Clinical practice guidelines for the care and treatment of breast cancer: 16. Locoregional post-mastectomy radiotherapy Post mastectomy adjuvant radiotherapy in breast cancer: a comparision of three hypofractionated protocols. Regional Nodal Irradiation: Examining the Clinical Implications of Randomized Trials Hypofractionated Regional Nodal Irradiation for Women With Node-Positive Breast Cancer. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: Final analysis of the EORTC AMAROS trial (10981/22023). Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial [Optimal treatment of the axilla after positive sentinel lymph node biopsy in early invasive breast cancer. Early results of the OTOASOR trial]. Hypofractionated Postmastectomy Radiation Therapy Is Safe and Effective: First Results From a Prospective Phase II Trial. Positive sentinel nodes without axillary dissection: implications for the radiation oncologist. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. Partial breast radiation therapy with proton beam: 5-year results with cosmetic outcomes. Prognostic index score and clinical prediction model of local regional recurrence after mastectomy in breast cancer patients. It is possible to omit postoperative irradiation in a highly selected group of elderly breast cancer patients DEGRO Practical Guidelines for Radiotherapy of Breast Cancer II Sequelae of axillary dissection vs. axillary sampling with or without irradiation for breast cancer. A randomized trial. Regional radiotherapy versus an axillary lymph node dissection after lumpectomy: a safe alternative for an axillary lymph node dissection in a clinically uninvolved axilla in breast cancer. A case control study with 10 years follow up Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. Long-Term Results of a Randomized Trial on the Sequencing of Radiotherapy and Chemotherapy in Breast Cancer Efficacy and tolerability of limited field radiotherapy with concurrent capecitabine in locally advanced pancreatic cancer. Endoscopic surgery to the axilla--a substitute for conventional axillary clearance? Short course radiotherapy with simultaneous integrated boost for stage I-II breast cancer, early toxicities of a randomized clinical trial Postsurgical adjuvant chemotherapy with or without radiotherapy in women with breast cancer and positive axillary nodes: a South-Eastern Cancer Study Group (SEG) Trial. Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: the Danish Breast Cancer Cooperative Group. Long-term complications associated with breast-conservation surgery and radiotherapy Clinical practice guidelines for the care and treatment of breast cancer: 11. Lymphedema. The Edinburgh randomized trial of axillary sampling or clearance after mastectomy The curative role of radiotherapy in the treatment of operable breast cancer. Conservative treatment versus mastectomy in early breast cancer: patterns of failure with 15 years of follow-up data. Institut Gustave-Roussy Breast Cancer Group. Intensity modulated radiotherapy (IMRT) with concurrent chemotherapy as definitive treatment of locally advanced esophageal cancer Axillary treatment in conservative management of operable breast cancer: dissection or radiotherapy? Results of a randomized study with 15 years of follow-up. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Chemoradiotherapy for advanced inoperable head and neck cancer: A phase II study. Randomized trial comparing locoregional resection of primary tumor with no surgery in stage IV breast cancer at the presentation (Protocol MF07-01): a study of Turkish Federation of the National Societies for Breast Diseases. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. Comparing radical mastectomy with quadrantectomy, axillary dissection, and radiotherapy in patients with small cancers of the breast. Radiation-induced brachial plexopathy: neurological follow-up in 161 recurrence-free breast cancer patients. Modified radical mastectomy with axillary dissection using the electrothermal bipolar vessel sealing system. Risk Factors for Lymphedema after Breast Cancer Treatment
Objective : To provide information and recommendations to assist women with breast cancer and their physicians in making decisions regarding the use of locoregional post-mastectomy radiotherapy ( PMRT ) . Outcomes : Locoregional control , disease-free survival , overall survival and treatment-related toxicities . Evidence : This guideline is based on a review of all meta-analyses , consensus statements and other guidelines published between 1966 and November 2002 . Search es of MEDLINE and CANCERLIT for English- language r and omized controlled trials published between 1995 and November 2002 were also conducted to supplement the literature previously review ed by the American Society of Clinical Oncology ( ASCO ) Health Services Research Committee panel in its published guideline . A non systematic review of the literature was continued through June 2003 . Recommendations : Locoregional PMRT is recommended for women with an advanced primary tumour ( tumour size 5 cm or greater , or tumour invasion of the skin , pectoral muscle or chest wall ) . Locoregional PMRT is recommended for women with 4 or more positive axillary lymph nodes . The role of PMRT in women with 1 to 3 positive axillary lymph nodes is unclear . These women should be offered the opportunity to participate in clinical trials of PMRT . Locoregional PMRT is generally not recommended for women who have tumours that are less than 5 cm in diameter and who have negative axillary nodes . Other patient , tumour and treatment characteristics , including age , histologic grade , lymphovascular invasion , hormone receptor status , number of axillary nodes removed , axillary extracapsular extension and surgical margin status , may affect locoregional control , but their use in specifying additional indications for PMRT is currently unclear . PMRT should encompass the chest wall and the supraclavicular , infraclavicular and axillary apical lymph node areas . To reduce the risk of lymphedema , radiation of the entire axilla should not be used routinely after complete axillary dissection of level I and II lymph nodes . A definite recommendation regarding the inclusion of the internal mammary lymph nodes in PMRT can not be made because of limited and inconsistent data . The use of modern techniques in radiotherapy planning is recommended to minimize excessive normal tissue exposure , particularly to the cardiac and pulmonary structures . Common short-term side effects of PMRT , including fatigue and skin erythema , are generally tolerable and not dose-limiting . Severe long-term side effects , including lymphedema , cardiac and pulmonary toxicities , brachial plexopathy , rib fractures and secondary neoplasms , are relatively rare . The optimal sequencing of PMRT and systemic therapy is currently unclear . Regimens containing anthracyclines or taxanes should not be administered concurrently with radiotherapy because of the potential for increased toxicity . Validation : The authors ' original text was su bmi tted for review , revision and approval by the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer . Subsequently , feedback was provided by 11 oncologists from across Canada . The final document was approved by the steering committee . Sponsor : The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer was convened by Health Canada . Completion date : November 2003 OBJECTIVES To compare three hypofractionated protocol s in postmastectomy cancinoma breast in terms of local control , toxicity and work load . METHODS A total of three hundred patients suffering from cancer breast stage T2 - 4 , N any were r and omized into three arms after mastectomy . All the patients were treated with four fields on Co60 i.e. two tangential portals for chest wall , one anterior supraclavicular and axillary field and a posterior axillary boost and were r and omized into three arms i.e. 2700 CGy in 5 fractions ( one week ) arm A , 3500 CGy in 10 fractions ( 2 weeks ) arm B and 4000 CGy in 15 fractions ( 3 weeks ) arm C. Skin , cardiac , pulmonary and haematological toxicities and lymphoedema were compared in addition to local control and work load . RESULTS The locoregional relapses were 11 % , 12 % and 10 % in arms A , B and C respectively . 26 % , 24 % and 28 % patients developed metastatic disease and 17 % , 18 % and 20 % died in the three arms . G3 and G4 skin toxicities were 37 % , 28 % and 14 % . G2 and G3 lymphedoema was 21 % , 22 % and 27 % . Cardiac toxicity was 5 % , 6 % and 5 % while pulmonary toxicity was 4 % , 5 % and 5 % respectively . All the differences except skin toxicity were statistically insignificant . There were no cases of haematological depression or rib fractures . CONCLUSION All the three short protocol s were equally effective in locoregional disease control and toxicity was also comparable . They were helpful in reducing the work load and can be safely recommended for routine clinical use COMMENTARY Recently , mature data were published from the MA.20 and European Organization for the Research and Treatment of Cancer ( EORTC ) 22922 trials , providing clinicians with increasing data supporting the value of regional nodal irradiation ( RNI ) . The MA.20 r and omized 1832 women with highrisk node-negative ( T3 , T2 with < 10 nodes removed and grade 3/estrogen receptor-negative/lymphovascular space invasion ) or node-positive disease to receive whole breast irradiation with or without RNI ( axillary apex , internal mammary , supraclavicular ) with > 80 % of patients having 1 to 3 nodes positive . Ten-year outcomes demonstrated an improvement in disease-free survival ( 82 % vs. 77 % ) with reductions in distant metastases and locoregional recurrences with the addition of RNI with modest increases in pneumonitis ( 1.2 % vs. 0.2 % ) and lymphedema ( 8.4 % vs. 4.5 % ) . Similarly , the EORTC trial r and omized 4004 women with centromedial tumors or lateral tumors with axillary disease to receive radiation with or without inclusion of the internal mammary chain and medial supraclavicular nodes ; 43 % of patients had 1 to 3 nodes involved . Results of the study demonstrated improvements in disease-free survival ( 72 % vs. 69 % ) , distant metastases-free survival , and reductions in breast cancer mortality with a trend for improved overall survival . These results confirm data from previous studies ( subset analyses of postmastectomy r and omized trials , meta-analyses ) that demonstrated improvement in outcomes with radiation therapy ( including RNI ) for patients with 1 to 3 nodes positive . Recent commentary following the publication of these studies has question ed the role of RNI despite the aforementioned improvements in disease-free survival , distant metastases , and locoregional control due to a lack of survival benefit in these trials . However , it should be noted that improvements in locoregional control , disease-free survival , distant metastases , and breast cancer mortality have justified the utilization of surgical , systemic , and radiotherapeutic techniques in the past and continue to do so . For instance , the National Surgical Adjuvant Breast and Bowel Project B28 trial has result ed in the widespread addition of taxanes to anthracycline-based chemotherapy , and the Cancer and Leukemia