 * 8-year PSA-DFS for low risk (T1c-T2a and PSA <=10 and GS <=6): RP 88% vs RT 78% (p<0.01)
 * 8-year PSA-DFS for intermediate-risk (T2b or GS=7 or PSA 10-20) with <34% positive bx: RP 79% vs. RT 65% (p=0.05)
 * 8-year PSA-DFS in intermediate-risk with >34% positive bx: RP 36% vs RT 35% (p=NS)
 * 8-year PSA-DFS in high risk (T2c or PSA>20 or GS 8-10): RP 33% vs RT 40% (p=NS)
 * Original paper, 1998 - PMID 9749478 - see above under section Definitions of Risk Groups

 * 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.

 * Wake Forest; 2001 (1998-1999) PMID 11597800 -- "A prospective quality-of-life study in men with clinically localized prostate carcinoma treated with radical prostatectomy, external beam radiotherapy, or interstitial brachytherapy." (Lee WR, Int J Radiat Oncol Biol Phys. 2001 Nov 1;51(3):614-23.)
 * Prospective. 90 men with T1-T2, treated with curative intent. Brachytherapy (50%), EBRT (25%), RP (25%). Completed QoL questionnaire prior and at 1 month, 3 months, and 12 months
 * Outcome: Scores not significantly different at 12 months amongh the 3 groups
 * Conclusion: Health-related QoL is treatment-specific

Review

 * Harvard; 2009 PMID 19417179 -- "A 64-year-old man with low-risk prostate cancer: review of prostate cancer treatment." (Sanda MG, JAMA. 2009 May 27;301(20):2141-51. Epub 2009 May 5.)

Point-Counterpoint

 * Journal of Urology 2009
 * AS PMID 19836767 -- "Active surveillance for favorable risk prostate cancer. Pro." (Klotz L, J Urol. 2009 Dec;182(6):2565-6. Epub 2009 Oct 17.)
 * AS risks PMID 19836809 -- "Active surveillance for favorable risk prostate cancer. Beware the risks." (Parekh DJ., J Urol. 2009 Dec;182(6):2566-8. Epub 2009 Oct 17.)

 * Oncology 2009
 * RP PMID 19839427 -- "Radical prostatectomy reigns supreme." (Rayala HJ, Oncology (Williston Park). 2009 Sep;23(10):863-7.)
 * RT PMID 19839425 -- "Radical radiotherapy for prostate cancer is the 'only way to go'." (Sandler HM, Oncology (Williston Park). 2009 Sep;23(10):840-3.)

 * Urology 2008
 * EBRT PMID 19022492 -- "Why External Beam Radiotherapy Is Treatment of Choice for Most Men With Early-stage Nonmetastatic Prostate Cancer." (Horwitz EM, Urology. 2008 Nov 19. [Epub ahead of print])
 * Brachytherapy PMID 19038423 -- "Brachytherapy for Localized Prostate Cancer." (Ciezki JP, Urology. 2008 Nov 25. [Epub ahead of print])

 * Urological Oncology 2008
 * Active treatment PMID 18774465 -- "Screen detected, low volume prostate cancer: the case for active treatment." (Montie JE., Urol Oncol. 2008 Sep-Oct;26(5):511-5.)
 * Observation PMID 18774462 -- "What is the best approach for screen-detected low volume cancers?--The case for observation." (Klotz L, Urol Oncol. 2008 Sep-Oct;26(5):495-9.)

Patient Decision-Making

 * US Multi-Institutional -- Patient intervention vs Patient + Support intervention vs Control
 * Randomized, 3 arms. 6 US sites. 256 patients with T1-T2b, GS <10, PSA <20. Arm 1) treatment direct (patient receives intervention) vs. Arm 2) treatment supplemented (patient and primary support person receive intervention) vs. Arm 3) control. Intervention was designed to improve communication strategies when meeting with their physician.
 * 2009 PMID 19819096 -- "Managing uncertainty about treatment decision making in early stage prostate cancer: a randomized clinical trial." (Mishel MH, Patient Educ Couns. 2009 Dec;77(3):349-59. Epub 2009 Oct 9.)
 * Outcome: Improvement in cancer knowledge at 4 weeks and 3 months in both intervention arms; significantly lower rate of decision regret
 * Conclusion: Intervention was effective in preparing patients for uncertainty management in prostate cancer

 * UCSF; 2009 PMID 19841280 -- "Patient decision aids for prostate cancer treatment: a systematic review of the literature." (Lin GA, CA Cancer J Clin. 2009 Nov-Dec;59(6):379-90. Epub 2009 Oct 19.)
 * Systematic review. 13 studies of decision aids for patients with low-risk prostate cancer
 * Outcome: Use of DA's can improve knowledge, encourage active patient involvement, and decrease anxiety. Impact on treatment choice less clear

 * Fred Hutchinson
 * 2009 PMID 19589564 -- "Access to information sources and treatment considerations among men with local stage prostate cancer." (Ramsey SD, Urology. 2009 Sep;74(3):509-15. Epub 2009 Jul 9.)
 * Prospective survey of men with local prostate cancer, prior to starting therapy
 * Outcome: On average, ~5 sources of info consulted. Physician (97%), lay literature (76%), other health professionals (71%), friends with PCA (67%), internet (58%)
 * Conclusion: Men consult wide range of information sources
 * 2006 PMID 16568450 -- "Why do men choose one treatment over another?: a review of patient decision making for localized prostate cancer." (Zeliadt SB, Cancer. 2006 May 1;106(9):1865-74.)
 * Literature review.
 * Outcome: Conflicting evidence on how men make decisions

Incidentally detected prostate cancer (T1a-b)

 * U.New Mexico, 1988 - PMID 3193495 - "Incidental carcinoma of the prostate: an analysis of the predictors of progression." Lowe BA et al. J Urol. 1988 Dec;140(6):1340-4.
 * Constructed probability tables for progression based on Gleason score and volume of disease.

 * Cantrell, 1981 - PMID 7218450 — "Pathological factors that influence prognosis in stage A prostatic cancer: the influence of extent versus grade." Cantrell BB et al. J Urol. 1981 Apr;125(4):516-20.
 * 117 pts. No pt with Gleason 2-4 had progression. Only 2% with Stage T1a (<5% cancer) had progression. Of Stage T1b (>5% cancer), 32% had progression, and for Gleason 5 and above, 17% progressed.
 * No additional treatment needed for Stage T1a with Gleason 2-4.

EBRT

 * Conventional (2D) RT can safely deliver maximum 65-70 Gy before causing significant GI and GU toxicity. Some subpopulations of tumor clonogens appear resistant to this dose.
 * 3D-CRT allows delivery of significantly higher doses, and is currently the standard of care
 * IMRT permits further dose escalation while providing lower GI toxicity. Its role is under evaluation

EBRT Outcomes

 * Multi-institutional PMID 15667961 -- Improved biochemical relapse-free survival with increased external radiation doses in patients with localized prostate cancer: the combined experience of nine institutions in patients treated in 1994 and 1995. (2005 Kupelian P, Int J Radiat Oncol Biol Phys. 2005 Feb)
 * 1325 patients with T1-T2 treated in 1994 and 1995; 1061 were treated with <72 Gy (median dose 68.4 Gy, median follow-up 5.8 years) and 264 with > or =72 Gy (median dose 75.6 Gy, median follow-up 5.7 years).
 * PSA-DFS estimates were 64% at 5-years and 62% at 8-years.
 * The 5-year PSA-DFS estimates for <72 Gy vs. > or =72 Gy were 63% vs. 69% (p = 0.046).

 * Multi-institutional PMID 14575822 -- Long-term multi-institutional analysis of stage T1-T2 prostate cancer treated with radiotherapy in the PSA era. (2003 Kuban DA, Int J Radiat Oncol Biol Phys. 2003)
 * 4839 patients with T1b, T1c, and T2; no hormones; median follow-up 6.3 years
 * PSA-DFS was 59% at 5 years and 53% at 8 years after treatment
 * Of the 4839 patients, 1582 (33%) had PSA failure, 416 (9%) had local failure, and 329 (7%) had distant failure.

