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Radiation Oncology/Breast/Post mastectomy

Postmastectomy Radiation Therapy

Official guidelines

 * Please see the Breast Guidelines page

Patterns of failure

 * With chemotherapy - LR for 4 or more positive LN: about 15-36%. LR for T3 tumor: about 20-30%. (multiple papers)
 * Postmastectomy RT reduces LR recurrence in high-risk group to about 5-10%.

Overall

 * Florence, 2007 (1971-2003) PMID 17368813 -- "Loco-regional recurrence in 2064 patients with breast cancer treated with mastectomy without adjuvant radiotherapy." (Livi L, Eur J Surg Oncol. 2007 Mar 15)
 * Retrospective. 2064 patients treated with mastectomy, without adjuvant RT
 * Loco-regional failure: 18%; only prognostic factor tumor size, not number of LN+
 * Conclusion: Number of LN+ not enough to justify adjuvant RT

 * MDACC, 2005 - PMID 16169678 — "Clinical investigation: regional nodal failure patterns in breast cancer patients treated with mastectomy without radiotherapy." Strom EA et al. Int J Radiat Oncol Biol Phys. 2005 Dec 1;63(5):1508-13.
 * Retrospective. 1031 patients treated with mastectomy + ALND and doxorubicin-based chemo. No RT. On 5 clinical trials. Median axillary LN dissected 17, but no cN2 disease. Median F/U 9.7 years
 * 10-year regional recurrence: axilla 3%, supraclav 8%
 * Predictors for SCV failure: >=4 LN+, >20% LN+, gross LN ECE
 * Conclusion: RT to axilla not necessary if ALND; RT to SCV if one of the risk factors

 * NSABP pooled analysis, 2004 - PMID 15452182 — "Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials." Taghian A et al. J Clin Oncol. 2004 Nov 1;22(21):4247-54. Epub 2004 Sep 27.
 * Included pts from B-15, B-16, B-18, B-22, and B-25. 90% had doxorubicin-based chemo.
 * At 10 yrs, 12.2% had isolated LRF, 19.8% had LRF with or without DF, and 43.3% had DF alone as a first event.
 * LRF (+/- DM) as a first event was 13% for 1-3 LN, 24.4% for 4-9 LN, and 31.9% for 10 or more LN. For tumor < 2 cm 14.9%, 2-5 cm 21.3%, and >5 cm 24.6%.
 * Conclusion: recommend post-mastectomy XRT for large tumors and 4 or more LN.

 * MDACC (1975-1994)
 * Retrospective analysis of 1031 pts enrolled on prospective clinical trials. Pts treated with mastectomy, chemotherapy w/o tamoxifen, and without RT. Stage II-IIIA.
 * 2001 PMID 11395242 -- "The influence of pathologic tumor characteristics on locoregional recurrence rates following mastectomy." (Katz A, Int J Radiat Oncol Biol Phys. 2001 Jul 1;50(3):735-42.)
 * Analysis of factors other than size and lymph node status that predict for increased risk of LRR. Multicentric disease defined as 2 or more separate areas of invasive carcinoma in more than one quadrant of the breast and separated by at least 4 cm. Multifocal disease defined as 2 or more areas within the same quadrant and/or separated by less than 4 cm.
 * Multicentric / Multifocal disease: pts with gross multicentric disease (clinically apparent, or seen on gross pathologic examination): LRR 37% vs 17% at 10 yrs. Pts with multifocal disease and those with microscopic multicentric disease did not have higher rates of LRR than those with unifocal disease.
 * LVSI: increased LRR 25% at 10 yrs.
 * Margins: positive or close (< 5 mm) margins, LRR 45%
 * Conclusion: Close or positive surgical margins, pectoral fascia involvement, clinical or gross multicentric disease, LVSI, and invasion of the skin or nipple predict for an increased risk of LRR in patients treated without RT.
 * 2000 PMID 10920129 -- "Locoregional recurrence patterns after mastectomy and doxorubicin-based chemotherapy: implications for postoperative irradiation." (Katz A, J Clin Oncol. 2000 Aug;18(15):2817-27.)
 * 10-yr rate of isolated LRR 4% (0 LN), 10% (1-3 LN), 21% (4-9), and 22% (10 or more). T-stage, tumor size, and >= 2 mm extranodal extension predicted for LRR.
 * For pts with T1-T2 and 1-3 LN: pts with <10 nodes examined, LRR 24% vs 11%. Tumor size > 4cm or extranodal extension, LRR > 20%.
 * Conclusion: For pts with tumors >= 4 cm or >= 4 involved nodes, LRR is > 20% and pts should be offered RT. Additionally, pts with 1-3 LN and large tumors, extranodal extension, or inadequate axillary dissection may benefit from RT.

 * ECOG
 * 1999 (1978-87) PMID 10561205 -- "Locoregional failure 10 years after mastectomy and adjuvant chemotherapy with or without tamoxifen without irradiation: experience of the Eastern Cooperative Oncology Group." (Recht A, J Clin Oncol. 1999 Jun;17(6):1689-700.)
 * 2016 pts on 4 ECOG trials (E5177, E6177, E4181, E5181). Pts N+ and had mastectomy and chemo +/- hormones but without RT.
 * 10-yr risk of LRF (with or without DF) was 12.9% (1-3 LN) and 28.7% (4 or more). Tumor size, number of involved LNs, ER-, and decreasing number of nodes examined were significant for increased risk of LRF. Pt age and menopausal status were not significant.
 * Note: tables in paper give risk of isolated LRF, LRF, or DF only for each TNM category as well as by tumor size in cm and number of involved nodes.
 * Conclusion: LRF is a substantial problem for node-positive pts treated with mastectomy + chemohormonal therapy
 * 1988 (1978-82): PMID 3292711 — "Identification of a subgroup of patients with breast cancer and histologically positive axillary nodes receiving adjuvant chemotherapy who may benefit from postoperative radiotherapy." (Fowble B, J Clin Oncol. 1988 Jul;6(7):1107-17.)
 * 627 pts on ECOG trials (E5177, E6177). 225 pts had relapse at 3 yrs. In 31% of failures (11% of pts) the relapse was LR without DM. Pts with 4 or more positive LN or tumor size 5 cm or more are more likely to have a local failure.

Node positive (1-3 LN+)

 * BIG 02-98 Trial
 * 2018 PMID 29534902 -- "Postmastectomy Radiation Therapy in Women with T1-T2 Tumors and 1 to 3 Positive Lymph Nodes: Analysis of the Breast International Group 02-98 Trial." (Zeidan YH, Int J Radiat Oncol Biol Phys. 2018 Jun 1; 101(2):316-324. doi: 10.1016/j.ijrobp.2018.01.105. Epub 2018 Feb 6.)
 * Retrospective analysis of chemotherapy trial (doxorubicin + docetaxel vs cyclophosphamide). PMRT given at discretion. 684 patients, T1-T2 and pN1, with axillary nodal dissection. PMRT in 49%
 * Outcome: 10-year LRR PMRT- 6.5% vs PMRT+ 2.5% (SS). Better LRR in non-taxane group (9.1% vs 3.4%, SS). No difference in BCSS (84%) or OS (~80%)
 * Conclusion: Excellent outcomes; PMRT improves LRR but events low compared to historical studies

 * Taiwan, 2002 (1991-98) - PMID 11958892 — "Locoregional failure of postmastectomy patients with 1-3 positive axillary lymph nodes without adjuvant radiotherapy." Cheng JC et al. Int J Radiat Oncol Biol Phys. 2002 Mar 15;52(4):980-8.
 * British Columbia, 2005 (1989-97) - PMID 15817335 — "Selecting breast cancer patients with T1-T2 tumors and one to three positive axillary nodes at high postmastectomy locoregional recurrence risk for adjuvant radiotherapy." Truong PT et al. Int J Radiat Oncol Biol Phys. 2005 Apr 1;61(5):1337-47.
 * 821 pts, pT1-2 with 1-3 LN positive, without RT. Systemic therapy in 94%.
 * median f/u 7.7 yrs. 10-yr isolated LRR 12.7% and LRR with or without simultaneous distant recurrence 15.9%. Risk of >20% LRR for pts with 1-3 LN+ and one of the following: age < 45, ER negative, medial location, >25% nodes positive.

Node negative

 * Data from EBCTCG (PMID 16360786) shows 5-year LR rate of 6% after mastectomy and axillary clearance (systemic therapy unspecified)
 * Similarly, data from NSABP (PMID 16921044) shows 10-year LR rate of 7% after mastectomy and axillary clearance (systemic therapy in 75%)
 * Data from the Danish trials (PMID 9395428, PMID 10335782) showed LRF rate of 17% and 23% respectively in patients not receiving PMRT. Because this figure is much higher than the EBCTCG and NSABP data, and because the LN axillary dissection is considered suboptimal, it is possible that some of these T3N0 patients were occult N+ (PMID 16921044)
 * Based on EBCTCG results, RT decreases the 6% LR rate to 2%, for an absolute 4% gain in local control. There is no impact on 15-year BCA mortality, but there is an overall survival decrement associated with RT.
 * Patients with T3N0 disease have historically (PMID 15667954) been treated with PMRT, but data now suggests that large tumors as a sole criterion probably do not require PMRT. LVI+ status however is an independent prognostic factor for LRF
 * Conversely, patients with T1-2N0 disease have not historically been treated with PMRT, but combination of some factors (young age, LVI+, tumors >2cm, and close margins) may increase LRF risk to 20-40%
 * A meta-analysis from UK suggests that patients with two or more risk factors (LVI, Grade 3, T2+, close SM, or age <50/premenopausal) should be treated with PMRT, since their LRR risk is >= 15%

Any T N0
 * NHS Trust, UK; 2009 PMID 18996609 -- "Radiotherapy to the chest wall following mastectomy for node-negative breast cancer: A systematic review." (Rowell NP, Radiother Oncol. 2009 Apr;91(1):23-32. Epub 2008 Nov 7.)
 * Meta-analysis.
 * Predictive factors for LRR: LVI, Grade 3, T2+, close SM, age <50/premenopausal
 * Local recurrence rate: no risk factors 5%, one risk factor ~10%, 2+ risk factors >=15%
 * Conclusion: Use of PMRT in N0 women requires re-evaluation; RT should be considered for those with 2+ factors

T1-2N0
 * Ankara, 2007 (Turkey) PMID 17398017 -- "Can a subgroup of node-negative breast carcinoma patients with T1-2 tumor who may benefit from postmastectomy radiotherapy be identified?" (Yildirim E, Int J Radiat Oncol Biol Phys. 2007 Mar 28; [Epub ahead of print])
 * Retrospective. 502 patients. T1-2 tumors, N0. Median F/U 6.4 years
 * Recurrence: local 3%, distant 11%
 * Local recurrence predictors: if <=40 years - LVI+ HR 9.0, tumor size (>2cm) HR 5.4; if >40 - LVI+ HR 18.0, tumor size (>3cm) HR 8.6, grade HR 7.0
 * Distant recurrence predictors: tumor size, grade, ER status, her2 status
 * Conclusion: Consider RT for N0 patients if <40 and large tumors or LVI+, or if >40 and large tumors or high grade

 * Mass General, 2005 (1980-2000) PMID 15990006 - Jagsi R et al. "Locoregional recurrence rates and prognostic factors for failure in node-negative patients treated with mastectomy: Implications for postmastectomy radiation." Int J Radiat Oncol Biol Phys. 2005 Jul 15;62(4):1035-9.
 * Retrospective. 877 patients. Node negative, mastectomy, no RT. Median F/U 8.3 years
 * Locoregional recurrence: 6% as first event; chest wall 80%
 * Independent risk factors: Size > 2 cm, margin less than 2 mm, premenopausal status, and lymphovascular invasion (LVI)
 * Recurrence stratified: no RFs 1%, 1 RF 10%, 2 RFs 18%, 3 RFs 41%
 * Conclusion: treating chest wall in patients with multiple RFs reasonable
 * 2011 Update (1980-2004) PMID 21420245 - Abi-Raad R et al. "Patterns and risk factors of locoregional recurrence in T1-T2 node negative breast cancer patients treated with mastectomy: implications for postmastectomy radiotherapy." Int J Radiat Oncol Biol Phys. 2011 Nov 1;81(3):e151-7.
 * 1136 pts. Median F/U 9 years. Risk factors: size, close margins, age < 50, LVSI, no systemic therapy. 10-yr LRR with 3 or more risk factors: 19.7%.