Group B 9741 results result ed in increasing utilization of dose-dense chemotherapy regimens despite lower than expected outcome events . Further , the EORTC trial demonstrated a trend for improvement in overall survival with the potential for improved survival with further follow-up . Arguments for limiting RNI presented include a reduction in the rates of local recurrence , improvements in systemic therapy , and differences in nodal sampling compared with recent studies . With regards to the improvement in locoregional control over time , recent data demonstrate locoregional recurrence rates exceeding 10 % in patients even in patients with low-volume nodal disease with modern systemic therapy . Systemic therapy has evolved over the past few decades ; however , taxanes were utilized in these studies ( 26 % in MA.20 ; unknown in EORTC 22922 ) and limited data are available suggesting an improvement in locoregional control with trastuzumab , with the benefit more likely associated with radiotherapy . Similarly , aromatase inhibitors have demonstrated a reduction in recurrences but these were primarily distant recurrences and contralateral breast cancers rather than local recurrences . Although management of the axilla continues to evolve , there is insufficient evidence to support that the results of the American College of Surgeons Oncology Group Z011 and After Mapping Axilla , Radiotherapy or Surgery trials is from systemic therapy and in the case of the After Mapping Axilla , Radiotherapy or Surgery trial is more likely due to the RNI . Similarly , although there is a difference in the number of nodes sample d ( 12 to 15 vs. 17 ) , there is insufficient evidence to support that this difference would lead to a difference in the clinical outcomes noted . RNI can be associated with toxicity though the rates remain low ; the EORTC trial demonstrated an increase in pulmonary fibrosis although it was < 5 % with no difference in other late toxicities . Similarly , MA.20 demonstrated a small increase in pneumonitis as well as chronic lymphedema and skin changes . However , the cost-benefit of an improvement in disease-free survival and potentially overall survival with longer follow-up outweighs the small increase in toxicity . There is a concern regarding the heterogeneity of these trials . A recent editorial recommended RNI for those with Z4 nodes positive but suggested that RNI be limited in patients with 1 to 3 nodes positive to those with high-risk From the * Department of Radiation Oncology , Clevel and Clinic , Taussig Cancer Institute , Clevel and ; wDepartment of Radiation Oncology , Northeast Ohio Medical University , Rootstown , OH ; zDepartment of Radiation Oncology , Rutgers Robert Wood Johnson Medical School , Cancer Institute of New Jersey , New Brunswick , NJ ; yDepartment of Radiation Oncology , Massey Cancer Center , Virgina Commonwealth University , Richmond , VA ; 8Tufts University School of Medicine , Boston , MA ; zAlpert Medical School of Brown University , Providence , RI ; # 21st Century Oncology , Fort Myers , FL ; * * Department of Radiation Oncology , University of Nebraska Medical Center , Omaha , NE ; and wwMichigan Healthcare Professionals/21st Century Oncology , Farmington Hills , MI . The authors declare no conflicts of interest . Reprints : Chirag Shah , MD , Department of Radiation Oncology , Clevel and Clinic , Taussig Cancer Institute , 9500 Euclid Avenue , Clevel and , OH 44195 . E-mail : csshah27@hotmail.com . Copyright r 2015 Wolters Kluwer Health , Inc. All rights reserved . ISSN : 0277 - 3732/16/3901 - 0090 DOI : 10.1097/COC.0000000000000250 CANCER MANAGEMENT PURPOSE To evaluate the effect of hypofractionated radiation therapy ( HFRT ) of the breast/chest wall and regional nodes on overall survival ( OS ) , disease-free survival ( DFS ) , locoregional control and on treatment-related toxicity in patients with breast cancer and nodal involvement . METHODS AND MATERIAL S Two hundred fifty-seven patients treated between October 2009 and June 2011 with hypofractionated locoregional radiation therapy ( 42 Gy in 15 fractions ) were retrospectively review ed , 51 ( 19.8 % ) after breast-conserving surgery and 206 ( 80.2 % ) after radical surgery .  Patients treated with breast-conserving surgery received a boost dose to the tumor bed ( delivered by photons , electrons , or interstitial high-dose-rate brachytherapy ) . Two hundred fifty-six ( 99.6 % ) patients underwent chemotherapy  , 209 ( 81.3 % ) had  hormonal treatment , and 65 ( 25.3 % ) had anti-HER2 targeted therapy . RESULTS The median follow-up time was 64 months ( range , 11 - 88 months ) . The rates of 5-year OS , DFS , locoregional recurrence (LRR)-free survival , and distant metastasis (DM)-free survival were 86.6 % , 84.4 % , 93.9 % , and 83.1 % , respectively . In multivariate analysis ( MVA ) , lymph node ratio > 65 % , lymphovascular invasion , and negative hormone receptor status predicted for OS , DSF , and DM . T3 to 4 stage was also associated with worse DFS and DM . Finally , for LRR the independent prognostic factors on MVA were N2 to 3 stage and grade 3 . Hyperpigmentation was observed in 19.2 % of patients , telangiectasia in 12.3 % , and fibrosis in 30.7 % . Grade ≥2 lymphedema was recorded in 5.8 % of cases . During the study follow-up , no cardiac or symptomatic pneumonitis was observed , nor were plexopathy or rib fractures . CONCLUSION According to the findings from this retrospective study , HFRT seems to be an acceptable alternative for patients with breast cancer who need regional nodal irradiation . However , prospect i ve r and omized trials are necessary to confirm these preliminary results LBA1001 Background : Sentinel node biopsy ( SNB ) is st and ard in assessing axillary lymph node status for cN0 breast cancer patients . In case of a positive SNB , if treatment is advised , axillary lymph node dissection ( ALND ) is the current st and ard . Although ALND provides excellent regional control , it may give harmful side effects . Axillary radiotherapy ( ART ) instead of ALND was hypothesized to provide comparable regional control and less side effects . METHODS From 2001 to 2010 , patients with cT1E2N0 primary breast cancer were enrolled in the EORTC phase III non-inferiority AMAROS trial . Patients were r and omized between ALND and ART in case of a positive SNB . Primary endpoint was 5-year axillary recurrence rate . Secondary endpoints were overall survival ( OS ) , disease-free survival ( DFS ) , quality of life ( QOL ) , shoulder movement and lymphedema at 1 and 5 years . RESULTS Of the 4,806 patients entered in the trial , 744 in the ALND-arm and 681 in the ART-arm had a positive SNB , 60 % with a macrometastasis . The two treatment-arms were comparable regarding age , tumor size , grade , tumor type , and adjuvant systemic treatment . With a median follow up of 6.1 years , the 5-year axillary recurrence rate after a positive SNB was 0.54 % ( 4/744 ) after ALND versus 1.03 % ( 7/681 ) after ART . The planned non-inferiority test was underpowered because of the unexpectedly low number of events . The axillary recurrence rate after a negative SNB was 0.8 % ( 25/3131 ) . There were no significant differences between treatment arms regarding OS ( 5 yr estimates : 93.27 % ALND , 92.52 % ART , p=0.3386 ) and DFS ( 5 yr estimates : 86.90 % ALND , 82.65 % ART , p=0.1788 ) . Lymphedema was found significantly more often after ALND ( 1yr : 40 % ALND , 22 % ART , p<0.0001 and 5yr : 28 % ALND , 14 % ART , p<0.0001 ) . There was a nonsignificant trend toward more early shoulder movement impairment after ART . These findings were compatible with a trend in two QOL items in the arm symptom scale : swelling ( ART better ) and movement ( ALND better ) . There were no other differences in QOL . CONCLUSION ALND and ART after a positive SNB provide excellent and comparable regional control . ART reduces the risk of short-term and long-term lymphedema compared to ALND . CLINICAL TRIAL INFORMATION NCT00014612 BACKGROUND Postmastectomy radiotherapy is associated with a lower locoregional recurrence rate and improved disease-free and overall survival when combined with chemotherapy in premenopausal high-risk breast-cancer patients . However , whether the same benefits apply also in postmenopausal women treated with adjuvant tamoxifen for similar high-risk cancer is unclear . In a r and omised trial among postmenopausal women who had undergone mastectomy , we compared adjuvant tamoxifen alone with tamoxifen plus postoperative radiotherapy . METHODS Between 1982 and 1990 , postmenopausal women with high-risk breast cancer ( stage II or III ) were r and omly assigned  adjuvant tamoxifen ( 30 mg daily for 1 year ) alone ( 689 ) or with postoperative radiotherapy to the chest wall and regional lymph nodes ( 686 ) . Median follow-up was 123 months . The endpoints were first site of recurrence ( locoregional recurrence , distant metastases , or both ) , and disease-free and overall survival . FINDINGS Locoregional recurrence occurred in 52 ( 8 % ) of the radiotherapy plus tamoxifen group and 242 ( 35 % ) of the tamoxifen only group ( p<0.001 ) . In total there were 321 ( 47 % ) and 411 ( 60 % ) recurrences , respectively . Disease-free survival was 36 % in the radiotherapy plus tamoxifen group and 24 % in the tamoxifen alone group ( p<0.001 ) . Overall survival was also higher in the radiotherapy group ( 385 vs 434 deaths ; survival 45 vs 36 % at 10 years , p=0.03 ) . INTERPRETATION Postoperative radiotherapy decreased the risk of locoregional recurrence and was associated with improved survival in high-risk postmenopausal breast-cancer patients after mastectomy and limited axillary dissection , with 1 year of adjuvant tamoxifen treatment . Improved survival in high-risk breast cancer can best be achieved by a strategy of both locoregional and systemic tumour control INTRODUCTION Sentinel lymph node biopsy alone has become an acceptable alternative to elective axillary lymph node dissection in patients with clinical ly node-negative early-stage breast cancer . Approximately 70 percent of the patients undergoing breast surgery develop side effects caused by the axillary lymph node dissection  ( axillary pain , shoulder stiffness , lymphedema and paresthesias ) . AIM The current st and ard treatment is to perform completion axillary lymph node dissection in patients with positive sentinel lymph node biopsy . However , r and omized clinical trials of axillary dissection versus axillary irradiation failed to show survival differences between the two types of axillary treatment . The National Institute of Oncology , Budapest conducted a single centre r and omized clinical study . The OTOASOR ( Optimal Treatment of the Axilla - Surgery or Radiotherapy ) trial compares completion axillary lymph node dissection to axillary nodal irradiation in patients with sentinel lymph node-positive primary invasive breast cancer . METHOD Patients with primary invasive breast cancer ( clinical ly lymph node negative and less than or equal to 3 cm in size ) were r and omized before surgery for completion axillary lymph node dissection ( arm A-st and ard treatment ) or axillary nodal irradiation ( arm B-investigational treatment ) . Sentinel lymph node biopsy was performed by the radio-guided method . The use of blue-dye was optional . Sentinel lymph nodes were investigated with serial sectioning at 0.5 mm levels by haematoxylin and eosin staining . In the investigational treatment arm patients received 50Gy axillary nodal irradiation instead of completion axillary lymph node dissection . Adjuvant treatment was recommended and patients were followed up according to the actual institutional guidelines . RESULTS Between August 2002 and June 2009 , 2106 patients were r and omized for completion axillary  lymph node  dissection  ( 1054 patients ) or axillary nodal irradiation ( 1052 patients ) . The two arms were well balanced according to the majority of main prognostic factors . Sentinel lymph node was identified in 2073 patients ( 98.4 % ) and was positive in 526 patients ( 25.4 % ) . Fifty-two sentinel lymph node-positive patients were excluded from the study ( protocol violation , patient 's preference ) . Out of the remaining 474 patients , 244 underwent completion axillary lymph node dissection and 230 received axillary nodal irradiation according to r and omization . The mean length of follow-up to the first event and the mean total length of follow-up were 41.9 and 43.3 months , respectively , and there were no significant differences between the two arms . There was no significant difference in axillary recurrence between the two arms ( 0.82 % in arm A and 1.3 % in arm B ) . There was also no significant difference in terms of overall survival between the arms at the early stage follow-up . CONCLUSIONS The authors conclude that after a mean follow-up of more than 40 months axillary nodal irradiation may control the disease in the axilla as effectively as completion axillary lymph node dissection and there was also no difference in terms of overall survival Purpose Conventionally fractionated postmastectomy radiation therapy ( PMRT ) takes approximately 5 to 6 weeks . Data supporting hypofractionated PMRT is limited . We prospect ively evaluated a short course of hypofractionated PMRT , in which therapy was completed in 15 treatment days . Patients and Methods We delivered PMRT at a dose of 36.63 Gy in 11 fractions of 3.33 Gy over 11 days to the chest wall and the draining regional lymph nodes , followed by an optional mastectomy scar boost of four fractions of 3.33 Gy . Our primary end point was freedom from any grade 3 or higher toxicities . We incorporated early stopping criteria on the basis of predefined toxicity thresholds . Results We enrolled 69 women with stage II to IIIa breast cancer , of whom 67 were eligible for analysis . After a median follow-up of 32 months , there were no grade 3 toxicities . There were 29 reported grade 2 toxicities , with grade 2 skin toxicities being the most frequent ( 16 of 67 ; 24 % ) . There were two patients with isolated ipsilateral chest wall tumor recurrences ( 2 of 67 ; crude rate , 3 % ) . Three-year estimated local recurrence-free survival was 89.2 % ( 95 % CI , 0.748 to 0.956 ) . The 3-year estimated distant recurrence-free survival was 90.3 % ( 95 % CI , 0.797 to 0.956 ) . Forty-one patients had chest wall reconstructions ; three had exp and ers removed for infection before radiation therapy . The total rate of implant loss or failure was 24 % ( 9 of 38 ) , and the unplanned surgical correction rate was 8 % ( 3 of 38 ) , for a total complication rate of 32 % . Conclusion To our knowledge , our phase II prospect i ve study offers one of the shortest courses of PMRT reported , delivered in 11 fractions to the chest wall and nodes and 15 fractions inclusive of a boost . We demonstrated low toxicity and high local control with this schedule . On the basis of our data , we have design ed a cooperative group phase III prospect i ve , r and omized trial of conventional versus hypofractionated PMRT that will activate soon The recent publication of the results of the American College of Surgeons Oncology Group trial Z0011 has generated substantial interest in the medical community and public press . This trial demonstrated equivalent survival in patients with breast cancer and one to two positive sentinel lymph nodes ( SLNs ) who were r and omly assigned to SLN biopsy ( SLNB ) alone or SLNB followed by axillary lymph node dissection ( ALND ) .  Equally important , regional recurrence with SLNB alone was less than 1 % , despite the fact that an estimated 27 % of patients had additional metastases in the undissected axillary nodes . All patients underwent breast-conserving surgery ( BCS ) , systemic therapy as appropriate , and whole-breast irradiation ( WBRT ) with tangential fields ( TFs ) . Regional nodal irradiation ( RNI ) was not allowed in Z0011 . The st and ard of care for patients with positive SLNs has traditionally been a completion ALND . This results in excellent regional control and provides information that can guide treatment decisions for the radiation and medical oncologists . Because systemic therapy decisions increasingly rely on tumor size , grade , receptor status , and a variety of molecular profiles , there has been less dependence on the number of positive nodes for systemic therapy decision making . The radiation oncologist , however , has historically relied on ALND findings in the design of the radiation treatment fields ; the number of positive nodes provides information concerning the risk of involvement of the level III/supraclavicular ( SCV ) nodes . When this risk is clinical ly relevant , radiation oncologists commonly treat the level III/SCV region with an SCV field . Typically this is used for patients with four or more positive nodes and selected patients with one to three positive nodes . With computed tomography – based planning , this involves contouring level I through III nodes , which ensures adequate radiation to the target nodes that are at risk . Although the combination of ALND and axillary radiation increases the risk of lymphedema , minimal morbidity is associated with radiation to the undissected level III/SCV region or to the undissected axilla . With the recent publication of Z0011 , the optimal design of radiation fields for patients with positive SLNs who do not undergo ALND is uncertain . This will be increasingly important given that many patients with positive SLNs will forego ALND . In weighing whether such patients should receive RNI , it is important to consider the reason for the less than 1 % regional recurrence rate in Z0011 , despite the fact that an estimated 27 % of patients had additional undissected positive nodes . Systemic therapy , which the majority of patients in Z0011 received , may have played a significant role . Studies of patients with positive nodes have demonstrated that approximately 25 % of patients who are treated with chemotherapy have complete eradication of nodal disease . The long-term use of hormonal therapy may also contribute . It is also possible that the low regional recurrence rate is a reflection of the extensive processing of SLNs and subsequent detection of a burden of disease so low that it is held in check by the host immune system , analogous to patients with bone marrow micrometastases who never develop clinical ly evident metastases . A final possibility , and one that we believe is highly relevant , is that TF radiation that was used to treat the breast coincidently delivered radiation treatment to the lower axilla and eradicated the disease . If a large component of the axilla were in the TF region , this is likely to have contributed significantly . We believe that this observation is important and consequently that the results of Z0011 should not be extrapolated to patients who are treated with mastectomy without radiation , partial breast irradiation , irradiation of the breast in the prone position , intraoperative irradiation , or other techniques in which the axilla may not be included in the radiation fields . It is estimated that , using st and ard TFs , more than 50 % of level I and 20 % to 30 % of level II nodes receive 95 % of the prescribed radiation dose ; this is dependent on patient anatomy and where the radiation oncologist sets the upper TF border . Although the Z0011 protocol did not allow RNI , the degree to which the TFs covered level I and II nodes , and whether the radiation oncologist placed the superior border of the TFs to treat more of the level I and II nodes ( high tangents ) , was not documented in the trial . ( Currently the American College of Surgeons Oncology Group is working to extract this data . ) Although the contribution of high TFs to regional control in Z0011 remains uncertain , and the data that support the use of high TFs are based primarily on retrospective dosimetric studies , the use of high TFs has been shown in several studies to include the majority of level I and II nodes . There are several important points to make regarding Z0011 when considering the risk of additional positive nodes . First , patients who participated in this trial had favorable disease characteristics : the median age was 55 years , 70 % had T1 tumors , 82 % had estrogen receptor – positive disease , 71 % had only one positive SLN , and 44 % JOURNAL OF CLINICAL ONCOLOGY COMMENTS AND CONTROVERSIES VOLUME 29 NUMBER 34 DECEMBER 1 BACKGROUND The British Columbia r and omized radiation trial was design ed to determine the survival impact of locoregional radiation therapy in premenopausal patients with lymph node-positive breast cancer treated by modified radical mastectomy and adjuvant chemotherapy . Three hundred eighteen patients were assigned to receive no further therapy or radiation therapy ( 37.5 Gy in 16 fractions ) . Previous analysis at the 15-year follow-up showed that radiation therapy was associated with a statistically significant improvement in breast cancer survival but that improvement in overall survival was of only borderline statistical significance . We report the analysis of data from the 20-year follow-up . METHODS Survival was analyzed by the Kaplan-Meier method . Relative risk estimates were calculated by the Wald test from the proportional hazards regression model . All statistical tests were two-sided . RESULTS At the 20 year follow up ( median follow up for live patients : 249 months ) chemotherapy and radiation therapy , compared with chemotherapy alone , were associated with a statistically significant improvement in all end points analyzed , including survival free of isolated locoregional recurrences ( 74 % versus 90 % , respectively ; relative risk [ RR ] = 0.36 , 95 % confidence interval [ CI ] = 0.18 to 0.71 ; P = .002 ) , systemic relapse-free survival ( 31 % versus 48 % ; RR = 0.66 , 95 % CI = 0.49 to 0.88 ; P = .004 ) , breast cancer-free survival ( 48 % versus 30 % ; RR = 0.63 , 95 % CI = 0.47 to 0.83 ; P = .001 ) , event-free survival ( 35 % versus 25 % ; RR = 0.70 , 95 % CI = 0.54 to 0.92 ; P = .009 ) , breast cancer-specific survival ( 53 % versus 38 % ; RR = 0.67 , 95 % CI = 0.49 to 0.90 ; P = .008 ) , and , in contrast to the 15-year follow-up results , overall survival ( 47 % versus 37 % ; RR = 0.73 , 95 % CI = 0.55 to 0.98 ; P = .03 ) . Long-term toxicities , including cardiac deaths ( 1.8 % versus 0.6 % ) , were minimal for both arms . CONCLUSION For patients with high-risk breast cancer treated with modified radical mastectomy , treatment with radiation therapy ( schedule of 16 fractions ) and adjuvant chemotherapy leads to better