Systemic therapy in the curative treatment of head-and-neck squamous cell cancer: Cancer Care Ontario clinical practice guideline. Systemic Therapy for Stage IV Non-Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. Primary systemic therapy for operable breast cancer. Systemic Therapy for Stage IV Non-Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. Exercise for people with cancer: a clinical practice guideline. Management of Depression in Patients With Cancer: A Clinical Practice Guideline. DEGRO Practical Guidelines for Radiotherapy of Breast Cancer II Chemotherapy and targeted therapy for women with human epidermal growth factor receptor 2-negative (or unknown) advanced breast cancer: American Society of Clinical Oncology Clinical Practice Guideline. Economic Analysis of Gene Expression Profile Data to Guide Adjuvant Treatment in Women with Early-Stage Breast Cancer DEGRO practical guidelines for radiotherapy of breast cancer V Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology clinical practice guideline update. Treatment of stage III non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Time to initiation of adjuvant chemotherapy in patients with rapidly proliferating early breast cancer. American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer. New Edinburgh primary breast cancer trials. Clinical practice guidelines for the care and treatment of breast cancer: 16. Locoregional post-mastectomy radiotherapy Stereotactic body radiation therapy for early-stage non-small cell lung cancer: Executive Summary of an ASTRO Evidence-Based Guideline.
OBJECTIVE The aim of the present work was to make recommendations about the use of systemically administered drugs in combination or in sequence with radiation ( rt ) or surgery , or both , for cure or organ preservation , or both , in patients with locally advanced nonmetastatic ( stages iii-ivb ) squamous cell carcinoma of the head and neck ( lascchn ) . METHODS The Meta- analysis of Chemotherapy in Head and Neck Cancer ( mach-nc ) reports have , de facto , guided practice since 2000 , and so we search ed the literature for systematic review s published from January 2000 to February 2015 in reference to five research questions . A search was also conducted up to February 2015 for r and omized trials ( rcts ) not included in the meta-analyses . Recommendations were constructed using the Cancer Care Ontario Program in Evidence -Based Care practice guidelines development cycle . RESULTS In addition to up date d mach-nc reports , five additional meta-analyses and thirty rcts were identified . Five recommendations for lascchn treatment were generated based on those data . Concurrent chemoradiation ( ccrt ) is recommended to maximize the chance of cure in patients less than 71 years of age when rt is used as definitive treatment . The same recommendation also applies to patients with resected lascchn considered to be at high risk for locoregional recurrence . For lascchn patients who are c and i date s for organ preservation strategies and would otherwise require total laryngectomy , either ccrt or induction chemotherapy , followed by rt or surgery based on tumour response is recommended . The addition of cetuximab to intensified rt ( concomitant boost or hyperfractionated schedule ) is an alternative to ccrt . Routine use of induction chemotherapy to improve overall survival is not recommended . CONCLUSIONS We were able to use high-level evidence from patients receiving rt as definitive or postoperative treatment to generate recommendations for the use of systemic therapy in the treatment of lascchn . A limitation is a lack of stratification for human papillomavirus-related cancers of the oropharynx . One rct provided evidence for the use of cetuximab as an alternative to chemotherapy in the definitive rt setting . Concurrent chemoradiation provides one strategy for larynx preservation , but the best strategy is unclear . Use of induction chemotherapy does not improve overall survival , and its use should be limited to patients requiring immediate tumour downsizing before local therapy Purpose Provide evidence -based recommendations updating the 2015 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer ( NSCLC ) . Methods The ASCO NSCLC Expert Panel made recommendations based on a systematic review of r and omized controlled trials from February 2014 to December 2016 plus the Cancer Care Ontario Program in Evidence -Based Care 's up date of a previous ASCO search . Results This guideline up date reflects changes in evidence since the previous guideline up date . Fourteen r and omized controlled trials provide the evidence base ; earlier phase trials also informed recommendation development . Recommendations New or revised recommendations include the following . Regarding first-line treatment for patients with non-squamous cell carcinoma or squamous cell carcinoma ( without positive markers , eg , EGFR/ALK /ROS1 ) , if the patient has high programmed death lig and 1 ( PD-L1 ) expression , pembrolizumab should be