 * British Columbia, 2005 (1989-99) PMID 15850919 -- "Patient subsets with T1-T2, node-negative breast cancer at high locoregional recurrence risk after mastectomy." (Truong PT, Int J Radiat Oncol Biol Phys. 2005 May 1;62(1):175-82.)
 * 1505 pts with pT1-T2 N0 breast cancer, negative margins, s/p mastectomy without RT.
 * Median f/u 7.0 yrs. 10-yr total LRR 7.8%. LRR risk of approximately 20% in pts with grade 3 disease and +LVI or with grade 3, T2 tumor, with no systemic therapy.
 * Conclusion: "Women with pT1-T2N0 breast cancer experienced a LRR risk of approximately 20% in the presence of Grade 3 disease with LVI or Grade 3 disease, T2 tumors, and no systemic therapy. These subsets of node-negative patients warrant consideration of for postmastectomy radiotherapy."

 * British Columbia & Mass General, 2014; Biologic subtype (1998-9) PMID 24161421 -- "Is Biological Subtype Prognostic of Locoregional Recurrence Risk in Women With pT1-2N0 Breast Cancer Treated With Mastectomy?" (Truong PT, Int J Radiat Oncol Biol Phys. 2014 Jan 1;88(1):57-64.)
 * 1994 pts (1582 from BC and 412 from MGH) treated with MRM without RT. All had subtyping based on ER/PR/Her2 and grade. 5 subtypes defined as: 1) luminal A (ER or PR+, HER2-, grade 1-2), luminal B (ER/PR+, HER-, gr 3), luminal HER 2 (ER/PR+, HER2+), HER2 (ER/PR-, HER2+), triple negative TNBC (ER-, PR-, HER2-).
 * 60.3% were luminal A, 14.7% luminal B, 11.1% LumHER2, 5.3% HER2, 8.6% TNBC. Median f/u 4.3 yr. 5-yr LRR: no significant difference by subtype -- 1.8% lumA, 3.1% lumB, 1.7% lumHER2, 1.9% HER2, and 1.9% TNBC. 5-yr DR highest in TNBC 9.6%; 5% lumB, 2.4% lumHER2, 1.8% lmA, 1.1% HER2. On MVA, factors predictive of higher LRR: tumors > 2cm, lobular histology, close/positive margins.
 * Conclusion: The 5-year risk of LRR in our pT1-2N0 cohort treated with mastectomy was generally low, with no significant differences observed between approximated subtypes.

T3N0
 * Emory University, 2017 (2003-2011) PMID 28387923 -- "The role of postmastectomy radiotherapy in women with pathologic T3N0M0 breast cancer." (Cassidy RJ, Cancer. 2017 Aug 1;123(15):2829-2839. doi: 10.1002/cncr.30675. Epub 2017 Apr 7.)
 * Retrospective NCDB data. 3437 patients, PMRT in 48% (chest wall alone 67%, chest wall and regional lymph nodes 33%). PMRT more likely if age <40, tumor >=7 cm, and chemotherapy or endocrine therapy
 * Outcome: 5-year OS PMRT+ 86% vs PMRT- 66% (SS). No benefit to regional lymph node radiation on OS
 * Conclusion: PMRT is associated with improved overall survival, regardless of SM status, tumor size, or systemic therapy

 * University of Utah; 2017 (2004-2012) PMID 28193571 -- "Outcomes and utilization of postmastectomy radiotherapy for T3N0 breast cancers." (Francis SR, Breast. 2017 Apr;32:156-161. doi: 10.1016/j.breast.2017.02.001. Epub 2017 Feb 10.)
 * Retrospective NCDB analysis. 4291 patients, no neoadjuvant chemotherapy. PMRT given in 47%
 * Outcome: Improved overall survival if PMRT given (HR 0.7, SS), if chemotherapy given (HR 0.51, SS), and if endocrine therapy given (HR 0.63, SS). Propensity matched cohort of 2800 patients analyzed. 5-year OS PMRT+ 84% vs PMRT- 80% (SS); 10-year OS 67% vs 59%
 * Conclusion: PMRT was associated with improved survival in pT3N0 breast cancer

 * NSABP, 2006 PMID 16921044 -- "Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials." (Taghian AG, J Clin Oncol. 2006 Aug 20;24(24):3927-32.)
 * Retrospective. 313 patients with tumors >=5cm. NSABP B13, B14, B19, B20, B23 treated with MRM, no RT, no systemic therapy 25%. Median F/U 15 years
 * 10-year outcome: isolated LRF 7%, LRF+DM 3%, DM 24%. Majority on chest wall 86%. If 1-5 LN removed, isolated LRF 17%
 * By systemic treatment: none 13% vs. chemo alone 6% vs. TAM alone 5% vs. chemo+TAM 5% (NS).
 * No multivariate predictors for LRF
 * Conclusion: If LN- and T3 tumors at MRM, LRF as first event remains low and PMRT should not be routinely used for these patients

 * MGH/MDACC/Yale, 2006 (1981-2002) PMID 16887288 -- "Low local recurrence rate without postmastectomy radiation in node-negative breast cancer patients with tumors 5 cm and larger." (Floyd SR, Int J Radiat Oncol Biol Phys. 2006 Oct 1;66(2):358-64.)
 * Retrospective. 70 patients with tumor size >=5cm and N0, treated with mastectomy + systemic chemo, but no RT. Three institutions. Median F/U 7 years
 * 5-year LRF: 8%; 4/5 in chest wall. DFS 83%, OS 86%
 * LVI+ significantly associated with LRF (21% vs. 4%), DFS, and OS
 * Conclusion: Large tumors alone may not need RT after mastectomy/chemo. But, LVI+ highly correlated with poor outcome

HER2+

 * HERA HER2+ Trial; 2020 PMID 31654782 -- "Post-Mastectomy Radiation Therapy in Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer Patients: Analysis of the HERA Trial" (Jaoude JA, Int J Radiat Oncol Biol Phys. 2020 Mar 1;106(3):503-510. doi: 10.1016/j.ijrobp.2019.10.022. Epub 2019 Oct 22.)
 * Post-hoc analysis. 1633 patients. Enrolled in HERA trial, mastectomy, adjuvant chemotherapy, adjuvant maintenance trastuzumab. PRMT (58%) vs no PMRT (42%). PMRT 50 Gy in 25 fractions, volumes and boosts at discretion. Median F/U 11 years
 * Outcome: For N0 patients (PMRT n=98 vs no PMRT n=390): LRR ~95% both arms (NS). For N1 patients: LRR PMRT 97% vs no PMRT 90% (p=0.004). For ER+ 97% vs 89% (SS), for ER- 97% vs 91% (NS). OS 87% vs 82% (p=0.06)
 * Conclusion: PMRT decreases LRR for HER2+ with pN1 disease, though benefit smaller than historically.

Positive Margins

 * Harvard, 2012 (1998-2005) PMID 22543200 -- "Surgical margins and the risk of local-regional recurrence after mastectomy without radiation therapy." (Childs SK, Int J Radiat Oncol Biol Phys. 2012 Dec 1;84(5):1133-8.)
 * Retrospective. 397 pts treated with MRM and no RT.
 * superficial margin: positive in 41 pts (10%) and close margin (<2 mm) in 56 (14%).
 * deep margin: positive in 23 (6%) and close in 34 (9%).
 * Median f/u 6.7 yr.
 * Margin status associated with time to isolated LRR. Positive margins: 5-yr LRR of 6.2%. Close margins: 1.5%. Negative margins: 1.9%.
 * Conclusion: "Patients with positive mastectomy margins had a significantly higher rate of LRR than those with a close or negative margin. However, the absolute risk of LRR in patients with a positive surgical margin in this series was low, and therefore the benefit of postmastectomy radiation in this population with otherwise favorable features is likely to be small."

 * Fox Chase, 1998 (1984-93) PMID 9635708 -- "A close or positive margin after mastectomy is not an indication for chest wall irradiation except in women aged fifty or younger." (Freedman GM, Int J Radiat Oncol Biol Phys. 1998 Jun 1;41(3):599-605.)
 * Retrospective. 34 pts treated with MRM, tumor < 5 cm, 0-3 LN, margins < 1 cm, and no postoperative RT.
 * 5 chest wall recurrences (1 isolated, 1 with axillary recurrence, 3 with distant mets). Chest wall recurrence rate 9% 5-yr and 18% 8-yr. For patient age ≤50, 28% vs 0% for age > 50.
 * The subgroup of patients age 50 or younger with T1-T2 tumor size and 0-3 positive nodes with a close (<5mm) or positive margin are at high risk (28%) for chest wall recurrence and should receive chest wall irradiation.

Dermal Lymphatic Invasion

 * Fox Chase; 2009 PMID 19194121 -- "Dermal lymphatic invasion and inflammatory breast cancer are independent predictors of outcome after postmastectomy radiation." (Abramowitz MC, Am J Clin Oncol. 2009 Feb;32(1):30-3.)
 * Retrospective. 70 patients, either inflammatory breast cancer alone (n=31), or dermal lymphatic invasion alone (n=21), or both dermal lymphatic invasion and inflammatory breast cancer (n=18). All treated with postmastectomy radiation.
 * Outcome: LRR for DLI 10%, IBC 8%. DM 45%, 44%. Dead of disease 50%, 48%. DLI only independent predictor for LRR (HR 4.8, SS). IBC, >=4 involved lymph nodes predicted for DM and OS
 * Conclusion: Dermal lymphatic involvement and inflammatory breast cancer independent predictors of poor outcome. DLI associated with increased LRR, IBC with DM and OS

Predictive models

 * Taiwan, 2006 - PMID 16472935, 2006 — "Prognostic index score and clinical prediction model of local regional recurrence after mastectomy in breast cancer patients." Cheng SH et al. Int J Radiat Oncol Biol Phys. 2006 Apr 1;64(5):1401-1409.
 * Divided pts into low, intermediate, and high-risk groups based on nodal status, ER status, LVI, and age.
 * Score: 1 pt for age (<=40), ER (negative), and LVI (prominent vs absent or focal). For nodes, score 1 pt for 1-3 LN+, 2 pt for 4-9, and 3 pt for 10 or more.
 * Low risk = score 0-1. Intermediate risk = 2-3. High risk = 4-6.
 * In low risk group, no influence of PMRT on LRR or survival. For intermediate risk, PMRT involves LRC but not metastasis-free or overall survival. For high risk, PMRT improves LRC, DFS, and OS.

 * IBCSG, 2003 PMID 12663706 -- "Risk factors for locoregional recurrence among breast cancer patients: results from International Breast Cancer Study Group Trials I through VII." (Wallgren A, J Clin Oncol. 2003 Apr 1;21(7):1205-13.)
 * Retrospective. 5352 women treated with MRM without RT on seven protocols (1275 N0, 4077 N+). Median F/U 12-15.5
 * N0 risk factors: premenopausal: LVI+, >=T2; postmenopausal: LVI+
 * 10-year high risk recurrence rate: premenopausal 16%, postmenopausal 19%
 * N+ risk factors: premenopausal: number of nodes, grade, LVI+; postmenopausal - number of nodes, grade, size
 * 10-year high risk recurrence rate: premenopausal 35%, postmenopausal 34%
 * Conclusion: Locoregional failure significant problem, even for some N0 patients

PMRT Target

 * Traditionally includes chest wall, supraclavicular/axillary nodes, +/- IMN
 * Information may be gleamed from:
 * EORTC 22922/10925 (for intact breast) - randomizes RT to SCLV + IMN only
 * See details at:
 * SUPREMO - randomizes RT to chest wall only (no nodes)
 * See details at:

Historical use of post-op RT

 * Adair (1943) - No PMID — "The role of surgery and irradiation in cancer of the breast." Adair FE. JAMA. 1943;121:553.
 * 3535 pts who received RT after mastectomy.
 * Marshall and Hare (1947) - No PMID — "Carcinoma of the breast: results of combined treatment with surgery and roentgen rays." Marshall SF and Hare HF. Ann Surg. 1947;125:688.
 * Guttmann (1958) - PMID 13487893 — "Effects of radiation on metastatic lymph nodes from various primary carcinomas." Guttmann RJ. Am J Roentgenol Radium Ther Nucl Med. 1958 Jan;79(1):79-82.
 * Guttmann (1963) - PMID 13951487 — "Radiotherapy in the treatment of primary operable carcinoma of the breast with proved lymph node metastases: approach and results." Guttmann RJ. Am J Roentgenol Radium Ther Nucl Med. 1963 Jan;89:58-63
 * These two studies by Guttmann showed that radiotherapy could effectively treat metastatic lymph nodes.