 * Multi-institutional PMID 10235152 -- Radiation therapy for clinically localized prostate cancer: a multi-institutional pooled analysis. (1999 Shipley WU, JAMA. 1999)
 * Retrospective, nonrandomized, multi-institutional pooled analysis of patients treated with EBRT alone between 1988 and 1995 at 6 US medical centers. Conventional + 3D-CRT techniques
 * 1765 men with stage T1b, T1c, and T2 tumors
 * 5-year OS 85%, DFS 95%, bNED 66%
 * for more info: see at page Prostate Overview

 * MGH PMID 7751173 -- The treatment of prostate cancer by conventional radiation therapy: an analysis of long-term outcome. (1995 Zietman AL, Int J Radiat Oncol Biol Phys. 1995)
 * Retrospective, single institution (MGH) review. PSA failure defined >4ng/ml
 * 1044 total patients, 504 with T1/T2;median follow-up 49 months
 * 5-year bNED: 60%
 * 10-year bNED: 40%

 * RTOG PMID 8270458 -- Patterns of Care and RTOG [75-06 and RTOG 77-06] studies in prostate cancer: long-term survival, hazard rate observations, and possibilities of cure. (1994 Hanks GE, Int J Radiat Oncol Biol Phys. 1994)
 * 10-year clinical DFS: 85-96%

 * Stanford PMID 3173503 -- Status of radiation treatment of prostate cancer at Stanford University. (1988 Bagshaw MA, NCI Monogr. 1988;(7):47-60.)
 * 900 patients (T0-T4) treated in 30-year Stanford review
 * 15-year OS: T0 was 45%, T1 was 35%, and T2 was 33%
 * 15-year clinical DFS: T0 was 85%, T1 was 64%, and T2 was 45%

Dose escalation vs ADT

 * See also: Adjuvant ADT
 * See also: Dose Escalation (Dose Escalation and ADT)

 * UCSF; 2007 PMID 18167004 -- "Dose escalated external beam radiotherapy versus neoadjuvant androgen deprivation therapy and conventional dose external beam radiotherapy for clinically localized prostate cancer: do we need both?" (Roach M 3rd, Strahlenther Onkol. 2007 Dec;183 Spec No 2:26-8.)
 * Review. 4 RCT comparing EBRT +/- short-term neoadjuvant ADT. 4 RCTs comparing dose escalation to 74-79 Gy
 * Conclusion: Quality of evidence supporting NADT with EBRT is stronger than evidence supporting dose escalation. However, with low cure rates, higher dose EBRT combined with NADT and whole pelvic RT may be indicated

 * PMID 16007687 -- "Optimal treatment of intermediate-risk prostate carcinoma with radiotherapy." (Nichol AM, Cancer. 2005 Jul 8;104(5):891-905)
 * There is Level I evidence that patients with intermediate-risk prostate carcinoma benefit from dose-escalated EBRT or AD plus conventional-dose EBRT. However, clinical evidence is lacking to support the uniform use of AD plus dose-escalated EBRT.

Locally advanced or higher-risk cancer (T3, select T1/2)
Please also see the Hormones section for in-depth discussion

 * Oslo; 2007 (Norway)(1989-1996) PMID 17703896 -- "10-year survival and quality of life in patients with high-risk (p)n(0) prostate cancer following definitive radiotherapy." (Berg A, Int J Radiat Oncol Biol Phys. 2007 Nov 15;69(4):1074-83. Epub 2007 Aug 20.)
 * Retrospective. 164/203 patients with T3-4N0 or GS>=7B, treated with 3D-CRT to 65-70 Gy and no hormones
 * Outcome: 10-year OS 52%, CSS 66%, cPFS 39%
 * Conclusion: RT <=70 Gy as monotherapy insufficient to control T3-4N0 or GS >=7B

 * EORTC trial PMID 20933466 -- External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. (2010 Bolla M, Lancet Oncol. 2010 Nov;11(9327):1066-73.)
 * Randomised PIII trial of 415 patients (90% T3-4, 10% T1-2 G3) to EBRT alone (50Gy pelvis + 20Gy boost) vs. EBRT + AST x 3 years; median follow-up 9.1 years
 * 10-year OS: 39·8% in patients receiving radiotherapy alone and 58·1% for combined treatment (p=0.0004)
 * 10-year clinical DFS: 22·7% in the radiotherapy-alone group and 47·7% in the combined treatment group (p<0.0001)
 * Conclusion : "The combination of radiotherapy and 3 years of androgen suppression improved long-term overall survival, without increasing late cardiovascular mortality, and should be regarded as standard of care for treatment of men with prostate cancer who are at high metastatic risk, with a WHO performance status of 0–2, and who have no contraindicating coexisting conditions."

 * MDACC PMID 10386637 -- Conventional external-beam radiation therapy alone or with androgen ablation for clinical stage III (T3, NX/N0, M0) adenocarcinoma of the prostate. (1999 Zagars, Int J Radiat Oncol Biol Phys 1999; 44:809-19.)
 * Retrospective review; 344 men with T3 N0/Nx who received RT alone (260; median follow-up 68 months) or with androgen ablation (84; median follow-up 44 months)
 * RT (<68Gy) alone: bNED <50%
 * RT (68-70Gy) alone: PSA >10 had 6-year bNED <50%; PSA <10 had 6-year bNED 76%
 * RT + AST: 6-year bNED 78%
 * Conclusion : "Conventional radiation alone has little curative potential for Stage III disease. Doses < 68 Gy are particularly ineffective. Patients with PSA < or = 10 ng/ml may be candidates for conventional radiation to a dose of 70 Gy. Other patients are probably best served by combined radiation-androgen ablation or high-dose conformal radiation."

 * Stanford PMID 3173503 -- Status of radiation treatment of prostate cancer at Stanford University. (1988 Bagshaw MA, NCI Monogr. 1988;(7):47-60.)
 * 900 patients (T0-T4) treated in 30-year Stanford review
 * 15-year OS was 20% for T3 and 10% for T4 (lymph node status was unknown).
 * 15-year DFS was 33% for T3 and 15% for T4 for same patients

Bone Marrow Status

 * Oslo; 2007 PMID 17230512 -- "Impact of disseminated tumor cells in bone marrow at diagnosis in patients with nonmetastatic prostate cancer treated by definitive radiotherapy." (Berg A, Int J Cancer. 2007 Apr 15;120(8):1603-9.)
 * Prospective. 131/272 patients with cT1-4pN0 disease with bone marrow aspirates with 1+ unfavorable feature (cT3-4, GS >=7B, PSA >=10). Definitive treatment with RT 66-72 Gy +/- hormones
 * Disseminated tumor cells in 18% (with pN0)
 * Outcome: 7-year risk of DM: BM- 6% vs. BM+ 21% (p=0.07); if no AST 9% vs. 28% (SS). No difference if GS <7B, or if long-term AST
 * Conclusion: Presence of tumor cells in bone marrow increases risk of DM after RT

Outcome Prediction

 * MSKCC Nomogram

Outcome: Disease-specific mortality
 * Harvard, 2005 (1989-2002) - PMID 16046650 — "Pretreatment PSA velocity and risk of death from prostate cancer following external beam radiation therapy." D'Amico AV et al. JAMA. 2005 Jul 27;294(4):440-7.
 * 358 men treated with RT alone
 * PSA velocity >2 ng/mL/year (i.e. more than 2 pts per yr) associated with increased all-cause and cancer-related mortality. 7-yr cancer-specific mortality for velocity >2 vs velocity < 2 is 19% vs 0% for low risk, and 24% vs 4% for high risk pts.
 * Conclusion: pts with high PSA velocity before treatment may need more aggressive treatment (i.e. should be treated like high risk pts)

Outcome: Distant Metastases
 * UT Southwestern, 2007 PMID 17264329 -- "Association of the circulating levels of the urokinase system of plasminogen activation with the presence of prostate cancer and invasion, progression, and metastasis." (Shariat SF, J Clin Oncol. 2007 Feb 1;25(4):349-55.)
 * Prospective. Measured plasma levels of urokinase-type plasminogen activator (uPA) and its receptor (uPAR), in patients s/p RP for localized CaP (429 preop, 76 postop), in patients with LN+ (19) and with DM (10)
 * Conclusion: elevation associated with biologically aggressive CaP, disease progression, and DM

 * MSKCC/Cleveland Clinic, 2003 PMID 14673043 -- Pretreatment nomogram that predicts 5-year probability of metastasis following three-dimensional conformal radiation therapy for localized prostate cancer. (Kattan MW, J Clin Oncol.)
 * Retrospective, nonrandomized analysis of 1,677 patients with stage T1c-T3 treated with 3D-CRT at MSKCC to develop the nomogram, validated with 1,626 patients at the Cleveland Clinic; median follow-up 38 months
 * At 5 years, 11% of patients experienced DM
 * Nomogram was developed, and is available at MSKCC's web site. Concordance was 0.81
 * Conclusion : "A nomogram with reasonable accuracy and discrimination has been constructed and validated using an external data set to predict the probability that a patient will experience metastasis within 5 years after three-dimensional CRT."