used alone ; if the patient has low PD-L1 expression , clinicians should offer st and ard chemotherapy . All other clinical scenarios follow 2015 recommendations . Regarding second-line treatment in patients who received first-line chemotherapy  , without prior immune checkpoint therapy , if NSCLC tumor is positive for PD-L1 expression , clinicians should use single-agent nivolumab , pembrolizumab , or atezolizumab ; if tumor has negative or unknown PD-L1 expression , clinicians should use nivolumab or atezolizumab . All immune checkpoint therapy is recommended alone plus in the absence of contraindications . For patients who received a prior first-line immune checkpoint inhibitor , clinicians should offer st and ard chemotherapy . For patients who can not receive immune checkpoint inhibitor after chemotherapy , docetaxel is recommended ; in patients with nonsquamous NSCLC , pemetrexed is recommended . In patients with a sensitizing EGFR mutation , disease progression after first-line epidermal growth factor receptor tyrosine kinase inhibitor therapy , and T790 M mutation , osimertinib is recommended ; if NSCLC lacks the T790 M mutation , then chemotherapy is recommended . Patients with ROS1 gene rearrangement without prior crizotinib may be offered crizotinib , or if they previously received crizotinib , they may be offered chemotherapy Eighty-eight patients presenting with operable breast cancer of 4 cm or greater in diameter ( T2 , T3 , N0 , N1 , M0 ) have received primary systemic therapy .  Response was assessed following 12 weeks of systemic therapy by linear regression analysis of changes in tumour volume . Definitive locoregional surgery ( mastectomy n = 82 , wide local excision n = 6 ) was performed on completion of systemic therapy ( 3 - 6 months ) . Response was observed in 24 ( 39 % ) of the 61 patients who received endocrine therapy ;  all 24 had tumours with an oestrogen receptor ( ER ) concentration of greater than or equal to 20 fmol mb-1 cytosol protein . Cytotoxic therapy was reserved for patients with tumours of ER concentration less than 20 fmol mg-1 cytosol protein ( n = 27 ) or when endocrine therapy had failed ( n = 20 ) . Response was observed in 34 patients ( 72 % ) . The overall survival rate at 3 years was 86 % , with 81 % remaining free from local relapse . We propose that the treatment policy outlined in this paper should now be tested against orthodox management by controlled r and omised trial Purpose To provide evidence -based recommendations to up date the American Society of Clinical Oncology guideline on systemic therapy for stage IV non – small-cell lung cancer ( NSCLC ) . Methods An Up date Committee of the American Society of Clinical Oncology NSCLC Expert Panel based recommendations on a systematic review of r and omized controlled trials from January 2007 to February 2014 . Results This guideline up date reflects changes in evidence since the previous guideline . Recommendations There is no cure for patients with stage IV NSCLC . For patients with performance status ( PS ) 0 to 1 ( and appropriate patient cases with PS 2 ) and without an EGFR-sensitizing mutation or ALK gene rearrangement , combination cytotoxic chemotherapy is recommended , guided by histology , with early concurrent palliative care . Recommendations for patients in the first-line setting include platinum-doublet therapy for those with PS 0 to 1 ( bevacizumab may be added to carboplatin plus paclitaxel if no contraindications ) ; combination or single-agent chemotherapy or palliative care alone for those with PS 2 ; afatinib , erlotinib , or gefitinib for those with sensitizing EGFR mutations ; crizotinib for those with ALK or ROS1 gene rearrangement ; and following first-line recommendations or using platinum plus etoposide for those with large-cell neuroendocrine carcinoma . Maintenance therapy includes pemetrexed continuation for patients with stable disease or response to first-line pemetrexed-containing regimens , alternative chemotherapy , or a chemotherapy break . In the second-line setting , recommendations include docetaxel , erlotinib , gefitinib , or pemetrexed for patients with nonsquamous cell carcinoma ; docetaxel , erlotinib , or gefitinib for those with squamous cell carcinoma ; and chemotherapy or ceritinib for those with ALK rearrangement who experience progression after crizotinib . In the third-line setting , for patients who have not received erlotinib or gefitinib , treatment with erlotinib is recommended . There are insufficient data to recommend routine third-line cytotoxic therapy . Decisions regarding systemic therapy should not be made based on age alone . Additional information can be found at http://www.asco.org/ guidelines /nsclc and http://www.asco.org/ guidelines wiki . J Clin Oncol 33:3488 - 3515 . © 2015 by American Society of Clinical BACKGROUND Development of this guideline was undertaken by the Exercise for People with Cancer Guideline Development Group , a group organized by Cancer Care Ontario 's Program in Evidence -Based Care ( pebc ) . The purpose of the guideline was to provide guidance for clinicians with respect to exercise for patients living with cancer , focusing on the benefits of specific types of exercise , recommendations about screening requirements for new referrals , and safety concerns . METHODS Consistent with the pebc 's st and ardized approach , a systematic search was conducted for existing guidelines , and systematic literature search es were performed in medline and embase for both systematic review s and primary literature . Content and methodology experts performed an internal review , which was followed by an external review by targeted experts and intended users . RESULTS The search identified three guidelines , eighteen systematic review s , and twenty-nine r and omized controlled trials with relevance to the topic . The present guideline provides recommendations for the duration , frequency , and intensity of exercise appropriate for people living with cancer . It also provides recommendations for pre-exercise assessment , safety concerns , and delivery models . CONCLUSIONS There is sufficient evidence to show that exercise provides benefits in quality of life and muscular and aerobic fitness for people with cancer both during and after treatment , and that it does not cause harm . The present guideline is intended to support the Canadian Society for Exercise Physiology 's Canadian physical activity guidelines . The recommendations are intended for clinicians and institutions treating cancer patients in Ontario , and for policymakers and program planners involved in the delivery of exercise programs for cancer patients PURPOSE This report up date s the Cancer Care Ontario Program in Evidence -Based Care guideline for the management of  depression in adult patients with cancer . This guideline covers pharmacologic , psychological , and collaborative care interventions , with a focus on integrating practical management tools to assist clinicians in delivering appropriate treatments for depression in patients with cancer . METHODS Recommendations were developed by synthesizing information from extant guidelines and review s and search ing for r and omized controlled trials from the date of data base inception ( 1964 for MEDLINE and 1974 for EMBASE ) to January 2015 . Quality assessment of guidelines and systematic review s were conducted by using the Appraisal of Guidelines for Research and Evaluation II ( AGREE II ) , Assessment of Multiple Systematic Review s ( AMSTAR ) , and Cochrane Risk of Bias tools . Final recommendations were developed through a st and ardized Program in Evidence -Based Care multidisciplinary expert and knowledge user review process . RESULTS Two high- quality relevant clinical practice guidelines , eight pharmacologic trials , nine psychological trials , and eight collaborative care intervention trials composed the evidence base upon which the recommendations were developed . Eight specific recommendations were made to establish a st and ard of care for the management of depression in patients with cancer . The recommendations and practical management tools were review ed as being well organized and helpful , although systemic barriers to implementation were identified . CONCLUSION This up date d guideline supports the previous general recommendation that patients with cancer who have depression may benefit from psychological and /or pharmacologic interventions , without evidence for the superiority of any specific treatment over another . New recommendations for a collaborative care model that incorporates a stepped care approach suggest that multidisciplinary mental health care restructuring may be required for optimal management of depression 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 PURPOSE To identify optimal chemo- and targeted therapy for women with human epidermal growth factor 2 (HER2)- negative ( or unknown ) advanced breast cancer . METHODS A systematic review of r and omized evidence ( including systematic review s and meta-analyses ) from 1993 through to current was completed . Outcomes of interest included survival , progression-free survival , response , quality of life , and adverse effects . Guideline recommendations were evidence based and were agreed on by the Expert Panel via consensus . RESULTS Seventy-nine studies met the inclusion criteria , comprising 20 systematic review s and /or meta-analyses , 30 trials on first-line treatment , and 29 trials on second-line and subsequent treatment . These trials form the evidence base for the guideline recommendations . RECOMMENDATIONS Endocrine therapy is preferable to chemotherapy as first-line treatment for patients with estrogen receptor-positive metastatic breast cancer unless improvement is medically necessary ( eg , immediately life-threatening disease ) . Single agent is preferable to combination chemotherapy , and longer planned duration improves outcome but must be balanced against toxicity . There is no single optimal first-line or subsequent line chemotherapy , and