Overall
see also: EBCTCG in section

 * NSABP B-02, 1970 (1961-68)
 * 1103 pts. All pts received radical mastectomy (Halsted). Until 1967, premenopausal pts randomized to 1 of 3 arms: post-op RT, triethylenethiophosphoramide (TSPA), or placebo. Institutions either randomized all postmenopausal women to 3 arms (as in premenopausal women) or they used a different scheme where only LN+ pts were randomized to 3 arms and LN- pts were randomized 1:1 between TSPA and 5-FU. After May 1967, placebo arm was dropped.
 * RT technique: used OLD radiation therapy equipment. Many were orthovoltage. Required at least 200 kV. Dose was 3500 Roentgens in 3 weeks up to 4500 R in 5 weeks. RT was to IMN, apex of axilla, and supraclavicular fossa only. They did not irradiate the chest wall or the whole axilla.
 * PMID 4989839 Full text, 1970 — "Postoperative radiotherapy in the treatment of breast cancer: results of the NSABP clinical trial." Fisher B et al. Ann Surg. 1970 Oct;172(4):711-32.
 * No benefit for RT.

 * Danish trial 82b (1982-89)
 * Importance: Previous trials of post-operative RT had not used chemotherapy.
 * Randomized. 1708 pts. Premenopausal high-risk pts, who had one or more of: positive axillary LN, tumor > 5 cm, invasion of skin or pectoral fascia.
 * Randomized after surgery to: RT + CMF chemotherapy, CMF alone, or CMF + tamoxifen. (enrollment in the third group was stopped after 1986 due to higher mortality).
 * Surgery consisted of total mastectomy + axillary node dissection (level I and part of level II). Median # of LN removed was 7. RT was to chest wall, SCLV fossa, infraclavicular LN, axillary, and IMN in first 4 intercostal spaces. 50 Gy in 25 fx (or 48 Gy in 22 fx, 4days/wk). Recommended use of anterior electron field to treat CW and IMN. Chemotherapy : 8 cycles of CMF with RT, or 9 cycles if given alone. RT was sandwiched between first 2 cycles of chemo.
 * PMID 9395428 Full text, 1997 — "Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial." Overgaard M et al. N Engl J Med. 1997 Oct 2;337(14):949-55.
 * Median f/u 114 months. LRR 9% (RT+CMF) vs 32% (CMF). 10-yr DFS 48% vs 34%. 10-yr OS 54% vs 45%. On MVA, RT improved DFS and OS irrespective of tumor size, number of positive LN, or grade, in these high risk pts. More than 50% of local recurrence were on the chest wall.
 * Conclusion: improved survival with post-op RT
 * Comment: influence of the number of positive LN is difficult to determine from this study because few nodes were removed (median: 7) and many pts had fewer than 4 nodes sampled.

 * Danish trial 82c (1982-90)
 * Randomized. 1375 pts. Postmenopausal high-risk pts. Randomized to: tamoxifen (for 1 yr), or to tam + RT.
 * 1999 PMID 10335782 — "Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial." Overgaard M et al. Lancet. 1999 May 15;353(9165):1641-8.
 * Median f/u 123 months. LRR 8% (RT) vs 35% (No RT). DFS 36% vs 24%. 10-yr OS 45% vs 36%.
 * Conclusion: improved survival with post-op RT

 * Combined Danish 82b and 82c
 * RT techniques; 2005 - PMID 16150503 — "Audit of the radiotherapy in the DBCG 82 b&c trials--a validation study of the 1,538 patients randomised to postmastectomy radiotherapy." Nielsen HM et al. Radiother Oncol. 2005 Sep;76(3):285-92.
 * Description of RT technique
 * Patterns of failure; 2006 - PMID 16618947 — "Study of Failure Patterns Among High-Risk Breast Cancer Patients With or Without Postmastectomy Radiotherapy in Addition to Adjuvant Systemic Therapy: Long-Term Results From the Danish Breast Cancer Cooperative Group 82 b and c Studies." Nielsen HM et al. J Clin Oncol. 2006 Apr 19. Page ?.
 * 18-yr rate of any breast cancer event was 73% (no RT) vs 59% (RT). LRR (with or without DM) was 49% vs 14%; DM subsequent to LRR 35% vs 6%; overall DM 64% vs 53%.
 * Conclusion: post-mastectomy RT changes the disease recurrence pattern. Fewer pts experience LRR and fewer pts overall have DM.
 * Loco-regional recurrences; 2006 - PMID 16647152 — "Loco-regional recurrence after mastectomy in high-risk breast cancer-risk and prognosis. An analysis of patients from the DBCG 82 b&c randomization trials." Nielsen HM et al. Radiother Oncol. 2006 Apr 25; (Epub)
 * 73% chance of DM after developing LRR. Initial randomization did not alter outcome after LRR. Combined treatment of LRR with surgery + RT improved LC over either modality alone.
 * Cardiac toxicity - see at Heart toxicity
 * Nodal status; 2007 - PMID 17306393 — "Is the benefit of postmastectomy irradiation limited to patients with four or more positive nodes, as recommended in international consensus reports? A subgroup analysis of the DBCG 82 b&c randomized trials." Overgaard M et al. Radiother Oncol. 2007 Mar;82(3):247-53.
 * Subgroup analysis. 1152 pts with positive nodes and >=8 nodes removed (i.e. above the median of 7). 552 pts with 1-3 positive nodes, 600 pts with 4+ positive nodes.
 * Median time after mastectomy was 18 yrs. At 15 yrs, LRR in 16% of pts; 15-yr LRR 6% (RT) vs 37% (no RT); RR=0.12. 15-yr OS 39% vs 29%, RR=0.63.
 * For subsets: LRR benefit for 1-3 +LN was 4% (RT) vs 27% (no RT); 4+ LN, 10% vs 51% (both were SS). OS, for 1-3 LN, 57% vs 48%; 4+ LN 27% vs 12% (both were SS).
 * Greater survival benefit for smaller tumors (<= 2cm) but greater LRR benefit for larger tumors
 * Conclusion: Similar and significant improvement in survival in irradiation pts in both groups (absolute survival of 9% at 15 yrs). Number needed to treat (NNTT) was the same in both groups. Pts with 1 or more positive nodes benefit from RT.
 * Receptor status; 2008 PMID 18285604 -- "Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: the Danish Breast Cancer Cooperative Group." (Kyndi M, J Clin Oncol. 2008 Mar 20;26(9):1419-26.)
 * Subset analysis. 1000 patients analyzed with tissue microarray for ER and PR (Rec), and her-2. Constructed 4 groups: Rec+/her2- (63%), Rec+/her2+ (10%), Rec-/her2- (triple negative, 15%), and Rec-/her2+ (12%). Median F/U of alive patients 17 years
 * Outcome: Improved OS after PMRT only in patients Rec+/her2-. No OS benefit for patients that were Rec- or her2+.
 * LR control: Worse LRC for Rec- and Rec-/her2- (triple negative) compared with Rec+/her2-. However, all subgroups significant benefit (p=0.001 or better) to RT over observation
 * Conclusion: Hormonal receptor status is predictive of loco-regional control and overall survival

 * British Columbia trial, 1997 (1979-86)
 * 318 pts. Premenopausal, pN+, s/p MRM + ALND. Randomized to +/- RT. Received six months of CMF (q3w x 9 cycles). 128 pts with ER+ tumors underwent 2nd randomization to oophorectomy (using RT to the ovaries). RT technique: Chest wall, 37.5 Gy (16 fx; 2.34 Gy/fx) using tangents; supraclav/axillary field (with PAB), 35 Gy/16 fx; bilateral IM, 37.5 Gy/16fx. RT given between 4th and 5th chemo cycles. RT was cobalt-60.
 * 15-year results, 1997 - PMID 9309100 Full text — "Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer." Ragaz J et al. N Engl J Med. 1997 Oct 2;337(14):956-62.
 * 20-year results, 2005 - PMID 15657341 — "Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial." Ragaz J et al. J Natl Cancer Inst. 2005 Jan 19;97(2):116-26.
 * 191 of 318 pts had relapse; 190 of 318 pts died (170 from breast cancer, 20 from other causes). There were isolated locoregional relapses in 18% (27 of 154) vs 7% (12 of 164); locoregional relapse at any time before a systemic relapse in 28% (43) vs 10% (17)
 * Event free survival 25% vs 35% (RR=0.70;p=0.09), DFS 30% vs 48% (RR=0.63), survival free of isolated locoregional disease 74% vs 90% (RR=0.36), survival free of locoregional relapse before systemic 61% vs 87% (RR=0.32), systemic breast cancer free survival 31% vs 48% (RR=0.66), breast cancer specific survival 38% vs 53% (RR=0.67), overall survival 37% vs 47% (RR=0.73) (all SS except as otherwise stated). Similar interaction for 1-3 LN and >4 LN.
 * Of 39 pts with isolated locoregional recurrence, 37 developed systemic recurrence and died from breast cancer, despite salvage therapy.
 * Arm edema in 3.2% vs 9.1% (severe in 3.7% vs 0.6%)
 * Conclusion: Improved overall survival. Control of locoregional disease leads to improved survival.

Failed studies:
 * NCI Canada MA25 - 1-3 positive nodes
 * Closed due to lack of accrual
 * Intergroup / SWOG 9927 / RTOG 99-15 (Closed) - post-mastectomy RT for Stage II with 1-3 positive LN (T1-2N1)
 * Protocol
 * pT1-2 pN1 only. MRM with level I-II (or III) nodal dissection, negative margins. May not have clinically matted nodes, gross ECE (microscopic ECE allowed), gross residual disease in the axilla. RT within 2 months of surgery. RT to chest wall, SCLV, and IM (spaces 1-3). No PAB. Allows multiple RT techniques. 50 - 50.4 Gy with optional 10 Gy boost. Bolus qd or qod.
 * Closed due to lack of accrual

Ongoing studies:
 * SUPREMO Website - S elective U se of P ostoperative R adiotherapy Aft E r M astect O my
 * 1-3 positive nodes or T2N0 grade 3 or LVSI. Randomized to RT to the chest wall (no nodal RT) or observation.

Triple negative

 * China (multicenter); 2011 (2001-2006) -- Randomized.
 * 681 women with triple negative Stage I-II breast cancer, s/p mastectomy. Randomized to 1) chemotherapy alone (315 pts), or 2) chemo and RT (366).
 * Majority of pts were <= 50 yrs old, clinical Stage I, pT2, pN0.
 * PMID 21852010 -- "Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: a prospective randomized controlled multi-center trial." (Wang J, Radiother Oncol. 2011 Aug;100(2):200-4.)
 * Median f/u 86 mos. 5-yr RFS 88.3% (RT) vs 74.6% (no RT)(SS). 5-yr OS 90.4% vs 78.7% (SS).
 * Conclusion: chemotherapy plus radiation therapy was more effective than chemotherapy alone in women with triple-negative early-stage breast cancer after mastectomy.

Node negative
see also: EBCTCG in section .. for further details on PMRT in node negative pts. T3N0
 * US NCDB; 2017 (Emory)(NCDB 2003-2011) PMID 28387923 -- "The role of postmastectomy radiotherapy in women with pathologic T3N0M0 breast cancer." (Cassidy RJ, Cancer. 2017 Aug 1;123(15):2829-2839. doi: 10.1002/cncr.30675. Epub 2017 Apr 7.)
 * Retrospective review of NCDB database, 3437 patients, pT3N0, mastectomy between 2003 and 2011. PMRT in 1644 (48%). PMRT given as chest wall 67% or chest wall +RNI (33%). PMRT associated with age <40, private insurance, location <10 miles, Charlson comorbidity 0, tumor >= 7 cm, and treatment with chemo/endocrine therapy
 * Outcome: 5-year OS PMRT 86% vs no PMRT 66% (SS). This was independent of age, facility type, comorbidity, grade, size, margin status and systemic therapy. Regional nodal radiation did not impact OS (p=0.09)
 * Conclusion: PMRT found to be associated with improved OS

 * SEER; 2014 (Fox Chase) (SEER 2000-2010) PMID 24985911-- "Postmastectomy radiation therapy for T3N0: A SEER analysis." (Johnson ME, Cancer. 2014 Nov 15;120(22):3569-74)
 * Retrospective SEER analysis. 2525 patients in SEER database, T3N0 breast cancer. PMRT rate 2000-2010 42.1%. Median FU 56 months.
 * Outcome: CSS: PMRT 85% vs. no PMRT 82.4% (p<0.01). OS: 76.5% vs. 61.8% (p<0.01). PMRT associated with improved CSS and OS on MVA.
 * Conclusion: In a modern cohort of patients, PMRT was associated with significant improvements in both CSS and OS in patients with T3N0M0 breast cancers treated with modified radical mastectomy from 2000-2010.