Outcome: Biochemical Failure
 * MSKCC, 2000 (1988-98) PMID 11013275 -- "Pretreatment nomogram for predicting the outcome of three-dimensional conformal radiotherapy in prostate cancer." (Kattan MW, J Clin Oncol. 2000 Oct 1;18(19):3352-9.)
 * Retrospective, 1042 pts.

 * Multi-institutional, 1999 PMID 10235152 -- Radiation therapy for clinically localized prostate cancer: a multi-institutional pooled analysis. (Shipley WU, JAMA)
 * Retrospective, nonrandomized, multi-institutional pooled analysis of 1765 men with stage T1b, T1c, and T2
 * At 5-years OS was 85%, DFS was 95%, and PSA-DFS was 66%
 * Risk groups were established by RPA with 5-year PSA-DFS:
 * (1) PSA <10: 81%
 * (2) PSA 10-20: 69%
 * (3) PSA 20+ and GS 2-6: 47%
 * (4) PSA 20+ and GS 7-10: 29%
 * Conclusion : "These rates indicate the probability of success for subsets of patients with tumors of several prognostic category groupings. These results represent a multi-institutional benchmark for evidence-based counseling of prostate cancer patients about radiation treatment."

 * Mayo, 1997 PMID 9179062 -- An enhanced prognostic system for clinically localized carcinoma of the prostate. (Pisansky TM, Cancer)
 * 500 patients with stage T1-4, NO or NX, MO
 * Risk score = (1.07 x tumor stage risk) + (1.21 x Gleason Score risk) + (1.2 x ln PSA)
 * Tumor risk (T1-2=0, T3-T4=1), GS risk (2-6=0, 7-10=1),
 * Risk groups with 5-year PSA-DFS:
 * (low) risk score <3.1: 92%
 * (intermediate) risk score 3.1-4.9: 67%
 * (high) risk score >4.9: 24%

Quality of life

 * Please see the Erectile dysfunction page for further information

Evaluation Scales

 * EPIC

Exercise

 * Perth, Australia (2007-2008) -- exercise x12 weeks vs control
 * Randomized. 57 patients with CaP, undergoing AST. Arm 1) resistance and aerobic exercise x12 weeks vs. Arm 2) usual care. Primary endpoint lean mass
 * 2010 PMID 19949016 -- "Combined resistance and aerobic exercise program reverses muscle loss in men undergoing androgen suppression therapy for prostate cancer without bone metastases: a randomized controlled trial." (Galvao DA, J Clin Oncol. 2010 Jan 10;28(2):340-7. Epub 2009 Nov 30.)
 * Outcome: Patients undergoing exercise improved lean mass (SS), muscle strength (SS), improved walk time (SS), QoL (SS), fatigue (SS), and CRP levels (SS)
 * Conclusion: Relatively brief exposure to exercise significantly improved AST-related adverse effects

 * Rochester -- exercise x4 weeks vs. control
 * Randomized. 38 breast or prostate cancer patients. Arm 1) Home-based aerobic and progressive resistance exercise x4 weeks at start of RT vs. Arm 2) control.
 * 2009 PMID 19831159 -- "A 4-week home-based aerobic and resistance exercise program during radiation therapy: a pilot randomized clinical trial." (Mustian KM, J Support Oncol. 2009 Sep-Oct;7(5):158-67.)
 * Outcome: Good adherence to intervention. At 3 months, significantly more daily steps walked, daily minutes of resistance exercise, number of resistance exercise days. Also significantly higher QoL and significantly lower cancer-related fatigue
 * Conclusion: Exercise during RT may be beneficial for cancer patients

 * Houston VA -- exercise x8 weeks vs. control
 * Randomized. 21 patients with localized PCA, undergoing therapy. Arm 1) RT + aerobic exercise 3x/week x8 weeks vs. Arm 2) RT only
 * 2007 PMID 17964881 -- "Exercise prevents fatigue and improves quality of life in prostate cancer patients undergoing radiotherapy." (Monga U, Arch Phys Med Rehabil. 2007 Nov;88(11):1416-22.)
 * Outcome: Significant benefit in fatigue, cardiac fitness, strength, flexibility, FACT-P, physical well-being, social well-being, and functional well-being
 * Conclusion: 8-week cardiovascular program during RT improves fatigues, well-being, and fitness

Quality of Life
Prostate Cancer Outcomes Study (1994-95)
 * NCI Prostate Cancer Outcomes Study website. Main publication: PMID 10528021 Free full text
 * Project of the NCI, based on the SEER population. 3500 men. All men were diagnosed from 1994-95 with positive biopsies. 88% had clinically localized disease. 42% treated with prostatectomy, 24 with RT, 13 with hormonal therapy, and 22 were not treated.


text:
User:Borbrav~enwikibooks

My Wikipedia page: Borbrav

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

title: User:Borbrav~enwikibooks


text:
Talk:Puzzles/Statistical puzzles/Summing n/Solution

Is this solution even correct? if you have 0's in your arsenal, then you can go 0,3; 0,0,3; 0,0,0,3; 0,0,0,0,3; and so on. Also, are the solutions 1,2 and 2,1 distinct?


text:
Cookbook:OpenCola

OpenCola is unique in that the instructions for making it are freely available and modifiable. Anybody can make the drink, and anyone can modify and improve on the recipe as long as they, too, license their recipe under the GNU General Public License. The legal grounds for this are dubious however, as recipes are exempted from copyright as they are techniques, not artworks.

Although originally intended as a promotional tool to explain free software/open source software, the drink took on a life of its own and 150,000 cans were sold. The Toronto-based company Opencola founded by Grad Conn, Cory Doctorow and John Henson became better known for the drink than the software it was supposed to promote. Laird Brown, the company's senior strategist, attributes its success to a widespread mistrust of big corporations and the "proprietary nature of almost everything."

As it turns out, mixing up a batch of cola's pretty easy. As with all undertakings of great moment, read and understand the instructions before attempting to commit cola on your own. Note that this is not the recipe for "OpenCola"—that is, the canned beverage from OpenCola that you may have received at a trade show, or other venue or outlet. Making canned cola requires millions of dollars in abstruse gear and manufacturing gizmos. It's easier to make nerve gas than manufacture cola. This is a kitchen-sink recipe that you can make all on your own.

Flavoring formula

 * 3.50 mL (¾ teaspoon) orange oil
 * 2.75 mL (½ teaspoon) lime oil
 * 1.25 mL (¼ teaspoon) cassia oil
 * 1.00 mL (¼ teaspoon) lemon oil
 * 1.00 mL (¼ teaspoon) nutmeg oil
 * 0.25 mL (5 drops) coriander oil
 * 0.25 mL (5 drops) neroli oil
 * 0.25 mL (5 drops) lavender oil
 * 10.0 g (2 teaspoons) food-grade gum arabic
 * 3.00 mL (⅔ teaspoon) water

Concentrate formula

 * 11 cups (2.36 kg / 5.2 lb) plain granulated white table sugar
 * 9½ cups (2.28 L / 4.41 quarts) water
 * 2 tablespoons (30 ml) caramel color
 * 3½ teaspoons 75% phosphoric acid or citric acid
 * 2 teaspoons Flavoring Formula
 * ½ teaspoons caffeine (optional)

Flavoring

 * 1) Mix oils together in a cup.
 * 2) Add gum arabic, and mix with a spoon.
 * 3) Add water and mix well. A mixer may be used for this step, mixing for 4–5 minutes. You can also transfer to a blender for this step.
 * 4) Store this mixture in a sealed glass jar in a refrigerator or at room temperature. Please note that this mixture will separate. The gum arabic is essential to this part of the recipe, as you are mixing oil and water.

Syrup

 * 1) In a one gallon container, combine 5 ml of the flavoring formula with the phosphoric or citric acid.
 * 2) Mix in the water, then the sugar.
 * 3) While mixing, add the caffeine, if desired. Make sure the caffeine is completely dissolved.
 * 4) Add the caramel color and mix thoroughly.

Cola

 * 1) To finish the drink, mix 1 part syrup with 5 parts carbonated water.

