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Radiation Oncology/Breast/Partial breast irradiation

Partial Breast Irradiation

Anatomical studies

 * Rationale for APBI is that majority of local recurrences occur in close proximity to tumor bed, and <20% appear "elsewhere" in the breast. Absolute number of "elsewhere" failures is quite low (<<1% per year) and is similar to rate of new contralateral tumors

 * Holland - Classic paper that justified the need for whole breast RT. Evaluated mastectomy specimens. 42% of extensive intraductal component (EIC) negative breasts had residual carcinoma; 74% of EIC+ had residual carcinoma. Most carcinoma was intraductal type. Most tumors were large and clinically detected.
 * PMID 2153190 — "The presence of an extensive intraductal component following a limited excision correlates with prominent residual disease in the remainder of the breast." Holland et al., 1990.

 * Vaidya - A paper that paradoxically justified the rationale for partial breast irradiation. Multicentric foci were plotted in an abstract 3-D space and the conclusion was that although 63% (same result as Holland) of otherwise occult cancers were present in mastectomy specimens, over 79% of them were in other quadrants. This was in contrast with the results of breast conserving surgery trials in which early local recurrence occurred most commonly (>90%) of the time in the area around the primary tumor, thus justifying the approach of TARGeted Intraoperative radioTherapy [TARGIT]
 * PMID 8795588 — "Multicentricity of breast cancer: whole-organ analysis and clinical implications." Vaidya JS, Vyas JJ, Chinoy RF, Merchant N, Sharma OP, Mittra I. 1996.
 * 3D studies of duct-lobular system
 * PMID 8630874 — "Intraductal extension of primary invasive breast carcinoma treated by breast-conservative surgery. Computer graphic three-dimensional reconstruction of the mammary duct-lobular systems." Ohtake et al. 1995.
 * 20 pts studied, all had quadrantectomy. Ductal anastomoses are present, and may be a risk for spread to other ductal-lobular systems. Maximum distance of spread, 11.9 mm.
 * PMID 11413514 — "Computer-assisted complete three-dimensional reconstruction of the mammary ductal/lobular systems: implications of ductal anastomoses for breast-conserving surgery." Ohtake et al. 2001.
 * 3D reconstruction of a single entire breast

 * PMID 11072782 Full Text — "Relationship between the morphological and biological characteristics of intraductal components accompanying invasive ductal breast carcinoma and patient age." Imamura et al. 2000.
 * Median extension of intraductal component 9 mm. Related to patient age, with older patients having less extension.

 * PMID 15465188 (2004) — "Defining the clinical target volume for patients with early-stage breast cancer treated with lumpectomy and accelerated partial breast irradiation: a pathologic analysis." Vicini et al. Int J Radiat Oncol Biol Phys. 2004 Nov 1;60(3):722-30.
 * Recommend 10 mm margin around tumor bed

Dosimetry

 * MD Anderson; 2012 PMID 22884255 -- "A new paradigm for calculating skin dose." (Gifford KA, Brachytherapy. 2012 Aug 8. [Epub ahead of print])
 * Evaluation of skin volumetric models. Literature review showed average breast epidermal thickness 1.68 mm. Clinical plan developed with 2 mm skin contour, as contraction of the external surface contour, to estimate epidermis thickness. Second plan 5 mm expansion of the external contour
 * Outcome: median difference for Dmax (01. cc) skin -2 mm vs skin +2 mm was 12% (SS), maximum was 24% (SS)
 * Conclusion: Surface model for skin may underestimate dose delivered to epidermis by as much as 24%
 * Dose Homogeneity Index, Tufts; 1988 PMID 3352544 --"A dose homogeneity index for evaluating 192Ir interstitial breast implants." (Wu A, Med Phys. 1988 Jan-Feb;15(1):104-7.)
 * Dose homogeneity index defined as DHI = [V(TDR)-V(HDR)]/V(TDR), where V(TDR) denotes the total treatment volume enclosed by the prescribed treatment dose rate (TDR) and V(HDR) denotes the volume enclosed by high-dose rate (HDR), which is 1.5 X TDR or greater. Also can be written as (V100% - V150%)/V100%

Ongoing

 * NSABP B-39/RTOG 0413 -- ONGOING
 * Randomized. Whole breast vs. APBI for stage 0, I and II patients
 * Technique: multi-catheter brachytherapy (34 Gy), MammoSite (34 Gy) or External Beam (38.5 Gy)

 * Ontario RAPID NCT00282035 -- ONGOING
 * Randomized. Whole breast 42.5/16 vs 3D-CRT APBI 38.5/10 BID.
 * Inclusion criteria: >=40, DCIS or invasive carcinoma, SM-, LN-

 * MRC IMPORT LOW Trial -- ONGOING
 * Randomized. 40/15 to index quadrant vs. 40/15 index quadrant + 36/15 remaining quadrants vs. 40/15 to center of breast (whole breast control). No boost.
 * Eligibility: Low risk early stage BCA (>50 and BCS and T1 and invasive ductal and unifocal and GI-II/III and SM > 2mm and LVI- and LN- and DM-)

 * University of Florence (ONGOING) -- WBRT 50/25 vs APBI 30/5
 * Randomized. Ongoing. 259 patients out of planned 520. Arm 1) WBRT 50/25 using conventional tangents vs Arm 2) IMRT APBI 30/5. Mean CTV 44 cm3, mean PTV 123 cm3, mean PTV/breast volume 21%
 * 2009 PMID 19700248 -- "Accelerated Partial Breast Irradiation with IMRT: New Technical Approach and Interim Analysis of Acute Toxicity in a Phase III Randomized Clinical Trial." (Livi L, Int J Radiat Oncol Biol Phys. 2009 Aug 21. [Epub ahead of print])
 * Toxicity: Skin toxicity Grade 2 WBRT 19% vs. IMRT 1%
 * Conclusion: APBI is feasible, with very low acute toxicity

 * Milan ELIOT -- ONGOING?
 * Randomized. Intraoperative electron RT vs. whole breast RT

Meta-Analysis

 * Heraklion University, Greece; 2010 PMID 20210799 -- "Partial Breast Irradiation or Whole Breast Radiotherapy for Early Breast Cancer: A Meta-Analysis of Randomized Controlled Trials." (Valachis A, Breast J. 2010 Feb 23. [Epub ahead of print])
 * Meta-analysis. 3 trials with 1,140 patients.
 * Outcome: No difference in OS (OR 0.9, NS), DM (OR 0.7, NS), or SCV recurrences (OR 1.4, NS). However, PBI increased risk of local recurrence (OR 2.1, SS), and axillary recurrence (OR 3.4, SS) compared with whole breast RT
 * Conclusion: PBI doesn't jeopardize survival but issue of locoregional recurrence needs to be addressed
 * Letter to editor (Polgar C, PMID 20127229): Inappropriate to include the 2 "old" British trials using inadequate patient selections criteria

 * Aarhus, Denmark; 2009 PMID 18783840 -- "Accelerated partial breast irradiation as part of breast conserving therapy of early breast carcinoma: A systematic review." (Offerssen BV, Radiother Oncol. 2009 Jan;90(1):1-13. Epub 2008 Sep 8.)

 * University College London; 2016 PMID 27478165 -- "Reduced Mortality With Partial-Breast Irradiation for Early Breast Cancer: A Meta-Analysis of Randomized Trials." (Vaidya JS et al, Int J Radiat Oncol Biol Phys. 2016 May 13. pii: S0360-3016(16)30200-0. doi: 10.1016/j.ijrobp.2016.05.008.)
 * Meta-analysis. 5 trials for non breast cancer mortality (n=4489) and 4 trials for breast cancer mortality (4251)
 * Outcome: The overall mortality was 4.9%. There was no detectable heterogeneity between the trials for any of the outcomes. There was no difference in the proportion of patients dying of breast cancer (difference, 0.000% [95% confidence interval (CI), -0.7 to +0.7]; P=.999). Non-breast cancer mortality with PBI was lower than with WBI (difference, 1.1% [95% CI, -2.1% to -0.2%]; P=.023). Total mortality with PBI was also lower than with WBI (difference, 1.3% [95% CI, -2.5% to 0.0%]; P=.05).
 * Conclusion: Use of PBI instead of WBI in selected patients results in a lower 5-year non-breast cancer and overall mortality, amounting to a 25% reduction in relative terms. This information should be included when breast-conserving therapy is proposed to a patient.

Retrospective

 * Medicare claims analysis (MDACC) (2000-2007)
 * Review of medicare claims; patients > age 66 with invasive breast cancer diagnosed 2000-2007, treated with surgery followed by standard whole-breast irradiation (WBI) or accelerated partial breast brachytherapy (APBI)
 * 2011 Abstract only: No PMID Abstract San Antonio Breast Cancer Symposium 2011; Abstract #S2-1 "Partial Breast Brachytherapy Is Associated with Inferior Effectiveness and Increased Toxicity Compared with Whole Breast Irradiation in Older Patients." (Smith GL, Dec 7, 2011)
 * Use of APBI-brachytherapy increased over time: from <1% in 2000 to 13% of patients in 2007. At 5 yrs, cumulative incidence of subsequent mastectomy was significantly higher: 4.0% (APBI) vs 2.2% (WBI); HR = 2.14. Higher risk of hospitalization: 9.6% v 5.7% (O.R. 1.71), infection: 8.1% vs 4.5% (O.R. 1.85); rib fracture 4.2% vs. 3.6%; fat necrosis 9.1% vs. 3.7%; breast pain 14.9% vs. 11.7%. Lower incidence of pneumonitis: 0.1% vs. 0.8%.
 * Conclusion: APBI-brachy was associated with inferior effectiveness (as evidenced by increased utilization of mastectomy) as well as increased acute and late toxicities compared with WBI.

APBI-Preoperative RT

 * University of North Carolina; 2010 (2003-2007) PMID 20395062 -- "Cosmetic Outcomes for Accelerated Partial Breast Irradiation Before Surgical Excision of Early-Stage Breast Cancer Using Single-Dose Intraoperative Radiotherapy." (Kimple RJ, Int J Radiat Oncol Biol Phys. 2010 Apr 13. [Epub ahead of print])
 * Phase II. 53 patients, age ≥ 48, IDC, <3 cm, cN0. Ultrasound driven treatment to select electron energy and cone size, target tumor + 1.5-2.0 cm circumferential margin and +1.0 cm deep margin. Dose 15 Gy electrons prior to segmental mastectomy. Additional WBRT in 20%. Median F/U 3.1 years (minimum 1 year)
 * Toxicity: "Good or excellent" RTOG cosmesis physician 80%, patient 76%. Grade 1-2 acute toxicity 6%, no Grade 3-4 toxicities
 * Conclusion: RT delivered to in-situ tumor feasible, with acceptable acute tolerance

