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. A Comparative Study of Hypofractionated and Conventional Radiotherapy in Postmastectomy Breast Cancer Patients Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. Increased risk of locoregional recurrence for women with T1-2N0 triple-negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy. DEGRO practical guidelines: radiotherapy of breast cancer III—radiotherapy of the lymphatic pathways Regional Nodal Irradiation: Examining the Clinical Implications of Randomized Trials 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. Prognostic index score and clinical prediction model of local regional recurrence after mastectomy in breast cancer patients. Sequential induction chemotherapy and concomitant chemoradiotherapy in the management of locoregionally advanced laryngeal cancer. Postoperative radiotherapy following mastectomy for high-risk breast cancer. A randomised trial. Effect of local therapy on locoregional recurrence in postmenopausal women with breast cancer in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Phase III randomized equivalence trial of early breast cancer treatments with or without axillary clearance in post-menopausal patients results after 5 years of follow-up. Hypofractionated Regional Nodal Irradiation for Women With Node-Positive Breast Cancer. DEGRO Practical Guidelines for Radiotherapy of Breast Cancer II Accelerated fractionation (AF) compared to conventional fractionation (CF) improves loco-regional control in the radiotherapy of advanced head and neck cancers: results of the EORTC 22851 randomized trial. Long-term improvement in treatment outcome after radiotherapy and hyperthermia in locoregionally advanced cervix cancer: an update of the Dutch Deep Hyperthermia Trial.
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 Objective : The aim of this study was to compare toxicity and locoregional control of short duration hypofractionated ( HF ) radiotherapy ( RT ) with conventional RT in breast cancer patients . Methods : A total of 100 postmastectomy breast cancer patients were r and omized for adjuvant RT in control group ( comprising fifty patients who received the st and ard conventional dose of 50 Gy in 25 fractions with 2 Gy per fraction ) and study group ( comprising fifty patients who received HF RT with dose of 42.72 Gy in 16 fractions with 2.67 Gy per fraction ) . All patients were treated on linear accelerator with 3-dimensional conformal RT technique . Outcome was analyzed in terms of toxicity , tolerability , and locoregional control . Results : In the present study , at a median follow-up of 20 months , almost similar results were seen in both the groups in terms of toxicity , tolerability , and locoregional control .  Adjuvant postmastectomy HF RT was found to be well tolerated with mild-to-moderate side effects that neither reached statistical significance nor warranted any treatment interruption/hospitalization . Conclusions : HF postmastectomy RT is comparable to conventional RT without evidence of higher adverse effects or inferior locoregional tumor control and has an added advantage of increased compliance because of short duration ; hence , it can help in accommodating more breast cancer patients in a calendar year , ultimately result ing in decreased waiting list , increased turnover , and reduced cost of treatment 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 PURPOSE To evaluate the risk of locoregional recurrence ( LRR ) associated with locoregional treatment of women with primary breast cancer tumors negative for estrogen receptor , progesterone receptor , and human epidermal growth factor receptor 2 ( triple-negative breast cancer [ TNBC ] ) . PATIENTS AND METHODS Patients diagnosed with TNBC were identified from a cancer registry in a single institution ( n=768 ) .  LRR-free survival was estimated using Kaplan-Meier analysis . The Cox proportional hazards regression model was used to determine risk of LRR on the basis of locoregional management : breast-conserving therapy ( BCT ; ie , lumpectomy and adjuvant radiation therapy [ RT ] ) and modified radical mastectomy ( MRM ) in the TNBC population and T1 - 2N0 subgroup . RESULTS At a median follow-up of 7.2 years , 77 patients ( 10 % ) with TNBC developed LRR . Five-year LRR-free survival was 94 % , 85 % , and 87 % in the BCT , MRM , and MRM + RT groups , respectively ( P < .001 ) . In multivariate analysis , MRM ( compared with BCT ) , lymphovascular invasion and lymph node positivity were associated with increased LRR . Conversely , adjuvant chemotherapy was associated with decreased risk of LRR . For patients with T1 - 2N0 tumors , 5-year LRR-free survival was 96 % and 90 % in the BCT and MRM groups , respectively ( P = .027 ) , and MRM was the only independent prognostic factor associated with increased LRR compared with BCT ( hazard ratio , 2.53 ; 95 % CI , 1.12 to 5.75 ; P = .0264 ) . CONCLUSION Women with T1 - 2N0 TNBC treated with MRM without RT have a significant increased risk of LRR compared with those treated with BCT . Prospect i ve studies are warranted to investigate the benefit of adjuvant RT after MRM in TNBC Aim The purpose of this work is