Notes, tips, and variations

 * The sugar can be replaced with artificial sweeteners for a diet drink. The opensoda.org formula from 2009 calls for replacement with Splenda at ⅛ the mass of the original sugar amount.
 * Try measuring the flavoring oils with an eyedropper.
 * Alcohol can be used to aid with mixing the flavoring. Cube-cola instead uses a kitchen whisk attached to power tools.
 * Use only food-grade flavoring oils. Note that these oils can cause skin irritation. Wear food-prep or surgical gloves. If oils come in contact with skin, wash with soap and water.
 * It is very important that you get only food-grade gum arabic, as art-grade can be toxic.
 * 75% phosphoric acid is corrosive to the eyes and skin. Handle with gloved hands, and use extreme caution. If comes in contact with the eyes or skin, immediately flush with plenty of water for at least 15 minutes. Get medical attention. Rinse any spills on clothing or other surfaces thoroughly. Store in a secure area. Do not store more than 50.0 ml.
 * Caffeine can kill people in relatively small doses. The median lethal dose for an adult human is around 10 grams, or approximately ⅓ ounce. You can find out more by looking up the material safety data sheet (MSDS) for caffeine. Don't yield to the temptation to create a "Super-Jolt" by adding tons and tons of the white stuff to your cola, or you'll be in a world of hurt. It's best not to store caffeine in any amount. If stored, store in a secure area away from children.

Adapted from

 * http://alfredo.octavio.net/soft_drink_formula.pdf
 * View as HTML with Google
 * View as images with view.samurajdata.se

Libro di cucina/Ricette/OpenCola

title: Cookbook:OpenCola


text:
User:Strongbad

Introduction and Important Stuff
My name is Jeff Hankins, and I have a variety of interests, including mathematics and www.homestarrunner.com, which is where my user name originates. As of late July 2005, I have also begun enjoying football. Although I supported the Steelers during my childhood, I decided that since I only supported them because my father did, I had enough reason to turn to the Buccaneers. I've supported the Tennessee Volunteers all my life. As for other sports, I haven't worked out who I'm going for unless the Volunteers are in it. I created the Pokémon Colosseum walkthrough and finally finished it. By the way, I managed to catch a shiny Pokémon other than Red Gyarados! I really am excited about this. Also, it turns out that Wikipedia was founded on my birthday. I turned 15 that day.

By the way, I will not be editing Wikibooks from July 16, 2005 to August 1, 2005, which means that I should be able to get back to editing on August 2. Do not take this as a reason not to edit any pages that I have created. If something needs to be changed, change it, but please make sure that all changes are appropriate.

As an update, I may do some edits beginning July 24, 2005, but I won't be able to edit nearly as often as usual until August 2, 2005. I hope to be well on my way to adminship.

Interesting note
One time, for the Games bookshelf, I suggested that a Sports section should be included. Seeing that there is a Sports section now, I see that someone has taken my idea to heart.

No MGS2 guide?
It's amazing that there isn't a guide for this game. I think that such a guide would be a good thing to add to Wikibooks, considering that there are already plenty of guides and a guide satisfies the criterion for being on Wikibooks because it is basically a manual.

German language wikibook
The German language wikibook is a great wikibook. I can't believe how much time and effort has been put into it. Anyone who says that Wikibooks isn't going anywhere should check that book out.

title: User:Strongbad


text:
Ada Programming/Attributes/'Last

Description
, where  is any scalar subtype (for example integer, enumerated, real), is an attribute that represents the last value (upper bound) in the range of.

, where  is an array, denotes the last index value. For more-dimensional arrays,  denotes the last index value of the Nth dimension (N must be static).

Example
My_Enum (Enum1, Enum2, Enum3); My_Int   -1 .. 5; ...  (My_Enum'Last = Enum3); (My_Int'Last = 5); (My_Int'Last = 4);

Wikibook

 * Ada Programming
 * Ada Programming/Attributes
 * Ada Programming/Attributes/'First
 * Ada Programming/Attributes/'Range

Ada Reference Manual

|Last

title: Ada Programming/Attributes/'Last


text:
User talk:24.231.186.142

Hello and welcome to Wikibooks!

Here are some tips to help you get started:

 * Remember to conduct any editing experiments in the sandbox.
 * Check out our help page if you need additional help.
 * Eventually, you might want to read the Manual of Style and Policies and Guidelines.
 * Remember to maintain a Neutral point of view.
 * Explore, be bold in editing pages, and have fun!

Good luck!

(Donovan|Geocachernemesis|Interact) 01:30, 23 Jun 2005 (UTC)

title: User talk:24.231.186.142


text:
User talk:196.11.134.77

Hello and welcome to Wikibooks!

Here are some tips to help you get started:

 * Remember that comment should only be added to the appropriate talk pages.
 * Check out our help page if you need additional help.
 * Eventually, you might want to read the Manual of Style and Policies and Guidelines.
 * Remember to maintain a Neutral point of view.
 * Explore, be bold in editing pages, and have fun!

Good luck!

(Donovan|Geocachernemesis|Interact) 01:34, 23 Jun 2005 (UTC)

title: User talk:196.11.134.77


text:
Ada Programming/Attributes/'Succ

Description
X'Succ(Y) is an Ada attribute where X is any discrete type and Y is a value of that type. This attribute represents the discrete value that has a position number of one greater than the input parameter.

The returned discrete value type is the base type of discrete type. If the input parameter is the value of the discrete type, then a CONSTRAINT_ERROR exception will be raised.

Example
My_Enum (Enum1, Enum2, Enum3); ... (My_Enum'Succ(Enum2) = Enum3); (My_Enum'Succ(Enum3) = Enum1);

Wikibook

 * Ada Programming
 * Ada Programming/Attributes/'Pred

Ada Reference Manual

|Succ

title: Ada Programming/Attributes/'Succ


text:
Talk:JavaScript/Debugging

Page too short
This is a useful link. But, it should be merged directly into its parent articles if it's not going to grow further. If a page is only a dictionary definition or a few words with an external link, then it risks being deleted (under Wikibook's current policy). (Donovan|Geocachernemesis|Interact) 02:12, 23 Jun 2005 (UTC)

It's now under Debugging, but we need to write something about debugging JavaScript. --CarbonUnit

It's looking really good. Don't forget to sign your name with ~ on talk pages though. (Donovan|Geocachernemesis|Interact) 05:22, 26 Jun 2005 (UTC)

I removed the memory link section because it consisted of two dead links -- James Anon

title: Talk:JavaScript/Debugging


text:
User talk:Strongbad

Hi there, it seems that you have taken an interest in contributing to the Pokémon wikibook. However, please be aware of our naming conventions as well as the notes from Pokémon:Contributor's Guide and move/reformat your pages as necessary. Also note that, as per our forking policy there is only one walkthrough for any game at a time, so your walkthrough at Pokémon Colosseum Walkthrough should be better suited at Pokémon:Pokémon Colosseum:Walkthrough or something similar (as per the book's naming conventions) KelvSYC 02:24, 23 Jun 2005 (UTC)

title: User talk:Strongbad


text:
Mambo Open Source/Hiding pathway on frontpage

If you want to hide the pathway on the front page, you simply have to wrap it in a piece of PHP code. Here is an example of the code all together:

This returns nothing if the variable option = com_frontpage, and gives the code between the php tags if option is anything else than "com_frontpage". This variable can be exchanged with other variables if that is needed, but this works with the default homepage setting in mambo.


text:
Talk:Blender 3D: Noob to Pro/Furry 2.40

Can someone please enlighten me if this page will/ can be filled out with meaningful content? If not we can Speedy Delete this. Lynx7725 05:22, 23 Jun 2005 (UTC)

title: Talk:Blender 3D: Noob to Pro/Furry 2.40


text:
User talk:130.220.39.90

Hello and welcome to Wikibooks!

Here are some tips to help you get started:

 * Remember to conduct any editing experiments in the sandbox.
 * Check out our help page if you need additional help.
 * Eventually, you might want to read the Manual of Style and Policies and Guidelines.
 * Remember to maintain a Neutral point of view.
 * Explore, be bold in editing pages, and have fun!

Good luck!

(Donovan|Geocachernemesis|Interact) 05:51, 23 Jun 2005 (UTC)

title: User talk:130.220.39.90


text:
Chess/Puzzles

Chess piece placement puzzles are puzzles where certain pieces have to be placed on the board and satisfy certain conditions.

Chess checkmates are problems where White starts and mates in a clearly stated number of moves (or less).