choice of treatment will be determined by multiple factors including prior therapy , toxicity , performance status , comorbid conditions , and patient preference . The role of bevacizumab remains controversial . Other targeted therapies have not so far been shown to enhance chemotherapy outcome in HER2-negative breast cancer Breast cancer is the second most common type of cancer among women in the United States with more than 200,000 women diagnosed with invasive disease and with approximately 40,000 dying annually from the disease ( 1 ) . As a result of early detection efforts , nearly half of these women present with lymph node negative hormone receptor positive disease . Current treatment for early-stage breast cancer ( ESBC ) with adjuvant hormonal therapy and /or chemotherapy is based on clinical and pathological criteria including the presence and number of involved lymph nodes , tumor size and grade , hormone receptor status , and the presence of HER2/neu overexpression among others . Treatment decisions may also take into consideration patient age or menopausal status due to the anticipated lower risk of cancer recurrence , and the potential for smaller benefit and greater toxicity with aggressive systemic chemotherapy in older women . These considerations form the basis for clinical practice guidelines for the management of patients with ESBC ( 2 , 3 ) . Current guidelines recommend adjuvant systemic chemotherapy and endocrine therapy for most women with lymph node negative , hormone receptor positive , ESBC . Unfortunately , such systemic chemotherapy is associated with considerable cost , proximal morbidity , as well as increasing evidence for serious delayed toxicities including neurocognitive dysfunction and secondary malignancies . The risk of distant recurrence is generally low among ESBC patients with lymph node negative , hormone receptor positive disease regardless of treatment with adjuvant chemotherapy . However , several r and omized controlled trials of adjuvant chemotherapy and meta-analyses have shown the value of adjuvant chemotherapy in reducing the risk of disease Aim The purpose of this work is to give practical guidelines for radiotherapy of locally advanced , inflammatory and metastatic breast cancer at first presentation . Methods A comprehensive survey of the literature using the search phrases “ locally advanced breast cancer ” , “ inflammatory breast cancer ” , “ breast cancer and synchronous metastases ” , “ de novo stage IV and breast cancer ” , and “ metastatic breast cancer ” and “ at first presentation ” restricted to “ clinical trials ” , “ r and omized trials ” , “ meta- analysis ” , “ systematic review ” , and “ guideline ” was performed and supplemented by using references of the respective publications . Based on the German interdisciplinary S3 guidelines , up date d in 2012 , this publication addresses indications , sequence to other therapies , target volumes , dose , and fractionation of radiotherapy . Results International and national guidelines are in agreement that locally advanced , at least if regarded primarily unresectable and inflammatory breast cancer should receive neoadjuvant systemic therapy first , followed by surgery and radiotherapy . If surgery is not amenable after systemic therapy , radiotherapy is the treatment of choice followed by surgery , if possible . Surgery and radiotherapy should be administered independent of response to neoadjuvant systemic treatment . In patients with a de novo diagnosis of breast cancer with synchronous distant metastases , surgery and radiotherapy result in considerably better locoregional tumor control . An improvement in survival has not been consistently proven , but may exist in subgroups of patients . Conclusion Radiotherapy is an important part in the treatment of locally advanced and inflammatory breast cancer that should be given to all patients regardless to the intensity and effect of neoadjuvant systemic treatment and the extent of surgery . Locoregional radiotherapy in patients with primarily distant metastatic disease should be prescribed on an individual basis . ZusammenfassungZielZiel der Arbeit ist die Entwicklung von Praxis-Leitlinien zur Strahlentherapie des lokal fortgeschrittenen einschließlich des inflammatorischen Mammakarzinoms sowie zur lokalen Therapie bei synchroner Fernmetastasierung . Method enEs erfolgte eine Literaturübersicht basierend auf den Suchbegriffen „ locally advanced breast cancer “ , „ inflammatory breast cancer “ , „ breast cancer and synchronous metastases “ , „ de novo stage IV and breast cancer “ und „ metastatic breast cancer “ sowie „ at first presentation “ . Stratifiziert wurde nach „ clinical trials “ , „ r and omized trials “ , „ meta- analysis “ , „ systematic review “ und „ guideline “ , ergänzt von kürzlich veröffentlichten Abstract s. Ergänzend zu den Stellungnahmen der deutschen interdisziplinären S3-Leitlinie der Deutschen Krebsgesellschaft und der AWMF zum Mammakarzinom von 2012 bezieht diese Publikation Stellung zu den Indikationen , zur zeitlichen Abfolge mit and eren Therapien , zum Zielvolumen sowie zur Dosis und Fraktionierung der Strahlentherapie . ErgebnisseInternationale und nationale Leitlinien stimmen darin überein , dass Patientinnen mit einem lokal fortgeschrittenen , zumindest primär als irresektabel eingestuften , sowie Patientinnen mit einem inflammatorischen Mammakarzinom zunächst eine neoadjuvante Systemtherapie erhalten sollen , gefolgt von einer Operation und einer Strahlentherapie . Falls nach der Systemtherapie eine Operation nicht durchführbar ist , sollte zunächst eine Radiotherapie erfolgen und anschließend noch einmal die Möglichkeit einer Operation bedacht werden . Operation und Bestrahlung erfolgen unabhängig vom Ansprechen auf die neoadjuvante Systemtherapie . Bei Patientinnen mit primärer Fernmetastasierung führt die lokale Beh and lung mittels Operation und/oder Strahlentherapie zur besseren lokalen Tumorkontrolle . Ein Überlebensvorteil besteht wohl nicht , möglicherweise aber doch für einige Subgruppen der Patientinnen . SchlussfolgerungEine Strahlentherapie ist wichtiger Best and teil der Beh and lung lokal fortgeschrittener und inflammatorischer Mammakarzinome für alle betroffenen Patientinnen , unabhängig von der Intensität und dem Ergebnis der neoadjuvanten systemischen Therapie und des Ausmaßes einer eventuellen Chirurgie . Bei Patientinnen mit primärer Fernmetastasierung muss i m Tumorboard die Indikation zur lokoregionären Strahlentherapie individuell gestellt werden PURPOSE To provide evidence -based recommendations to practicing oncologists , surgeons , and radiation therapy clinicians to up date the 2005 clinical practice guideline on the use of sentinel node biopsy ( SNB ) for patients with early-stage breast cancer . METHODS The American Society of Clinical Oncology convened an Up date Committee of experts in medical oncology , pathology , radiation oncology , surgical oncology , guideline implementation , and advocacy . A systematic review of the literature was conducted from February 2004 to January 2013 in Medline . Guideline recommendations were based on the review of the evidence by Up date Committee . RESULTS This guideline up date reflects changes in practice since the 2005 guideline . Nine r and omized clinical trials ( RCTs ) met systematic review criteria for clinical questions 1 and 2 ; 13 cohort studies informed clinical question 3 . RECOMMENDATIONS Women without sentinel lymph node ( SLN ) metastases should not receive axillary lymph node dissection ( ALND ) .  Women with one to two metastatic SLNs planning to undergo breast-conserving surgery with whole-breast radiotherapy should not undergo ALND ( in most cases ) . Women with SLN metastases who will undergo mastectomy should be offered ALND . These three recommendation are based on RCTs . Women with operable breast cancer and multicentric tumors , with ductal carcinoma in situ ( DCIS ) who will undergo mastectomy , who previously underwent breast and /or axillary surgery , or who received preoperative/neoadjuvant systemic therapy may be offered SNB . Women who have large or locally advanced invasive breast cancer ( tumor size T3/T4 ) , inflammatory breast cancer , or DCIS ( when breast-conserving surgery is planned ) or are pregnant should not undergo SNB . These recommendations are based on cohort studies and /or informal consensus . In some cases , up date d evidence was insufficient to up date previous recommendations OBJECTIVES Stage III non-small cell lung cancer ( NSCLC ) describes a heterogeneous population with disease presentation ranging from apparently resectable tumors with occult microscopic nodal metastases to unresectable , bulky nodal disease . This review up date s the published clinical trials since the last American College of Chest Physicians guidelines to make treatment recommendations for this controversial subset of patients . METHODS Systematic search es were conducted through MEDLINE , Embase , and the Cochrane Data base for Systematic Review up to December 2011 , focusing primarily on r and omized trials , selected meta-analyses , practice guidelines , and review s. RESULTS For individuals with stage IIIA or IIIB disease , good performance scores , and minimal weight loss , treatment with combined chemoradiotherapy results in better survival than radiotherapy alone . Consolidation chemotherapy or targeted therapy following definitive chemoradiation for stage IIIA is not supported . Neoadjuvant therapy followed by surgery is neither clearly better nor clearly worse than definitive chemoradiation . Most of the arguments made regarding patient selection for neoadjuvant therapy and surgical resection provide evidence for better prognosis but not for a beneficial impact of this treatment strategy ; however , weak comparative data suggest a possible role if only lobectomy is needed in a center with a low perioperative mortality rate . The evidence supports routine platinum-based adjuvant chemotherapy following complete resection of stage IIIA lung cancer encountered unexpectedly