survival outcomes than chemotherapy alone , and it is well tolerated , with acceptable long-term toxicity PURPOSE We up date d our previous report of a phase 2 trial using proton beam radiation therapy to deliver partial breast irradiation ( PBI ) in patients with early stage breast cancer . METHODS AND MATERIAL S Eligible subjects had invasive nonlobular carcinoma with a maximal dimension of 3 cm . Patients underwent partial mastectomy with negative margins ; axillary lymph nodes were negative on sampling . Subjects received postoperative proton beam radiation therapy to the surgical bed . The dose delivered was 40 Gy in 10 fractions , once daily over 2 weeks . Multiple fields were treated daily , and skin-sparing techniques were used . Following treatment , patients were evaluated with clinical assessment s and annual mammograms to monitor toxicity , tumor recurrence , and cosmesis . RESULTS One hundred subjects were enrolled and treated . All patients completed the assigned treatment and were available for post-treatment analysis . The median follow-up was 60 months . Patients had a mean age of 63 years ; 90 % had ductal histology ; the average tumor size was 1.3 cm . Actuarial data at 5 years included ipsilateral breast tumor recurrence-free survival of 97 % ( 95 % confidence interval : 100%-93 % ) ; disease-free survival of 94 % ; and overall survival of 95 % . There were no cases of grade 3 or higher acute skin reactions , and late skin reactions included 7 cases of grade 1 telangiectasia . Patient- and physician-reported cosmesis was good to excellent in 90 % of responses , was not changed from baseline measurements , and was well maintained throughout the entire 5-year follow-up period . CONCLUSIONS Proton beam radiation therapy for PBI produced excellent ipsilateral breast recurrence-free survival with minimal toxicity . The treatment proved to be adaptable to all breast sizes and lumpectomy cavity configurations . Cosmetic results appear to be excellent and unchanged from baseline out to 5 years following treatment . Cosmetic results may be improved over those reported with photon-based techniques due to reduced breast tissue exposure with proton beam , skin-sparing techniques , and the dose fractionation schedule used in this trial PURPOSE To develop clinical prediction models for local regional recurrence ( LRR ) of breast carcinoma after mastectomy that will be superior to the conventional measures of tumor size and nodal status . METHODS AND MATERIAL S Clinical information from 1,010 invasive breast cancer patients who had primary modified radical mastectomy  formed the data base of the training and testing of clinical prognostic and prediction models of LRR . Cox proportional hazards analysis and Bayesian tree analysis were the core method ologies from which these models were built . To generate a prognostic index model , 15 clinical variables were examined for their impact on LRR . Patients were stratified by lymph node involvement ( < 4 vs. > or = 4 ) and local regional status ( recurrent vs. control ) and then , within strata , r and omly split into training and test data sets of equal size . To establish prediction tree models , 255 patients were selected by the criteria of having had LRR ( 53 patients ) or no evidence of LRR without postmastectomy radiotherapy ( PMRT ) ( 202 patients ) . RESULTS With these models , patients can be divided into low- , intermediate- , and high-risk groups on the basis of axillary nodal status , estrogen receptor status , lymphovascular invasion , and age at diagnosis . In the low-risk group , there is no influence of PMRT on either LRR or survival . For intermediate-risk patients , PMRT improves LR control but not metastases-free or overall survival . For the high-risk patients , however , PMRT improves both LR control and metastasis-free and overall survival . CONCLUSION The prognostic score and predictive index are useful methods to estimate the risk of LRR in breast cancer patients after mastectomy and for estimating the potential benefits of PMRT . These models provide additional information criteria for selection of patients for PMRT , compared with the traditional selection criteria of nodal status and tumor size The purpose of this study was the evaluation of the necessity of routinely applied postoperative radiotherapy in a highly selected patient-group after breast conserving surgery . Between 1983 and May 1994 , 356 women over 60 years of age with Stage I or II breast cancer were treated by quadrantectomy and axillary dissection followed by either adjuvant irradiation or no radiotherapy . We have analysed our data retrospectively to investigate whether irradiation has any benefit in elderly patients with respect to locoregional recurrence rates . After a median follow-up of 60 months the multivariate model revealed lymph node status ( p=0.002 ) as highly significant with regard to local recurrence free survival . We were not able to identify a positive effect of adjuvant irradiation in patients with negative lymph nodes and positive receptor status : both patient groups with or without irradiation had similar locoregional recurrence rates of 3 % . In a subgroup of patients who were lymph node negative , receptor positive , and received adjuvant tamoxifen therapy , the local recurrence rates were as low as 2 % in both groups . Concerning these results it may be possible to avoid the morbidity and potential psychological side effects of radiotherapy in breast cancer patients over 60 years of age treated by breast conserving surgery  ( T1 , N0 , positive hormone receptor , adjuvant tamoxifen ) without increasing risk of locoregional recurrence . These data have to be confirmed in a prospect ively r and omized fashion Background and Purpose : The aim of the present paper is to up date the practical guidelines for radiotherapy of breast cancer published in 2006 by the breast cancer expert panel of the German Society for Radiooncology ( DEGRO ) . These recommendations were complementing the S3 guidelines of the German Cancer Society ( DKG ) elaborated in 2004 . The present DEGRO recommendations are based on a revision of the DKG guidelines provided by an interdisciplinary panel and published in February 2008 . Methods : The DEGRO expert panel ( authors of the present manuscript ) performed a comprehensive survey of the literature . Data from lately published meta-analyses , recent r and omized trials and guidelines of international breast cancer societies , yielding new aspects compared to 2006 , provided the basis for defining recommendations referring to the criteria of evidence -based medicine . In addition to the more general statements of the DKG , this paper emphasizes specific radiooncologic issues relating to radiotherapy after mastectomy ( PMRT ) , locally advanced disease , irradiation of the lymphatic pathways , and sequencing of local and systemic treatment . Technique , targeting , and dose are described in detail . Results : PMRT significantly reduces local recurrence rates in patients with T3/T4 tumors and /or positive axillary lymph nodes ( 12.9 % with and 40.6 % without PMRT in patients with four or more positive nodes ) . The more local control is improved , the more substantially it translates into increased survival . In node-positive women the absolute reduction in 15-year breast cancer mortality is 5.4 % . Data referring to the benefit of lymphatic irradiation are conflicting . However , radiotherapy of the supraclavicular area is recommended when four or more nodes are positive and otherwise considered individually . Evidence concerning timing and sequencing of local and systemic treatment is sparse ; therefore , treatment decisions should depend on the dominating risk of recurrence . Conclusion : There is common consensus that PMRT is m and atory for patients with T3/T4 tumors and /or four or more positive axillary nodes and should be considered for patients with one to three involved nodes . Irradiation of the lymphatic pathways and the optimal time point for onset of radiotherapy are still under debate . Hintergrund und Ziel : Ziel der Arbeit ist eine Aktualisierung der 2006 publizierten Leitlinie der „ Expertengruppe Mammakarzinom “ der Deutschen Gesellschaft für Radioonkologie ( DEGRO ) . Diese war seinerzeit in Ergänzung zur interdisziplinären S3-Leitlinie der Deutschen Krebsgesellschaft ( DKG ) von 2004 verfasst worden . Zwischenzeitlich erfolgten eine Überarbeitung und Aktualisierung der S3-Leitlinie der DKG , die i m Februar 2008 publiziert wurde . Method ik : Die Expertengruppe ( identisch mit den Autoren dieses Manuskripts ) führte eine umfassende Literaturrecherche durch . Aktuelle Metaanalysen und r and omisierte Studien , die neue Aspekte gegenüber 2006 ergaben , sowie Empfehlungen internationaler Fachgesellschaften wurden in die Bewertung von Therapieindikationen einbezogen . Diese orientieren sich an den Kriterien evidenzbasierter Medizin . In Ergänzung zu den eher allgemeinen Statements der DKG 2008 werden spezielle radiotherapeutische Fragestellungen beh and elt , die eine Strahlentherapie nach Mastektomie ( PMRT ) und/oder bei fortgeschrittenen Tumoren , die Bestrahlung der Lymphabflusswege und die Sequenz von Radio- und Systemtherapie betreffen . Zielvolumendefinition und Dosierung werden i m Detail beschrieben . Ergebnisse : Die PMRT senkt die Lokalrezidivrate bei Patientinnen mit hohem Rückfallrisiko ( T3/T4-Tumoren und/oder befallene axilläre Lymphknoten ; 12,9 % mit und 40,6 % ohne PMRT ) . Je ausgeprägter die durch die Radiotherapie bewirkte lokale Tumorkontrolle ist , desto stärker wirkt sich dies auf die Überlebenswahrscheinlichkeit aus . Bei lymphonodal positiven Patientinnen ergab sich eine absolute Verminderung der tumorspezifischen Sterblichkeit um 5,4 % nach 15 Jahren . Hinsichtlich des Nutzens einer Strahlentherapie der Lymphabflusswege ist die Date nlage widersprüchlich . Eine Bestrahlung der Supraklavikularregion ist jedoch bei vier oder mehr befallenen axillären Lymphknoten stets indiziert und sollte bei ein bis drei positiven Lymphknoten erwogen werden . Bezüglich der Sequenz von Radio- und Systemtherapie gibt es keine richtungweisenden Evidenzen zugunsten einer Therapiemodalität . Postoperativ sollte die Sequenz vom dominierenden Risiko abhängig gemacht werden . Schlussfolgerung : Nach Mastektomie ist die PMRT bei T3/T4-Tumoren , Resttumor und/oder axillären Lymphknotenmetastasen obligat . Die Bestrahlung der regionalen Lymphabflusswege und die Sequenz von Radio- und Systemtherapie bleiben bei unzureichender Date nlage Gegenst and interdisziplinärer Diskussionen One hundred women with operable breast cancer were r and omized to two equal groups . In group A the aim was to remove all fat tissue in the axilla . In group B suspectedly pathologic nodes were removed , and if no nodes were palpable the lower half of the axillary fat was excised . Irrespective of this grouping , partial mastectomy was generally performed for T1 tumour ( 17 in each group ) and mastectomy for T2 tumour ( 33 in each group ) . Also irrespective of A and B grouping , radiotherapy including the axilla was given after partial mastectomy , and to women under 70 with T2 tumour and /or lymph-node secondaries .  