Chess endgames and middlegames are problems where the number of moves is indefinite, and White (or Black) has to either win or tie, as stated by the question.

 * Piece placement puzzles
 * Directmates
 * Endgame problems
 * Middlegame problems

title: Chess/Puzzles


text:
Chess/Puzzles/Placement

 * /8 Queens/
 * /14 Bishops/
 * /32 Knights/

title: Chess/Puzzles/Placement


text:
Chess/Puzzles/Placement/8 Queens

1. Place 8 chess queens on a chessboard so no two attack each other. Left-click on a piece to move.

Hint (0) - Check Answer (Enter)

title: Chess/Puzzles/Placement/8 Queens


text:
Cookbook talk:Vegan Substitutions

NPOV: advertising
Begin section copied from Talk:Cookbook:Vegan_cuisine

G'day all,

I removed a bunch of links to specific forms of vegan cheese and milk. I really think if we are going to mention specfic brands then we should do it in a table sinilar to the ones on wikipedia comparing different software and the like. We HAVE to stay NPOV, so we cant go around advertising this or that brand.

It is open to manipulation by companies, and it is also not international, since most of the linked brands are only avaliable in one or two countries. The bellman 13:02, 25 Apr 2005 (UTC)
 * (duplicate of what I put on your talk page:) I added most of those companies (some while not logged in) for the express purpose of people being able to find vegan products. These could perhaps be split off to another page, but I think it's unreasonable to eliminate them. Vegan substitute products are difficult to find and it's even more difficult to find good ones. I am curious about your thoughts on this. Kellen 17:07, 17 May 2005 (UTC)
 * expanding on this: I think that having links to specific products (especially "basic" ones) is important with respect to veganism. Many of these basic things are prohibitively difficult, specialized, or time consuming to prepare (vegan cheese, for example) and it's unreasonable to just note that they exist without providing possibilities for people to find them (vegan substitutes like this are notoriously hard to get a hold of). I do agree that these are country specific, even region-specific, but I don't think there's a solution for this except maybe to denote that they are indeed region specific.
 * With respect to NPOV, I think that the difficulty in finding certain replacements trumps the "neutrality" of a non-mention. I'd like to see this software comparison table you're referring to, as this could satisfy both of our desires here. Kellen 17:16, 17 May 2005 (UTC)

End section copied from Talk:Cookbook:Vegan_cuisine

 * I am looking for some consensus (or at least some suggestions) on this, but there hasn't been much interest in this issue. Kellen 07:16, 23 Jun 2005 (UTC)

User:Gentgeen responded on the Talk:Cookbook page. Kellen 19:34, 27 Jun 2005 (UTC)

Begin section copied from Talk:Cookbook:

advertising
A while back I added a bunch of info about vegan ingredient substitutes, with specifics of brand names and links to their respective webpages User:The_bellman did some amount of purging of these with a NPOV complaint. I responded both on his user talk page and the Talk:Cookbook:Vegan_cuisine page, with no replies on either. I am going to reinstate these links for the reasons I have written in both places. If somebody can think of a better format, I am open to suggestions, but I think the info itself is useful. Kellen 02:50, 17 Jun 2005 (UTC)

 * I have no problems with product recomendations. Our NPOV policy is much looser than our big sister's, and specifying specific brand name products is common for a cookbook. Gentgeen 21:08, 26 Jun 2005 (UTC)
 * Agree that recommendation of specific brands - particularly for tricky things like vegan substitutions - is OK. A similar thing would perhaps apply to kitchen equipment, where someone might want to suggest that Acme Food Processors are a reputed product, etc. Redlentil 17:36, 29 Jun 2005 (UTC)

End section copied from Talk:Cookbook

I am going to remove NPOV banner since at least 3 active contributors have no problems with reccomendations and there has been no other input for 3 months. I would like to sort out how to deal with the region-specific issues though. Kellen 21:08, 12 July 2005 (UTC)

Minor addition
I added a very small comment that some grocery store brands of Worcestershire sauce are also vegan, for the very same reason mentioned above re brand names. Not everyone may have access to, or even may have heard of, the vegan brands mentioned, and store brands are often a godsend when it comes to looking for vegan alternatives generally. I'm new to this, hope I did it right!

As I understand it
As I understand it this selection should not include, or at least set off to the side, recommendations using any animal products including milk, cheese, eggs, and butter. From veganism... "Veganism is the practice of eliminating the use of animal products." Merry Christmas! // Fra nkB 02:10, 15 December 2011 (UTC)

Just wanted to say, I think this is lovely! :) JonathanHopeThisIsUnique (discuss • contribs) 19:20, 3 September 2014 (UTC)

title: Cookbook talk:Vegan Substitutions


text:
Portuguese/Contents/Preterite tense regular verbs

Preterite (Simple Past) Tense
This tense is used to describe an action that has happened in the past and which is now finished.

To form the preterite tense, use the following guide for regular verbs. The endings in bold can be put on the stem of the regular "AR", "ER" and "IR" verbs you wish to conjuagate.


text:
User talk:192.218.140.157

Hello and welcome to Wikibooks!

Here are some tips to help you get started:

 * Remember to conduct any editing experiments in the sandbox.
 * Check out our help page if you need additional help.
 * Eventually, you might want to read the Manual of Style and Policies and Guidelines.
 * Remember to maintain a Neutral point of view.
 * Explore, be bold in editing pages, and have fun!

Good luck!

(Donovan|Geocachernemesis|Interact) 09:03, 23 Jun 2005 (UTC)

title: User talk:192.218.140.157


text:
Puzzles/Physics puzzles/Eleatic School

Puzzles | Physics puzzles |Problems of the Eleatic School

Some background about these riddles is given on the Puzzles in science page. There is no strict solution to any of these puzzles. So rather than searching for a solution try to find support in favor or against the following postulates.

Achilles and the tortoise
Achilles is racing against a tortoise. Starting the race the tortoise is 10 m ahead. However, Achilles runs 20 times faster than the tortoise which runs at 1 m/sec (or any other positive speed). Shouldn't Achilles overtake the tortoise? In fact we shall see he does not. We start with the tortoise ahead at point A and Achilles behind at point B. When Achilles reaches point B a certain amount of time has passed which allowed the tortoise to move on to point C. Again Achilles reaching point C leaves the tortoise ahaed of some positive length, ad infinitum. Therefore Achilles is not going to catch up with the tortoise which is a contradiction to the initial notion of motion.

Therefore motion does not exist. Do you agree? comment

Here is a variant of the above puzzle:

Reaching point B
Suppose you intend to travel from point A to point B on a straight line. In order to do that you have to reach the midpoint C between A and B. In order to reach point C you have to reach the midpoint of A and C, say D, ad infinitum. Therefore it takes you an infinite amount of finite movements to reach point B which is in contrast with the notion of constant speed.

Therefore motion does not exist. Do you agree?

The flying arrow
Suppose an arrow is being shot from a bow. At any fixed point in time the arrow is motionless at a certain point. This directly contradicts the idea of motion since at any conceivable point in time motion is not present.

Therefore motion does not exist. Do you agree?

title: Puzzles/Physics puzzles/Eleatic School


text:
User talk:Djdoyle~enwikibooks

Dear Mr. Doyle,

I have changed the format of the headlines in the bioethics course that you are currently writing. This will allow other modules to link a section directly. It will also be possible to edit individual sections. I have also thought that you might want to link the references with the main text, in such a way that by clicking on the reference number, the browser jumps to the reference and back. This would save a lot of scrolling.(Alex beta 12:25, 23 Jun 2005 (UTC))

Dear Mr. Doyle,

I have been reading some of the recent additions to your bioethics course and have been puzzled by the fact that the section on "Principlism" is before the "Bioethics and moral theory section". Shouldn't "principlism" be included in the latter section? Should "utilitarianism", "principlism", "Equity issues in health care" (and so on) be subsections of "Bioethics and moral theory"?

Would you like me to link the references to the main text?

Thank you very much for your attention. (Alex beta 21:12, 23 Jun 2005 (UTC))

Your account will be renamed
Hello,

The developer team at Wikimedia is making some changes to how accounts work, as part of our on-going efforts to provide new and better tools for our users like cross-wiki notifications. These changes will mean you have the same account name everywhere. This will let us give you new features that will help you edit and discuss better, and allow more flexible user permissions for tools. One of the side-effects of this is that user accounts will now have to be unique across all 900 Wikimedia wikis. See the announcement for more information.