Randomized

 * ELIOT (2000-2007) -- IORT 21/1 vs WBRT 50 Gy + 10 Gy boost
 * Randomized, equivalence trial. Italian. 1305 patients, age 48-75, tumor <= 2.5 cm, eligible for breast conserving therapy
 * Patients received either intraoperative radiotherapy (21 Gy in 1 fraction) or whole breast radiotherapy (50 Gy in 25 fractions plus a 10 Gy boost)
 * 2010 PMID 24225155 -- "Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial" (Veronesi Lancet Oncol. 2013 Dec;14(13):1269-77.)
 * Outcome: 5-year IBTR was 4.4% with IORT versus 0.4% with WBRT (HR was 9.3). 5-year OS was similar (96.8% with IORT and 96.9% with WBRT).
 * Toxicity: Lower skin toxicity with IORT
 * Conclusion: Although the rate of IBTR with IORT was within the prespecified equivalence margin, the rate was significantly greater than with WBRT. Improved selection of patients could reduce the rate of IBTR with intraoperative radiotherapy with electrons.
 * TARGIT-A (2000-2012) -- IORT 20/1 vs WBRT 40-56 Gy
 * Randomized, non-inferiority. 11 countries. 3451 patients, age ≥ 45 (median age 63, ≥ 70 in 15%), IDC (ILC excluded), unifocal, breast-conserving surgery + SNB/ALND. Mostly T1 (86%), N0 (83%), and low/intermediate grade (84%). Allowed entry prior to surgical pathology results(66%) or post pathology results (34%). Arm 1) Intra-op RT with Intrabeam 50 kV device 20 Gy at surface vs Arm 2) WBRT (as per each individual center, typically 40-56 Gy with/without boost 10-16 Gy). Postop RT for predefined factors (e.g. LCIS, EIC, N+, LVI+ or others pre-defined per each individual center) done as WBRT without boost (a prior expected rate 15%, actual rate 15.2%). Primary endpoint local recurrence. Non-inferiority 2.5% absolute difference in LR.
 * 2010 PMID 20570343 -- "Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial" (Vaidya JS, Lancet. 2010 Jul 10;376(9735):91-102.)
 * Outcome: 4-year LF IORT 1.2% vs WBRT 0.95% (NS)
 * Toxicity: Major toxicity (including skin breakdown) IORT 3.3% vs WBRT 3.9% (NS); Grade 3-4 toxicity 0.5% vs 2.1% (SS)
 * Conclusion: For select patients, single dose IORT should be considered an alternative to EBRT
 * Criticisms: PMID 21060332, PMID 20888981, PMID 20888982 -- Median f/u only 2 years (not directly stated in manuscript but inferred from figures), premature to draw conclusions from only 11 events in 2232 patients, 21% in APBI arm received mastectomy or WBRT, delivered only 5-7 Gy at 1cm from radiation source
 * 2014 PMID 24224997 -- "Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial" (Vaidya JS, The Lancet, Early Online Publication, 11 November 2013). 5-year median F/U in 1222 patients, 4 year MF in 2020 patients, 2 year MF in 3451 patients
 * Outcome: 5-year LF TARGIT 3.3% versus EBRT 1.3% (p=0.04, NS). If concurrent with lumpectomy, 2.1% versus 1.1% (p=0.3, NS); if delayed after lumpectomy 5.4% versus 1.7% (p=0.07, NS but larger than the non-inferiority margin). Breast cancer mortality 2.6% vs 1.9% (p=0.56, NS); non-breast-cancer mortality 1.4% vs 3.5% (p=0.0086, significant); overall mortality 3.9% vs 5.3% (p=0.099, NS)
 * Toxicity: Wound-related complications same, Grade 3/4 skin toxicity lower 0.2% versus 0.7%
 * Conclusion: TARGIT concurrent with lumpectomy should be considered an option for eligible patients
 * Criticisms: PMID 24835608, PMID 24835610, PMID 24835611, PMID 24835612, PMID 24835609, PMID 24929161 -- The chairman of the Data Monitoring Committee for TARGIT, Dr. Cuzick, (but without the support of the rest of the DMC) suggested that 5-year estimates should be used for calculating non-inferiority; authors responded that their method using complete raw data was the standard method and 5-year estimates, being mere estimates would give misleading results. Analysis restricted to the patients randomised in the first 8 years of the trial - these patients had a median follow up of 5 years - had given the same results and met the non-inferiority criteria. The authors pointed out that although recurrences may occur after 5 years, the effect of radiation on local recurrence is only in the first 5 years and most of this is seen in the first 2-3 years, the period very adequately covered by the follow up period as published. A robust response to scientifically weak criticisms for use of TARGIT IORT during lumpectomy breast cancer, including a decision aid (figure 4) is given in the Red Journal.
 * 2016 The full comprehensive report of the TARGIT-A trial (226 pages) was published in September 2016 PMID 27689969

Non-Randomized

 * Baton Rouge, LA; 2009 PMID 19945859 -- "Accelerated partial breast irradiation: Initial experience with the Intrabeam System." (Elliott RL, Surg Oncol. 2009 Nov 27. [Epub ahead of print])
 * Retrospective. 67 patients, preop U/S diameter <3.5 cm. IORT with Intrabeam System
 * Outcome: 4 patients required later total mastectomy, 11 whole breast RT. No local failures
 * Toxicity: Good to excellent
 * Conclusion: IORT with Intrabeam is feasible in the community setting

 * Milan ELIOT study; 2008 (1999-2006) No PMID Full Text (PDF) -- "Full Dose Intraoperative Radiotherapy With Electrons (ELIOT) During Breast Conserving Surgery - Experience with 1246 Cases" (Veronesi U, ecancermedicalscience DOI 10.3332/eCMS 2008.65
 * Prospective. 1246 patients, tumor <2.5 cm. Electron IORT 21 Gy single dose. Median F/U 2.2 years
 * Outcome: Local recurrence 1.9%. 5-year OS 96%
 * Toxicity: Severe breast fibrosis 0.5%, mild fibrosis 3%
 * Conlusion: ELIOT is a safe method, with encouraging toxicity and local control

Randomized

 * Hungary (1998-2004) -- partial breast RT vs WBRT
 * Randomized. Trial stopped prematurely, since patients offered entry onto GEC-ESTRO Phase III APBI trial. 258 of expected 570 patients with T1N0-1mic, G1-2 nonlobular BCA, no EIC, SM-. WLE + ALND/SLND. Arm 1) WBI 50/25 vs. Arm 2) PBI 36.4/7 @ 5.2 Gy/fx BID multicatheter HDR (69%) or limited field electron PBI 50/25 if unsuitable for HDR (tumor bed + 2cm margin). Primary endpoint 5-year LR, noninferiority was 6% difference. Adjuvant chemo/hormones 72%
 * 5-years; 2007 PMID 17531400 -- "Breast-conserving treatment with partial or whole breast irradiation for low-risk invasive breast carcinoma-5-year results of a randomized trial." (Polgar C, Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):694-702.). Median F/U 5.5 years
 * Outcome: 5-year LR WBI 3.4% vs. PBI 4.7% (NS); no difference in DFS or OS
 * Toxicity: excellent/good cosmesis WBI 63% vs. PBI 78% (SS); HDR 81% and EB-APBI 70%
 * Conclusion: Similar outcomes, better cosmesis with HDR APBI
 * Fat necrosis; 2007 PMID 17524571 -- "Fat necrosis after partial-breast irradiation with brachytherapy or electron irradiation versus standard whole-breast radiotherapy-4-year results of a randomized trial." (Lovey K, Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):724-31.)
 * 4-year fat necrosis: overall WBI 32% vs. HDR 36% vs. EB-APBI 18% (SS); symptomatic 8% vs. 11% vs. 7% (NS)
 * Conclusion: asymptomatic fat necrosis common; symptomatic fat necrosis comparable after conventional WBI and APBI

Non-Randomized

 * National Institute of Oncology, Hungary; 2010 PMID 20181401 -- "Accelerated partial-breast irradiation using high-dose-rate interstitial brachytherapy: 12-year update of a prospective clinical study." (Polgar C, Radiother Oncol. 2010 Mar;94(3):274-9. Epub 2010 Feb 22.)
 * Prospective. 45 patients, T1N0-N1mic, IDC, no EIC, SM-. APBI using interstitial HDR BT, 30.3/7 (n=8) or 36.4/7 (n=37) over 4 days BID, tumor bed + 1-2cm margin. Median F/U 11 years for surviving patients
 * Outcome: IBTR 9%; 5-year IBTR 4.4%, 10-year IBTR 9.3%, 12-year IBTR 9.3%. Regional recurrence 4.4%. 12-year DFS 75%, CSS 91%, OS 89%.
 * Toxicity: Grade 3 fibrosis 1 patient (2%), no Grade 3 telangiectasia, fat necrosis requiring surgery 2%. Excellent/good cosmesis 78%
 * Conclusion: Continued excellent long-term local tumor control and cosmetic results

 * Tufts/Brown U. (1995- ) - ASTRO 2005 Abstract #12 — "Accelerated Partial Breast Irradiation (APBI): An Analysis of Variables Associated with Late Toxicity after HDR Interstitial Brachytherapy." Kaufman S et al. IJROBP Volume 63, Supplement 1, 1 October 2005, Page S7.
 * 75 pts. T1-2 N0-1 (0-3 nodes positive). Used HDR implant 34 Gy in 10 fractions BID over 5 consecutive days.
 * Median f/u 73 mo. Excellent/good cosmesis in 67%/24% (91%). Poor cosmesis associated with higher V150 and V200 and poor dose homogeneity index.

 * U. Wisconsin (2000-05) - ASTRO 2005 Abstract #13 — "Multi-catheter Breast Brachytherapy Following Lumpectomy in Select Early Stage Breast Cancer Patients: The University of Wisconsin Experience." Patel RR et al. IJROBP Volume 63, Supplement 1, 1 October 2005, Pages S7-S8.
 * 268 pts (240 treated with interstitial, the rest with MammoSite).
 * Median f/u 30 mos. IBTR in 1.4%. Symptomatic fat necrosis in 8.9%.

 * RTOG 95-17 (1997-2000)
 * Phase I-II. 99 pts. Brachytherapy with LDR (45 Gy in 3.5 - 5 days) or HDR (34 Gy in 10 fractions BID). Stage T1-2 (<3 cm), pN0-1
 * Toxicity: PMID 16503383, 2006 — "Phase II trial of brachytherapy alone after lumpectomy for select breast cancer: Toxicity analysis of RTOG 95-17." Kuske RR et al. Int J Radiat Oncol Biol Phys. 2006 May 1;65(1):45-51.
 * Median f/u 2.7 yrs. Grade 3-4 acute toxicity in 3% (HDR) or 9% (LDR). Grade 3 late toxicity in 18% (LDR) and 4% (HDR).

 * Ochsner Clinic, 2000 (1992-1993) PMID 11113440 -- "Long-term results of wide-field brachytherapy as the sole method of radiation therapy after segmental mastectomy for T(is,1,2) breast cancer." (King TA, Am J Surg. 2000 Oct;180(4):299-304.)
 * Original Phase I-II. 50 patients, Tis-T2, <=4cm, N0-1, SM-. Retrospective comparison to EBRT during same time. Median F/U 6.25 years
 * RT: Wide-field brachy (target volume 2cm peripheral and 1cm superficial/deep). Either LDR (45 Gy over 4 days) or HDR (32/8 in 4 Gy/fx BID) in blocks of 10 patients.
 * Outcomes: No difference in toxicity, local/regional recurrence, or cosmesis
 * Toxicity: 6% Grade 3 complications (3.8% LDR vs 7.7% HDR) - 2 severe fat necrosis on HDR requiring surgery (resulting in dosimetry adjustment) and 1 abscess from infected seroma. 56% Grade 2 complications (24% symptomatic fat necrosis, 12% telangiectasia, breast shrinkage, infection, pain, fibrosis). Fat necrosis worse if chemo (50% vs. 12%, SS), and if bad dosimetry gradient >30% (40% vs. 17%)
 * Conclusion: Brachytherapy attractive alternative to EBRT
 * Comment: Original fractionation scheme based on soft-tissue sarcomas, as per PMID 8407399

APBI-SAVI

 * Arizona Breast Cancer Specialists; 2011 PMID 20817617 -- "Dosimetric performance of Strut-Adjusted Volume Implant: a new single-entry multicatheter breast brachytherapy applicator." (Gurdalli S, Brachytherapy. 2011 Mar-Apr;10(2):128-35.)
 * Phase II. 19 patients enrolled, 15 treated. PTV_eval defined as 1 cm expansion of excision cavity, less skin and pectoralis muscle Prescribed at 3.4 Gy x 10 fractions twice daily
 * Outcome: Average D90 96%, average D100 91%. Average DHI 56%. Average skin distance 15 mm and skin Dmax 2.49 Gy/fx; average CW distance 23 mm and rib Dmax 1.99 G/fx.
 * Conclusion: Able to optimize dose distribution to obtain clinically acceptable dose plans

 * Multi-institutional; 2011 (2006-2009) PMID 20646847 -- "Initial clinical experience with the Strut-Adjusted Volume Implant (SAVI) breast brachytherapy device for accelerated partial-breast irradiation (APBI): first 100 patients with more than 1 year of follow-up." (Yashar CM, Int J Radiat Oncol Biol Phys. 2011 Jul 1;80(3):765-70. Epub 2010 Jun 18.)
 * Retrospective. Arizone Oncology Services and UC San Diego. 102 patients treated with SAVI; none pulled prior to treatment completion. PTV = tumor bed + 1cm, minus CW/ribs/skin. 34/10 twice daily. Median F/U 1.7 years
 * Outcome: V90 = 96%; max median skin dose 2.8 Gy. Local recurrence 1%
 * Toxicity: grade 1 hyperpigmentation 10%, Grade 2 fibrosis 2%, telangiectasia 2%, fat necrosis 2%
 * Conclusion: SAVE appears safe and increase eligibility for APBI over balloon brachytherapy