 * British Columbia; 2011 PMID 20646860 -- "Outcomes of node-negative breast cancer 5 centimeters and larger treated with and without postmastectomy radiotherapy." (Goulart J, Int J Radiat Oncol Biol Phys. 2011 Jul 1;80(3):758-64.)
 * 10-yr LRR 2.3% (+PMRT) vs 8.9% (-PMRT). All pts not undergoing PMRT who had LRR had grade 3 and did not receive hormonal therapy. On multivariate analysis, PMRT did not significantly improve the LRR or BCSS rates.
 * Conclusion: Low LRR rate for node-negative breast cancer ≥ 5 cm. PMRT should be considered for grade 3 and for patients not undergoing hormonal therapy.

 * Harvard; 2009 PMID 19201501 -- "Post-mastectomy radiation in large node-negative breast tumors: Does size really matter?" (Floyd SR, Radiother Oncol. 2009 Apr;91(1):33-7. Epub 2009 Feb 7.)
 * Systematic literature review

 * SEER; 2008 (Colorado) (SEER 1988-2002) PMID 18543316 -- "Impact of postmastectomy radiotherapy in T3N0 invasive carcinoma of the breast: a Surveillance, Epidemiology, and End Results database analysis." (McCammon R, Cancer. 2008 Aug 15;113(4):683-9.)
 * Retrospective SEER analysis. 1865 patients in SEER database, T3N0 breast cancer. PMRT rate 1988-1997 22%, 1998-2002 41%.
 * Outcome: 10-year CSS PMRT 82% vs. no PMRT 80% (NS); no subgroup benefit. 10-year OS 71% vs. 58% (SS), confined to women >50 years
 * Conclusion: No improvement in cancer-specific survival with PMRT for T3N0 patients. Increased OS in absence of CSS likely reflects patient selection

 * SEER; 2008 (Yale) (SEER 1988-2003) PMID 18442108 -- "Postmastectomy radiation therapy for lymph node-negative, locally advanced breast cancer after modified radical mastectomy: analysis of the NCI Surveillance, Epidemiology, and End Results database." (Yu JB, Cancer. 2008 Jul 1;113(1):38-47.)
 * 1777 patients, T3N0 treated with MRM. 568 pts (32%) received PMRT. Median number of LNs examined: 14.
 * No improvement in OS with the delivery of PMRT in this group. Local control was not analyzed.
 * Conclusion: The use of PMRT for T3N0M0 breast carcinoma after MRM is not associated with an increase in overall survival.

Node positive (1-3 LN+)
see also: EBCTCG in section  .. for further details on PMRT in pts with 1-3+ LN.

PMRT alone vs PMRT + Chemo vs Chemo Alone

 * Scotland (1976-1982) -- PMRT alone vs PMRT + Chemo vs Chemo Alone
 * Randomized, 3 arms. 322 women, age ≤ 70, operable breast cancer, pN+. Arm 1) PMRT vs Arm 2) PMRT followed by CMF vs Arm 3) CMF alone
 * 2010 PMID 20673353 -- "Adjuvant radiotherapy and chemotherapy in breast cancer: 30 year follow-up of survival." (McArdle CS, BMC Cancer. 2010 Jul 30;10:398.) Median F/U 27 years (25-31 years)
 * Outcome: Deaths 81%, BCA deaths 63%. No difference in OS or CSS between the 3 arms (if RT+CMF baseline, HR for CSS for RT alone 1.24 (p=0.3) and HR for chemo alone 1.43 (p=0.08). CSS 10-years 41%, 20-years 34%, 30-years 33%.
 * Conclusion: No difference in long-terms survival between the different adjuvant regimens

Internal mammary involvement

 * Milan, 1983 (1965-80) - PMID 6639172 Full text — "Risk of internal mammary lymph node metastases and its relevance on prognosis of breast cancer patients." Veronesi U et al. Ann Surg. 1983 Dec;198(6):681-4.
 * 1085 pts. Treated with radical mastectomy plus internal mammary dissection.
 * IMN risk associated with younger age, larger size of primary tumor, and axillary node involvement. Worst prognosis for pts with both axillary and IM involvement.

Internal mammary surgery
Randomized trials:

 * Milan, 1999 (1964-1968) PMID 10658521 -- "The dissection of internal mammary nodes does not improve the survival of breast cancer patients. 30-year results of a randomised trial." (Veronesi U, Eur J Cancer. 1999 Sep;35(9):1320-5.)
 * Randomized. 737 patients with T1-3N0-1. Treated with 1) Halsted mastectomy vs. 2) extended mastectomy + IMN dissection. No RT or chemo. 30 year F/U
 * No difference in OS or DSS. 71% died from BCA
 * Conclusion: Removal of IM nodes does not improve survival. Prognostic value however is high

 * U. Chicago, 1989 (1973-82) - PMID 2642730 — "A controlled trial of extended radical versus radical mastectomy. Ten-year results." Meier P et al. Cancer. 1989 Jan 1;63(1):188-95.
 * 123 pts (including 112 treated by one surgeon) randomized to radical vs extended mastectomy.
 * For the pts treated by one surgeon, 10-yr OS was 60% (RM) vs 74% (EXT), p=0.13. For pts with central or medial tumors, 60% vs 86%, S.S. No benefit for lateral tumors.

 * International Cooperative Trial, 1976 (1963-68) - PMID 1247957, 1976 — "Radical mastectomy versus radical mastectomy plus internal mammary dissection. Five-year results of an international cooperative study." Lacour J et al. Cancer. 1976 Jan;37(1):206-14.
 * Randomized 1580 pts to radical mastectomy vs extended mastectomy (with IMN dissection).
 * No difference in OS for the overall group. Benefit for extended mastectomy for the subgroup of N+ with inner or medial quadrant tumors. Highly signficant for T1-T2 tumors within this subgroup.

Internal mammary irradiation

 * See also: Internal mammary irradiation after lumpectomy

Unknown benefit. Low risk of relapse in IM chain. Likely covered by tangent fields.

Randomized:
 * EORTC 22922/10925 (ongoing), 1996-ongoing
 * Purpose: to evaluate the effects of internal mammary node irradiation on loco-regional control and survival.
 * Randomized to treat the breast or chest wall only or to include the internal mammary lymph nodes and medial supraclavicular nodes (IM-MS).
 * Technique: Mixed beam. Fields: Recommended standard fields, but treatment centers may use their own variations. SCLV field: superior border - 3 cm above head of clavicle, lateral border - middle of clavicle, medial - 1 cm across midline. Block to shield larynx. IMN field: inferior border - lower border of 4th rib. Dose: 50 Gy in 25 fx (26 Gy delivered with photons, 24 Gy with electrons). Photons prescribed at 3 cm depth.
 * Irradiation techniques: PMID 11514005 — "A glance on quality assurance in EORTC study 22922 evaluating techniques for internal mammary and medial supraclavicular lymph node chain irradiation in breast cancer." Lievens Y et al. Radiother Oncol. 2001 Sep;60(3):257-65.
 * French 2013 (1991-97) - Post-mastectomy RT + SCF +/- IMN RT
 * See details at Internal mammary RT
 * There was a completed randomized trial for +/- IMN RT in the intact breast setting. See Internal mammary irradiation after lumpectomy.

Non-randomized:

 * Israel (1994-98)
 * Prospective, non-randomized. 100 pts, high-risk Stage II-IIIA. Treated on protocol with induction chemotherapy followed by high-dose chemotherapy with autologous stem-cell support and regional radiotherapy + tamoxifen. Surgery was mastectomy or lumpectomy. First 32 pts (1994-95) treated with RT including internal mammary nodes (with anterior electron beam). For the next 33 pts (1996-7), IMN irradiation was omitted but treatment was otherwise identical. Last 35 pts (1997-on) were treated similarly to the first group.
 * PMID 12860949 Full text, 2003 — "The role of irradiation of the internal mammary lymph nodes in high-risk stage II to IIIA breast cancer patients after high-dose chemotherapy: a prospective sequential nonrandomized study." Stemmer SM et al. J Clin Oncol. 2003 Jul 15;21(14):2713-8.
 * Median f/u 77 months. DFS 73% (IM) vs 52% (no IM), S.S. OS 78% vs 64%, p=0.08. No difference in locoregional recurrence.
 * Conclusion: improved DFS and OS for pts treated with IM RT. Caveat, non-randomized.

Indications for radiotherapy following neoadjuvant chemotherapy

 * Based on MD Anderson retrospective data (all patients treated with mastectomy + ALND)
 * If no PMRT was given: 5-year LRR is 23%, with 15% being isolated first failure. In patients with pCR, LRR is 19% . Predictive factors were clinical Stage IIIB+ or pathological LN+ >=4, or lack of tamoxifen use. Clinical T1-2 had LRR 4% vs. cT3-4 LRR 46% (SS). Clinical N0 had LRR 23% vs. N+ 27% (NS)
 * When neoadjuvant patients without PMRT were compared to mastectomy only patients without PMRT by pathologic stage, neoadjuvant patients had significantly higher risk of LRR. When compared by initial clinical stage, the LRR was comparable
 * PMRT was typically given for higher stage patients. Overall 10-LRR without PMRT was 22%, with PMRT (despite higher clinical stage) 11% (SS). Subsets of patients that gained significant benefit were clinical T3, clinical Stage III-IV, and pathological >=4 LN+
 * For patients who achieve pCR after neoadjuvant chemo, there is no benefit for PMRT in clinical Stage I-II, but dramatic benefit in clinical Stage III-IV for LRR (7% vs. 33%), DMFS, DSS, and OS with the addition of PMRT
 * Two two major Phase III US neoadjuvant chemo trials (NSABP B-18 and NSABP B-27) which enrolled patients with cT-3N1 patients (no fixed LNs) did not allow post-mastectomy RT
 * A large National Cancer Database Analysis demonstrated improved OS with PMRT for all women with positive lymph nodes at diagnosis (cN1) regardless of pathologic nodal response to neoadjuvant chemotherapy (PMID 26861597)
 * The 2016 NCCN guidelines recommend PMRT decisions based on the pre-chemotherapy staging and risk factors.
 * An ongoing randomized trial (NSABP B-51/RTOG 1304: NCT01872975) is evaluating PMRT and regional nodal RT for for women with cN1 disease who convert to ypN0 after neoadjuvant chemotherapy

Recurrence after neoadjuvant chemotherapy without PMRT
 * NSABP
 * 3088 pts. Combined analysis of NSABP B-18 and B-27. Neoadjuvant chemotherapy was either AC alone or AC + Taxane. Pts treated with mastectomy did not receive PMRT. Lumpectomy pts received adjuvant RT.
 * 2012: PMID 23032615 Full text -- "Predictors of Locoregional Recurrence After Neoadjuvant Chemotherapy: Results From Combined Analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27." (Mamounas EP, J Clin Oncol -- online before print, Oct 1, 2012.)
 * 335 LRR events after 10 yrs f/u. In mastectomy pts (treated w/o RT), 10-yr cumulative LRR 12.3%. In lumpectomy pts (+RT), LRR 10.3%.
 * Predictors of LRR. In lumpectomy pts -- age, clinical N-stage (before neoadj chemo), pathologic nodal status / breast tumor response. In mastectomy pts -- clinical tumor size (before neoadj chemo), clinical N-stage (before chemo), and pathologic nodal status / breast tumor response.
 * Defined groups at low, intermediate, and high risk of LRR after neoadjuvant chemotherapy.
 * Conclusion: "In patients treated with NC, age, clinical tumor characteristics before NC, and pathologic nodal status/breast tumor response after NC can be used to predict risk for LRR and to optimize the use of adjuvant radiotherapy."