Unfortunately, your account clashes with another account also called Djdoyle. To make sure that both of you can use all Wikimedia projects in future, we have reserved the name Djdoyle~enwikibooks that only you will have. If you like it, you don't have to do anything. If you do not like it, you can pick out a different name.

Your account will still work as before, and you will be credited for all your edits made so far, but you will have to use the new account name when you log in.

Sorry for the inconvenience.

Yours, Keegan Peterzell Community Liaison, Wikimedia Foundation 23:10, 17 March 2015 (UTC)

Renamed
 This account has been renamed as part of single-user login finalisation. If you own this account you can |log in using your previous username and password for more information. If you do not like this account's new name, you can choose your own using this form after logging in: . -- Keegan (WMF) (talk) 04:53, 19 April 2015 (UTC)

title: User talk:Djdoyle~enwikibooks


text:
Buddhism Manual of Practice

This Wikibook is about the way and practice of Buddhism. If you believe in "to know the practice by knowing the theory", then welcome to the other side of it, that is "to understand and realize the theory by knowing and doing the practice". For some people, the first way might work but for other people the second might be better.

The first way is more suited for people with deep wisdom. Seeing the theory, they can understand it. Understanding the theory, they can deduce their way of practice. People with lesser wisdom will be confused when they see the theory. Even when they are reading it, they do not understand it. However, simply stating what they should do and then practicing it is much better.

Repeating what has been written, this book
 * is not about theories, but about ways of practicing
 * lets people know the way of practice so that they will understand the theory
 * is not tied to a particular method; instead it will try to describe several methods that are available.

Morality
Morality is a quality of mind. It produces a level of calmness and happiness in oneself and produces a basic level of security in society, making it a reasonably safe place to live. Morality can be developed by following certain guidelines, IF one has the right attitude.

The first set of guidelines that a lay Buddhist (who is still interested in family life) undertakes are known as The Five Precepts. They are:

 * 1) Don't kill any living creature
 * 2) Don't take what is not given to you
 * 3) Don't commit sexual immorality
 * 4) Don't speak falsely
 * 5) Don't become intoxicated such that you lose your ability to judge properly (this includes, drugs, alcohol etc.)

The next set of guidelines that a lay Theravada Buddhist (who is losing interest in family life - they could still live at home) undertakes for shorter to longer lengths of time, are known as The Eight Precepts. The change of precept number three above and the extra precepts (6-8) are related to restraining the six senses and support the meditative practice of looking inwards for true happiness, rather than outwards for sense pleasures. They are:

 * 1) Don't kill any living creature
 * 2) Don't take what is not given to you
 * 3) Don't have intentional sexual activity
 * 4) Don't speak falsely (don't lie, not even white lies)
 * 5) Don't become intoxicated such that you loose your ability to judge properly (this includes, drugs, alcohol etc.)
 * 6) Don't eat after noon
 * 7) Don't dance, sing, play or listen to music, go to see entertainments, wear garlands, use perfumes, or beautify the body with cosmetics
 * 8) Don't use high or luxurious furniture

Novice monks of the Theravada tradition follow 10 precepts, but actually it is only one more than the eight above, because number seven above is divided into two. The 10 are:
 * 1) Don't kill
 * 2) Don't steal
 * 3) Don't have intentional sexual activity
 * 4) Don't speak falsely (don't lie, not even white lies)
 * 5) Don't become intoxicated such that you loose your ability to judge properly (this includes, drugs, alcohol etc.)
 * 6) Don't eat after noon
 * 7) Don't dance, sing, play or listen to music, go to see entertainments
 * 8) Don't wear garlands, use perfumes, or beautify the body with cosmetics
 * 9) Don't use high or luxurious furniture
 * 10) Don't accept and use money

The only difference between the 8 and 10 Precepts is number 10. The last precept marks the giving up of addiction to sense pleasures. If we have money, we can buy whatever we want (depending on how much money we have, of course).

Monks and nuns follow even more precepts, many of which are specific to a monk's or nun's life in a monastery or as a wanderer. These are around 230 precepts for a monk and around 300 for a nun (it varies depending on which Buddhist tradition is being referred to).

Concentration
Meditation is a part of Buddhist concentration that helps to purify karma. Devout Buddhists should meditate on a daily basis.

Wisdom
Wisdom is insight into dependent origination; it's insight that believes that everything is caused and hence impermanent, based on suffering and not-self. This is seeing with insight the Four Noble Truths. This is consciousness and perception and feeling which are conjoined and inseparable from wisdom. "Wisdom is to be developed and consciousness is to be understood", said the Buddha in the sutta spoken by Bhikkhuni Visakha.

The Way of Practicing Satipatthana
Satipatthana comes from two words; sati and patthana. Sati meaning mindfulness, and patthana meaning foundation. Thus, the Satipatthana Practice is the foundation for the development of mindfulness.

Thinking Tilakkhana
Here are the thoughts that comply with the concept of anattā (non-self) in the Tilakkhana (the three marks of existence in Buddhist theory):
 * The thought of anger appears
 * A bad action has been done

And here are the thoughts that do not comply with the concept of anattā (non-self) in the Tilakkhana.
 * I am angry
 * I have done a bad thing

title: Buddhism Manual of Practice


text:
Movie Making Manual/Submitting to a broadcaster

When submitting to a broadcaster, you should check with them to ask what format they prefer. Often, the required format is:

 * DigiBeta
 * 4:3 FHA (full height anamorphic)
 * clocked
 * colour bars for 1 minute, 30 sec clock, 3 sec black before the first frame of audio or video
 * ensure that your colourspace is legal for broadcast

One possible way of configuring your timecode:
 * 09 57 45 00 = Black
 * 09 58 00 00 = Bars & Tone
 * 09 59 00 00 = Black
 * 09 59 20 00 = 40 Second clock
 * 09 59 57 00 = Black
 * 10 00 00 00 = Programme Start
 * Plus at least 1 minute of black on end.

/Sales and exhibition /Post-production /Short films


text:
Chess/Puzzles/Placement/14 Bishops

2. Place 14 bishops on a chessboard so no two attack each other. Left-click on a piece to move.

Hint (0) - Check Answer (Enter)

title: Chess/Puzzles/Placement/14 Bishops


text: Template:Chess position

title: Template:Chess position


text:
Category:NPOV disputes

Pages whose neutrality is disputed. Please check the talk page for each module with an NPOV dispute before editing.

To add a page here, use NPOV

__HIDDENCAT__

id:Kategori:NPOV diperselisihkan it:Categoria:Segnalazioni NPOV ro:Categorie:Dispute PDVN

title: Category:NPOV disputes


text:
Chess/Puzzles/Placement/14 Bishops/Solution

There are several solutions to this puzzle, but they are all quite similar.

Here's a possible one:

Proof of maximality
There are 15 diagonals on the chessboard running from bottom left to top right. They are:
 * a8-a8
 * a7-b8
 * a6-c8
 * a5-d8
 * a4-e8
 * a3-f8
 * a2-g8
 * a1-h8
 * b1-h7
 * c1-h6
 * d1-h5
 * e1-h4
 * f1-h3
 * g1-h2
 * h1-h1

Each of these diagonals can only contain one bishop. Also, the first and last diagonals cannot both contain a bishop, since both are on the diagonal a8-h1. Therefore, we can place at most 13 bishops on the other 13 diagonals, and one bishop on those two diagonals, for a total of 14 bishops. Since 14 bishops is possible, 14 is the maximum number of bishops we can place so no two attack each other.


text:
Chess/Puzzles/Placement/32 Knights/Solution

Here's a possible solution to the puzzle:

Proof of maximality
Pair up the squares of the board, demonstrated by the pairs of chess pieces on the board below.

Continue this pairing onto the rest of the board. On each pair of such squares, only one knight may be located. Since there are 32 such pairs, it's impossible to place more than 32 knights on the board. Since placing 32 knights is possible, 32 is the maximum number of knights that can be placed on a chessboard so no two attack each other.

This solution is only best if we assume the board cannot have other pieces besides knights. Given that no such presumption is stated, by using king pins at least a few more than 32 knights may be placed with none able to legally capture each other. Here is a simple example of a 35 knight solution by adding 11 on-color-kings, 9 off-color-queens, and 3 new knights to the board state in image 1 of this page (though more optimal answers likely exist).

(edit) Wiki won't allow any picture uploads, but surely the advancements are not hard to imagine if you begin with the 32 single color square solutions and from there apply on-color-kings and off-color-queens to secure safe and immobile knight squares to occupy.