to up date the practical guidelines for adjuvant radiotherapy of the regional lymphatics of breast cancer published in 2008 by the breast cancer expert panel of the German Society of Radiation Oncology ( DEGRO ) . Methods A comprehensive survey of the literature concerning regional nodal irradiation ( RNI ) was performed using the following search terms : “ breast cancer ” , “ radiotherapy ” , “ regional node irradiation ” . Recent r and omized trials were analyzed for outcome as well as for differences in target definition . Field arrangements in the different studies were reproduced and superimposed on CT slices with individually contoured node areas . Moreover , data from recently published meta-analyses and guidelines of international breast cancer societies , yielding new aspects compared to 2008 , provided the basis for defining recommendations according to the criteria of evidence -based medicine . In addition to the more general statements of the German interdisciplinary S3 guidelines up date d in 2012 , this paper addresses indications , targeting , and techniques of radiotherapy of the lymphatic pathways after surgery for breast cancer . Results International guidelines reveal substantial differences regarding indications for RNI .  Patients with 1–3 positive nodes seem to profit from RNI compared to whole breast ( WBI ) or chest wall irradiation alone , both with regard to locoregional control and disease-free survival . Irradiation of the regional lymphatics including axillary , supraclavicular , and internal mammary nodes provided a small but significant survival benefit in recent r and omized trials and one meta- analysis . Lymph node irradiation yields comparable tumor control in comparison to axillary lymph node dissection ( ALND ) , while reducing the rate of lymph edema . Data concerning the impact of 1–2 macroscopically affected sentinel node ( SN ) or microscopic metastases on prognosis are conflicting . Conclusion Recent data suggest that the current restrictive use of RNI should be scrutinized because the risk – benefit relationship appears to shift towards an improvement of outcome .ZusammenfassungZielAktualisierung der DEGRO-Leitlinie von 2008 zur adjuvanten Strahlentherapie des regionalen Lymphabflusses bei Mammakarzinom und Ergänzung der allgemeinen Empfehlungen der interdisziplinären S3-Leitlinie der Deutschen Krebsgesellschaft von 2012 durch spezifisch radioonkologische Leitlinien zur Indikation , Zielvolumendefinition und Technik der postoperativen Radiotherapie . Method enDie DEGRO-Expertengruppe Mammakarzinom führte eine systematische Literaturrecherche nach r and omisierten Studien , Metaanalysen sowie internationalen Leitlinien durch , die nach 2008 publiziert wurden und sich an den Kriterien evidenzbasierter Medizin orientierten . Suchbegriffe waren „ breast cancer “ , „ radiotherapy “ und „ regional node irradiation “ . Die Studien wurden sowohl auf ihre Ergebnisse als auch hinsichtlich der Unterschiede in den Zielvolumina analysiert und auf 3-D-Planungsschnittbilder mit CT-konturierten Lymphabflussgebieten projiziert . ErgebnisseDie Indikation zur regionalen Lymphabflussbestrahlung ( RNI ) wird in internationalen Leitlinien unterschiedlich gestellt . Bei Patientinnen mit 1–3 befallenen axillären Lymphknoten wurden nach RNI i m Vergleich zur alleinigen Bestrahlung der Brust oder Brustw and Verbesserungen der lokoregionalen Kontrolle und des Überlebens beobachtet . Mehrere r and omisierte Studien und eine Metaanalyse zeigten nach RNI ( mit unterschiedlichen Zielvolumina ) eine zwar geringe , jedoch signifikante Verbesserung des Überlebens . Bei positivem Sentinel-Lymphknoten ( SN ) ist die Lymphabflussbestrahlung einer axillären Lymphonodektomie ( ALND ) gleichwertig in der lokalen Tumorkontrolle , geht aber mit einer deutlich geringeren Lymphödemrate einher . Zur Frage , ob ein solch limitierter Lymphknotenbefall und selbst eine Mikrometastasierung langfristig einen Einfluss auf die Prognose haben , ist die Date nlage widersprüchlich . SchlussfolgerungDie restriktive Indikationsstellung zur Lymphabflussbestrahlung muss angesichts neuer Date n aus r and omisierten Studien kritisch überdacht werden 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 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 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 PURPOSE To determine overall survival , progression-free survival , rate of voice preservation , and patterns of failure in locoregionally advanced laryngeal cancer treated with induction chemotherapy with or without surgery followed by concomitant chemoradiation . BACKGROUND Locoregionally advanced laryngeal cancer has been conventionally treated with either surgery and adjuvant radiotherapy or radiotherapy alone , and clinical and functional outcomes have been poor . Chemoradiotherapy has been demonstrated to improve functional outcome and disease control over conventional treatment in recent r and omized head and neck trials . PATIENTS AND METHODS Advanced head and neck cancer patients were enrolled onto two consecutive phase II studies . Induction treatment consisted of three cycles of cisplatin , 5-fluorouracil ( 5-FU ) , leucovorin , and