Arm volume and shoulder mobility were measured before and 3 , 6 and 12 months after surgery . Arm oedema ( greater than or equal to 10 % volume increase ) was found in 14 group A patients , but none in group B. Twelve of the 14 patients with arm oedema had been irradiated . Subjective sensation of arm swelling in the absence of an objective ly measurable increase in arm volume was also more common after axillary dissection plus irradiation than after the other forms of treatment . Impairment of shoulder mobility was more frequent after axillary irradiation Background The st and ard treatment of the axilla in breast cancer used to be an axillary lymph node dissection . An axillary lymph node dissection is known to give substantial risks of morbidity . In recent years the sentinel node biopsy has become common practice . Future r and omized study results will determine whether the expected decrease in morbidity can be proven . Methods Before the introduction of the sentinel node biopsy , we conducted a study in which 180 women of 50 years and older with T1/T2 cN0 breast cancer were treated with breast conserving therapy .  Instead of an axillary lymph node dissection regional radiotherapy was given in combination with tamoxifen ( RT-group ) . The study group was compared with 341 patients , with the same patient and tumour characteristics , treated with an axillary lymph node dissection ( S-group ) . Results The treatment groups were comparable , except for age . The RT-group was significantly older than the S-group . The median follow up was 7.2 years . The regional relapse rates were low and equal in both treatment groups , 1.1 % in RT-group versus 1.5 % in S-group at 5 years . The overall survival was similar ; the disease free survival was significant better in the RT-group . Conclusion Regional recurrence rates after regional radiotherapy are very low and equal to an axillary lymphnode dissection BACKGROUND Irradiation after mastectomy can reduce locoregional recurrences in women with breast cancer , but whether it prolongs survival remains controversial . We conducted a r and omized trial of radiotherapy after mastectomy in high-risk premenopausal women , all of whom also received adjuvant systemic chemotherapy with cyclophosphamide , methotrexate , and fluorouracil ( CMF ) . METHODS A total of 1708 women who had undergone mastectomy for pathological stage II or III breast cancer were r and omly assigned to receive eight cycles of CMF plus irradiation of the chest wall and regional lymph nodes ( 852 women ) or nine cycles of CMF alone ( 856 women ) . The median length of follow-up was 114 months . The end points were locoregional recurrence , distant metastases , disease-free survival , and overall survival . RESULTS The frequency of locoregional recurrence alone or with distant metastases was 9 percent among the women who received radiotherapy plus CMF and 32 percent among those who received CMF alone ( P<0.001 ) . The probability of survival free of disease after 10 years was 48 percent among the women assigned to radiotherapy plus CMF and 34 percent among those treated only with CMF ( P<0.001 ) . Overall survival at 10 years was 54 percent among those given radiotherapy and CMF and 45 percent among those who received CMF alone ( P<0.001 ) . Multivariate analysis demonstrated that irradiation after mastectomy significantly improved disease-free survival and overall survival , irrespective of tumor size , the number of positive nodes , or the histopathological grade . CONCLUSIONS The addition of postoperative irradiation to mastectomy and adjuvant chemotherapy reduces locoregional recurrences and prolongs survival in high-risk premenopausal women with breast cancer Objective : A prospect i ve , phase III r and omized study was undertaken to compare the outcomes of 2 different radiotherapy and chemotherapy sequences  in conservatively treated patients with breast cancer . Methods : Between January 1997 and November 2002 , 206 patients operated of quadrantectomy and axillary dissection for breast cancer , c and i date s to receive adjuvant CMF chemotherapy ( cyclophosphamide , methotrexate , and fluorouracil )  were assigned to concurrent or sequential radiation treatment by using a balanced r and omization method . Before r and omization patients were stratified by tumor diameter , age , and lymph node status . The primary end point was the freedom from breast recurrence , and secondary end points were overall and disease-free survival . Overall outcomes were analyzed according to the intention-to-treat principle . Results : All 206 patients enrolled and r and omized in the trial were analyzed . The median follow-up was 111 months , with no patient lost for follow-up . No difference in 10-years breast recurrence-free , disease-free , metastasis-free , and overall survival rates was observed in the 2 treatment sequence groups . The Hazard Ratios , calculated for each prognostic factor , showed no difference in all outcomes between the 2 treatment sequences . Conclusions : No influence of the treatment sequence on long-term outcomes was observed in this trial . This finding suggests that to avoid an increased risk of distant recurrence or an excessive toxicity , radiation therapy may be delayed until after the end of the more , recently used , anthracycline-based chemotherapy without increasing the risk of breast recurrences , thus allowing the delivery of full-dose chemotherapy in patients at risk for systemic disease spread AIMS Patients with locally advanced pancreatic cancer ( LAPC ) are most commonly managed with chemotherapy or concurrent chemoradiotherapy ( CRT ) , which may or may not include non-involved regional lymph nodes in the clinical target volume . We present our results of CRT for LAPC using capecitabine and delivering radiotherapy to a limited radiation field that excluded non-involved regional lymph nodes from the clinical target volume . MATERIAL S AND METHODS Thirty patients were studied . Patients received 50.4 Gy external beam radiotherapy in 28 fractions , delivered to a planning target volume exp and ed from the primary tumour and involved nodes only . Capecitabine ( 500 - 600 mg/m2 ) was given twice daily continuously during radiotherapy .  Toxicity and efficacy data were prospect ively collected . RESULTS Nausea , vomiting and tumour pain were the most common grade 2 toxicities . One patient developed grade 3 nausea . The median time to progression was 8.8 months , with 20 % remaining progression free at 1 year . The median overall survival was 9.7 months with a 1 year survival of 30 % . Of 21 patients with imaged progression , 13 ( 62 % ) progressed systemically , three ( 14 % ) had local progression , two ( 10 % ) had locoregional progression and three ( 14 % ) progressed with both local/locoregional and systemic disease . CONCLUSION CRT using capecitabine and limited field radiotherapy is a well-tolerated , relatively efficacious treatment for LAPC . The low toxicity and low regional progression rates support the use of limited field radiotherapy , allowing evaluation of this regimen with other anti-cancer agents Nonpalpable , mammographically detected breast cancers are on the increase . The percentage of patients with histologically involved nodes is therefore decreasing . Axillary clearance aims at reducing the probability of later clinical involvement of the axilla and at establishing a sound basis for adjuvant treatment planning . Minimally invasive techniques have been applied to a growing number of surgical procedures now including exploration of the axilla . The technique used and results achieved in a series of 50 consecutive patients treated by liposuction and axilloscopy by one single surgeon , including all the patients from the very first attempt , are presented here . Patients were excluded with palpable lymph nodes or a primary tumor in the direct vicinity of the axilla that could be injured by the liposuction canula .  The average number of lymph nodes removed was 13.4 . Thirty-four percent of patients had involved nodes . The mean number of involved nodes in these patients was 3.1 . After a median follow-up time of only 15 months no axillary recurrences or trocar site metastases have been found in the first 40 patients . Using a self- assessment question naire , the patients rate this technique as excellent . There was no lymphedema . The cosmetic result is certainly better than after conventional axillary clearance . Great experience of laparoscopic surgery and an excellent knowledge of the axillary anatomy are prerequisites for the practice of axilloscopic treatment of the axilla . The working space within the axilla is small and a number of structures need absolutely to be preserved . A longer follow-up period than the one so far achieved in this series or any other in the literature to date is necessary before this technique can be generally recommended Background TomoBreast is a unicenter , non-blinded r and omized trial comparing conventional radiotherapy ( CR ) vs. hypofractionated Tomotherapy ( TT ) for post-operative treatment of breast cancer . The purpose of the trial is to compare whether TT can reduce heart and pulmonary toxicity . We evaluate early toxicities . Methods The trial started inclusion in May 2007 and reached its recruitment in August 2011 . Women with stage T1 - 3N0M0 or T1 - 2N1M0 breast cancer completely resected by tumorectomy ( BCS ) or by mastectomy ( MA ) who consented to participate were r and omized , according to a prescribed computer-generated r and omization schedule , between control arm of CR 25x2 Gy/5 weeks by tangential fields on breast/chest wall , plus supraclavicular-axillary field if node-positive , and sequential boost 8x2 Gy/2 weeks if BCS ( cumulative dose 66 Gy/7 weeks ) , versus experimental TT arm of 15x2.8 Gy/3 weeks , including nodal areas if node-positive and simultaneous integrated boost of 0.6 Gy if BCS ( cumulative dose 51 Gy/3 weeks ) . Outcomes evaluated were the pulmonary and heart function . Comparison of proportions used one-sided Fisher 's exact test . Results By May 2010 , 70 patients were r and omized and had more than 1 year of follow-up . Out of 69 evaluable cases , 32 were assigned to CR ( 21 BCS , 11 MA ) , 37 to TT ( 20 BCS , 17 MA ) . Skin toxicity of grade ≥1 at 2 years was 60 % in CR , vs. 30 % in TT arm . Heart function showed no significant difference for left ventricular ejection fraction at 2 years , CR 4.8 % vs. TT 4.6 % . Pulmonary function tests at 2 years showed grade ≥1 decline of FEV1 in 21 % of CR , vs. 15 % of TT and decline of DLco in 29 % of CR , vs. 7 % of TT ( P = 0.05 ) . Conclusions There were no unexpected severe toxicities . Short course radiotherapy of the breast with simultaneous integrated boost over 3 weeks proved feasible without excess toxicities . Pulmonary tests showed a slight trend in favor of Tomotherapy , which will need confirmation with longer follow-up of patients .Trail registration Clinical Trials.gov In a prospect i ve study of 622 women with breast cancer , those with one to three histologically positive axillary lymph nodes were r and omised after mastectomy  to receive cyclophosphamide 100 mg/m2 orally on days 1 - 14 , methotrexate 40 mg/m2 intravenously on days 1 and 8 , and fluorouracil 600 mg/m2 intravenously on days 1 and 8 every 28 days for six cycles ( CMF x six ) , or for twelve cycles of the same chemotherapy ( CMF x 12 ) . Those with > or = four positive nodes were r and omised to one of these two groups or to 5000 cGy of postmastectomy regional radiotherapy ( RT ) followed by six cycles of the same chemotherapy ( RT + CMF x six ) . With about 10 years median follow-up , there was no significant difference in survival or disease-free survival among the three groups . There was evidence of decreased locoregional recurrence in patients with > or = four nodes who received RT + CMF x six ( relative risk 0.53 , P = 0.067 ) . Multivariate analysis indicated that the presence of > or = four positive nodes ( negatively ) and the percentage of ideal ( full ) dose of CMF received ( positively ) were the strongest factors predictive of survival . This study shows no advantage for 12 over six cycles of CMF chemotherapy in women with breast cancer and positive axillary nodes . There was a suggestion of decreased locoregional recurrence but no improvement in survival with radiotherapy for women with > or = four positive nodes PURPOSE To examine the importance of estrogen receptor ( ER ) , progesterone receptor ( PgR ) , human epidermal growth factor receptor 2 ( HER-2 ) , and constructed subtypes in a large study r and omly assigning patients to receive or not receive postmastectomy radiotherapy ( PMRT ) .  