 * MD Anderson (1974-98)
 * Retrospective review of multiple institutional prospective trials. 150 patients treated with mastectomy after neoadjuvant chemo who did not receive post-mastectomy RT. Inflammatory BCA excluded. cT3-T4 stage 59%, cLN+ 70%. Stage III or IV (SCLV involvement) 56%. Median number LN at surgery 15. Additional adjuvant chemo after surgery 92%.
 * 2002 PMID 11773149, 2002 — "Predictors of local-regional recurrence after neoadjuvant chemotherapy and mastectomy without radiation." (Buchholz TA, J Clin Oncol. 2002 Jan 1;20(1):17-23.). Median F/U 4.1 years
 * Outcome: 10% pCR, pN0 41%. Overall recurrence 47%; LRR 23% (15% isolated first failure) and DM 42%. OS at 5-yr 57% and 10-yr 40%.
 * 5-year LRR rates:
 * Clinical stage: cT-stage: cT1 0%, cT2 12%, cT3 25%, cT4 51%. cN-stage: cN0 23%, cN+ 27% (NS). However, higher LRR for advanced N-stage (N2-3 vs. N0-1).
 * Pathologic stage: pT-stage: ypT1 18%, ypT2 36%, ypT3-4 46%. pN-stage: (0 LN, 12%; 1-3, 18%; 4-9, 57%; >10 no 5-year survivors). pCR: 19% vs. pPR 28% (NS, but small numbers). Use of tamoxifen: 7% vs 36%.
 * Nodal status: cN0 and pN0 3%, cN+ and pN0 14%, cN0 and pN+ 63%, cN+ and pN+ 32% (wide confidence intervals)
 * 3 factors associated with LRR: 1) clinical stage IIIB+ (cT4 or cN3=SCV/IM LN+) (HR 4.5), 2) >=4 positive LN (HR 2.7), and 3) lack of tamoxifen use (HR 3.9). No clear relationship between disease response to chemo and LRR. LRR 46% for cT3-4 vs 4% for cT1-T2.
 * Conclusion: Both clinical (pre-neoadjuvant chemo) and pathologic factors impact risk for LRR
 * 2002 PMID 12095553, 2002 — "Pathologic tumor size and lymph node status predict for different rates of locoregional recurrence after mastectomy for breast cancer patients treated with neoadjuvant versus adjuvant chemotherapy." Buchholz TA et al. Int J Radiat Oncol Biol Phys. 2002 Jul 15;53(4):880-8.
 * Retrospective. 150 patients treated with neoadjuvant chemo + mastectomy (NEO) vs. 1031 treated with mastecomy + adjuvant chemo (ADJ). Neither group received PMRT. NEO group significantly higher clinical disease
 * Outcome: pathologic stage for NEO group significantly lower than for ADJ group. However, 5-year LRR NEO 27% vs. ADJ 15% (SS); true for all pathologic size, and for >= 4 LN+. If matched for clinical stage, no difference in LRR. Subset ypT2 and 1-3 LN+ worse outcome (32% vs. 8%)
 * Conclusion: RT should be offered for tumor >5 cm, clinical Stage IIIA, or >= 4 LN+ regardless of neoadjuvant/post-op chemo

Outcomes after neoadjuvant chemo with PMRT
 * Paris/Ruijin Hospital China; 2018 (2005 - 2012) PMID 29306555 -- "Outcome of postmastectomy radiotherapy after primary systemic treatment in patients with clinical T1-2N1 breast cancer." (Cao L, Cancer Radiother. 2018 Feb;22(1):38-44. doi: 10.1016/j.canrad.2017.07.051. Epub 2018 Jan 3.)
 * Retrospective. Two institutions. Clinical T1-2N1 breast cancer, status post neoadjuvant systemic therapy, and mastectomy, +/- regional nodal radiation. At surgery 53/88 patients had ypN0. Median F/U 5 years
 * Outcome. 5-year locoregional control PMRT(+) 97% vs PMRT(-) 78% (SS). If ypN0, locoregional control PMRT(+) 95% vs PMRT(-) 73%, DMFS 93% vs 75%, and DFS 93% vs 63%.
 * Conclusion: PMRT could significantly improve locoregional control, including in patients with good response to initial chemotherapy

 * National Cancer Database, 2016 (Rusthoven CG et al, Ann Oncol 2016) (PMID 26861597)
 * >15,000 women (2003-2011) with cN1 breast cancer receiving neoadjuvant chemotherapy, surgery, and varying RT approaches.
 * On propensity score-matched and multivariate analyses, PMRT associated with improved OS for cN1 patients regardless of pathological nodal status, including ypN0, ypN1, and ypN2-3.
 * Post-chemotherapy pathologic nodal status was not predictive of the relative survival benefit obtained from PMRT.

 * MD Anderson
 * Overall; 2004 (1974-2000) PMID 15570071 — "Postmastectomy radiation improves local-regional control and survival for selected patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and mastectomy." (Huang EH et al. J Clin Oncol. 2004 Dec 1;22(23):4691-9.)
 * Retrospective. 542 patients treated on 6 prospective trials with neoadjuvant chemo, mastectomy, and PMRT compared to 134 patients on same trials treated without PMRT. Adjuvant chemo 95%. Median number of LN recovered 15. PMRT patients significantly higher clinical stage. RT CW+lymphatics 50 Gy + 10 Gy CW boost. Median F/U 5.7 years
 * Outcome: 10-year LRR PMRT 11% vs. no PMRT 22% (SS); rate of isolated LRR 8% vs. 20% (SS)
 * Clinical stage LRR: I-IIA no benefit for PMRT. Stage IIB+ PMRT 11% vs. no PMRT 26% (SS), cT3-T4 8% vs. 22% (SS), cN2-3 12% vs. 40%.
 * Pathologic stage LRR: ypT2+ PMRT 14% vs. no PMRT 59% (SS). Stage II with 1-3 LN+ no benefit for PMRT (but small n). pN0 4% vs. 11% (SS), >=4 LN+ 16% vs. 59% (SS)
 * Survival benefit: CSS cStage IIIB+ PMRT 44% vs. no PMRT 22% (SS), cT4 45% vs. 24% (SS), cN2-3 49% vs. 27% (SS), >=4 LN+ 44% vs. 18%
 * Predictors for LRR: no PMRT, >20% LN+, no tamoxifen, cStage IIIB+, no response to neoadjuvant chemo
 * Conclusion: PMRT should be considered for clinical T3, clinical Stage III-IV and patients with >=4 LN+ at surgery, regardless of response to chemotherapy
 * Recurrences; 2005 PMID 15890574 -- "Predictors of locoregional recurrence in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy, mastectomy, and radiotherapy." (Huang EH, Int J Radiat Oncol Biol Phys. 2005 Jun 1;62(2):351-7.)
 * Retrospective. 542 patients (same as Huang, 2004). Median F/U 5.8 years
 * Outcome: LRR 5-years 9%, 10-years 11%.
 * Univariate predictors: Clinical: cStage IV (21%), cT4 (14%), pT3+ (23-47%), clinical response to neoadjuvant, and hormonal therapy. Pathological: multifocal/multicentric disease (13-30%), skin/nipple involvement (19%), LVI+ (15%), <10 LN sampled (19%), positive >=4 LN+ (16%), ER-
 * Multivariate predictors: skin/nipple involvement (19%), SCV LN+ (21%), ECE+ (15%), ER- and no hormonal treatment. 10-year LRR 0-1 factors 4%, 2 factors 8%, 3+ factors 28%
 * Conclusion: Predictors for recurrence after neoadjuvant chemo, mastectomy, and PMRT identified.
 * pCR; 2007 (1982-2002) PMID 17418973 -- "Postmastectomy radiation improves the outcome of patients with locally advanced breast cancer who achieve a pathologic complete response to neoadjuvant chemotherapy." (McGuire SE, Int J Radiat Oncol Biol Phys. 2007 Jul 15;68(4):1004-9. Epub 2007 Apr 6.)
 * Retrospective. 106 patients, no inflammatory BCA, neoadjuvant chemotherapy and pCR at surgery. Clinical Stage I 2%, II 31%, IIIA 30%, IIIB 25%, IIIC 11%. Antracycline in 92%, taxane in 38%. PMRT in 72, no PMRT in 34. Median F/U of survivors 5 years
 * Outcome: 10-year LRR Stage I-II 0% regardless of PMRT. Stage III PMRT 7% vs. no PMRT 33% (SS). 10-year DMFS 88% vs. 41% (SS), DSS 87% vs. 40% (SS), OS 77% vs. 33% (SS)
 * Conclusion: PMRT improves significantly LRR and OS for patients with clinical Stage III and achieve pCR

 * GEPAR Analysis
 * DOI: 10.1200/jco.2015.33.15_suppl.1008 Journal of Clinical Oncology 33, no. 15_suppl (May 20, 2015) 1008-1008.
 * Post hoc analysis of 3 prospective German trials. 3481 patients treated with neoadjuvant chemotherapy 209 patients did not receive adjuvant radiation (extent of RT not indicated). Median FUP 56 months.
 * 5 yr LRFS 90% with RT, 82% without (p < 0.001)
 * 5 yr DFS 75% with RT, 67% without (p < 0.001)
 * With cN+ prior to chemotherapy 5 yr LRFS and DFS improved with PMRT (HR 2.32, 95% CI 1.54-3.50; p < 0.001; HR 1.97, 95% CI 1.48-2.62; p < 0.001)
 * Patients with pCR
 * 5-yr LRFS was 95.7%% with RT vs 86.6% without RT (HR 3.32, 95% CI 1.00-11.08; p = 0.051)
 * 5-yr DFS was 86.9% and 56.1% (HR 3.52, 95% CI 1.82-6.83; p < 0.001)
 * Patients without pCR
 * 5-yr LRFS was 88.6% with RT vs 80.7% without RT (HR 1.86, 95% CI 1.29-2.67; p < 0.001)
 * 5-yr DFS was 72.6% vs 65.7%; HR 1.39, 95% CI 1.07-1.81; p = 0.014)

T3 N0 subset:
 * MD Anderson
 * 2011 PMID 21885207 -- "Local-regional recurrence with and without radiation therapy after neoadjuvant chemotherapy and mastectomy for clinically staged T3N0 breast cancer." (Nagar H, Int J Radiat Oncol Biol Phys. 2011 Nov 1;81(3):782-7.)
 * 162 pts clinical T3N0 treated with neoadj chemo and mastectomy. 119 pts received PMRT and 43 did not.
 * 5-yr LRR 4% (+PMRT) vs 24% (-PMRT). For -PMRT pts: pN+ predicted LRR (53% LRR for N+ vs 14% for N0).
 * Conclusion: "Breast cancer patients with clinical T3N0 disease treated with NAC and mastectomy but without PMRT had a significant risk of LRR, even when there was no pathologic evidence of LN involvement present after NAC. PMRT was effective in reducing the LRR rate. We suggest PMRT should be considered for patients with clinical T3N0 disease."

Meta-analysis

 * Early Breast Cancer Trialists' Collaborative Group (EBCTCG) (1964-86)
 * 2014 PMID 24656685 -- "Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials." (EBCTCG, Lancet. 2014 Mar 19. [Epub ahead of print])
 * 8135 pts; 22 trials of +/- RT to chest wall and regional lymph ndoes.
 * For pN0(n=700), RT had no effect on LRR, overall recurrence, or BCSM.
 * For pN+(any), OS difference 5% at 10-years in favor of RT.
 * For pN+(1-3 nodes)(n=1314), RT reduced LRR (3.8% vs 20.3%), overall recurrence (34.2% vs 45.7%, RR 0.68), and BCSM (42.3% vs 50.2%, RR 0.80).
 * For pN+(1 LN)(n=318), RT reduced LRR (2.3% vs 17.8%), overall recurrence (24.1% vs 36.4%, RR 0.60), and BCSM (31.7% vs 38.2%, RR 0.79).
 * For pN+(4+ nodes)(n=1772), RT reduced LRR (13.0% vs 32.1%), overall recurrence (66.3% vs 75.1%, RR 0.79), and BCSM (70.7% vs 80.0%, RR 0.87).
 * Conclusion: "After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given. For today's women, who in many countries are at lower risk of recurrence, absolute gains might be smaller but proportional gains might be larger because of more effective radiotherapy."

 * Whelan (Ontario), 2000 - PMID 10715291 — "Does locoregional radiation therapy improve survival in breast cancer? A meta-analysis." Whelan et al. J Clin Oncol. 2000 Mar;18(6):1220-9.
 * Meta-analysis. 18 trials, 6,367 pts. 1967-1999. Most were N+ treated with mastectomy. Radiation reduced any recurrence, LR, and mortality (17% reduction).

 * Cuzick et al. (United Kingdom)
 * First report (1987): PMID 2856861 — "Overview of randomized trials of postoperative adjuvant radiotherapy in breast cancer." Cuzick J et al. Cancer Treat Rep. 1987 Jan;71(1):15-29.
 * Meta-analysis. 7941 pts. Randomized to RT vs no RT after simple or radical mastectomy.
 * No difference in survival before 10 years. After 10 years, there was an increase in the number of deaths in pts who received RT.
 * Update (1994): PMID 8120544 — "Cause-specific mortality in long-term survivors of breast cancer who participated in trials of radiotherapy." Cuzick J et al. J Clin Oncol. 1994 Mar;12(3):447-53.
 * Trials started before 1975.
 * Previous increase in mortality after 10 years is no longer significant. Benefit in overall survival associated with RT. Excess of cardiac deaths with RT offset by reduced deaths due to breast cancer.
 * Radical mastectomy vs simple mastectomy + RT (1987): PMID 3539330 — "Overview of randomized trials comparing radical mastectomy without radiotherapy against simple mastectomy with radiotherapy in breast cancer." Cuzick J et al. Cancer Treat Rep. 1987 Jan;71(1):7-14.
 * No difference in survival, but a trend for pts who received RT to do worse after 15 yrs.