Overview

 * Usual dose: 34 Gy in 10 fractions (BID) over 5 consecutive days. Dose usually prescribed at 1 cm depth.
 * Ideal dosimetric criteria (see PMID 20378268):
 * PTV_EVAL: breast tissue bounded by expansion of balloon by 10 mm, limited to 5 mm from skin surface, and limited by posterior breast tissue extent (chest wall and pectoralis muscles are not included), less balloon volume
 * 95% of prescribed dose covers 95% of PTV_EVAL
 * Skin maximum: ≤ 125% prescribed dose
 * Rib maximum: ≤ 145% prescribed dose
 * Volume of breast receiving 150% of prescribed dose (V150): ≤ 50 cc
 * Volume of breast receiving 200% of prescribed dose (V200): ≤ 10 cc

Outcomes

 * TRIUMPH-T Trial; 2019 PMID 30611839 -- "Three-Fraction Accelerated Partial Breast Irradiation (APBI) Delivered With Brachytherapy Applicators Is Feasible and Safe: First Results From the TRIUMPH-T Trial" (Khan A, Int J Radiat Oncol Biol Phys. 2019 May 1;104(1):67-74. doi: 10.1016/j.ijrobp.2018.12.050. Epub 2019 Jan 4.)
 * Phase II multi-institutional trial. 200 patients, age >=45, unicentric invasive or DCIS, <=3 cm, ER+, pN-, surgical margin negative. Interstitial or SAVI or Contoura applicators. 22.5 Gy in 3 fractions. Minimum f/u 6 months
 * Dosimetry parameters: PTV-eval 90%/90%, skin (surface) and rib dose <100% (<120% permitted), V150 <40cm3; V200 <15 cm3 (17 cm3 permitted); interstitial homogeneity >0.75. S
 * Outcome: 97% good/excellent cosmetic outcome
 * Conclusion: Ultrashort breast brachy dosimetrically feasible, and excellent short-term toxicity

 * American Society of Breast Surgeons MammoSite Registry
 * True recurrence; 2012 PMID 22836556 -- "Tumor bed control with balloon-based accelerated partial breast irradiation: incidence of true recurrences versus elsewhere failures in the American Society of Breast Surgery MammoSite(®) Registry Trial." (Beitsch PD, Ann Surg Oncol. 2012 Oct;19(10):3165-70. doi: 10.1245/s10434-012-2489-x. Epub 2012 Jul 27.)Randomized trials demonstrate that lumpectomy plus whole-breast irradiation (WBI) yields survival equivalent to mastectomy. Studies that use WBI, however, typically report higher tumor bed recurrence rates than elsewhere failures (EF) (historically considered new primary lesions). The rate of true recurrence (TR) versus EF was queried for a large patient cohort treated with accelerated partial breast irradiation (APBI).
 * Registry trial. 1449 cases, lumpectomy with MammoSite APBI (34/10 BID). Invasive 87%, DCIS 13%. Comparison of true recurrence (TF) versus elsewhere failure (EF). Median F/U 5 years
 * Outcome: IBTR 3.5%; 5-year invasive IBTR 3.6%, DCIS 3.4%. True recurrence 1.1% versus elsewhere failure 2.6%. ER- status associated with increased risk of IBTR and EF. No pathologic factors associated with TF
 * Conclusion: IBTR after balloon-based APBI is low, and similar (and potentially better) than whole breast irradiation
 * Axillary recurrence; 2011 PMID 21537870 -- "Axillary Failure in Patients Treated with MammoSite Accelerated Partial Breast Irradiation." (Aburabia M, Ann Surg Oncol. 2011 May 3. [Epub ahead of print])
 * Registry trial. 1440 patients / 1449 cases treated with Mammosite (87% invasive, 13% DCIS). Median F/U 5 years
 * Outcome: 5-year axillary failure 0.8%, only risk factor high grade. 5-year OS 78%
 * Conclusion: Rate of axillary failure after MammoSite APBI is low and comparable to whole breast RT
 * DCIS; 2010 (2002-2004) PMID 20577822 -- "Update on DCIS Outcomes from the American Society of Breast Surgeons Accelerated Partial Breast Irradiation Registry Trial." (Jeruss JS, Ann Surg Oncol. 2010 Jun 25. [Epub ahead of print])
 * Registry trial. 194 patients, DCIS, MammoSite registry. Placement at lumpectomy 45%, post-lumpectomy 55%. SLN 26%. SM negative 88%, <2 mm 11%, positive 1%. Grade 3 37%. Median F/U 4.5 years
 * Outcome: IBTR 3.1%, breast/axilla recurrence 0.5%, 5-year local recurrence 3.4%
 * Toxicity: Seroma 24%, associated with lumpectomy placement. Favorable cosmesis 92% (minimum 5 year follow-up)
 * Conclusion: APBI via MammoSite well tolerated for patients with DCIS
 * ASTRO Unsuitable; 2010 PMID 20853036 -- "Five-year outcome of patients classified in the "unsuitable" category using the American Society of Therapeutic Radiology and Oncology (ASTRO) Consensus Panel guidelines for the application of accelerated partial breast irradiation: an analysis of patients treated on the American Society of Breast Surgeons MammoSite® Registry trial." (Beitsch P, Ann Surg Oncol. 2010 Oct;17 Suppl 3:219-25. Epub 2010 Sep 19.)
 * Retrospective. 176 patients (<50 age, SM+, LN+, tumor size/EIC >3 cm) of 1449 treated. Median F/U 4.5 years
 * Outcome: 5-year IBTR 5.2%. For comparison, all registry patients IBTR 3.9% (NS), non-unsuitable 3.6% (NS), invasive 3.9% (NS). Only predictor for IBTR was ER- status
 * Conclusion: ASTRO guideline did not differentiate patients with significantly worse rate of IBTR after MammoSite brachytherapy
 * Beaumont Hospital
 * 5 years; 2007 PMID 17826055 -- "Five-year results: the initial clinical trial of MammoSite balloon brachytherapy for partial breast irradiation in early-stage breast cancer." (Benitez PR, Am J Surg 2007 Oct; 194(4):456-62)
 * Prospective study of MammoSite therapy, enrolled 70 pts, implanted in 54 pts, 43 pts treated, 36 with long term f/u. Excluded 7% of treated pts due to death from metastatic disease.
 * Outcome: IBTR = 0%; Cosmesis improved with >= 7 mm from skin surface.
 * Complications: Infection 9%; Seroma 33%
 * 12 years; 2011 PMID 21497927 -- "Twelve-year clinical outcomes and patterns of failure with accelerated partial breast irradiation versus whole-breast irradiation: Results of a matched-pair analysis." (Shah C, Radiother Oncol. 2011 Apr 15. [Epub ahead of print])
 * Retrospective. Matched-pair analysis, 199 patients WBRT vs 199 patient APBI.
 * Outcome: No difference in outcome. 12-year LR 3.8% vs 5.0% (NS), RR 0% vs 1.1% (NS), DM 10% vs 4% (p=0.05), DFS 87% vs 91% (NS), CSS 93% vs 95% (NS), OS 78% vs 71% (NS). After LR, no difference in DFS, CSS, OS
 * Conclusion: APBI produced equivalent outcomes to WBI

 * University of Minnesota/SEER; 2011 (2000-2007) PMID 21287535 -- "Trends in the use of implantable accelerated partial breast irradiation therapy for early stage breast cancer in the United States." (Abbott AM, Cancer. 2011 Feb 1. doi: 10.1002/cncr.25927. [Epub ahead of print])
 * Retrospective. SEER database. 127,257 women, Stage I-II. Evaluated proportion receiving implantable APBI
 * Outcome: Proportion receiving implantable APBI 2000 0.4% to 2007 6.8% (SS), significant across all stage and age categories >40. Significant variation by region
 * Conclusion: Marked increase since 2000, concerning, because large RCT have not demonstrated long-term effectiveness compared with whole breast RT

 * Multi-Institutional; 2008 (2000-2004) PMID 18037585 -- "Multi-Institutional Experience Using the MammoSite Radiation Therapy System in the Treatment of Early-Stage Breast Cancer: 2-Year Results." (Cuttino LW, Int J Radiat Oncol Biol Phys. 2008 May 1;71(1):107-14. Epub 2007 Nov 26.)
 * Retrospective. 483 patients from 9 institutions. 34/10 BID. Median F/U 2 years
 * Outcome: 1% in-breast failure, of these 2/3 were remote from lumpectomy site
 * Complications: infection 9%, but 5% if placement after lumpectomy. Predictors for acute toxicity: open cavity placement, skin spacing <6 mm, no prophylactic ABX, single dwell position
 * Conclusion: MammoSite acceptable toxicity and cosmetic outcome

 * U. Pittsburgh (2002-04) - ASTRO 2005 Abstract #11 — "Accelerated Partial Breast Irradiation: Single Institutional Experience of 100 Patients Using MammoSite Brachytherapy." Agarwal A et al.
 * 100 pts. All surgical margins >= 2mm. Median age 64 (45-89). Cosmetic outcome excellent good in 56%/37% (93%). Palpable seroma beyond 6 months in 27%.

Toxicity

 * Dartmouth; 2013 (2003-2008) PMID 23830216 -- "Increased Rates of Long-Term Complications after MammoSite Brachytherapy Compared with Whole Breast Radiation Therapy." (Rosenkranz KM, J Am Coll Surg. 2013 Jul 2. pii: S1072-7515(13)00321-9. doi: 10.1016/j.jamcollsurg.2013.03.028. [Epub ahead of print])
 * Retrospecitve. 71 MammoSite patients and 245 WBRT patients. Median F/U 4 years
 * Toxicity: Palpable mass MammoSite 27% vs WBRT 7% (SS). Telangiectasias 24% vs 4% (SS). Either palpable mass or telangiectasias MammoSite 42%
 * Conclusion: Palpable masses or telangiectasias frequent long-term complications after MammoSite

 * WellStar Kennestone Hospital, Georgia; 2011 (2004-2011) PMID 22245195 -- "Factors associated with chest wall toxicity after accelerated partial breast irradiation using high-dose-rate brachytherapy." (Brown S, Int J Radiat Oncol Biol Phys. 2012 Jul 1;83(3):801-5. doi: 10.1016/j.ijrobp.2011.08.033. Epub 2012 Jan 13.)
 * Retrospective. 89 patients, APBI 34/10 using single or multi-lumin device. Rib doses at D0.008cc, D0.5cc, D1cc, D2cc, D3cc Rib pain evaluated at F/U visit; no grade
 * Outcome: Any rib pain 21.3%. Median point rib dose if pain 132% prescribed dose versus no rib pain 95% prescribed dose (SS)
 * Dose statistics: D0.5cc mean 234% versus 324%, max 462% versus 485%; D2cc mean 178% versus 241%, max 367% versus 328%
 * Conslusion: Incidence of chest wall/rib pain low, but attempt should be made to keep volume of rib to minimum

Dosimetry

 * US Multi-institutional Contura; 2011 PMID 20378268 -- "Improvements in critical dosimetric endpoints using the Contura multilumen balloon breast brachytherapy catheter to deliver accelerated partial breast irradiation: preliminary dosimetric findings of a phase iv trial." (Arthur DW, Int J Radiat Oncol Biol Phys. 2011 Jan 1;79(1):26-33. Epub 2010 Apr 6.)
 * Phase IV registry trial. 144 cases. Contura multilumen catheter.
 * Outcome: All dosimetric criteria met in 76%; skin dose met 92%, rib dose met 89%, target volume coverage 93%, homogeneity criteria (V150, V200) met 99%
 * Conclusion: Contura MLB catheter provides means of achieving higher standard of dosimetric goals in majority of clinical scenarios