PATIENTS AND METHODS The present analysis included 1,000 of the 3,083 high-risk breast cancer patients r and omly assigned to PMRT in the Danish Breast Cancer Cooperative Group ( DBCG ) protocol 82 trials b and c. Tissue microarray sections were stained for ER , PgR , and HER-2 . Median follow-up time for patients alive was 17 years . End points were locoregional recurrence as isolated first event , distant metastases , and overall survival . For statistical analyses four subgroups were constructed from hormonal receptors ( Rec ) . Rec+ was defined as ER+ and /or PgR+ . Rec-as both ER- and PgR- . The four subgroups were Rec+/HER-2- , Rec+/HER-2 + , Rec-/HER-2-(triple negative ) , and Rec-/HER-2 + . RESULTS A significantly improved overall survival after PMRT was seen only among patients characterized by good prognostic markers such as hormonal receptor-positive and HER-2- patients ( including the two Rec+ subtypes ) . No significant overall survival improvement after PMRT was found among patients with an a priori poor prognosis , the hormonal receptor-negative and HER-2 + patients , and in particular the Rec-/HER-2 + subtype . Furthermore , comparing hazard ratios and 95 % CIs , significantly smaller improvements in locoregional recurrence control after PMRT were found for ER- and PgR-tumors compared with the ER+ and PgR+ tumors ( P = .003 and .04 , respectively ) , and for the triple-negative ( P = .02 ) , and the Rec-/HER-2 + subtypes ( P = .003 ) compared with the Rec+/HER-2-subtype . CONCLUSION Hormonal receptor status , HER-2 , and the constructed subtypes may be predictive of locoregional recurrence and survival after postmastectomy radiotherapy Background Breast-conservation surgery plus radiotherapy has become the st and ard of care for early-stage breast cancer ; we evaluated its long-term complications . Methods We selected patients treated with surgery and radiotherapy between January 1990 and December 1992 ( an era in which st and ard radiation dosages were used ) with follow-up for at least 1 year . Patients were prospect ively monitored for treatment-related complications . Median follow-up time was 89 months . Results A total of 294 patients met the selection criteria .  Grade 2 or higher late complications were identified in 29 patients and included arm edema in 13 patients , breast skin fibrosis in 12 , decreased range of motion in 4 , pneumonitis in 2 , neuropathy in 2 , fat necrosis in 1 , and rib fracture in 1 . Arm edema was more common after lumpectomy plus axillary node dissection than after lumpectomy alone . Arm edema occurred in 18 % of patients who underwent surgery plus irradiation of the lymph nodes and 10 % who underwent surgery without nodal irradiation . Conclusions Breast-conservation surgery plus radiotherapy was associated with grade 2 or higher complications in only 9.9 % of patients . Half of these complications were attributable to axillary dissection , it is hoped that lower complication rates can be achieved with sentinel lymph node biopsy OBJECTIVE To provide information and recommendations for women and their physicians when making decisions about the management of lymphedema related to breast cancer . OPTIONS Compression garments , pneumatic compression pumps , massage and physical therapies , other physical therapy modalities , pharmaceutical treatments . OUTCOMES Symptom control , quality of life , cosmetic results . EVIDENCE Systematic review of English- language literature retrieved primarily from MEDLINE ( 1966 to April 2000 ) and CANCERLIT ( 1985 to April 2000 ) . Non systematic review of breast cancer literature published to October 2000 . RECOMMENDATIONS Pre- and postoperative measurements of both arms are useful in the assessment and diagnosis of lymphedema . Circumferential measurements should be taken at 4 points : the metacarpal-phalangeal joints , the wrists , 10 cm distal to the lateral epicondyles and 15 cm proximal to the lateral epicondyles . Clinicians should elicit symptoms of heaviness , tightness or swelling in the affected arm . A difference of more than 2.0 cm at any of the 4 measurement points may warrant treatment of the lymphedema , provided that tumour involvement of the axilla or brachial plexus , infection and axillary vein thrombosis have been ruled out . Practitioners may want to encourage long-term and consistent use of compression garments by women with lymphedema . One r and omized trial has demonstrated a trend in favour of pneumatic compression pumps  compared with no treatment . Further r and omized trials are required to determine whether pneumatic compression provides additional benefit over compression garments alone . Complex physical therapy , also called complex decongestive physiotherapy , requires further evaluation in r and omized trials . In one r and omized trial no difference in outcomes was detected between compression garments plus manual lymph drainage versus compression garments alone . Clinical experience supports encouraging patients to consider some practical advice regarding skin care , exercise and body weight . [ A patient version of these guidelines appears in Appendix 2 . ] VALIDATION An initial draft of this document was developed by a task force sponsored by the BC Cancer Agency . It was up date d and revised substantially by a writing committee and then su bmi tted for further review , revision and approval by the Steering Committee for Clinical Practice Guidelines for the Care and Treatment of Breast Cancer . SPONSOR The steering committee was convened by Health Canada . COMPLETION DATE : October 2000 Between January 1980 and October 1983 , 417 patients were r and omized for mastectomy followed by axillary node sampling or full axillary clearance .  The aim of the study was to determine whether a st and ard ‘ four‐node ’ axillary sample , followed by careful dissection of removed tissue , could accurately indicate the extent of local treatment required . Axillary radiotherapy was given only to patients with histological involvement of sample d nodes and not to any having axillary clearance .  The incidence of involved nodes was similar for both groups , as were distant relapse and survival rates . Currently 62.6 per cent are alive after clearance and 65.0 per cent after sampling . A non‐significant increase in the rate of locoregional relapse was observed for those treated by axillary node clearance , this being due mainly to increased relapse on the unirradiated chest wall ( clearance 21 per cent versus sampling 12 per cent in patients with node‐positive disease ) . There was only a minor difference in axillary relapse , favouring axillary clearance ( 3.0 versus 5.4 per cent ) . In patients with operable breast cancer , mastectomy with axillary node sampling gives equal control to mastectomy with axillary node clearance but , as morbidity is greater , surgical clearance of the axilla is the preferred option The last quarter of the twentieth century has brought about sweeping changes in the loco-regional treatment of breast cancer . R and omised trials have consistently established that survival rates after conservation surgery and breast irradiation are equivalent to those observed after modified radical mastectomy [ 1 ] . Moreover , during the same period the use of mammography in asymptomatic women has led to a relative increase in small tumours , ideally suitable for breast conservation . As a consequence , the use of conservation surgery has risen progressively during the 1980s and 1990s , with a corresponding increase in the importance of breast irradiation . In addition , recent meta-analyses of r and omised trials have established that breast cancer mortality can be significantly reduced by loco-regional radiotherapy ( RT ) , and that the increased intercurrent mortality observed in older trials was caused by an excess in cardiovascular deaths , presumably avoidable , associated with the earlier techniques [ 2,3 ] . Newer trials of postmastectomy radiotherapy ( PMRT ) have demonstrated a clear survival improvement , without excess cardiac morbidity , leading to an increased confidence in the use of adjuvant loco-regional RT [ 4,5 ] . The extent of the swing to conservative surgery varies amongst geographical regions , depending , at least in part , on the availability of radiotherapy services . With the increasing diffusion of medical technology throughout Europe , this factor will probably assume a decreasing importance for the choice of primary breast cancer therapy . In urban areas with a high socio-economic st and ard , it is likely that mastectomy will come to be practised in a dwindling minority of patients . According to the Geneva Tumour Registry , the proportion of all curative breast operations that were conservative rose from 3 % before 1985 , to 51 % in 1990 , then to 67 % since 1998 ( Registre genevois des tumeurs , unpublished data , 2000 ) . As a consequence , patients currently requiring mastectomy are likely to have larger tumours and positive lymph nodes , and will frequently be considered for PMRT . In such a setting , a substantial majority of primary breast cancer patients will therefore receive RT as part of their initial treatment . These changes come at a time when the prevalence of breast cancer  is increasing significantly due , at least partly , to the ageing of the European population . For Geneva , an increase of more than 50 % in the number of new breast cancer cases is projected for the period between 2000 and 2010 ( Registre genevois des tumeurs , unpublished data , 1998 ) . The dem and for radiotherapy services required to treat breast cancer patients may thus be expected to increase substantially . Accordingly , the European Society of Mastology ( EUSOMA ) believes that a position paper regarding the use of RT in breast cancer is timely and useful . This document discusses the indications for adjuvant RT in operable breast cancer ( clinical stages T0 - 3 , N0 - 1 , M0 ) , the technical principles for its proper execution , and where possible , notions of its optimal co-ordination with other treatment modalities . As the breast cancer literature is vast , analysis was necessarily restricted to data having a high likelihood of being reliable , making every effort to draw conclusions likely to be pertinent PURPOSE S A r and omized trial was conducted to compare tumorectomy and breast irradiation with modified radical mastectomy . We have analyzed the patterns of failure in each arm of the trial and the prognostic factors that have an independent effect on treatment failures and overall survival . PATIENTS AND METHODS The trial included 179 patients with breast cancer of up to 20 mm in diameter at macroscopic examination . Eighty-eight patients had conservative management and 91 a mastectomy . All patients had axillary dissection with frozen-section examination .  