Hypofractionation

 * Rangsit University, Thailand; 2011 (2004-2006) PMID 21717886 -- "A retrospective study comparing hypofractionated radiotherapy and conventional radiotherapy in postmastectomy breast cancer." (Pinitpatcharalert A, J Med Assoc Thai. 2011 Mar;94 Suppl 2:S94-102.)
 * Retrospective. 215 patients, 31% treated with conventional RT (1.8-2.0 Gy in 25 fxs) and 69% with hypofractionated RT (2.65 Gy in 16-18 fxs). Median F/U 3.2 years
 * Outcome: 5-year LRC CRT 87% vs HFRT 86% (NS), 5-year OS 63% vs 70% (SS)
 * Toxicity: No difference in CW appearance, skin fibrosis, braxial plexopathy, arm edema, pulmonary fibrosis, rib fractures or carciovascular events
 * Conclusion: Hypofractionated radiation as effective as conventional in postmastectomy breast cancer

 * INMOL, Pakistan -- PMRT 27/5 vs 35/10 vs 40/15
 * Randomized. 300 patients, BCA Stage T2-4N+. Arm 1) 27/5 in one week vs Arm 2) 35/10 in 2 weeks vs Arm 3) 40/15 in 3 weeks. Delivered using Co-60 with 4 fields
 * 2009 PMID 19438129 -- "Post mastectomy adjuvant radiotherapy in breast cancer: a comparision of three hypofractionated protocols." (Shahid A, J Pak Med Assoc. 2009 May;59(5):282-7.)
 * Outcome: LRR 27/5 was 11%, 35/10 was 12%, and 40/15 was 10% (NS); OS 83% vs 82% vs 80% (NS).
 * Toxicity: Grade 3-5 skin 37% vs. 28% vs. 14% (SS); cardiac toxicity 5% vs 6% vs 5%; pulmonary toxicity 4% vs 5% vs 5% (NS). No rib fractions
 * Conclusion: All 3 protocols equally effective, with similar toxicity, and were helpful in reducing work load

 * Beijing, 2003 (1987-1993) PMID 12839697 -- "[Post-mastectomy radiotherapy with different fractionated dose schemes in early breast cancer] - [Article in Chinese]" (Wu JX, Zhonghua Zhong Liu Za Zhi. 2003 May;25(3):285-8.)
 * Retrospective. 367 patients with early BCA, treated with 50/25/5 weeks (149 patients) vs. 45/15/5 weeks (177 patients) vs. 23/4/3 weeks (41 patients). 257 chemotherapy
 * 5-year DFS: 91% vs. 86% vs. 85% (NS)
 * 5-year LR: 2.7% vs. 2.8% vs. 2.4% (NS)

 * St. Thomas Hospital (UK)
 * Randomized. 411 patients s/p mastectomy. Treated with BIW (12 fx in 28 days) vs. TIW (6 fx in 18 days) regimens. Max dose 36 Gy. CW treated with 70kV RT, axilla with Co-60
 * 1975 5 year results. PMID 1201630 -- "A prospective clinical trial of post-operative radiotherapy delivered in three fractions per week versus two fractions per week in breast carcinoma." (Bates TD, Clin Radiol. 1975 Jul;26(3):297-304.)
 * 5-year outcomes: early and late radiation effects comparable and acceptable
 * 1988 10 year results. PMID 3044476 -- "The 10-year results of a prospective trial of post-operative radiotherapy delivered in 3 fractions per week versus 2 fractions per week in breast carcinoma. (Bates TD, Br J Radiol. 1988 Jul;61(727):625-30.)
 * 10-year outcomes: 6 fx technique better than 12 fx technique (equally effective, fewer late sequelae)

DCIS
See Radiation_Oncology/Breast/DCIS

Breast Reconstruction
See also: for RT combined with breast reconstruction, see Irradiation after breast reconstruction

 * Memorial Sloan Kettering; 2008 PMID 18843123 -- "Breast reconstruction after surgery for breast cancer." (Cordeiro PG, N Engl J Med. 2008 Oct 9;359(15):1590-601.)
 * Review

Reviews

 * European Perspective; 2009 PMID 19164209 -- "Postmastectomy Radiotherapy: Will the Selective Use of Post Mastectomy Radiotherapy Study End the Debate?" (Russells NS, J Clin Oncol. 2009 Jan 21. [Epub ahead of print])

 * Duke; 2008 PMID 18445836 -- "One to three versus four or more positive nodes and postmastectomy radiotherapy: time to end the debate." (Marks LB, J Clin Oncol. 2008 May 1;26(13):2075-7.)

 * MD Anderson; 2002 PMID 12490741, 2002 — "Controversies regarding the use of radiation after mastectomy in breast cancer." Buchholz TA et al. Oncologist. 2002;7(6):539-46.

Local recurrence after mastectomy

 * MD Anderson/British Columbia; 2010 PMID 20306128 -- "Among women who experience a recurrence after postmastectomy radiation therapy irradiation is not associated with more aggressive local recurrence or reduced survival." (Woodward WA, Breast Cancer Res Treat. 2010 Mar 20. [Epub ahead of print])
 * Retrospective. 229 LRR/1500 MDACC patients and 66 LRR/318 BCCA patients. Evaluated outcomes depending on whether PMRT was given or not
 * Outcome: If LRR, 10-year OS PMRT- 34% vs PMRT+ 19% (SS); however, PMRT+ patients developed more mets prior to LRR (34% vs 63%), and had higher TN stages. However, if isolated LRR, no difference in DM and OS
 * Conclusion: Irradiation does not promote biologically aggressive local recurrence


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User:Brianjd

See my pages on Meta-Wiki and the English Wikipedia. In particular, see the legal information (including Wikipedia:User:Brianjd) on the English Wikipedia page.

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

title: User:Brianjd


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oz.

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User talk:60.26.34.33

Please do not add commercial links to Wikibooks. Wikibooks is not a vehicle for advertising or a mere collection of external links. See the welcome page if you would like to learn more about contributing to our project. Thanks.

title: User talk:60.26.34.33


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Radiation Oncology/Ovary

Ovarian Tumors

 * Official Guidelines
 * Staging
 * Overview
 * /Benign Ovarian Masses/
 * Epithelial Ovarian Cancer
 * Sex cord-stromal tumors
 * Granulosa Cell Tumor

title: Radiation Oncology/Ovary


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User talk:64.229.168.41

Come introduce yourself at the new users page. If you have any questions, you can ask there or contact me personally.
 * —Brim 11:39, 26 Feb 2005 (UTC)

title: User talk:64.229.168.41


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SPM/fonts

SPM-FONT-FIXES
Some users may experience problems with fonts being too small. This entry is a compilation of suggested fixes.

Note: Some of these these fixes may work on some platforms and not others. You may have to combine several fixes.

Fix #1 This fix has worked on some Windows machines, but does not resolve all problems.

if nargin<2, FS=1:36; else FS=varargin{2}; end with: if nargin<2, FS=2:36; else FS=varargin{2}; end
 * 1) Open spm.m
 * 2) *This file is generally located under ~/spm8/spm.m on *NIX systems, and under C:\spm\spm8\spm.m on Windows
 * 3) On or around line 631 replace:

Fix #2 sf = offset + 0.85*(min(spm('WinScale'))-1); with: sf = offset - 0.85*(min(spm('WinScale'))-1); Combining Fix #1 and Fix #2 may resolve the problem in some situations.
 * 1) Open spm.m
 * 2) *This file is generally located under ~/spm8/spm.m on *NIX systems, and under C:\spm\spm8\spm.m on Windows
 * 3) On or around line 636 replace:

Mac specific fix If you are using a Mac open up the spm.m file as indicated above, scroll to line 664 and replace offset    = 1; with: offset    = 1.4; and this will solve all your font issues.

Other suggestions for font and display issues have included turning on the Graphics window resize property and viewing the output after printing to a ps file.

title: SPM/fonts


text:
Systems Theory/Systems Learning

Systems Learning
Systems Learning is a complex concept that involves understanding and gathering information about systems that entail small organizations all the way up to global entities. Systems learning can be placed beside the term organizational learning and has been more evident in recent knowledge management research. This subject encompasses a variety of disciplines such as mathematics, physics, engineering, as well as, sociology and economics. Most research has experimented with organizational learning only on one specific discipline and has not taken it to the next level by using it with other known models. This curriculum diversification has hindered an accurate definition of organizational learning. Several meanings exist which some stand out in the research than others. One definition expressed by popular researchers is “it is undertaken by members of an organization to achieve organizational purposes, takes place in teams or small groups, is distributed widely throughout the organization, and embeds its outcomes in the organization’s system, structures and culture (Snyder and Cummings, 1998). Since there is no hard evidence of what really goes on in an organization, it is difficult to state whether organizational learning is a reality for the organization. The traditional view of learning in an organization involves informal processes. Today, organizational learning is more structured, as employees are expected to direct and inform in a way that is highly correlated to work performance. Argyris and Shcon are the two pioneers of organizational learning who brought forth the sociocultural approach and described it as “the growth of a culture of open communication, in which members of an organization collaborate in ‘organizational enquiries’ to discover better ways of achieving the organizations purpose”(Borham and Morgan, 2004).

Systems Dynamics
Systems dynamics suggest that learning is a process that can be acquired through making choices and learning from them. By learning from your mistakes an individual can grow and become more able to adapt to certain circumstances. Since systems dynamics experiment with models that can only imitate reality, it is hard to create an experimental environment to enable a successful learning atmosphere. Some say that there is an underlined political dynamics influence that cannot be ignored by organizational learning. The works of Crossan, Lane and White (1999) developed a model of organizational learning, which involves a four-step process. The 4I process starts with individual learning and then graduates to group learning which ends up with organizational learning. Crossan’s four processes included in this model are intuiting, interpreting, integrating, and institutionalizing. Intuiting by Crossan is defined as, “the preconscious recognition of the pattern and/or possibilities inherent in a personal stream of experience” (1999:525). Intuiting starts with the individual where they learn from their experiences and then use these experiences for future mental models. Interpreting is explained by Crossan as, “the explaining of, through words and/or actions, of an insight or idea to one’s self and to others” (Crossan 1999:525). Interpreting allows one to map out ideas to use in external domains. Group level starts at the interpreting process and is explained as, “the process of developing shared understanding among individuals and of taking coordinated action through mutual adjustment” (Crossan 1999:525). The victory of collective behavior and action is the group feel of interpretation. Institutionalizing is described by Crossan as, “systems, structures, procedures and strategies” (Crossan 1999:525) that is the core piece of organizational learning. A learning loop begins to form with the involvement of these four processes and take hold of the organizational learning entity. The transformation into the institutional element of organizational learning has a definite political component as individuals deal with power in an organization and how ideas are reflected through this underlying element.

title: Systems Theory/Systems Learning


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Talk:Macroeconomics/Macroeconomic Equilibrium

not so sure about 'boom' but a recession is defined in which there is 2 consecutive periods of negative growth the economy. Therefore, it cannot be in a position of macroeconomic equilibrium! Correct the flaw in my reasoning please! Mark Lewis 19:14, 26 Feb 2005 (UTC)


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Cookbook:Cuisine of Finland

| European cuisines

Finnish cuisine is generally healthy, thanks in part to wholemeal products (rye, barley, oats) and berries (such as blueberries, lingonberries, cloudberries, and sea buckthorn). Traditionally families gather berries from forests in the autumn. Various turnips were common in older cooking, but these were largely supplanted by the potato when it was introduced in the 18th century.

The Finnish cuisine combines traditional country fare and upper-class cuisine with modern continental style cooking. Spices have been adopted from West and East. Finnish cuisine is pleasing to the eye and the taste buds and has something special for every month of the year.

Fish and meat play a prominent role in any traditional Finnish dish, vegetarianism being historically non-existent.

In the new Finnish kitchen, dishes are lighter, smaller and generally contains several different vegetables. This mode of cooking is highly influenced by European and American cuisine.

Introduction from Wikipedia.