Randomized

 * RAPID Trial (2006-2011) -- Whole breast (42.5/16 (82%) or 50/25(18%); boost in 21%) versus APBI (38.5/10 BID; no boost)
 * Randomized. 2135 patients. IDC/DCIS (invasive lobular excluded), SM-, pN0, age >40, tumor size >3 cm. Most patients were age >50, ER+, tumor <1.5 cm. Chemotherapy 15%
 * Interim Cosmesis/Toxicity; 2013 PMID 23835717 -- "Interim Cosmetic and Toxicity Results From RAPID: A Randomized Trial of Accelerated Partial Breast Irradiation Using Three-Dimensional Conformal External Beam Radiation Therapy." (Olivotto IA, J Clin Oncol. 2013 Jul 8. [Epub ahead of print]). Median F/U 3.0 years
 * Toxicity: 3-year adverse cosmesis by trial nurse assessment APBI 29% vs WBI 16% (SS); 5-year rate 33% vs 13% (SS). By patient assessment 3-years 26% vs 18% (SS); 5-years 32% vs 21% (SS). Grade 3 toxicity rare (1.4% vs 0%), grade 1/2 toxicity worse with APBI
 * Conclusion: 3D conformal APBI increased rate of adverse cosmesis and late radiation toxicity compared with standard whole breast irradiation

 * Yorkshire Breast Cancer Group (1986-1990) -- WBRT 40/15 vs PBI 55/20
 * Randomized. Trial closed prematurely due to non-accrual. 174 out of expected 400 patients. pT1-T2, pN0-N1. SM-. Arm 1) conventional WBRT 40/15 vs Arm 2) APBI 55/20 (tangents, appositional Co-60 teletherapy, appositional Cs-137 teletherapy, electrons)
 * 2005 PMID 16372487 -- "A randomised study of whole-breast vs tumour-bed irradiation after local excision and axillary dissection for early breast cancer." (Dodwell DJ, Clin Oncol (R Coll Radiol). 2005 Dec;17(8):618-22.)
 * Outcome: IBTR WBRT 4% vs. APBI 12% (NS). LRF 24% vs 9% (NS). No difference in DM and OS
 * Conclusion: Conclusions are limited due to failure to complete accrual

 * Christie Hospital (1982-1987) -- electron tumor bed RT vs WBRT
 * Randomized. 708 patients. Tumor <4cm, SM-. No ALND. No systemic therapy. Randomized to tumor bed electron RT (Dose 40-42.5/8, majority 10 MeV, majority 8x6 cm field) or 4 field whole breast with regional LNs, no IMN (40/15). No adjuvant therapy
 * 5-years; 1993 PMID 8305334 -- "The Christie Hospital breast conservation trial: an update at 8 years from inception." (Ribeiro GG, Clin Oncol (R Coll Radiol). 1993;5(5):278-83.) Median F/U 5.4 years
 * Outcome: IBTR tumor bed for infiltrating ductal CA 15% vs. WBRT 11%, for infiltrating lobular CA 34% vs 8%, for extensive DCIS 21% vs 14%
 * Conclusion: Lumpectomy with limited field RT is feasible, albeit with higher breast recurrence rate. Later could be reduced by improved selection and refined technique
 * Prognostic factors; 1996 PMID 8783398 -- "Prognostic factors for breast recurrence after conservative breast surgery and radiotherapy: results from a randomised trial." (Magee B, Radiother Oncol. 1996 Jun;39(3):223-7.)
 * Outcome: 8-year local recurrence tumor bed 25% vs. WBRT 13% (SS). Majority of recurrences within treated quadrant. 8-year DSS 72% vs 73% (NS). IDC 22% vs 12%; ILC 43% vs 17%. Axillary failure 24% vs 12% (SS), supraclav failure 6% vs 5%
 * Predictors for recurrence: field size, grade, LVI
 * Conclusion: Clear superiority for whole breast radiation therapy

Non-Randomized

 * Rocky Mountain Cancer Center, Colorado (2004-2007)
 * Phase II. 136 patients, Stage 0/I, SM-. IMRT APBI, 38.5/10
 * 4-year update; 2013 PMID 23824363 -- "Four-year clinical update from a prospective trial of accelerated partial breast intensity-modulated radiotherapy (APBIMRT)." (Lei Ry, Breast Cancer Res Treat. 2013 Jul;140(1):119-33. doi: 10.1007/s10549-013-2623-x. Epub 2013 Jul 4.). Median F/U 4.4 years
 * Outcome: 4-year IBTR 0.7%, distant failure 0.9%, OS 97%, CSS 100%
 * Toxicity: Excellent/good cosmesis patient-rated 88% vs physicians-rated 90%. Breast pain none/mild 97%. Telangiectasia 3.6%. Rib fracture 1.4%
 * Conclusion: Excellent local control, survival, cosmetic results and toxicity
 * IGRT; 2010 PMID 19467799 -- "Clinical experience with image-guided radiotherapy in an accelerated partial breast intensity-modulated radiotherapy protocol." (Leonard CE, Int J Radiat Oncol Biol Phys. 2010 Feb 1;76(2):528-34. Epub 2009 May 19.)
 * Retrospective. 19 patients. APBI with IGRT using 3 fiducial markers around surgical cavity. Total 200 IGRT sessions
 * Outcome: Average vector displacement 4mm (2-7mm), SI 2mm (0-5mm), lat 2mm (1-4mm), AP 3mm (1-5mm)
 * Conclusion: IGRT can be successful in APBI
 * Initial; 2007 (2004-2005) PMID 17234359 -- "Prospective trial of accelerated partial breast intensity-modulated radiotherapy." (Leonard C, Int J Radiat Oncol Biol Phys. 2007 Apr 1;67(5):1291-8.)
 * Prospective. 55 patients, Stage I BCA. IMRT 7 patients 34/10, then 48 patients 38.5/10. Median F/U 10 months
 * Outcome: no local or distant recurrences
 * Cosmesis: patient: excellent 73%, good 22%; physician: excellent 80%, good 18%. Pain: none 62%, mild 35%, moderate 4%. One telangiectasia. No significant edema
 * Dosimetry: compared to historical controls, reduced volume of breast within 100%, 75%, and 50% isodose
 * Conclusion: Feasible; deserves additional investigation

 * Michigan
 * Prospective Phase II. Trial closed prematurely due to unacceptable toxicity. 32 patients, age >40, Stage 0-I, breast conserving surgery. APBI 38.5/10 BID using IMRT at deep-inspiration breath-hold. PTV = cavity + 1.5 cm margin.
 * 5-years; 2014 PMID 24613813 -- "Decline of Cosmetic Outcomes Following Accelerated Partial Breast Irradiation Using Intensity Modulated Radiation Therapy: Results of a Single-Institution Prospective Clinical Trial." (Liss Al, Int J Radiat Oncol Biol Phys. 2014 Mar 7. pii: S0360-3016(14)00061-3. doi: 10.1016/j.ijrobp.2014.01.005. [Epub ahead of print])
 * Median F/U 5 years
 * Outcome: 5-yera local control 97%
 * Cosmesis: Further decline in 5 women. Excellent 43%, good 30%, fair 20%, poor 7%. Fibrosis 3%
 * Conclusion: Excellent rate of tumor control. Cosmetic rates continued to decline over time, wit 27% having fair/poor cosmetic result
 * 2010 PMID 19409733 -- "Unacceptable cosmesis in a protocol investigating intensity-modulated radiotherapy with active breathing control for accelerated partial-breast irradiation." (Jagsi R, Int J Radiat Oncol Biol Phys. 2010 Jan 1;76(1):71-8.) Median F/U 2.5 years
 * Toxicity: Unacceptable cosmesis in 20%. All but one plan adhered to requirements of NSABP trial. V50 and V100 correlated with cosmesis
 * Conclusion: The schedule and parameters used in the ongoing national trial may be suboptimal

 * Tufts University; 2009 PMID 19395195 -- "Toxicity of three-dimensional conformal radiotherapy for accelerated partial breast irradiation." (Hepel JT, Int J Radiat Oncol Biol Phys. 2009 Dec 1;75(5):1290-6. Epub 2009 Apr 22.)
 * Retrospective. 60 patients treated with APBI. Dose 38.5/10. Median F/U 15 months
 * Toxicity: Moderate/severe late toxicity 10%. Fibrosis Grade 3+ in 8%. Cosmesis good/excellent 82%, fair 12%, poor 7%. Multiple dosimetric parameters correlated with development of fibrosis and cosmetic outcome
 * Conclusion: 3D-CRT per B-39 protocol results in remarkably high rate of late normal tissue effects

 * RTOG 0319 (2003-2004) PMID 19910132 -- "Initial Efficacy Results of RTOG 0319: Three-Dimensional Conformal Radiation Therapy (3D-CRT) Confined to the Region of the Lumpectomy Cavity for Stage I/ II Breast Carcinoma." (Vicini F, Int J Radiat Oncol Biol Phys. 2009 Nov 10. [Epub ahead of print])
 * Phase I/II. 52 patients, Stage I-II BCA, lesion <= 3cm, SM-, LN1-3. (Median age 61, 46% <1cm, 87% IDC, 94% Stage I, 83% no chemo, 71% no hormones). CTV = 10-15 mm over surgical cavity, PTV 10 mm. 3D-CRT 38.5/10 BID, IMRT not allowed. Median F/U 4.5 years
 * Outcome: 4-year ipsilateral breast failure 6% (4% in-field), ipsilateral nodal failure 2%, DM 8%, DFS 84%, OS 96%
 * Toxicity: Grade 3 in 4% (1 patient fibrosis/telangiectasia, 1 patient dermatitis/myositis). Grade 2 pain 13%
 * Conclusion: Initial efficacy and toxicity appears comparable to other experiences

 * William Beaumont
 * 2003 (2000-2001) PMID 12527042 -- "Accelerated partial breast irradiation using 3D conformal radiation therapy (3D-CRT)." (Baglan KL, Int J Radiat Oncol Biol Phys. 2003 Feb 1;55(2):302-11.)
 * Prospective. 16 patients (7 archived to develop technique, 9 on study), IDC <= 3cm, EIC-, SM-, ALND-, surgical clips in place.
 * Technique: CTV = lumpectomy cavity + 15mm. ITV +5 mm. PTV +5 mm. Noncoplanar 4-5 beam arrangement. Dose 35/10 BID patients, then 38.5/10 BID in 4 patients. Median F/U 8 months
 * Toxicity: No skin changes during treatment, mild hyperpigmentation/erythema at 4 week follow up
 * Conclusion: APBI feasible using 3D-CRT
 * 2003 (2000-2002) PMID 14630258 -- "Ongoing clinical experience utilizing 3D conformal external beam radiotherapy to deliver partial-breast irradiation in patients with early-stage breast cancer treated with breast-conserving therapy." (Vicini FA, Int J Radiat Oncol Biol Phys. 2003 Dec 1;57(5):1247-53.)
 * Phase II. 31 patients, lumpectomy + 3D CRT PBI. Dose 34/10 BID (n=6) or 38.5/10 BID (n=25). CTV +10-15 mm. PTV +10mm. Median F/U 10 months
 * Toxicity: At initia 4-8 week visit: no toxicity 29%, Grade 1 toxicity 61%, Grade 2 10%, no Grade 3. Cosmesis good/excellent in all patients
 * Conclusion: 3D-CRT for PBI is feasible and acute toxicity is minimal
 * 2007 (2000-2005) PMID 17967306 -- "Interim cosmetic results and toxicity using 3D conformal external beam radiotherapy to deliver accelerated partial breast irradiation in patients with early-stage breast cancer treated with breast-conserving therapy." (Vicini FA, Int J Radiat Oncol Biol Phys. 2007 Nov 15;69(4):1124-30.)
 * Phase II. 91 patients. Lumpectomy + 3D-CRT APBI. Dose 38.5/10 BID. Median F/U 2 years
 * Outcome: No local failures.
 * Cosmesis: Good/excellent at 6 months 100%, 1 year 93%, 2 years 91%, and 3 years 90%. Grade 3 toxicity (breast pain) in 3%. Grade 1-2 fibrosis 18%, fat necrosis 9%
 * Conclusion: Minimal chronic toxicity with good/excellent cosmetic outcomes
 * 4-years; 2009 PMID 19515514 -- "Four-Year Efficacy, Cosmesis, and Toxicity Using Three-Dimensional Conformal External Beam Radiation Therapy to Deliver Accelerated Partial Breast Irradiation." (Chen PY, Int J Radiat Oncol Biol Phys. 2009 Jun 8. [Epub ahead of print])
 * Prospective. 94 patients with Stage 0-II, tumor <=3cm (68% <1cm), SM-, LN-. Postmenopausal 88%. 3D-CRT 38.5/10 BID. Median F/U 4.2 years
 * Outcome: 4-year IBTR 1.1%, ipsilateral node failure 0%, contralateral breast failure 1%, DM 4%, DFS 95%, OS 97%, CSS 99%
 * Toxicity: Grade 3 in 4% (breast pain, fibrosis). Cosmesis good/excellent 89%
 * Conclusion: Efficacy, cosmesis, and toxicity appear comparable to other experiences