The necessity(?) of multiple same-color kings to this method can be argued to its invalidity, but of course, 32 knights––let alone 32 white knights as shown above––is an equally impossible board state given standard starts.


text:
Chess/Puzzles/Placement/32 Knights

Place 32 knights on a chessboard so no two attack each other.

/Solution/

title: Chess/Puzzles/Placement/32 Knights


text:
Biblical Studies/Christianity/John 3

Chapter 3

verses 1-4 (done)
1 Now there was one of the Pharisees whose name was Nicodemus−a ruler among the Judeans. 2 He came to Jesus by at night and said, "Rabbi, we know that you are a teacher come from God; for no one can do perform these signs which as you are have been doing, unless God is with him.

3 "In all truthfulness, I tell you," answered Jesus, "that unless a man person is born anew again he (or she) cannot see the Kingdom of God."

4 "How is it possible," Nicodemus asked, "for a man to be born when he is old? Can he a second time enter his mother's womb the second time and be born again?"

verses 5-8 (done)
5 "Again, truthfully I tell you," replied Jesus, "that unless a man person is born of water and the Spirit, he (or she) cannot enter the Kingdom of God.

6 Whatever is born of the flesh woman is flesh of the body, and whatever is born of the Spirit is spirit.

7 Do not be astonished at my telling you, `You must all be born anew again.'

8 The wind blows where wherever it chooses; and you hear its sound, but you do not know where it comes from or where it is going. So is it with And in the same way everyone who has been born of the Spirit is moved by the Spirit."

verses 9-12 (done)
9 "Still, how is all this possible?" asked Nicodemus.

10 Are you," replied Jesus Jesus answered, saying, "Are you `’the Teacher of Israel,' and yet do you do not understand these things principles?

11 In all truthfulness, I tell you that we speak what we know, and give evidence concerning what we have witnessed, and yet, you all of you reject our testimony.

12 If I have told you of such things on earth and none of you believe me, how will you believe me if I tell you of heavenly things in heaven ?

verses 13-16 (done)
13 There is no one who has gone up to Heaven, except One who has come down from Heaven, namely the Son of Man whose home is in heaven itself.

14 For even And just as Moses lifted high up the serpent in the desert, so must the Son of Man be lifted up elevated,

15 in order that everyone who believes in Him may have eternal Life."

16 For so greatly did God love the world that He gave His only born Son, that everyone who believes in Him should not perish  experience be subject to death but have eternal Life.

verses 17-20 (done)
17 For God did not send His Son into the world to judge the world, but that the world might be saved through Him.

18 He who believes in Him does not come up for judgement Believers in Him do not come under condemnation: He who does not believe has while those who do not believe have already received their judgment sentence, because he has not believed of lack of belief in the name person of God's only Son.

19 And Then this is the test by which men are judged judgment process − that the Light has come into the world, and men people have loved the darkness rather than the Light, because their deeds have been wicked evil.

20 For every wrongdoer hates the Light, and does not come into it the Light, for fear his/her actions should be exposed.

verses 21-24 (done)
21 But the one he whose actions are true comes into the light, that his/her actions may be plainly shown to have been done through in God.

22 After this, Jesus and His disciples went into the Judean countryside; and there He remained stayed in company with them and baptized.

23 And John too was baptizing at Aenon, near Salim, because there were many pools of water and streams there; and a long procession of people came and received baptism.

24 (For John the Baptist had was not yet been thrown into prison.)

verses 25-30 (done)
25 So At that time, a discussion having arisen on the part of John's disciples had a serious discussion with a Jew Judean partisan about purification, 26 and they came to John and reported to him with the report, "Rabbi, he the one who was with you on the other side of the Jordan, and to about whom you bore testimony is now baptizing, and great numbers of many people are resorting turning to him."

27 "A man cannot obtain gain anything," replied John, "unless it has been granted to given him from Heaven.

28 You yourselves can bear witness to my having were there when I said, `I am not the Christ,' but, `I am His appointed acknowledged forerunner.'

29 He who has is with the bride is the bridegroom; and even so, the bridegroom's friend who stands expectantly by his side and listens to him, rejoices heartily greatly on upon account of hearing the bridegroom's voice. This is In this my joy is now complete. 30 He must grow greater His work must increase, but I must grow less and mine must decrease.

verses 31-36 (done)
31 He who comes from above is above all. He who springs comes from the earth not only springs from the earth, but speaks of the earth. He who comes from heaven is above all. 32 What He has seen and heard, to that He bears witness gives testimony; but His evidence no one accepts.

33 Any All man who has accept ed His testimony has have solemnly declared set their seal on the declaration that God is true.

34 For He is the One whom God has sent and speaks God's words; for God does not give the Spirit in sparing small measure."

35 The Father loves the Son and has entrusted placed everything in to His hands.

36 He Those who believe in the Son has have eternal Life; he those who do es not believe the Son will not see experience that Life, but bear the brunt of God's anger remains upon him.

The Updated Modernity Version (Parallel, Annotated) John 3

 THE NEW TESTAMENT

John 1 − 2  − 3  − 4  − 5  − 6  − 7  − 8  − 9  − 10  − 11  − 12  − 13  − 14  − 15  − 16  − 17  − 18  − 19  − 20  − 21

title: Biblical Studies/Christianity/John 3


text:
Puzzles/Physics puzzles/A boat, a pool, and a lead ball

Puzzles | Physics puzzles | A boat, a pool, and a lead ball

There's a boat floating in a pool. First, you place the (large) ball of lead in the boat, and measure the water's level. Then, you take the ball out and drop it into the pool, and measure the water's level again. Assuming the boat doesn't sink from the lead ball being in it, during which measurement will the water's level be higher?

/Solution/


text:
Puzzles/Physics puzzles/A boat, a pool, and a lead ball/Solution

Puzzles | Physics puzzles | A boat, a pool, and a lead ball

The water's level will be higher when the ball is in the boat.

When the ball is in the boat, it displaces the volume of water that weighs the same as the ball (see buoyancy). When the ball is in the water, it only displaces as much water as its volume.

For example, assume the ball's volume is 1.000 cubic metre. Then its mass is 11340 kg, and when placed in the boat it displaces 11340kg of water, which is the same as 11.340 cubic metres. When the ball is in the water, it onl displaces its own volume, which equals 1.000 cubic metre.

More water is displaced when the ball is in the boat, and so the water level rises more, leading to our result.


text:
Instructional Technology/Analysis

Types of Instructional Design Analyses

 * /Needs Assessment/
 * /Learner Analysis/
 * /Audience Analysis/ (when a non-instructional solution is identified)
 * /Organizational Analysis/
 * /Job Analysis/
 * /Task Analysis/
 * /Content Analysis/

title: Instructional Technology/Analysis


text:
User:Dalf~enwikibooks

Yea so this is the same dalf as wikipedia:User:Dalf and wikipedia:ro:user:Dalf though I have not made edits on the latter.

title: User:Dalf~enwikibooks


text: File:1 proto 1.gif

title: File:1 proto 1.gif


text: File:2 massive panel with ic send.gif

title: File:2 massive panel with ic send.gif


text: File:3 gate replace.gif

title: File:3 gate replace.gif


text: File:4 ic send to ic receive.gif

title: File:4 ic send to ic receive.gif


text: File:5 mod seq id 12.gif

title: File:5 mod seq id 12.gif


text:
Reaktor/Tutorials/Use of IC Send module with any sequencer

This simple tutorial shows how you can use IC Send module to control any desired parameter of your favourite instrument with a cool sequencer from another instrument. You just need to understand how to browse through Reaktor structure.

'''The idea of this tutorial was created on Reaktor User Forum. See the whole story.'''

In addition you can download a demonstration ensemble from the User Library.