interferon-alpha 2b ( PFL-IFN ) followed by surgery for residual disease . Surgical intent was to spare the larynx when possible . All patients then proceeded to concomitant chemoradiation consisting of seven or eight cycles of 5-FU , hydroxyurea , and a planned total radiotherapy dose of 7000 cGy ( FHX ) . RESULTS A subset of thirty-two laryngeal cancer patients with predominantly stage IV disease comprises the study group for this report . Clinical CR was observed in 59 % of patients following induction therapy . The median follow-up was 63.0 months for surviving patients and 44.5 months for all patients . At five years , overall survival is 47 % , progression-free survival is 78 % , and locoregional control is 78 % . No distant failures were observed . Voice preservation with disease control was 75 % at five years . Only two total laryngectomies were performed during the course of treatment and follow-up . Treatment-related toxicity accounted for two deaths . CONCLUSIONS The addition of concomitant chemoradiotherapy to induction chemotherapy for locoregionally advanced laryngeal cancer appears to increase locoregional control and survival rates . PFL-IFN-FHX result ed in high rates of disease cure and voice preservation in a group of patients that has traditionally fared poorly in both clinical and functional outcome Grade III , node-positive breast cancer carries a high risk of loco-regional relapse after simple mastectomy . A r and omised trial was conducted to assess whether this would be significantly reduced by postoperative radiotherapy .  Between 1985 and 1991 , 76 patients who had undergone a simple mastectomy and axillary sampling , and whose tumours had been found to be grade III and node-positive , were r and omised to receive postoperative radiotherapy to the chest wall and axilla or no further loco-regional treatment . Radiotherapy was delivered with 8 MV X-rays to the axilla and supraclavicular fossa and with 8 MeV electrons to the chest wall , to a dose of 45 Gy in 15 fractions over 3 weeks . All patients have been followed-up until death , or for a minimum of 10 years . All loco-regional recurrences occurred within the first 4 years after mastectomy . There were 26 such events in the 40 patients r and omised to the ' watch ' policy ( 65 % ) , as opposed to 9 out of 36 ( 25 % ) who received radiotherapy ( P<0.01 ) . Ten-year survival was 39 % in the radiotherapy arm as opposed to 25 % in the no radiotherapy arm . Recruitment to the trial was closed in 1991 , when a preliminary safety analysis revealed the size of the effect of radiotherapy , and from then on all node-positive patients with grade III tumours have routinely been given this treatment . Further follow-up has confirmed this finding , as borne out by these 10-year results , which shows that radiotherapy has a significant impact on reducing loco-regional recurrence in patients at high risk after mastectomy . There is an apparent survival benefit although , because of the small numbers in this trial , this has not reached statistical significance BACKGROUND AND PURPOSE The TEAM trial investigated the efficacy and safety of adjuvant endocrine therapy consisting of either exemestane or the sequence of tamoxifen followed by exemestane in postmenopausal hormone-sensitive breast cancer . The present analyses explored the association between locoregional therapy and recurrence ( LRR ) in this population . MATERIAL AND METHODS Between 2001 and 2006 , 9779 patients were r and omized . Local treatment was breast conserving surgery plus radiotherapy ( BCS+RT ) , mastectomy without radiotherapy ( MST-only ) , or mastectomy plus radiotherapy ( MST+RT ) .  Patients with unknown data on surgery , radiotherapy , tumor or nodal stage ( n=199 ) , and patients treated by lumpectomy without radiotherapy ( n=349 ) were excluded . RESULTS After a median follow-up of 5.2 years , 270 LRRs occurred ( 2.9 % ) among 9231 patients . The 5-years actuarial incidence of LRR was 4.2 % ( 95 % CI 3.3 - 4.9 % ) for MST-only , 3.4 % ( 95 % CI 2.4 - 4.2 % ) for MST+RT and 1.9 % ( 95 % CI 1.5 - 2.3 % ) for BCS+RT . After adjustment for prognostic factors , the hazard ratio ( HR , reference BCS+RT ) for LRR remained significantly higher for MST-only ( HR 1.53 ; 95 % CI 1.10 - 2.11 ) , not for MST+RT ( HR 0.78 ; 95 % CI 0.50 - 1.22 ) . CONCLUSION This explorative analysis showed a higher LRR risk after MST-only than after BCS+RT , even after adjustment for prognostic factors . As this effect was not seen for MST+RT versus BCS+RT , it might be explained by the beneficial effects of radiation treatment BACKGROUND Axillary lymph node clearance ( ALNC ) improves locoregional control and provides prognostic information for early breast cancer treatment , but effects on survival are controversial . This multicentre , r and omized pragmatic equivalence trial compares outcomes for post-menopausal early invasive breast cancer patients after locoregional treatment with ALNC and adjuvant therapies to outcomes after locoregional treatment  without ALNC and adjuvant therapies . METHODS From 1995 - 2005 , women aged ≥ 50 years with early breast cancer ( tumor ≤ 10 mm ) and clinical ly-negative axillary nodes were r