Non-Randomized

 * Loma Linda; 2014 PMID 25084608 -- "Partial Breast Radiation Therapy With Proton Beam: 5-Year Results With Cosmetic Outcomes." (Bush DA, Int J Radiat Oncol Biol Phys. 2014 Jul 30. pii: S0360-3016(14)01959-2. doi: 10.1016/j.ijrobp.2014.05.1308. [Epub ahead of print])
 * Phase II. 100 patients. Invasive, nonlobular carcinoma, max dimension 3 cm (average 1.3 cm). Negative SM and pN0. Dose 40/10 once daily x2 weeks. Median F/U 5 years
 * Outcome: 5-year LRFS 97%; DFS 94%; OS 95%
 * Toxicity: No grade 3 or higher skin toxicity. Telangiectasia grade 1 in 7%. Good/excellent cosmesis 90%
 * Conclusion: PBT excellent control with minimal toxicity

 * National Cancer Center, Goyang, Korea; 2013 PMID 23891102 -- "Phase II trial of proton beam accelerated partial breast irradiation in breast cancer." (Chang JH, Radiother Oncol. 2013 Jul 25. pii: S0167-8140(13)00284-3. doi: 10.1016/j.radonc.2013.06.008. [Epub ahead of print])
 * Phase II. 30 paitnets, breast conservation surgery, proton beam APBI, single field or two fields. 30/6 CGE once daily. Median F/U 5.0 years
 * Outcome: No IBTR, regional or distant mets. All alive
 * Toxicity: good/excellent at end of RT 83%, at 2 months 80%, at 3 years 69%. In patients treated with 2 fields, good/excellent outcomes in all patients and time points but one. Breast retraction assessment (pBRA)increased for patients with single field but not two-field
 * Conclusion: Proton beam APBI 30 Gy in 6 fractions daily can be delivered with excellent control and tolerable toxicity, particularly with multiple-field technique

 * MGH; 2006 (2004-2005) PMID 17011445 -- "Accelerated partial-breast irradiation using proton beams: initial clinical experience." (Kozak KR, Int J Radiat Oncol Biol Phys. 2006 Nov 1;66(3):691-8.)
 * Phase I/II. 20 patients, Stage I BCA. Proton 3D-CPBI 32 CGE/8 fractions BID over 4 days. PTV=lumpectomy + 1.5-2cm, but <5 mm from skin. 1-3 beams, inhomogeneity <15%. Median F/U 1 year
 * Cosmesis: good/excellent 100% at 1 year; bt significant acute skin toxicity, moderate/severe skin color changes in 79% at 3-4 weeks, moderate/severe moist desquammation 22% at 6-8 weeks
 * Conclusion: Significant acute skin toxicity, but good/excellent cosmetic outcome at 1 year

Dosimetric

 * MD Anderson; 2010 PMID 20708848 -- "External-Beam Accelerated Partial Breast Irradiation Using Multiple Proton Beam Configurations." (Wang X, Int J Radiat Oncol Biol Phys. 2010 Aug 12. [Epub ahead of print])
 * Treatment plan comparison. 11 patients, APBI. Passive scatter proton (including Monte Carlo verification) multiple beams vs 3D-CRT photons
 * Outcome: Protons reduced V100 by 3%, V90 by 9%, V75 by 12%, V50 by 18% and V20 by 24%. Skin similar V90. Reduced lung and heart dose
 * Conclusion: APBI using multiple proton beams spares significantly more normal tissue

 * Loma Linda
 * 2007 PMID 17476139 -- "A technique of partial breast irradiation utilizing proton beam radiotherapy: comparison with conformal x-ray therapy." (Bush DA, Cancer J. 2007 Mar-Apr;13(2):114-8.)
 * Prospective. 20 patients. Technique described. 2-4 proton beams. 40/10 CGE. Comparison with conformal XRT
 * Plan comparison: Protons significantly less to ipsilateral breast, skin; eliminating dose to heart and lung
 * Acute toxicity: occasional radiation dermatitis Grade 1-2
 * Conclusion: Well tolerated, reproducible, with substantial normal tissue sparing
 * Editorial (PMID 17476135)

 * MGH (2004-2005)
 * 2006 PMID 16863934 -- "Dosimetric comparison of proton and photon three-dimensional, conformal, external beam accelerated partial breast irradiation techniques." (Kozak KR, Int J Radiat Oncol Biol Phys. 2006 Aug 1;65(5):1572-8.)
 * 24 patients, Stage I, treated with proton 3D-CPBI. Treatment plans also generated using photon-electron 3D-CPBI. PTV and prescribed dose held constant.
 * Outcome: PTV coverage: 95% received >90% of prescribed dose in all cases. Only one case >10% inhomogeneity. Significantly better volume of nontarget breast, lung, and heart for proton plans
 * Conclusion: Proton 3D-CPBI significantly reduces volume of irradiaated nontarget breast tissue
 * 2006 PMID 16730137 -- "Accelerated partial breast irradiation using proton beams: Initial dosimetric experience." (Taghian AG, Int J Radiat Oncol Biol Phys. 2006 Aug 1;65(5):1404-10. Epub 2006 May 26.)
 * Retrospective. 25 patients. Tumor <=2 cm, N0. Proton 3D-CPBI 32 CGE/8 fractions BID over 4 days. 1-3 beams.
 * Dosimetry: Median PTV receiving >95% prescribed dose 100%. Dose inhomogeneity >10% in 1 patient (4%). Median volume of nontarget breast tissue receiving 50% of prescribed dose 23%. Median lung receiving 20 CGE 0%, 10 CGE 1%, 5 CGE 2%
 * Cost-analysis: modestly more expensive (25%) than whole breast RT
 * Conclusion: Technically feasible, excellent PTV coverage and normal tissue sparing

Economics

 * Sweden; 2005 PMID 15885828 -- "Economic evaluation of proton radiation therapy in the treatment of breast cancer." (Lundkvist J, Radiother Oncol. 2005 May;75(2):179-85.)
 * Markov model simulation, 55 year old patient with left-sided BCA
 * Outcome: Euro 67,000 cost per QALY gained; better if high risk cardiac patients treated
 * Conclusion: Proton therapy for BCA can be cost-effective if appropriate risk groups are chosen

Outcomes by patient subgroups
Invasive Lobular Carcinoma:
 * William Beaumont; 2011 (1993-2010) PMID 21640491 -- "Clinical outcomes using accelerated partial breast irradiation in patients with invasive lobular carcinoma." (Shah C, Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):e547-51.)
 * 16 pts with ILC; compared with 410 pts with IDC. APBI technique was interstitial LDR or HDR, balloon, or 3D conformal.
 * Median f/u 3.8 yrs for ILC pts, 6.0 yrs for IDC. ILC pts were more likely to have positive margins (20% vs 3.9%), larger tumors (1.4 cm vs 1.1 cm), less likely to be N+ (0% vs 9.5%) than pts with IDC. 5-yr LR was 0% for ILC and 2.5% for IDC. No differences in regional recurrence, DM, DFS, or OS.
 * Conclusion: "Women with ILC had excellent clinical outcomes after APBI. No difference in local control was seen between patients with invasive lobular versus invasive ductal histology."

Consensus Statements

 * ASTRO Updated Consensus Statement (2016) PMID 27866865-- "Accelerated Partial Breast Irradiation: Executive Summary for the Update of an ASTRO Evidence-Based Consensus Statement" (Correa Candace, et. al. Practical Radiation Oncology 2016 Sep 17. pii: S1879-8500(16)30184-9)

Summary of updated 2016 consensus statement

 * ASTRO Consensus Statement (2009) PMID 19545784 -- "Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO)." (Smith BD, Int J Radiat Oncol Biol Phys. 2009 Jul 15;74(4):987-1001.)
 * see also Task Force Statement (2009) PMID 19545782 -- "Accelerated partial breast irradiation: caution and concern from an ASTRO task force." (Prosnitz LR, Int J Radiat Oncol Biol Phys. 2009 Jul 15;74(4):981-4.)

 * American Society of Breast Surgeons (2008) Consensus Statement
 * Inclusion criteria: Age >=45, IDC or DCIS, size <= 3cm, SM-, SLN-

 * California Technology Assessment Forum (2008)
 * CTAF link
 * Recommendation: The use of breast brachytherapy does not meet Technology Assessment Criteria 4 or 5 for safety, effectiveness and improvement in health outcomes when used as primary radiation therapy following breast conserving surgery for localized breast cancer.

 * American Brachytherapy Society Task Group (2007) Guideline
 * Inclusion criteria: age >= 50, infiltrating ductal carcinoma, T1 and T2 <= 3cm N0M0
 * Not yet fully evaluated: age <45, non-IDC, 1-3 nodes without ECE
 * Relative contraindications: EIC, multifocal disease
 * Absolute contraindications: inappropriate for standard breast conservation, autoimmune disorders, distant mets

 * 3 German Oncology Societies (2007) PMID 17647249 -- "Accelerated partial breast irradiation: consensus statement of 3 German Oncology societies." (Sauer R, Cancer. 2007 Sep 15;110(6):1187-94.)
 * "The authors expressly discourage the routine use of APBI outside clinical trials. Until definite results show that APBI neither impairs therapeutic outcome nor cosmetic results, WBRT remains the gold standard in the treatment of early breast cancer"
 * Update (2009) PMID 19806329: "DEGRO expert panel recommends to refrain from APBI outside prospective studies as this would not only jeopardize the completion of the necessary clinical trials but also neglect the lack of data that are mature enough to permit definitive conclusions regarding long term tumor control, overall survival and cosmetic outcome of thousands of women"

Review

 * Royal Marsden; 2009 PMID 19178972 -- "Accelerated partial breast irradiation trials: Diversity in rationale and design." (Mannino M, Radiother Oncol. 2009 Apr;91(1):16-22. Epub 2009 Jan 27.)

Pacemakers / ICDs

 * Allegheny General, Pittsburgh
 * Distance-dose estimate; 2012 PMID 22330105 -- "Pacemaker/implantable cardioverter-defibrillator dose in balloon high-dose-rate brachytherapy for breast cancer treatment." (Kim Y, Brachytherapy. 2012 Sep-Oct;11(5):380-6. doi: 10.1016/j.brachy.2012.01.001. Epub 2012 Feb 11.)
 * Retrospective. 3 patients treated with HDR APB. 34/10. Implants evaluated. Phantom study performed.
 * Dosimetry: Minimal balloon-device distance 10.9 cm, 18.4 cm, and 4.3 cm. Graph developed correlating dose to distance. To meet 2 Gy cummulative dose, minimum distance depended on fill volume: 35 cc - 10.5 cm, 60 cc - 12 cm, 80 cc - 12.5 cm, 100 cc - 13 cm, and 125 cc - 14 cm
 * Conclusion: The proposed distance-dose graph and/or table enable to approximately predict the maximal device dose based on the measurement of minimal distance between lumpectomy and the device before balloon implantation for the suitability of balloon HDR brachytherapy
 * Dose assessment; 2011 (2007-2010) PMID 21607774 -- "Avoiding mastectomy: accelerated partial breast irradiation for breast cancer patients with pacemakers or defibrillators." (Croshaw R, Ann Surg Oncol. 2011 Nov;18(12):3500-5. doi: 10.1245/s10434-011-1784-2. Epub 2011 May 24.)
 * Retrospective. 8 patients treated with APBI (3 HDR with dose 34/10, 5 EBRT with dose 38.5/10). Mean F/U 6 months.
 * Dosimetry: HDR maximum dose 1.03 Gy, mean pacer-lumpectomy distance 9.1 cm. EBRT maximum dose 1.68 Gy, mean distance 9 cm
 * Toxicity: maximum grade 1; no adverse device events
 * Conlusion: APBI in patients with pacemakers/AICDs seems to be safe and reasonable


text:
Cookbook talk:Meatloaf I

It would be useful to include what kind of pot or pan to use for baking this, because I for example was wondering and didn't know.