Use IC Send to send gate (rhythm) signal

 * 1) First, you have to find the sequencer in Massive. Normally, you would right-click on the sequencer in panel and choose Show in structure, but Massive uses Mouse Area, which detects mouse-clicks, and therefore the right button doesn't work. But it's not difficult to find the sequencer in the structure: open Massive and go down into the structure:
 * 2) *Massive
 * 3) *Drums
 * 4) *Drum1 (Kick/snare)
 * 5) *Proto1
 * 6) Insert IC Send module (Build-In Module, Terminal, IC Send) and wire it to G1 terminal of "Macro" macro: [[Image:1 proto 1.gif]]
 * 7) Look at the Massive panel. You may need to move the visible IC Send module to a desired position: [[Image:2 massive panel with ic send.gif]]
 * 8) Insert new instrument into the ensemble - a desired drum synthesizer or sampler (sampler doesn't really make sense, because Massive is a sampler!). In this tutorial, we will use HiHat synthesizer from DSQ-32.ens.
 * 9) Connect the sound output of HiHat to Audio Out (your sound card) in the highest level of Reaktor structure.
 * 10) Go inside of HiHat Instrument and find Gate input terminal.
 * 11) Insert IC Receive (Buil-In Module, Termina, IC Receive) and wire it to input HiHat macro: [[Image:3 gate replace.gif]]
 * 12) From the Massive panel, open the menu of IC Send module and select HiHat > IC Receive: [[Image:4 ic send to ic receive.gif]] This way you create a wireless connection between the sequencer in Massive and Gate input of HiHat instrument. Please note, that this connection works between two instruments! That's a very fast and creative feature! Without doing much cables etc, you can quickly connect any sequencer to your favourite instrument.
 * 13) Have fun!

Modulate a knob with Massive modulation track
The idea here is to automate a knob with sequencer from Massive. It means, that the knob will automatically turn or jump, along with a sequence you can co compose. This can be very cool, it will add life to the "flat" sound of your instrument. Using this method you can automate any knob, or many knobs at the same time. Can you turn 10 knobs at the same time? With this method you can! Note that for this use, it’s not necessary to add an additional IC Receive module anywhere in the target instrument, even if you haven’t added one before; the Send module will automatically see all the available parameters on its own; pretty cool!
 * 1) Open Massive structure and go to macro Aux. MOD seq 12-13-14-, Stacked Macro. That's the modulation sequencer of Massive.
 * 2) Insert Out Port (Build-In Module, Terminal, Out Port)
 * 3) Rename the Out Port to G and wire it to G output of MOD SEQ id 12 macro: [[Image:5 mod seq id 12.gif]]
 * 4) Go one level higher, insert IC Send module (Build-In Module, Terminal, IC Send) and wire it G output of the Stacked Macro: [[Image:6 ic send from stacked.gif]]. The reason why IC Send is not placed inside of Stacked Macro is that it would mess up the way stacked macro is displayed. This way it's just more convenient and flexible in panel design.
 * 5) Go back to Massive panel, unlock it, and move IC Send module to desired position. Then lock the panel again. Open IC Send menu and select ClosedHihat:Cut: [[Image:8 ic send to cut.gif]] It will send the modulation track values to Cutoff knob in HiHat instrument and move it automatically! Make sure to select MOD 1 sequence in Massive panel, because this is the modulation sequence we use, one of three at your disposal in Massive. Just imagine - if you add 2 more IC Send modules to the other two modulation sequencers, and send the signal to different knobs, you will get a lively modulated drum track, especially if the length of modulation sequences is not the same, they can make nice, varied permutations...
 * 6) Have fun!

Comment
In this example we use IC Send to transmit gate signal, which is usually a range 0..1. IC Send and IC Receive modules can send a range of values, which is defined in their properties. The default range is 0..1 - and it works fine for gate signal. It won't work though with note pitch, which is range 0..127. To send pitch through IC Send and IC Receive you must change the range of both modules in their properties to 0..127. If you don't change it and leave the default min and max values, the receive module will always show 1 (the default max value) since the values incoming to IC Send are usually above 1 (60 for C3).


text: File:6 ic send from stacked.gif

title: File:6 ic send from stacked.gif


text:
Puzzles/Arithmetical puzzles/Four 4s Equal.../Solution

Solution to ../

1
$$\frac{4+4}{4+4}$$

2
$$\frac{4}{4}+\frac{4}{4}$$

3
$$\frac{4+4+4}{4}$$

4
$$\frac{4-4}{4}+4$$

5
$$\frac{4\times4+4}{4}$$

6
$$\frac{4+4}{4}+4$$

7
$$4+4-\frac{4}{4}$$

8
$$4+4+4-4 \,\!$$

9
$$4+4+\frac{4}{4}$$

10
$$4\times4-\frac{4!}{4}$$

11
$$4^2-4-\frac{4}{4}$$

12
$$4+4+\frac{4^2}{4}$$

13
$$4^2-4+\frac{4}{4}$$

14
$$4^2-\frac{4+4}{4}$$

15
$$4\times4-\frac{4}{4}$$

16
$$4\times4+4-4 \,\!$$

17
$$4\times4+\frac{4}{4}$$

18
$$4^2+\frac{4+4}{4}$$

19
$$4^2+4-\frac{4}{4}$$

20
$$4\times\left(4+\frac{4}{4}\right)$$

21
$$4^2+4+\frac{4}{4}$$

22
$$4!-\frac{4+4}{4}$$

23
$$4!-\frac{4^2}{4\times4}$$

24
$$4\times4+4+4 \,\!$$

25
$$4!+\frac{4^2}{4\times4}$$

26
$$4!+\frac{4+4}{4}$$

27
$$4!+4-\frac{4}{4}$$

28
$$4!+4+4-4 \,\!$$

29
$$4!+4+\frac{4}{4}$$

30
$$4!+\frac{4\times4!}{4^2}$$

31
$$4^2+4^2-\frac{4}{4}$$

32
$$4\times4+4\times4 \,\!$$

33
$$4^2+4^2+\frac{4}{4}$$

34
$$4!+4+\frac{4!}{4}$$

35
$$\left(\frac{4!}{4}\right)^2-\frac{4}{4}$$

36
$$\left(\frac{4!}{4}\right)^2+4-4$$

37
$$\left(\frac{4!}{4}\right)^2+\frac{4}{4}$$

38
$$4^2+4^2+\frac{4!}{4}$$

39
$$4!+4^2-\frac{4}{4}$$

40
$$4!+4^2+4-4 \,\!$$

41
$$4!+4^2+\frac{4}{4}$$

42
$$4!+4!-\frac{4!}{4}$$

43
$$44-\frac{4}{4}$$
 * This is the only solution that requires 4410

44
$$4!+4!-\frac{4^2}{4}$$

45
$$\left(\frac{4!+4}{4}\right)^2-4$$

46
$$4!+4^2+\frac{4!}{4}$$

47
$$4!+4!-\frac{4}{4}$$

48
$$4!+4!+4-4 \,\!$$

49
$$4!+4!+\frac{4}{4}$$

50
$$\frac{(4!-4)^2}{4+4}$$


text:
Puzzles/Arithmetical puzzles/Four 4s Equal...

Puzzles | Arithmetical puzzles | Four 4's equal...

Use exactly four 4's to form every integer from 1 to 50, using only the operators '$$+$$', '$$-$$', '$$\times$$', '$$/$$', '' (brackets) $$x^2$$ (square), and '!' (factorial). The square and factorial operators should be used as sparingly as possible. If 44 (which is 4 x 10 + 4) can be avoided, avoid it. In this version of the problem, the square root operator is not allowed.

solution


text:
User talk:69.211.45.158

Hello and welcome to Wikibooks!

Here are some tips to help you get started:

 * Remember to conduct any editing experiments in the sandbox.
 * Check out our help page if you need additional help.
 * Eventually, you might want to read the Manual of Style and Policies and Guidelines.
 * Remember to maintain a Neutral point of view.
 * Explore, be bold in editing pages, and have fun!

Good luck!

(Donovan|Geocachernemesis|Interact) 01:55, 24 Jun 2005 (UTC)

title: User talk:69.211.45.158


text:
User talk:84.65.211.231

Hello and welcome to Wikibooks!

Here are some tips to help you get started:

 * Remember to conduct any editing experiments in the sandbox.
 * Check out our help page if you need additional help.
 * Eventually, you might want to read the Manual of Style and Policies and Guidelines.
 * Remember to maintain a Neutral point of view.
 * Explore, be bold in editing pages, and have fun!

Good luck!

(Donovan|Geocachernemesis|Interact) 02:12, 24 Jun 2005 (UTC)

title: User talk:84.65.211.231


text:
User talk:204.69.4.81

Hello and welcome to Wikibooks!

Here are some tips to help you get started:

 * Remember to conduct any editing experiments in the sandbox.
 * Check out our help page if you need additional help.
 * Eventually, you might want to read the Manual of Style and Policies and Guidelines.
 * Remember to maintain a Neutral point of view.
 * Explore, be bold in editing pages, and have fun!

Good luck!

(Donovan|Geocachernemesis|Interact) 02:25, 24 Jun 2005 (UTC)

title: User talk:204.69.4.81