Finnish dishes

 * Baltic herring – silakka
 * Joulupöytä – Christmas board
 * Erikoiskeksit – Special Cookies
 * Kaalikääryleet – cabbage rolls
 * Kalakukko
 * Karjalanpaisti – Karelian stew
 * Karjalanpiirakat – Karelian pastries
 * Mashed potato - perunamuusi
 * Meatballs (possibly originally from Swedish meatballs) - lihapullat
 * Mustamakkara – blood sausage
 * Pea soup - hernekeitto
 * Pepu
 * Pottilohko
 * Reindeer stew - poronkäristys
 * Rusupiirakka
 * Salmon – lohi
 * Särä

Bread

 * Ruisleipä – Rye bread
 * Maitorieska – milk azyme

Drinks

 * Glögi – mulled wine
 * Mead – a fermented honey drink
 * Sima – a fermented lemon drink (either with sugar or honey)
 * Sahti – traditional beer
 * Kilju – a beverage whose ingredients in its traditional form consists solely of water, sugar and yeast

Desserts

 * Mämmi
 * Golden cloudberry dessert
 * Tippaleipä – variant of funnel cake eaten during the 1st of May celebrations
 * Vappumunkki – sugar covered donut eaten during the 1st of May celebrations

title: Cookbook:Cuisine of Finland


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Talk:Blender 3D: Noob to Pro/3D View Windows

First topic
With all respect to the contributors to this book, the manual mainained at blender.org was a real relief after reading the confusing stuff and blog-like notes in this chapter.

on Placing the 3d cursor: The exercise at the end:  after putting the cursor inside the camera, I can't get it back in the cube. Every time I click within the cube, it de/selects it. How to manipulate only the cursor and not select the cube?

Once a long time ago in a galaxy far far away, mouse pointers has three buttons. What do you do if you have no MMB?

 * Your input is valid and adding more information for users of two button mice is definately in the works. However, instead of providing feedback like this, please just add whatever you think needs to be added.  That's the whole point of a wikibook!  --Spiderworm 22:08, 12 Mar 2005 (UTC)

Some people have "scroll" wheels rather than than MMBs. Maybe some instructions for us as well? I've added the stuff for pan-up/pan-down- user:Borisblue

Rotating
It would have saved me a bit of googling if it was pointed out the SHIFT-F to enter "Camera Fly Mode" only works in "Object Mode"... in "Edit Mode" it appears to do nothing... Thanks!

Placing 3D cursor

 * With all due respect to all contributors to this great work. Is it possible to remove all the 'Another reader' and 'Yet another reader' notes? The original author was only trying to illustrate a point (although it was more about different respective editing plan than 3d cursor). All these readers' notes are only making it more confusing and out of focus (and making me tired from reading them...) -- Webber 15:48, 08 Mar 2007 (EST)

 * I've put the added notes in a nice little box off to the right, so they are clearly not part of the body text --68.6.52.59 04:28, 9 May 2007 (UTC)

 * I think this is the right move, until the exercise has been reworded or clarified. For me the challenge was remembering to deselct the cube first before trying to place the 3D cursor back into the cube. The most effective method IMO was to use AKEY to deselect everything. However this presupposes knowledge of selecting and deselecting, which has not yet been covered if you read the tutorial in sequence (I believe). I would recommend partially re-sequencing to have a short tutorial on selecting and deselecting. Does it make sense to talk about selecting first? Garmon Sutrix 15:27, 15 May 2007 (UTC)

 * About having people press the "a" key to solve their dilemma, we haven't gotten to selecting and deselecting yet. I agree with the above person, and I believe we need to try to keep everything as organized as possible (especially near the beginning), and that includes separating the tutorial of selecting with the tutorial of using the cursor. The same goes for telling people to turn off the 3D transform manipulator. It should not only be saved for another time, but will only cause more confusion later on when they don't turn it back on. Instead of reorganizing the whole thing and muddling things up, I'm going to change the instructions to, on the 3D view header, go to Object > Snap > Cursor to selection. We've covered the header and navigating menus, and it fits neatly in the section. We don't need that junk that gets in the way of instructing them to do it and explaining its difficulty.

Buy one
They are pretty cheap. There are modifier keys, such as shift, alt, and ctrl, also try reading the blender help for information on which do what.

shift+scroll on ibook with scroll wheel mouse.
the whole SHIFT+Scroll to pan up and down does not seem to work on my ibook with a logitec mouse with a scroll button that seems to work dandy. any ideas? thanks. CTRL-scroll to pan left and right works great though.

3D cursor
Anyone know how to set 3D cursor in XYZ (0, 0, 0)? I mean not with mouse clicking, but by numerical way or some shortcut. --Popski 11:25, 12 Jun 2005 (UTC)

 * I found it. SHIFT-CKEY
 * YAY!!

Rotation MMB / Rotation around what point?
It's not clear how to get some control over what point you are orbiting when you use the MMB. When I'm building, I would like to have the mmb function orbit the object but i have no idea how.
 * Agree to this 85.177.158.59 (talk) 14:04, 14 January 2009 (UTC)

 * This is done with the use of NUM. which will adjust the view rotation centre to the selected object, while remaining in global view (ie. all other objects remain visible.) 16:02, 28 November 2009 (UTC)

"The object the viewport orbits around (the object you see) can be changed to a new object by first selecting it with the RMB and then pressing NUM/" This is too advanced for the tutorial. I have just one object a box and i have no motivation to move the camera yet.
 * Yes, this is a cool hint, the mode is called LOCAL VIEW. But then, all other objects are hidden. Thats not what i need, but it's a step towards it. I might be simple minded, but when i model, i need to orbit (pan&zoom without roll) around selected parts AND see all neighbourhood.85.177.149.254 (talk) 13:57, 15 January 2009 (UTC)
 * OK, found it. For this, in the Buttons Window "View Rotation" the modes "Turntable" and "Around Selection" have to be switched on, e.g. "be darkened". I prefer this very easy mode for simple and fast checks on correct modeling. 85.177.149.254 (talk) 14:25, 15 January 2009 (UTC)

"In Blender there is a big difference between the number keys on your numberpad (numpad) and the number keys along the top of the keyboard. For example, NUM7 refers to the number 7 on the numberpad, while 7KEY refers to the number 7 that's above the YKEY and UKEY on the standard US keyboard." This has already been explained and it's not Rotation specific.

IMHO, this point should be flattened, too. There are many things that don't have to do with rotation at all, eg. Numpad 1,3,7 where this should be explained separatedly and earlier.85.177.158.59 (talk) 14:04, 14 January 2009 (UTC)

num-period
It's not really completely clear which key is meant with NUM-period. Firstly, the use of the hyphen is inconsistent (NUM1 to NUM9 don't have a hyphen) and secondly, other keyboards don't have a period there but a comma or perhaps something else.

Indeed, I was on my way in to mention that NUM and NUM were mentioned twice, thinking the period and comma were simple punctuation. DavidJaquay 23:21, 8 May 2006 (UTC)

Camera navigation.
Hope I'm not missing something obvious, but it seems to be a mystery how one can navigate in the camera view; i.e. pan, dolly, etc by moving the camera itself. Using controls described in the article of course just take one to a new viewpoint (user) without altering the postion or orientation of the camera.

I'm having the same problem --Wladston 13:41, 15 January 2006 (UTC)

to pan the camera you can just select it (by rightclicking the black border) while your in camera view (numpad 0) and push g to move it. you can also tilt it with r but I don't know about rotating it up and down or side to side.

 * Camera Navigation is outside of the scope of this section. I'm glad you got assistance, but the order in which you learn these things is intended to assist you in learning new items. A strong point needs to be made that this section is focusing on the user view, and not the camera's view.  I'm a noob here, but I trust that's being left to a later section. --Deadguy (talk) 20:29, 24 August 2009 (UTC)

Selecting all layers
My backtick key doesn't seem to do anything - selecting all layers **appears** to be my single-quote key, 'KEY. I'm hesitant to edit the page because it explicitly says that it's /not/ the single-quote key.. but that's what's working for me. I'm using a UK keyboard; the single-quote button shares the key with @, and is to the left of # (and ~) which is to the right of Return. Should the page be fixed, or is my install behaving weirdly?

On German Keyboard the "toogle all visible" key is ö (o with umlaut) on version 2.49b-win64 of blender.

Re: Selecting all layers
My backtick key does select all layers (US keyboard). Perhaps it is just the mapping on your UK keyboard.

Panning the View
"To pan is to move the camera" To my understanding, panning does not move *the* camera. It just changes your view in the 3D View.

The segment that states: "You also have choice of keyboard alternatives:

CTRL+NUM8                      Up CTRL+NUM4           CTRL+NUM6       Left      Right CTRL+NUM2                     Down

Panning is an important skill to master; try it now."

The Up Left Right Down part is not clear if i should be in the Numpad or in the arrows left of it.

Readers' Comments
The insertion of readers' comments in line with the main text makes things confusing. Comments need to be made slightly separate from the main text. One possible way might be to indent all comments.

Reply: There's no need for comments in the text. Comments are to be in the discussion page, I think. Sevcsik 18:11, 20 March 2007 (UTC)

Removed discussions
I removed a discussion from the "Adding and Deleting Objects" part:

(Huh? I needed Edit Mode for this - You must not have selected it at first, you really do need object mode.) (They both work...ObjectMode for the object...EditMode for various parts, including All...Ver. 2.42a. And BTW the version reference should, IMHO, be at the top of ALL tutorials, at the top of each Section, and referenced by responders to avoid miss communicatin(s)...)

I think they belong here. Sevcsik 17:31, 20 March 2007 (UTC)

Adding or Deleting Objects

 * In light of the discussion around the 3D Cursor Tutorial, perhaps this section can be moved just above that tutorial, and expanded a little to include a discussion about AKEY to deselect all / select all.
 * In this section it tells the reader to "make sure the 3D cursor is inside the cube" before pressing Del. Why is this? Should this be explained? I tried without the 3D cursor inside the cube and it still deleted just fine.
 * Also, it appears that this is the first time the contextual SPACE menu is mentioned, rather cavalierly. Shall we make it simpler by just having the user choose from the Add menu for now? And introduce the SPACE menu and the gestural interface a little later on? Garmon Sutrix 15:40, 15 May 2007 (UTC)

Placing the 3D cursor section could use more snapshots
Just finished this chapter and even though this is a great book so far I'd recommend having a few more photos in this section to give an example of what the user is supposed to do. 71.228.155.181 23:33, 20 October 2007 (UTC)

Reformated the page
I've edited this page and restructured some content. This should allow for a better adhesion to the 80/20 rule. Please redirect the following protip elsewhere:

Pro Tip
EvanCarroll 01:21, 28 October 2007 (UTC)
 * If you can, find a mouse with side buttons. Anything like Microsoft's Intellimouse, or Logitech's Mediaplay, that have back/forth buttons, will do. Map those buttons to the MMB. This makes camera control feel a LOT more intuitive (plus it frees up a finger).

All [NOTE: ... ] need to be worked into prose, or removed. Or, made into Footnotes They are an eyesore and prevent fast-scanning of the material. I would take a gander this material could be presented in a fashion which would cut learning time down by 70% by reworking the assumed policies of this book. EvanCarroll 01:36, 28 October 2007 (UTC)

Object vs. Edit View
One of the hints that was provided is that the status bar in the top right corner has text that says Ob:... or Ed:... depending on the mode. While this is correct, it may be worth pointing out that Ed stands for Edges, not edit. 124.171.128.48 (talk) 10:18, 9 January 2008 (UTC)

"A status bar at the top-right of the user preferences window will indicate the current mode by displaying 'Ob' or 'Ed' depending on the currently toggled mode." This should rather be mentioned as an optional way of checking it - the Object Mode/Edit Mode can be plainly read from the 3d window border, which is now given as a "secondary" way of checking your mode. It took me several minutes to just find the Ob/Ed in the top right corner status bar (Yes, the STATUS BAR is in the top-right corner, no, Ob/Ed-text is not.)

Object Orientation
''Why not add a monkey? Choose Add > Mesh > Monkey. [If you prefer the monkey to be facing frontwards, make sure to be in FRONT view (NUM1) before adding the mesh - note: in Blender 2.48a, it's complicated. If Blender is in Object Mode, the monkey is always facing up. If it's in edit mode then the direction the monkey faces depends on the view (top, side or front)]''

I don't know if it's appropriate to mention changing preferences this early in the book (I doubt it)... but you can change that behaviour in 2.48a with Preferences / Edit Methods / Aligned to View. 210.56.81.102 (talk) 13:31, 24 May 2009 (UTC)

Uncertainty about state of the "3D Transform Manipulator"
Thanks very much for this documentation! The line "2. Disable the "Use 3D transform manipulator" option by using the icon located on the 3D viewport's window header (shaped like a pointing hand). Or, hit CTRL+SPACE to toggle." doesn't help me understand which state is enabled or disabled. In both states, the mouseover text for the hand is the same: "Use 3d transform manipulator (Ctrl Space)". I guess the enabled mode is when the red triangle, green circle and blue square appears. Newbies have never heard of this thang, so it might be helpful to tell them how to tell whether it is enabled or not. Robin Whittle

I think it's pretty obvious when the manipulator is on. It's kinda hard to miss large, colored arrows. --JamesNZ (discuss • contribs) 05:55, 27 July 2011 (UTC)

laptop function (virtual) numpad
As I read in the tutorial that the viewport movement would only be done through numpad (numeric pad), I started to shop for a wireless numpad for my laptop but I found out that there was already a virtual one on it and it works in blender where it says only a numpad would do : using the function key, there a slanted rectangles of the keyboard starting on the number row on its right-side, all the numbers are placed the same (slanted) so it's pretty intuitive.