and omized to receive treatment with ALNC ( Ax ) or without ( no-Ax ) . Adjuvant therapies were prescribed according to hormonal receptor status and individual histological results . The primary endpoint was overall survival ( OS ) ; secondary endpoints were event-free survival ( EFS ) and functional outcomes . The trial was terminated due to lack of equivalence and low accrual after first interim analyses . TRIAL REGISTRATION NCT00210236 . RESULTS Of 625 patients , 297 no-Ax and 310 Ax patients were maintained for final per- protocol analyses . OS and EFS at five years were not equivalent ( Ax vs. no-Ax : 98 % vs. 94 % and 96 % vs. 90 % respectively ) . Recurrence was higher for no-Ax , particularly in the first five years after surgery . Axillary nodes were positive for 14 % Ax patients but only 2 % no-Ax patients experienced axillary node recurrence . Functional impairments were greater after ALNC . CONCLUSION Our results fail to demonstrate equivalence of outcomes when ALNC is omitted from post-menopausal early breast cancer patient treatment . However the low locoregional recurrence rates warrant further examination over a longer duration , in particular to consider whether these would impact on survival 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 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 BACKGROUND AND PURPOSE A 5 week-hyperfractionated and accelerated radiotherapy regimen without reduction of the total dose was developed to fight tumour re population during treatment and tumour hypoxia . The purpose of the study was to try to improve loco-regional control in high risk head and neck carcinoma treated with curative radiotherapy .  METHODS AND MATERIAL S From 1985 to 1995 , a r and omised controlled trial of the EORTC Cooperative Group of Radiotherapy ( EORTC 22851 ) compared the experimental regimen ( 72 Gy/45 fractions/5 weeks ) to st and ard fractionation and overall treatment time ( 70 Gy/35 fractions/7 weeks ) in T2 , T3 and T4 head and neck cancers ( hypopharynx excluded ) . The end-point criteria were local and loco-regional control , overall and disease-free survival , and acute and late toxicities .  Five hundred twelve patients were accrued . RESULTS Patients in the AF ( accelerated fractionation ) arm did significantly better with regard to loco-regional control ( P = 0.02 ) result ing at 5 years in a 13 % gain ( 95 % CI 3 - 23 % gain ) in loco-regional control over the CF ( conventional fractionation ) arm . This improvement is of larger magnitude in patients with poorer prognosis ( N2 - 3 any T , T4 any N ) than in patients with more favourable stage . Multivariate analysis confirmed AF as an independent prognostic factor of good prognosis for loco-regional control ( P = 0.03 ) . Specific survival shows a trend ( P = 0.06 ) in favour of the AF arm . ACUTE AND LATE TOXICITIES : Acute and late toxicity were increased in the AF arm . Late severe functional irradiation damage occurred in 14 % of patients of the AF arm versus 4 % in the CF arm . Two cases of radiation-induced myelitis occurred after doses of 42 and 48 Gy to the spinal cord . CONCLUSIONS This trial shows that accelerated radiotherapy improves loco-regional control in head and neck squamous cell carcinomas . A less toxic scheme should , however , be investigated and documented before using accelerated radiotherapy as a st and ard regimen of curative radiotherapy for head and neck cancers PURPOSE The local failure rate in patients with locoregionally advanced cervical cancer is 41 - 72 % after radiotherapy ( RT ) alone , whereas local control is a prerequisite for cure . The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia ( HT ) improved 3-year local control rates of 41 - 61 % , as we reported earlier . In this study , we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up . METHODS AND MATERIAL S From 1990 to 1996 , a total of 114 women with locoregionally advanced cervical carcinoma were r and omly assigned to RT or RT+HT . The RT was applied to a median total dose of 68 Gy . The HT was given once weekly . The primary end point was local control . Secondary end points were overall survival and late toxicity . RESULTS At the 12-year follow-up , local control remained better in the RT+HT group ( 37 % vs. 56 % ; p=0.01 ) . Survival was persistently better after 12 years : 20 % ( RT ) and 37 % ( RT+HT ; p=0.03 ) . World Health Organization ( WHO ) performance status was a significant prognostic factor for local control . The WHO performance status , International Federation of Gynaecology and Obstetrics ( FIGO ) stage , and tumor diameter were significant for survival . The benefit of HT remained significant after correction for these factors . European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups . CONCLUSIONS For locoregionally advanced cervical cancer , the addition of HT to RT result ed in long-term major improvement in local control and survival without increasing late toxicity . This combined treatment should be considered for patients who are unfit to receive chemotherapy . For other patients , the optimal treatment strategy is the subject of ongoing research
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 .