Terrible!
This is the worst-written of the three Meatloaf recipes. For example:

"Drain off grease when brown 10-20 minutes." What does that even mean? And then there's "Bake until done." Is this a joke?

When the writing's not just plain bad, it's still pretty obtuse. Anbody feel like taking a crack at fixing it? --63.25.238.58 (talk) 23:10, 1 July 2008 (UTC) -- Just a little bit of chili or some jalapenos make any meatloaf excellent. (I would add a recipe but, why bother, chili makes everything perfect, and those who noticed it will add it anyways.) Or instead of worcestershire sauce, use habanero tabasco. A teaspoon will be enough for a little bit of spice.

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

title: Cookbook talk:Meatloaf I


text:
User:Ylikojol

Tämä on nyt tällaista testiä vain. Kokeillaan.

VAU! Mitäs siihen sanot, jos mä tätä tästä alan muokata tällai? Just muuten viime viikolla yksi BSCW:ssä oleva opiskelija ehdotti, että olisi hyvä jos meidän alalle sais tällaisen Wikipedia-tyyppisen avoimen tieto- ja hakuteoksen.

Täähän sujuu kuin tanssi.

No juu, niin sujuu. Tätähän voisi ihan testikäyttää jollain kurssilla. Periaatteessahan tänne voi joku eksyä ja laittaa spämmejään, mutta ehkä se ei ole todennköistä.

Niin, tämä voisi toimia keskustelualustana ainakin. Vaikka mitään ketjuja tähän kyllä ei saa muodostettua. Saako tähän lisättyä liitetiedostoja jotenkin? Edelleen olen eniten mua kiinnostaa just nyt sellainen väline, jolla voisi tehdä tutkimusyhteistyötä. Oonko tylsä, jos olen sitä mieltä, että tämä ei taida toimia ihan juuri sellaisena....Mutta johonkin juttuun tämä varmasti käy. En aio ruveta vielä teknopessimistiksi.

1.2. Ei tänne vielä ole ainakaan mitkään spämmit eksyneet / LY

6.2. Eikä vieläkään... / LY

title: User:Ylikojol


text:
Wikibooks talk:Templates/User pages

If there are pictures which are not available at Wikibooks, can we copy them also (for userboxes). --213.42.2.22 07:12, 26 January 2006 (UTC)
 * Do not copy any images from Wikipedia to Wikibooks. If they are free images with confirmed license, upload them to Commons. --Derbeth talk 08:39, 26 January 2006 (UTC)

title: Wikibooks talk:Templates/User pages


text:
Asset Allocation/United States

I am trying to make a comprehensive list of based on a 20 to 50 year data set in regard to a 5, 10, & 20 year time period for the following Asset Class  which use a Bottom-Up Market Segment approach will entail their Average Annual Rate of Return, Standard Deviation, Average Beta, and a corresponding Indices that go with it. This page is geared towards the U.S. Economy.

Stocks
I would further categorize the stocks into Value & Growth, but the decision to allocate these investments are very subjective, and in regard to a mutual fund the decision ultimately rests with the mutual fund manager to determine. Also common among mutual funds what is considered to be large-cap growth can actally have an allocation of 40% small-cap value and 60% large-cap growth and still be considered "Large-Cap Growth" thus defining and analyzing would succumb to an individual selection basis, which the investor can do by himself.

External Link

 * SmartMoney's asset allocation planner
 * Investor Home

title: Asset Allocation/United States


text:
Talk:Asset Allocation/United States

Goal / Purpose
To provide investors in regard to specific asset catagories if applicable: Default Risk, Average Annual Rate of Return, Standard Deviation, Average Beta of those Returns for a 5, 10, & 20 year time frame (full market cycle) and corresponding  Indices. Over all it is to help simplify an overly complex system.

Target Audience
Investors that wish to diversify thier portfolio using either passive or active investing approach.

Information Benefit
Even though I am getting very specific about the maturity for fix income based on a 5, 10, & 20 year scale. I would like the data set to be based on 20 years or more thus a full market cycle. As a result the need to update this information will not be necessary. In regards to the subjectivity of rates and other variable, it will have minimal inpact due to the longer time scale that is use for historic return based on each asset class.

Factors Impact

 * Factors such as management fees, stock selection and market timing do have an impact upon one's portfolio but more in a negative way than a positive way. Market Timing’s Flaw by Larry Swedroe The Evidence on Timing by Larry Swedroe
 * It has been proven that asset allocation can determine up to 94% of your rate of return. These are the following sources:
 * The Informed Investor Ch6 The Asset Allocation Decision by Frank Armstrong
 * Gary P. Brinson, Brian D. Singer, and Gilbert L. Beebower, "Determinants of Portfolio Performance II: An Update," Financial Analysts Journal, May/June 1991. (can not seem to find a link for this source, if you find one add it Paul.Paquette)
 * Gary P. Brinson, L. Randolph Hood, and Gilbert L. Beebower, Determinants of Portfolio Performance, Financial Analysts Journal, July/August 1986.
 * Does Asset Allocation Policy Explain 40%, 90%, or 100% of Performance? by Roger G. Ibbotson

Counter Argument
 * Bad Practices by William Jahnke

Comparative Study
 * The Asset Allocation Debate: Then and Now by The Vanguard Group 06/08/2005

Topics that should not be in the article

 * Different ways to allocate portfolio or techniques use based on some formula i.e. age.
 * Asset allocation rules, however an appropriate link is applicable.
 * Not an article about stress or stomach acid test.

Topics that should be in the article

 * How to determine an appropriate benchmark and type of benchmark, should be brief and concise.
 * Numerical in nature thus a data set that can be used by an informed investor.

Image copyright violation
This is mainly a notice to let the contributors of this Wikibook know that Image:Asset allocation.gif is a copyright violation. If you have any reason to believe that you had formal copyright permission granted to release this image under the terms of the GFDL or compatable licenses, I would ask you to please note those terms here on this page or on Image talk:Asset allocation.gif. This image will not be deleted immediately, but it will eventually have to go. --Rob Horning 07:39, 2 February 2006 (UTC)

Links
Maybe the links to wikipedia should be trimmed back a bit. Just about every time a dollar sign appears it is linked to wikipedia. This seems excessive, and i think it is a breach of policy. Those that stay should probaly be formetted in the form W: and then the name of the page on wikipedia. Dolive35 10:55, 25 April 2006 (UTC)

title: Talk:Asset Allocation/United States


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User:Fosk~enwikibooks

Contacts: www.fosk.it/?about_me, fosk 22:08, Giu 30, 2005 (CEST)

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User:Mammal

See w:nl:Gebruiker:Mammal

nl:Gebruiker:Mammal

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User:Deepraj

Deepraj grew up in Tezpur, India and is currently living in The Netherlands.

Check out Deepraj's userbox in wikipedia.

title: User:Deepraj


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Hindi/Colors

Colors - रंग (rang)
Yipee! We have covered all the basic colors. Make sure you practice writing them down on a notebook and read them aloud to print them Into memory. Best of luck!

title: Hindi/Colors


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Beginning Mathematics/Where To Start? With Nothing!

=Where To Start? With Nothing!=

Clear your mind and assume nothing. When you achieve this blank state you have arrived at the starting point for Mathematics: the big Nothing (with a capital "N"). To move on from Nothing using the Language of Mathematics we will need a framework to build on. The framework we need has to allow us to expand the reach of the language as we go. To find such a framework Mathematics looks to the world of Logic.

A Brief Glimpse of Logic
First, a description of Logic1:

''[Logic] is most often said to be the study of arguments, although the exact definition of logic is a matter of controversy among philosophers. [The task] of the logician is the same: to advance an account of valid and fallacious inference to allow one to distinguish good from bad arguments.''

From this description it is clear that a solid system of logic requires arguments to work with. A Logical Argument is the ordered process of going from some definitions to reaching a conclusion. Obviously you can't have an argument (or reach a conclusion!) without something to argue over. A Definition is a simple statement and can form the basis for an argument. A Conclusion is the endpoint of an argument. A useful argument results in a conclusion which tells us something about the original definitions.

An Example is in order:
 * Definition: Something which has water on it is wet.
 * Definition: Something not protected from the rain gets water on it.
 * Conclusion: Something not protected from the rain gets wet.

These three statements make up a logical argument. Using the conclusion from this logical argument, we can now identify the things around us in jeopardy of getting wet the next time it rains. The couch in the house is safe; the trees outside are not. Notice that the conclusion comes directly from the definitions -- for this example there is no Body to the Argument.

Thinking deeper about this argument it becomes clear that we jumped into the middle of something. You could ask: What is Rain? What is Water? What is a "Something"?

Obviously there are a lot of logical arguments which could have preceded this one. For example, we could define Water as a collection of molecules with the chemical formula of H2O and define rain as a collection of collections of H2O molecules. An argument relating rain to water can then be made.

But then what is a Molecule? Again, we could define a Molecule as a collection of atoms. Still, what is an Atom? For that matter, what is a Collection?? It quickly becomes obvious why philosophers spend so much time quietly thinking to themselves.

Fortunately we're thinking about Mathematics, not the Meaning of Existence (which can easily take a lifetime2). Remember that a useful logical argument results in a conclusion which tells us something about the original definitions. In our example above we discovered that we can combine the two definitions into a more compact form as the conclusion. In this case, it's hard to say that the conclusion is much more useful than the definitions. However, some logical arguments can take many, many definitions and arrive at a simple conclusion which itself becomes tremendously useful. This is called Reduction3. Reduction will be the first goal of our Mathematics framework.

Starting The Framework For Mathematics
Time to start building! Since the starting point is Nothing there can be no arguments. We need a definition!

Definition: An Object is something that can be described.

Any logical argument leading to this (as a conclusion) we will disregard as being in the realm of pure Philosophy. We will also assert (not assume!) this definition is true. Consider the previous assertion of truth carefully! The implication is powerful: from the very beginning Mathematics ceases to be tangible. With this definition we can say "The Universe is an Object" or "Emptiness is an Object" or "Words are Objects"; indeed, even a Thought, a Color, a Feeling, or even Something That Has Not Been Discovered is an object! Ahhh, the freedom! No boundaries! If this fundamental definition is preserved (and it will be) our Mathematical Framework will have tremendous reach and breadth.

Wait! There is one problem -- our definition is written in words, specifically English, and we don't want to be limited as to who can understand or use this definition. There are concepts in other languages as well as things undiscovered which we want to include in the realm of Mathematics. To keep the limitation of language from putting boundaries on the framework, symbols are used in place of words. For now, we will use lowercase English letters to represent objects. Remember, they are symbols in Mathematics, not letters. Letters have sound; symbols do not. Symbols can represent any Object as defined above. We can now add a definition to our framework: Definition: A Symbol is a written character.

Next comes a decision on how to use Symbols which brings up another problem: there are not nearly (not even close) to enough symbols to give every Object its own symbol. Adding to the problem is the confusion caused in other people if symbols are assigned to objects. Other people will have to know what each symbol specifically represents, which means creating a gigantic Symbol Dictionary. The Symbol Dictionary would have to be updated every time a new object is found, created, or considered. That is no good!

To solve the problem of Symbols, we add the following definition to our framework: Definition: A Variable is a Symbol which represents a property of some object(s).

Whew!! Our Dictionary just got much, much smaller. Reality requires us to have at least some symbols that are specifically defined and universal -- those situations are not far away. However, any symbol that does not have such a concrete definition can be used as a variable. The key point of the definition of a variable is "represents a property". Fortunately this definition is wide open since "represents a property" is not a restrictive phrase. Success!! Our language is universal AND our freedom has returned.