For patients with positive axillary nodes ( N+ ) , a second r and omization was performed : lymph node irradiation versus no further regional treatment . Patterns of failure were determined by a competing-risk approach and multivariate analysis . A prognostic-score was determined by multivariate analysis . RESULTS Overall survival , distant metastasis , contralateral breast cancer , new primary malignancy , and locoregional recurrence rates were not significantly different between the two surgical groups , or between lymph node irradiation groups . Most recurrences appeared during the first 10 years . Three distinct prognostic groups were determined taking into account age , tumor size , histologic grading , and number of positive axillary nodes . CONCLUSION Long-term results support conservative treatment with limited surgery and systematic breast irradiation as a safe procedure for the management of small breast cancers . Four easily obtainable clinical and histologic factors may be combined in a prognostic score that is highly predictive of overall and event-free survival Background To report our experience with increased dose intensity-modulated radiation and concurrent systemic chemotherapy as definitive treatment of locally advanced esophageal cancer . Patients and methods We analyzed 27 consecutive patients with histologically proven esophageal cancer , who were treated with increased-dose IMRT  as part of their definitive therapy . The majority of patients had T3/4 and /or N1 disease ( 93 % ) . Squamous cell carcinoma was the dominating histology ( 81 % ) . IMRT was delivered in step- and -shoot technique in all patients using an integrated boost concept . The boost volume was covered with total doses of 56 - 60 Gy ( single dose 2 - 2.14 Gy ) , while regional nodal regions received 50.4 Gy ( single dose 1.8 Gy ) in 28 fractions . Concurrent systemic therapy was scheduled in all patients and administered in 26 ( 96 % ) . 17 patients received additional adjuvant systemic therapy .  Loco-regional control , progression-free and overall survival as well as acute and late toxicities were retrospectively analyzed . In addition , quality of life was prospect ively assessed according to the EORTC QLQs ( QLQ-OG25 , QLQ-H&N35 and QLQ-C30 ) . Results Radiotherapy was completed as planned in all but one patient ( 96 % ) , and 21 patients received more than 80 % of the planned concurrent systemic therapy . We observed ten locoregional failures , transferring into actuarial 1- , 2- and 3-year-locoregional control rates of 77 % , 65 % and 48 % . Seven patients developed distant metastases , mainly to the lung ( 71 % ) . The actuarial 1- , 2- and 3-year-disease free survival rates were 58 % , 48 % and 36 % , and overall survival rates were 82 % , 61 % and 56 % . The concept was well tolerated , both in the clinical objective examination and also according to the subjective answers to the QLQ question naire . 14 patients ( 52 % ) suffered from at least one acute CTC grade 3/4 toxicity , mostly hematological side effects or dysphagia . Severe late toxicities were reported in 6 patients ( 22 % ) , mostly esophageal strictures and ulcerations . Severe side effects to skin , lung and heart were rare . Conclusion IMRT with concurrent systemic therapy in the definitive treatment of esophageal cancer using an integrated boost concept with doses up to 60 Gy is feasible and yields good results with acceptable acute and late overall toxicity and low side effects to skin , lung and heart PURPOSE Axillary dissection is the st and ard management of the axilla in invasive breast carcinoma . This surgery is responsible for functional sequelae and some options are considered , including axillary radiotherapy . In 1992 , we published the initial results of a prospect i ve r and omized trial comparing lumpectomy plus axillary radiotherapy versus lumpectomy plus axillary dissection . We present an up date of this study with a median follow-up of 180 months ( range , 12 to 221 months ) . PATIENTS AND METHODS Between 1982 and 1987 , 658 patients with a breast carcinoma less than 3 cm in diameter and clinical ly uninvolved lymph nodes were r and omly assigned to axillary dissection or axillary radiotherapy .  All patients underwent wide excision of the tumor and breast irradiation . RESULTS The two groups were similar for age , tumor-node-metastasis system stage , and presence of hormonal receptors ; 21 % of the patients in the axillary dissection group were node-positive . Our initial results showed an increased survival rate in the axillary dissection group at 5 years ( P = .009 ) . At 10 and 15 years , however , survival rates were identical in both groups ( 73.8 % v 75.5 % at 15 years ) . Recurrences in the axillary node were less frequent in the axillary dissection group at 15 years ( 1 % v 3 % ; P = .04 ) . There was no difference in recurrence rates in the breast or supraclavicular and distant metastases between the two groups . CONCLUSION In early breast cancers with clinical ly uninvolved lymph nodes , our findings show that long-term survival does not differ after axillary radiotherapy and axillary dissection . The only difference is a better axillary control in the group with axillary dissection BACKGROUND If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node , axillary lymph node dissection is the present st and ard . Although axillary lymph node dissection provides excellent regional control , it is associated with harmful side-effects . We aim ed to assess whether axillary radiotherapy provides comparable regional control with fewer side-effects . METHODS Patients with T1 - 2 primary breast cancer and no palpable lymphadenopathy were enrolled in the r and omised , multicentre , open-label , phase 3 non-inferiority EORTC 10981 - 22023 AMAROS trial . Patients were r and omly assigned ( 1:1 ) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node , stratified by institution . The primary endpoint was non-inferiority of 5-year axillary recurrence , considered to be not more than 4 % for the axillary radiotherapy group compared with an expected 2 % in the axillary lymph node dissection group . Analyses were by intention to treat and per protocol . The AMAROS trial is registered with Clinical Trials.gov , number NCT00014612 . FINDINGS Between Feb 19 , 2001 , and April 29 , 2010 , 4823 patients were enrolled at 34 centres from nine European countries , of whom 4806 were eligible for r and omisation . 2402 patients were r and omly assigned to receive  axillary lymph node dissection and 2404 to receive axillary radiotherapy . Of the 1425 patients with a positive sentinel node , 744 had been r and omly assigned to axillary lymph node dissection and 681 to axillary radiotherapy ; these patients constituted the intention-to-treat population . Median follow-up was 6·1 years ( IQR 4·1 - 8·0 ) for the patients with positive sentinel lymph nodes . In the axillary lymph node dissection group , 220 ( 33 % ) of 672 patients who underwent axillary lymph node dissection had additional positive nodes . Axillary recurrence occurred in four of 744 patients in the axillary lymph node dissection group and seven of 681 in the axillary radiotherapy group . 5-year axillary recurrence was 0·43 % ( 95 % CI 0·00 - 0·92 ) after axillary lymph node dissection versus 1·19 % ( 0·31 - 2·08 ) after axillary radiotherapy . The planned non-inferiority test was underpowered because of the low number of events . The one-sided 95 % CI for the underpowered non-inferiority test on the hazard ratio was 0·00 - 5·27 , with a non-inferiority margin of 2 . Lymphoedema in the ipsilateral arm was noted significantly more often after axillary lymph node dissection than after axillary radiotherapy at 1 year , 3 years , and 5 years . INTERPRETATION Axillary lymph node dissection and axillary radiotherapy after a positive sentinel node provide excellent and comparable axillary control for patients with T1 - 2 primary breast cancer and no palpable lymphadenopathy . Axillary radiotherapy results in significantly less morbidity . FUNDING EORTC Charitable Trust The beneficial effects of chemotherapy in patients with advanced head and neck cancer remain controversial in terms of survival , but have shown some promise in improving locoregional control and quality of life . In an effort to improve locoregional control and survival , a prospect i ve phase II study was initiated using paclitaxel and carboplatin with concurrent conventional fractionated external-beam radiotherapy . Paclitaxel and carboplatin have both shown excellent radiosensitization through two discrete mechanisms , cell blockage in G2/M phase and inhibition of DNA repair , respectively . Patients were stratified as either operable or inoperable . This report pertains to the inoperable patient group , who received eight cycles of weekly paclitaxel ( 60 mg/m2 ) , carboplatin ( area under the concentration-time curve of 1 ) with conventional radiotherapy ( 72 Gy ) . Chemoradiotherapy was followed by neck dissection for those patients who presented with clinical ly palpable lymph nodes . Thirty-three patients were enrolled in this group ( 23 men and 10 women with a median age of 56 years ) . Eleven patients ( 33 % ) had stage III disease ; 22 ( 67 % ) , stage IV disease . The median follow-up period was 14 months . Clinical complete response occurred in 20 patients ( 60 % ) and partial response occurred in 10 ( 30 % ) , for an overall response rate of 90 % . Following completion of therapy , 18 patients have undergone biopsy at the primary tumor site and 17 were negative . Eight of the 16 patients with clinical ly palpable neck nodes at presentation underwent neck dissection ; five ( 63 % ) had negative nodes . Mucositis was the most common toxicity . Grade 3 or 4 mucositis occurred in 30 of the 33 ( 90 % ) patients . Other grade 3 or 4 toxicities included skin ( 22 % ) , c and idiasis ( 19 % ) , neutropenia ( 9 % ) , and dehydration ( 6 % ) . One patient with laryngeal carcinoma who had pathologic complete response developed cartilage necrosis and is undergoing hyperbaric oxygen therapy . Survival data are early but encouraging . Concurrent paclitaxel , carboplatin , and external-beam radiotherapy yielded excellent clinical and pathologic responses . Mucositis remains the most common and significant morbidity . The study will continue for necessary accrual The MF07 - 01 trial is a phase III r and omized controlled trial which compares breast cancer patients with distant metastases at presentation who receive locoregional treatment for intact primary tumor with those who do not receive such treatment . The primary objective of the study is to assess whether locoregional treatment of the primary tumor provides a better overall survival . Secondary objectives include progression-free survival , quality -of-life , and morbidity related to locoregional treatment . Locoregional treatments consist of either mastectomy or breast conserving surgery with level I-II axillary clearance in clinical ly or sentinel lymph node positive patients . Radiation therapy to the whole breast follows breast conserving surgery . St and ard systemic therapy is given to all patients either immediately after r and omization in no-locoregional treatment arm or after surgical resection of the intact primary tumor in locoregional treatment arm . The study is conducted in Turkey as a multicenter trial with central r and omization . Total accrual target is 271 . The trial was activated in October 2007 and authorized centers started to recruit patients since then . Clinical Trials.gov identifier number is NCT00557986 BACKGROUND Sentinel lymph node biopsy in women with operable breast cancer is routinely used in some countries for staging the axilla despite limited data from r and omized trials on morbidity and mortality outcomes . We conducted a multicenter r and omized trial to compare quality -of-life outcomes between patients with clinical ly node-negative invasive breast cancer who received sentinel lymph node biopsy and patients who received st and ard axillary treatment .  