I'm thinking of getting something that could make a border on those keys that's not distractive when I'm typing text and is temporary, perhaps vinyl ...

Minor point about creating new objects
I'm a Noob ... and am wondering if I'm missing something. I'm using Blender 2.49b and when I create a new object the display remains in Object Mode. The tutorial (and another book I'm reading) say "A new object will be added, and you will be in what's known as Edit Mode". Has there been a change in this version? Also my book says there should be a "Pose Mode" available but I only see "Sculpt Mode". Was there a change in this description? Great Tutorial by the way!

Information overload
Despite this section being basics, the exact use of it is questionable. Since the user (most likely newb/noob) hasn't done any actual editing of objects (that's what it seems like this guide assumes.), they won't know the real use for the hotkeys, perspectives etc. Its pretty hard to memorize everything here. Doing actual modeling like in 'quickie model' makes remembering this stuff wayyyyyy easier. It might be worth moving this section so it's after the quickie model.

The stuff here are basics, I think it'd be best to keep it here. --JamesNZ (discuss • contribs) 05:55, 27 July 2011 (UTC)

Orthographic vs. Perspective
This section claims that Blender gives an orthographic view by default, but my 3D View window (like the images in this book) is in perspective view by default. Am I crazy here, or is this text a relic from an earlier version of Blender? - Asterai

Rotation hotkeys
My factory-settings Blender uses Num1, Num7 and Num9 (NOT Num3) for perfect views. Update page? - Asterai Never mind. I was wrong about how my pseudo-numpad was set up. *Facepalm* - Asterai

Modes Deprecated?
My recently downloaded version of blender only has 2 modes available, Object mode and Edit mode...the other modes do not show up in the mode menu.


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Unsolved Problems in Biology/Protein folding

Protein structure can be viewed at four levels: I) Primary Structure: The amino acid sequence of a protein. II) Secondary Structure: Motifs which sections of a sequence organize themselves into. These are mainly alpha helices and beta sheets. III) Tertiary Structure: The overall structure of a single polypeptide. IV) Quaternary Structure: The way that two or more polypeptides join to form a single unit. (Not all proteins have a quaternary structure since many polypeptides function solo.)

The main question posed by the protein folding problem is "Can the final folded structure of a protein be predicted from its amino acid sequence?" In other words, given the primary structure, can the higher order structures be predicted. So, far there has been limited success with predicting portions of the secondary structure based on amino acid sequence. For instance, certain amino acid sequences are recognized as likely to fold into various motifs. Success in predicting tertiary structure has been even more limited. Further complicating this problem is that many proteins require the help of other proteins (molecular chaperones) to fold into their proper conformation.

Certain amino acids form attachments to other amino acids. Certain amino acids repel certain other amino acids. How do the right amino acids wind up attached to their corresponding amino acids? If the wrong amino acids wind up attached to other attractive, but inappropriate amino acids a nonfunctional conformation will be achieved. For a protein to function properly it must attain its proper conformation, otherwise it is just a tangled, useless mess!


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Blender 3D: Noob to Pro/Adding Lamps

You can quickly add several different types of lights to your blender scene

→ Lamp → Spot

A light will appear in the location of the 3D cursor. You can move a light just like any other object.

If you want to quickly light a scene just for illumination, not for a specific look, add four lamps around your subject. If you are interested in experimenting with a lighting arrangement, a nice quick way to experiment is to create a Monkey in the scene to test with.

→ Mesh → Monkey

The monkey is just as good of a test subject as a human face, so give it a try. You can throw various materials on the monkey and try different textures too. Don't bad mouth the monkey, she is really useful.

Explaining the Different Lamps

 * Point: Single point light source. Provides very localized light. The shadows can be sharp, or you can set its size to something nonzero to make the shadows fuzzy. Useful for representing light sources within the scene; e.g. if there is a lightbulb or candle or something in the scene, position one of these within it to give the impression of light coming from that object.
 * Sun: A light with parallel rays that will illuminate the scene with a bright even light. Because the sun is (effectively) infinitely far away, the position of this lamp does not matter, only its direction. Good to use in brightly-lit outdoor scenes (i.e. a sunny day).
 * Spot: Spot lights produce light in a cone shape, and have some special features. They are the only light source that can be made visible with the 'halo' option, to simulate light in a fog. They are also the only light source that can cast buffer shadows (see below).
 * Hemi: 180°-wide uniform, shadowless light source. Great for use as a fill light, or as a back light. Similar to Sun, its position does not matter, only its direction.
 * Area: These are similar to point lamps, except that they are rectangular. As a result they can cast accurate raytraced soft shadows. These are my lamp of choice for still shots, but they take a lot of time to render.

You might want to see the adjusted scene and play around with it for awhile.

Shadow Types
There are two different kinds of shadows that lights may cast: buffered and ray-traced. The main difference is that buffered shadows are much quicker to calculate, but take more memory, and can be of lower quality without some fiddling. Also strand-rendered materials (as can be used for hair or fur) cannot cast ray shadows with the Blender Internal renderer, so you have to use buffer shadows for them so their shadows look realistic.

Only spot lamps can cast buffered shadows. Hemi lamps cannot cast shadows at all.

Creating a basic scene with basic lighting

 * This addition is simply a way to apply what you know about lights and to discover a few settings like colors or creating simple shadows. The purpose here is to create a basic scene with a sphere over a plane, nicely lighted. You should already know the basics of Blender (creating a mesh, moving and rotating it, rendering).

Creating the scene

 * Okay, let's start! Open a new file. Add a UVsphere of 32 rings and 32 segments. Leave it in the center of the scene.

Click the Smooth button in the Tool Shelf on the left of the 3D view ( to make it visible if it’s not) so the sphere will render as a nicely smoothed sphere.

 * Add a Plane, and move it just under the sphere to be the floor. Scale it so it is very big. The ideal would that we can't see borders with the camera.

 * Then we will move the Camera. Grab it and rotate it so it looks at the sphere from top and a bit from the right. You can have an idea of what it sees pressing to have a CameraView.

Trick : First on the Camera, then  on the Sphere (the order is very important). Do a and select TrackTo Constraint.

The camera will be looking at the center of the sphere... You can then move either the camera or the sphere and the camera will still point at the sphere.

Adding the lights

 * Okay, what we have is a pretty beautiful scene, isn't it?... Well, it isn't! But it is enough to add some lights... Here I will describe a basic lighting scene I use as a default for fast renderings. I picked it out from another tutorial, you can find the link at the end of this page.
 * Now we will add our so-awaited lights. →Lamp→Spot. Yes, we will first use the Spot light. We can see it as a projector. This is the only light casting shadows. Place it so it is upper and on the left of the sphere. Rotate it so it looks at the Sphere (you can use a Trick I gave you before to have the light looking at the sphere).
 * Okay, let's see what we can tune with the spot light. Having the lamp selected, go in the Lamp settings: [[File:Blender267LampDataContextButton.png]]

You will see these buttons (right):

 * Yeah, really lots of options. Don't worry, I'll explain the basic ones.
 * Distance : Sets the maximum distance the light can reach. Increase it so the lighting cone really goes behind the sphere. I set it to Distance:40.
 * Energy : This is the force of the light. You can leave it at Energy:1.
 * RGB : You can change the colour of the light. Click on the colour and a little window will appear to select the colour you want. Leave it white.
 * Buffer Shadow : Enables the light to cast shadows, leave it pushed. BufShad.png
 * Only Shadow : This light only creates shadows, without casting light ( yeah quite unrealistic, but it can be useful ). Leave it unpushed.
 * Spot Shape Size : This is the angle of your cone, in degrees. Leave to Size:45.
 * Spot Shape Blend : This smoothes the circle cast by the light. We will smooth it so that it looks better. Set it to Blend:0.4.
 * Clip Start and Clip End : This is the distance from the light between which shadows will be cast. You can see the "line of effects" in the 3D windows when you change these. Set them so the line starts before the sphere and ends far ( well, a bit ! ) behind the plane. You should obtain something like this. (this is very important... If you do this badly, it can result in completely dark scene!)

 * Now, we have set our Spot light. This light will be our side light and shadowing light. You can make a fast preview pressing . You can see your so nice shadow. But there isn't enough light... Let's add some more!

 * Time to add a second light! →Lamp→Point. This time, we will create a point lamp. This is like a point which emits light in every direction from that point. You should place it at the opposite of the camera, quite at the same height. This light will be used to better see the form of the sphere and to add a sort of general lighting of the scene.

 * Go in the Lamp buttons, and set it to a higher energy like Energy:1.25. You can make a quick render to see how much this light is important to a scene.

 * Now, we will add a second basic lamp. →Lamp→Point and we will place it just behind the camera point of view, a bit moved at the opposite of the Spot light. This third light will slightly light the dark parts of the sphere.

 * Decrease the energy of this light, as it is only supposed to fake the reflections of the environment. I set it to Energy:0.8. Another little trick, as this is not supposed to be a direct light, there shouldn't be a little white glow called Specular on the sphere coming from this light. Uncheck specular checkbox.

 * Okay, it's time for the final rendering. Of course, this is a really basic lighting set you can use for rendering a simple mesh; but for more complicated scenes, lights can come from other places, with other colors, etc... Thus we didn't use the Sun, Hemi and Area lights, which are a bit more complicated.

Note that the following site contains nude figures: For a more in-depth tutorial, here is a tutorial from the Blender Documentation, which has been a great source of help for me.

User note: you might want to check this tutorial on lighting: http://www.youtube.com/watch?gl=US&v=YJiR2Q7uvbQ

Outdoor lighting

 * Here you will use a Sun in conjunction with a Spot light and some little Lamps.

Lighting Without Lamps
It is possible to light a scene without lamps, or with fewer lamps. In the World Context of the Properties Window, there are three options, for “Environment Lighting”, “Ambient Occlusion” and “Indirect Lighting”.

Environment Lighting adds a shadowless light that seems to come from all directions and fill all parts of the scene.

Ambient Occlusion (“AO” for short) is supposed to mimic the effect of shadows darkening corners and crevices of real-world objects (in theory this should naturally fall out of accurate lighting calculations, but it is easier to compute it separately); Blender also allows you to use AO to brighten parts of the scene outside those corners and crevices.

Indirect Lighting tries to mimic light bouncing off diffuse surfaces and illuminating other diffuse surfaces. It only works when the “Gather” option (next panel down) is set to “Approximate”.

 * Ambient Occlusion Video Tutorial: http://www.youtube.com/watch?v=rKUAemD7oo4
 * In older (pre-2.5) versions of Blender, there was an option called “Radiosity” (Video Tutorial), which is no longer supported.

title: Blender 3D: Noob to Pro/Adding Lamps


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Talk:Non-Programmer's Tutorial for Python 2.6/Front matter

I see there are two versions of this tutorial on Wikibooks: this one and another user's reworking of it which is linked to from the wiki's Programming Language Survey page (http://en.wikibooks.org/wiki/Computer_programming).

I prefer this version as it is written in a direct, plain language suitable for teaching new users, especially if they are also non-native English speakers. In fact, this tutorial is the only Python intro I've seen that maintains this standard of accessibility. I don't think the second author is justified in presenting his/her version as an improvement over this one.

The other Python Language
The other python language is a bit more advanced, and harder to learn [no tutorials to date] but we've managed to find an excerpt of a conversation in motion.

"Hsssssss.." "Hssshsssssssssss.." "Hssshss!"

 * Sadly this was removed as nonsense. I left it in because I thought it was funny, but I am not going to re-add it to the article. Jrincayc 02:39, 26 June 2007 (UTC)

I am reading this tutorial on July 1, 2009, and find that the links to the Tutorial for Programmers by Guido van Rossum are not working. Does anyone know where this publication can be found on the Internet?

Thanks

 * I fixed the link. Thanks for pointing that out. Jrincayc (talk) 16:04, 3 July 2009 (UTC)