Putting the previous definitions to use we can now define a variable: Let β (the Greek letter Beta) represent an object with two and only two wheels.

This statement does not require us to state exactly what object with two and only two wheels is represented by β. In fact, an object satisfying β does not even have to exist. But now we can tell what objects β could be. For example, β could be a bicycle, but not a car. β could be a motorcycle but not a motorboat. Notice the definition of β allows us to separate all objects into two groups of objects: one group which satisfies the conditions of β and another group which does not. This leads us to our next definition: Definition: A Set is a group of objects with one or more common properties.

Sets are vitally important in Mathematics. If you are not confident in how this definition was reached it is probably well worth your time to review some of the previous definitions for clarification! Sets are so important and occur so frequently in Mathematics they require universal symbols to represent them. For a Set, the universal symbols include the left and right curly braces used as follows: Definition: The Set B contains all objects represented by variable β. (Almost) Mathematical Notation: B is the same as {β} The Mathematical Notation is not pure -- it is "Almost" because it contains English words. Let's fix that immediately! Definition: Equivalence means two symbols represent the same value, state, or are the same thing. Another common term for this condition is Equal. In Mathematics, the symbol = represents Exact Equivalence. Let's look at this more closely. Since "equivalence" can refer to the "state or condition" two boxes containing three items in each could be considered "equivalent". However, if the three items are not the same kinds of things, say three cats in one and three dogs in the other, they are not "equal". For them to be equal, they must be exactly the same. This concept is recurrent in more advanced mathematical structures. This distinction is made now to avoid future confusion the student might have. Many students get the impression that mathematics in not consistent and contradictory when they have such an experience. Keep in mind that people sometimes take shortcuts when explaining material or are so caught up in the explanation at hand that things slip their mind. This is human nature and should be forgiven since perfection seldom exists.

In our (Almost) Mathematical Notation for Set B above, the phrase "is the same as" shows equivalence. Therefore, we can write the condition in pure Mathematical Language: B = {β}

Hopefully your mind hears "B is a Set of all objects that satisfy the conditions of the variable β". It is common in Mathematical literature to use uppercase English letters as symbols for Sets, and lowercase English letters as symbols for variables. Also, it is common for the Set symbol to be the uppercase equivalent of the Variable symbol. We will follow these conventions from this point forward.

Example: A = {a}

How did your mind hear that line? It is significant to note that Variable a has never been defined, yet we understand the concept of what is represented by the line above. It is important to understand that the line above also has not validated any of our previous definitions. This is a small taste of a special power of Mathematics:

Definition: Generalization is the ability of Mathematics to specify behaviors and relationships for a broad variety of objects without actually defining what the objects are.

There are not enough tools in our framework at this time to exploit Generalization completely. But we will eventually! For now, here's the definition of another set:

P = {p}

This is an abstract Set, since we do not know what the Variable p represents.

Q = {q: all words any word that starts with 'm'}

This is a concrete Set since a definition of Variable q is given. A new universal symbol has been presented here.

Definition: In the notation for a Set, a colon is used to represent the phrase "is defined as".

Using this definition, the Mathematical Language given above for Set Q reads "Q is a Set of all objects that satisfy the conditions of the variable q which is defined as all words that start any word that starts with 'm'".

There is an additional way to specify a Set when there are a specific group of objects contained within it.

X = {x: a donkey, a mushroom, a glass of water, a cloud}

There is NO spoken phrase for Variable x that correctly describes these objects in terms of a common or shared property. Nonetheless, this is a valid Mathematical Set. Again this demonstrates the ability of Mathematics to express concepts that formal written language cannot describe. This also demonstrates a small piece of the power of Mathematics which we will put to great use as we move forward.

References =
If the sources have changed, some quotes may not be word for word; please be forgiving!
 * 1See Logic (Return)
 * 2See Plato, Aristotle, and Socrates to name a few. (Return)
 * 3See Reduction (philosophy) (Return)

For college level math, it is necessary to become somewhat familiar with Greek as well as Latin letters (which is what the English alphabet is derived from), as both are used as Mathematical symbols. When learning new concepts, anxieties can be reduced if the symbols, at least, are familiar. Greek_Alphabet (Return)


text:
Geometry/Polyominoes

Polyominoes are shapes made from connecting unit squares together, though certain connections are not allowed.

Domino
A domino is the shape made from attaching unit squares so that they share one full edge. The term polyomino is based on the word domino. There is only one possible domino.

Tromino
A polymino made from three squares is called a tromino. There are only two possible trominoes.

Tetromino
A polymino made from four squares is called a tetromino. There are five possible combinations and two reflections:

Pentominoes
A polymino made from five squares is called a pentomino. There are twelve possible pentominoes, excluding mirror images and rotations.

title: Geometry/Polyominoes


text:
Talk:A-level Physics/Cosmology/Models of the known universe

 * 1) describe the models of the Universe as proposed by Copernicus and Kepler. ✔
 * 2) describe the progress in the understanding of the Universe as a result of the work of Copernicus, Kepler and Galileo. ✔
 * 3) use Newton’s law of Gravitation to derive an expression for the radius of the circular orbit of a planet around the Sun in terms of the period of the orbit. ✔
 * 4) recall and use Kepler’s laws as applied to circular orbits. ✔
 * 5) recall how the existence of Neptune was predicted from the orbit of Uranus. ✔
 * 6) appreciate the significance of Kepler’s third law as evidence of Newton’s law of Gravitation. ✔
 * 7) describe the contents of the Solar System in terms of the Sun, planets, planetary satellites and comets. Details of individual planets are not required.✔
 * 8) show awareness of the principal contents of the Universe, including stars, galaxies and radiation. Probably better to cover this in Stars & Galaxies
 * 9) define distances measured in astronomical units (AU), parsecs (pc) and light-years.✔
 * 10) recall the approximate magnitudes, in metres, of the AU, pc and light-year.✔
 * 11) recall the distances involved between objects in the Universe, including distance to nearest stars, distance across a galaxy, size of observable Universe. Probably better to cover this in Stars & Galaxies
 * 12) appreciate the range of magnitudes of the sizes and masses of objects in the Universe. Probably better to cover this in Stars & Galaxies


text:
Talk:Geometry/Polyominoes

Creating Block images
I see that you are going through the effort of having to create a whole bunch of images for this little project you are working on.

I have a suggestion: Why don't you try to use the HTML tables instead to create this content.

For example:

was created using the following table instructions

This can obviously be extended, and you can also change the colors. I hope this would be useful to you. More information about creating tables can be found at meta:Help:Table. I think this would save you a bunch of time. --Rob Horning 20:11, 26 January 2006 (UTC)

Good idea.

T

John Cross 18:56, 31 January 2006 (UTC)

title: Talk:Geometry/Polyominoes


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Muggles' Guide to Harry Potter/Magic/Obliviate

Overview
Obliviate is the verbal component of the Memory Charm, a spell which allows the erasure or modification of memory.

Extended Description
First seen when Gilderoy Lockhart attempted to use it on Harry and Ron, this spell, when done correctly, apparently allows a substantial amount of control over the subject's memories. We see it used a number of times through the series. The most prominent times are:

 * as mentioned above, in Harry Potter and the Chamber of Secrets, when Gilderoy Lockhart attempts to cast it on Ron and Harry so as to allow him to claim to have defeated the Monster in the Chamber. In this case, he is using a broken wand, which backfires; as a result, afterwards he is barely able to remember his own name.
 * in Harry Potter and the Goblet of Fire, when the Muggle keeper of the campground has his memory changed so that he forgets the odd magical things that he has seen the occupants of his campground doing.
 * in Harry Potter and the Order of the Phoenix, where Kingsley Shacklebolt casts it on Marietta Edgecombe so that she forgets that there were previous meetings of Dumbledore's Army.
 * in Harry Potter and the Deathly Hallows, Hermione casts this spell on a pair of Death Eaters and an innocent waitress so that they will not recall having seen Harry. She later uses it against Xenophilius Lovegood to make him forget the presence of Ron Weasley.

Like so many spells, a large part of the effect of this spell very likely depends on what the caster is thinking at the time the spell is cast. Presumably the caster must hold in their mind a representation of the memories needed to be changed, along with what the memories should be changed to.

Analysis
Apparently, this spell is most often used to clean up any 'spillage' in front of Muggles. The International Statute of Wizardry is specifically designed to try and keep the Muggles unaware of the Wizarding world, so this spell is apparently reasonably often used on Muggles to keep them unaware of what the wizards have been doing.

Questions

 * 1) Is there a way to reverse the effect of this spell?


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User:David G.V. Ray

http://finance.groups.yahoo.com/group/david_gv_ray

http://finance.groups.yahoo.com/group/david_gv_ray_de

title: User:David G.V. Ray


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User talk:David G.V. Ray

Welcome
Hello and welcome to Wikibooks!

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Naming policy
You might want to read Naming policy. Using slash convention has cerain benefits to your book:
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Leave me a message if you have any questions. --Derbeth talk 20:27, 26 January 2006 (UTC)

title: User talk:David G.V. Ray


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User talk:151.188.16.12

Thanks for experimenting with Wikibooks. Your test worked, and has now been removed. Please use Sandbox for any other tests you want to do, since testing material in modules will normally be removed quickly. Please see the welcome page if you would like to learn more about contributing to our project. Thanks. Brim 22:15, 26 January 2006 (UTC)

Welcome to Wikibooks. We invite everyone to contribute constructively to our collection. Take a look at the welcome page if you would like to learn more about contributing. However, unconstructive edits are considered vandalism, and if you continue in this manner you may be blocked from editing without further warning. Please stop, and consider improving rather than damaging the hard work of others. Thanks. Junesun 13:29, 22 May 2006 (UTC)

 * This IP address has been blocked from editing for 1 month. Its a shame that you couldn't play nice. --Whiteknight (talk) (projects) 13:55, 22 May 2006 (UTC)

title: User talk:151.188.16.12


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User talk:Tsca.bot

Please do not write here.

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If you want to request an action/comment on what the bot has done, write here: pl:user talk:tsca or here: m:user talk:tsca

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text: Software Engineers Handbook/Language Dictionary/ALGOL


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Muggles' Guide to Harry Potter/Characters/Professor Quirrell

Overview
Professor Quirinus Quirrell taught Defence Against the Dark Arts at Hogwarts during Harry Potter's first year. His class was held on the third floor of the castle, right in the Great Foyer near the Gryffindor tower.

Quirrell's wand is alder, 9 inches, and unicorn hair. He is a Half-blood, and his birthday is 26 September. As a Hogwarts student, he was sorted into Ravenclaw. Quirrell never married or had children.

Notes on his Name
Professor Quirrell is never given a first name in the books, in the film, or in the video game. He does appear in two other places:

 * A Wizards of the Coast trading card game based on the series included a card of Quirrell with the first name Quirinus. The Harry Potter Lexicon site states, however, that "these cards are not canon"

 * Master Foods produced a line of Chocolate Frog treats with collectable Famous Wizards cards; Quirrell being given the first name Slatero. J. K. Rowling states that she wrote the information on those cards.

J. K. Rowling has confirmed, in Pottermore, that Quirrell's first name is, indeed, Quirinus.

Philosopher's Stone
A very timid person, Professor Quirrell first appears in the Leaky Cauldron, where he is pleased to meet Harry; Hagrid comments at the time that he always seems nervous, ever since he took a year's holiday and met up with something he had been teaching about.

At the Arrival Feast, Harry notes that Quirrell looks rather odd, wearing a large purple turban on his head. It is while Professor Quirrell is speaking with Professor Snape that Harry first feels the searing pain in his scar that becomes his companion, on and off, for the nearly all the seven years in this series.

Harry and Ron get into trouble with Filch on the very first day of classes, when they are found trying to get through a locked door, which turns out to be the door to the forbidden third floor corridor. They are saved from being locked in the dungeons by Professor Quirrell, who happens to be passing by.