METHODS The primary outcome measures were arm and shoulder morbidity and quality of life .  From November 1999 to October 2003 , 1031 patients were r and omly assigned to undergo sentinel lymph node biopsy ( n = 515 ) or st and ard axillary surgery ( n = 516 ) . Patients with sentinel lymph node metastases proceeded to delayed axillary clearance or received axillary radiotherapy ( depending on the protocol at the treating institution ) . Intention-to-treat analyses of data at 1 , 3 , 6 , and 12 months after surgery are presented . All statistical tests were two-sided . RESULTS The relative risks of any lymphedema and sensory loss for the sentinel lymph node biopsy group compared with the st and ard axillary treatment group at 12 months were 0.37 ( 95 % confidence interval [ CI ] = 0.23 to 0.60 ; absolute rates : 5 % versus 13 % ) and 0.37 ( 95 % CI = 0.27 to 0.50 ; absolute rates : 11 % versus 31 % ) , respectively . Drain usage , length of hospital stay , and time to resumption of normal day-to-day activities after surgery were statistically significantly lower in the sentinel lymph node biopsy group ( all P < .001 ) , and axillary operative time was reduced ( P = .055 ) . Overall patient-recorded quality of life and arm functioning scores were statistically significantly better in the sentinel lymph node biopsy group throughout ( all P < or = .003 ) . These benefits were seen with no increase in anxiety levels in the sentinel lymph node biopsy group ( P > .05 ) . CONCLUSION Sentinel lymph node biopsy is associated with reduced arm morbidity and better quality of life than st and ard axillary treatment and should be the treatment of choice for patients who have early-stage breast cancer with clinical ly negative nodes From 1973 to 1980 , we carried out a controlled study at the National Cancer Institute in Milan to consider the value of a conservative procedure in patients with breast cancer of small size . We r and omized 701 patients with breast cancer measuring less than 2 cm in diameter and with no palpable axillary lymph nodes to Halsted radical mastectomy or to " quadrantectomy " with axillary dissection and radiotherapy to the ipsilateral residual breast tissue . We treated 349 patients with Halsted mastectomy and 352 with quadrantectomy .  The two groups were comparable in age distribution , size and site of primary tumor , menopausal status , and frequency of axillary metastases . There were three local recurrences in the Halsted group and one in the quadrantectomy group . Actuarial curves showed no difference between the two groups in disease-free or overall survival . From these results , mastectomy appears to involve unnecessary mutilation in patients with breast cancer of less than 2 cm and no palpable axillary nodes PURPOSE The purpose was to assess the incidence and clinical manifestations of radiation-induced brachial plexopathy in breast cancer patients , treated according to the Danish Breast Cancer Cooperative Group protocol s. METHODS AND MATERIAL S One hundred and sixty-one recurrence-free breast cancer patients were examined for radiation-induced brachial plexopathy after a median follow-up period of 50 months ( 13 - 99 months ) . After total mastectomy and axillary node sampling , high-risk patients were r and omized to adjuvant therapy .  One hundred twenty-eight patients were treated with postoperative radiotherapy with 50 Gy in 25 daily fractions over 5 weeks . In addition , 82 of these patients received cytotoxic therapy ( cyclophosphamide , methotrexate , and 5-fluorouracil ) and 46 received tamoxifen . RESULTS Five percent and 9 % of the patients receiving radiotherapy had disabling and mild radiation-induced brachial plexopathy , respectively . Radiation-induced brachial plexopathy was more frequent in patients receiving cytotoxic therapy ( p = 0.04 ) and in younger patients ( p = 0.04 ) . The clinical manifestations were paraesthesia ( 100 % ) , hypaesthesia ( 74 % ) , weakness ( 58 % ) , decreased muscle stretch reflexes ( 47 % ) , and pain ( 47 % ) . CONCLUSION The brachial plexus is more vulnerable to large fraction size . Fractions of 2 Gy or less are advisable . Cytotoxic therapy adds to the damaging effect of radiotherapy . Peripheral nerves in younger patients seems more vulnerable . Radiation-induced brachial plexopathy occurs mainly as diffuse damage to the brachial plexus HYPOTHESIS The use of the electrothermal bipolar vessel sealing system is feasible , safe , and effective in modified radical mastectomy with axillary dissection in terms of lymph vessel sealing , hemostasis , and perioperative complications . DESIGN Prospect i ve study . SETTING University surgical department . PATIENTS Between January 1 , 2003 , and December 31 , 2003 , 60 patients with locally advanced breast cancer ( T2 or T3 ) admitted for modified radical mastectomy with axillary dissection were included in this study . The entire procedure was performed by the same surgical team using the electrothermal bipolar vessel sealing system . MAIN OUTCOME MEASURES Final outcome , operative time , hospitalization stay duration , intraoperative blood loss , postoperative mastectomy and axillary drainage volume and duration , and postoperative complications ( seroma , bleeding , skin burn , hematoma , lymphedema , pneumothorax , and wound infection or necrosis ) . RESULTS The mean ( SD ) intraoperative blood loss was 45 ( 12 ) mL , and the mean ( SD ) operative time was 105 ( 7 ) minutes . No postoperative bleeding , seroma , hematoma , lymphedema , or other complications occurred . The mean ( SD ) mastectomy and axillary drainage volumes were 20 ( 8) and 155 ( 35 ) mL , respectively , and the mean ( SD ) drainage duration s were 1.3 ( 0.2 ) and 2.7 ( 0.5 ) days , respectively . The mean ( SD ) hospital stay was 3.7 ( 0.6 ) days . CONCLUSIONS In this first report ( to our knowledge ) of modified radical mastectomy with axillary dissection using the electrothermal bipolar vessel sealing system , the technique was feasible , safe , and effective . The device simplified the surgical procedure , while achieving efficient lymph vessel sealing and hemostasis . Compared with historical data regarding the conventional or harmonic scalpel , this technique seems to result in reduced operative time , perioperative blood loss , drainage volume and duration , and incidence of seroma or lymphedema . Prospect i ve r and omized controlled studies are necessary to evaluate the effect of this technique on perioperative complications Background : As cancer treatments evolve , it is important to reevaluate their effect on lymphedema risk in breast cancer survivors . Methods : A population -based r and om sample of 631 women from metropolitan Philadelphia , Pennsylvania , diagnosed with incident breast cancer in 1999 to 2001 , was followed for 5 years . Risk factor information was obtained by question naire and medical record review . Lymphedema was assessed with a vali date d question naire . Using Cox proportional hazards models , we estimated the relative incidence rates [ hazard ratios ( HR ) ] of lymphedema with st and ard adjusted multivariable analyses ignoring interactions , followed by models including clinical ly plausible treatment interactions . Results : Compared with no lymph node surgery , adjusted HRs for lymphedema were increased following axillary lymph node dissection [ ALND ; HR , 2.61 ; 95 % confidence interval ( 95 % CI ) , 1.77 - 3.84 ] but not sentinel lymph node biopsy ( SLNB ; HR , 1.04 ; 95 % CI , 0.58 - 1.88 ) . Risk was not increased following irradiation [ breast/chest wall only : HR , 1.18 ( 95 % CI , 0.80 - 1.73 ) ; breast/chest wall plus supraclavicular field ( + /− full axilla ) : HR , 0.86 ( 95 % CI , 0.48 - 1.54 ) ] . Eighty-one percent of chemotherapy was anthracycline based . The HR  for anthracycline chemotherapy versus no chemotherapy was 1.46 ( 95 % CI , 1.04 - 2.04 ) , persisting after stratifying on stage at diagnosis or number of positive nodes . Treatment combinations involving ALND or chemotherapy result ed in approximately 4- to 5-fold increases in HRs for lymphedema [ e.g. , HR of 4.16 ( 95 % CI , 1.32 - 12.45 ) for SLNB/chemotherapy/no radiation ] compared with no treatment . Conclusion : With st and ard multivariable analyses , ALND and chemotherapy increased lymphedema risk whereas radiation therapy and SLNB did not . However , risk varied by combinations of exposures . Impact : Treatment patterns should be considered when counseling and monitoring patients for lymphedema . Cancer Epidemiol Biomarkers Prev ; 19(11 ) ; 2734–46 . © 2010 AACR
Locoregional PMRT is recommended for women with 4 or more positive axillary lymph nodes .
The role of PMRT in women with 1 to 3 positive axillary lymph nodes is unclear .
Locoregional PMRT is generally not recommended for women who have tumours that are less than 5 cm in diameter and who have negative axillary nodes .
OBJECTIVE To provide information and recommendations to assist women with breast cancer and their physicians in making decisions regarding the use of locoregional post-mastectomy radiotherapy ( PMRT ) .
OUTCOMES Locoregional control , disease-free survival , overall survival and treatment-related toxicities .
To reduce the risk of lymphedema , radiation of the entire axilla should not be used routinely after complete axillary dissection of level I and II lymph nodes .
The use of modern techniques in radiotherapy planning is recommended to minimize excessive normal tissue exposure , particularly to the cardiac and pulmonary structures .
Common short-term side effects of PMRT , including fatigue and skin erythema , are generally tolerable and not dose-limiting .
Severe long-term side effects , including lymphedema , cardiac and pulmonary toxicities , brachial plexopathy , rib fractures and secondary neoplasms , are relatively rare .