In Defence Against the Dark Arts, Professor Quirrell says that his strange purple turban was a gift from an African prince for dealing with a troublesome zombie. When Seamus asked excitedly how he had fought the zombie, Quirrell turned all pink and started talking about the weather. (Note: this is the only mention of "zombies" in the series, and thus is highly suspect. The magical construct most closely allied to the Muggle concept of zombies is the Inferius.) There is also a strange smell of garlic that hangs about the classroom; the Weasley twins insist that it is because Quirrell has stuffed his turban full of garlic to ward off vampires.

We don't hear much about his teaching, except that it is not as interesting as Harry and the rest of his class had expected; we do find out that he is concealing something, and that he and Professor Snape may both be looking for something, possibly the mysterious little package that Hagrid removed from Gringotts.

He bursts into the Halloween feast warning that a troll is in the dungeons; Harry and Ron defeat it and save Hermione, thus bonding the three.

At the first Quidditch match of the year, against Slytherin, Harry's broom is jinxed and tries to buck him off. Hermione and Ron believe Snape is casting the jinx. In her haste to reach Snape and set his robes on fire to break his concentration, Hermione knocks over Quirrell.

The Weasley twins charmed several snowballs to bounce off the back of Profesor Quirrell's turban, in the snowfall during Christmas break.

Harry overhears Quirrell arguing with Snape about where his loyalties lie, and later hears him arguing with someone else about something he does not want to do.

At the conclusion, Harry, Ron, and Hermione pass through a series of chambers to find the Philosopher's Stone or also known as the Sorceror’s Stone. One chamber contains a Troll, who fortunately has been knocked out. Harry alone reaches the final chamber, where he finds Quirrell. Quirrell boasts about his skill with trolls, admitting that he let the one troll into the school at Halloween, and that it was his troll that Harry passed. He also says that Snape had been useful as misdirection, "flapping about like a great bat." Quirrell has been trying to kill Harry all year; Quirrell also jinxed Harry's broom during the Quidditch match against Slytherin, and Snape was attempting to counter the jinx. Quirrell's turban actually conceals Lord Voldemort's face that is attached to Quirrell's head, and Voldemort has been controlling Quirrell all year. Ordered to kill Harry, Quirrell is unable to touch him without getting burned; when Quirrell is preparing a killing curse, Harry grabs his face, causing him so much pain that he is disabled. Harry is also in much pain from his scar, triggered by Voldemort's nearness, and it causes him to pass out.

It is uncertain whether Quirrell actually dies here; it is suggested that he does, but while Professor Dumbledore does explain much of what happened, he never actually states that Quirrell is dead.

Goblet of Fire
Expounding to the Death Eaters as to what had occurred while he was disembodied, Lord Voldemort describes his stay on the back of Quirrell's head. He mentions that "The servant died when I left his body". Though Voldemort never names Quirrell, referring to him always as his "servant", context makes it certain that this refers to Quirrell.

Order of the Phoenix
Before the school year starts, Harry, Ron, and Hermione discuss the new Defence Against the Dark Arts teacher. While running down the list of Defence Against the Dark Arts teachers Ron and Harry have known, Fred and George Weasley mention "one died," which could only be Quirrell.

In her first Defence Against the Dark Arts class of the year, Professor Umbridge states that Quirrell was the only Defence Against the Dark Arts teacher that was up to standards for the Ministry. Harry gets into trouble for pointing out that he had Voldemort stuck to the back of his head.

Half-Blood Prince
When Bellatrix Lestrange and Narcissa Malfoy meet with Snape at his house, Bellatrix snaps at Snape for not helping Quirrell get the Philosopher's Stone for Voldemort. Snape however, tells her that he thought Quirrell only wanted it for himself, not Voldemort, whom he has already told and believed.

To convince Horace Slughorn that Hogwarts is safe from Death Eaters, Harry tells him that Professor Quirrell is the only teacher who has died at Hogwarts. (This is not strictly true, Professor Binns clearly died at the school, though as it was of natural causes it likely would not concern Slughorn either way. It is true that Quirrell's death is the only one Harry knows of that could be attributed to Voldemort or his organization.)

Strengths
Rather than magical ability, Quirrell's greatest strength was probably his intelligence, evidenced by his having been sorted into Ravenclaw House at Hogwarts, home to more intellectual students. Although timid in nature, he apparently had an adventurous spirit, traveling to many foreign countries whenever he could.

Quirrell, during the course of the first book, had been carrying what remained of Lord Voldemort on the back of his head. As such, he could partially utilize Voldemort's powers: for instance, Voldemort being a Legilimens, could inspect other wizards' minds and communicate what he found to Quirrell.

Weaknesses
Quirrell possessed an extremely timid and nervous disposition. And though intelligent, his magical powers may have been rather ordinary. This may all have contributed to his becoming susceptible to Lord Voldemort's powers, resulting in the disembodied Dark Lord riding on the back of Quirrell's head while he attempted to resurrect his own physical body. As a result, Quirrell had to bow to Voldemort's commands, whatever they were, and was subject to any punishment Voldemort chose to mete out. As he was a relatively weak-willed wizard, Quirrell attempted to attain distinction by attaching himself to a powerful being, though that power instead latched itself onto him.

Quirrell was never seen performing magic, so it is uncertain how powerful a wizard he actually was. However, he was apparently able to control Trolls, and most likely had been able to before his encounter with Voldemort, as he seems proud of that ability.

Relationships with Other Characters
The closest relationship Quirrell appears to have had was the one with Lord Voldemort after being controlled by him. Quirrell was basically Voldemort's slave, doing his bidding without question. To help deflect suspicion from himself, Quirrell adopted a stammering, rather bumbling pose. He admits that Snape's fluttering about like a huge black bat and acting suspiciously was actually useful to him, allowing Quirrell to carry out Voldemort's commands while others were focused on Snape. Quirrell and Snape seem competitive with one another, and as Snape grew more suspicious about Quirrell's behavior, they seem to have been arguing frequently.

Though he was likely always shy and rather aloof, Quirrell's increasingly quirky manner and sudden stammering seems to have distanced others from him, while it also aroused Snape's distrust. It appears Quirrell never had any close relationships with the other teachers or students at Hogwarts.

Analysis
Having been a Ravenclaw, Quirrell was obviously quite intelligent, but he appears to have been a rather ordinary wizard whose knowledge about magic and defensive arts may have been more academic than applied. Although Quirrell was commandeered by Voldemort, his lackluster distinction in life may have made him a somewhat cooperative accomplice, seeing this as an opportunity to obtain some significance and power. Unfortunately, he misjudged Voldemort's true intentions, failing to see that the Dark Lord considered him as little more than a disposable lackey. This ultimately cost Quirrell his life.

Quirrell, curiously, is apparently the only evil character that utters the name "Voldemort", though he does it ("at least", so to say) with the respectful "Lord" before it. Most wizards, of course, do not say the name, out of fear (in the good) and out of reverence (in the bad). Wizards on the side of good mostly say "You-Know-Who" and sometimes "He who must not be named"; dark wizards usually say "Dark Lord", and tend to keep that habit, even if they think better of it and cease to be Death Eaters. Regulus Black, Severus Snape, and (possibly) Karkaroff are cases of this habit in action. In a limited number of cases, the phrase "the Dark Lord" is also used by wizards on the good side. The braver from among the good side say "Voldemort" and, sometimes, "Lord Voldemort", but Quirrell – possibly because he is not technically a Death Eater, but was recruited afterwards, possibly because even though Voldemort could force him to give over his body, his mutilated nature was simply not enough to keep that sort of respect – is the only bad character to say "Lord Voldemort". Of course, it is also possible that this is simply a flint; it is certainly true, as early as the first chapter of the first book, that the good wizards largely fear to say the name, but it is uncertain whether the author had yet decided that dark wizards would be similarly affected.

According to Professor Dumbledore, speaking in Harry Potter and the Half-Blood Prince, the Defence Against the Dark Arts teaching post is apparently jinxed. Ever since Voldemort had been declined the job many years before, no teacher has lasted more than one year in that post. One question that has been raised is, given that jinx, how could Quirrell have remained in that post for more than a year? According to the author, he had not. In an interview, Rowling stated that Quirrell had requested a transfer to that post, and had been studying the source material so he could teach it, when he encountered Voldemort in Albania.

All the same, there is some question raised on some fan sites as to how long Quirrell had been in that post. One very well reasoned essay suggests strongly that Quirrell's "year-long tour" in preparation for his teaching of Defence Against the Dark Arts was not the year before Harry entered the school, but at least one year prior to that time. The essay predates publication of Harry Potter and the Half-Blood Prince, and does not attempt to reconcile Quirrell's postulated at least two-year tenure with Dumbledore's statement "we have never been able to keep a Defence Against the Dark Arts teacher for longer than a year since I refused the post to Lord Voldemort." We could attempt that reconciliation here, by suggesting that Quirrell was perhaps only filling in as Defence teacher during the year before Harry's arrival, while another, possibly chronically ill, teacher held the actual post. However, we consider it more likely that we are simply seeing one place where the author temporarily lost track of her timeline. It could, of course, also be implied that Voldemort lifted the jinx for Quirrell, who he knew to be his follower even if he hadn't yet started possessing him. In that case, Dumbledore either simply forgot about Quirrell's longer tenure, as even he can err, or understands better than we think that Voldemort is choosing to keep his lackey employed in the heart of his enemy's stronghold.

Questions

 * 1) Why did Quirrell allow Voldemort to attach himself to his head?
 * 2) What might Quirrell have been like before he met Voldemort?
 * 3) Was Quirrell a willing Voldemort accomplice?

Greater Picture
As noted in the info box, Professor Quirrell's true loyalty is something of a spoiler; that loyalty, and its eventual resolution, form much of the plot of the first book in the series. Of course, the fact that he supports Voldemort is obvious by the end of the first book, but knowing that before reading the book actually results in a greater spoiler: clearly Snape is acting to try to hinder Quirrell, could it be that Snape is not the great evil that Harry believes him to be? It is perhaps a measure of the author's ability that even in the final chapter, where Quirrell, with Voldemort on the back of his head, says that Snape had provided a great distraction for him, we still don't fully apprehend that Snape may be working against Voldemort. The author manages to keep us convinced that Harry's distrust of Snape is a valid indicator of Snape's allegiance.


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User:BarkingFish

=You've found my user page!=

Hi there. My name is Thorsteinn Malmjursson, I am 29 and I am a full blown member of no less than 4 Wikipediæ, English, German, Catalan and Meta. I am a citizen of Iceland, born in Reykjavik, currently living in the United Kingdom and waiting for status as a naturalised British Citizen.

I have already completed several studies at University, here and in Iceland. I hold my Batchelor of Education degree in Information Technology, I am fluent in 3 languages, advanced in 1, and speak another 6 to the point of politeness and I also hold both my Microsoft Certified Systems Engineer and Systems Developer (MCSE and MCSD) qualifications.

I am very happy to be working with Wikijunior, I registered originally over at Meta, before I discovered that the project had been moved to Wikibooks.

My main areas of expertise are ICT and Electronics, and also I would be willing to do some simple language lists for any Wikijunior books you may produce on language, such as lists of colors, numbers, shapes, food, drinks, and toys & games.

I currently work in the Education Support sector as an ICT Learning Support Assistant with 7 to 10 year old children.

If you have any questions, you can leave me a message in any of these places:

Meta: Meta Talk Page

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God Speed, and take care!

Tmalmjursson 00:29, 27 January 2006 (UTC)

title: User:BarkingFish


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User:Cromwellt

Cromwellt is a freelance interpreter and translator in central California, specializing in the medical field. He is more active on the English Wikipedia, which he joined in 2004, and he is working on becoming a worthwhile Wikipedian, etc. in the Spanish Wikipedia, the Simple English Wikipedia, the English Wiktionary, and the Simple English Wiktionary.

Cromwellt's interests include, but are not limited to, books and literature, English, languages, computers, and Wikipedia and its sisterprojects. As far as Wikiprojects are concerned, he loves proofreading and correcting typos, etc., but also enjoys creating new articles, etc. He would like to help out here as well.

For all the projects he is involved in, see his userpage matrix.

Oh, the joys of emendation Oh, the rapture and the fun Lost myself in contemplation Life and wiki, each a pun Viva Wikibooks!

title: User:Cromwellt