at surgery . Postoperative radiotherapy  improves local control without improving survival . CONCLUSIONS Multimodality therapy is preferable in most subsets of patients with stage III lung cancer . Variability in the patients included in r and omized trials limits the ability to combine results across studies and thus limits the strength of recommendations in many scenarios . Future trials are needed to investigate the roles of individualized chemotherapy , surgery in particular cohorts or setting s , prophylactic cranial radiation , and adaptive radiation AIM To evaluate the optimal time interval from definitive surgery to commencing chemotherapy in early breast cancer ( EBC ) . PATIENTS AND METHODS The relationship between time to initiation of adjuvant chemotherapy ( TTC ) , calculated in weeks , and disease-free ( DFS ) or overall survival ( OS ) , was assessed in 921 EBC patients with rapidly proliferating tumours ( thymidine labelling index > 3 % or G3 or Ki67 > 20 % ) , r and omised in a phase III clinical trial ( NCT01031030 ) to receive chemotherapy with or without anthracyclines ( epirubicin→cyclophosphamide , methotrexate and fluorouracil ( CMF ) versus CMF→epirubicin versus CMF ) . DFS , OS and 95 % confidence intervals ( 95 % confidence interval ( CI ) ) were calculated by the Kaplan-Meier method . Multivariate Cox analysis was performed in relation with nodal involvement , oestrogen receptor and human epidermal growth factor receptor 2 ( HER2 ) status , Ki67 value , type of adjuvant chemotherapy , menopausal status and tumour size . RESULTS At a median follow-up of 105 months ( range 2 - 188 ) , a prolonged TTC result ed in a significant increase in the risk of relapse : hazard ratio ( HR ) 1.15 ( 95 % CI 1.02 - 1.30 , p=0.019 ) . Using a backward elimination procedure , TTC , tumour size and nodal involvement remained significantly associated with DFS . A time-dependent receiver-operating characteristic ( ROC ) curve analysis was subsequently utilised to evaluate the best cut-off for TTC , identifying 7 weeks as the best threshold for longer OS ( p=0.043 ) : 8-year OS 88 % ( 95 % CI 85 - 90 ) for patients with a TTC < 7 weeks and 78 % ( 95 % CI 68 - 87 ) for the other group . CONCLUSIONS Our results confirm that a shorter TTC may reduce relapses and possibly also improve clinical outcome in patients with highly proliferating EBC The purpose of this article is to provide up date d recommendations for the treatment of patients with stage IV non-small-cell lung cancer . A literature search identified relevant r and omized trials published since 2002 . The scope of the guideline was narrowed to chemotherapy and biologic therapy . An Up date Committee review ed the literature and made up date d recommendations . One hundred sixty-two publications met the inclusion criteria . Recommendations were based on treatment strategies that improve overall survival . Treatments that improve only progression-free survival prompted scrutiny of toxicity and quality of life . For first-line therapy in patients with performance status of 0 or 1 , a platinum-based two-drug combination of cytotoxic drugs is recommended . Nonplatinum cytotoxic doublets are acceptable for patients with contraindications to platinum therapy . For patients with performance status of 2 , a single cytotoxic drug is sufficient . Stop first-line cytotoxic chemotherapy at disease progression or after four cycles in patients who are not responding to treatment . Stop two-drug cytotoxic chemotherapy at six cycles even in patients who are responding to therapy . The first-line use of gefitinib may be recommended for patients with known epidermal growth factor receptor ( EGFR ) mutation ; for negative or unknown EGFR mutation status , cytotoxic chemotherapy is preferred . Bevacizumab is recommended with carboplatin-paclitaxel , except for patients with certain clinical characteristics . Cetuximab is recommended with cisplatin-vinorelbine for patients with EGFR-positive tumors by immunohistochemistry . Docetaxel , erlotinib , gefitinib , or pemetrexed is recommended as second-line therapy . Erlotinib is recommended as third-line therapy for patients who have not received prior erlotinib or gefitinib . Data are insufficient to recommend the routine third-line use of cytotoxic drugs . Data are insufficient to recommend routine use of molecular markers to select chemotherapy THERE IS still doubt as to the best the addition of immediate post-operative form of treatment for primary cancer radiotherapy  does not confer an advanof the breast . However , an analysis of tage over a watching policy , in which r and omized comparisons of various methradiotherapy is given only when indicated ods of local treatment have allowed 3 by local recurrence ( Roberts et al. , 1973 ; broad conclusions ( Sutherl and , 1974 ) . Forrest et al. , 1974 ; Murray , 1974 ) . These are : However , the relevant trials are not 1 . When surgical treatment includes yet mature and only one includes informaresection of the breast and axillary nodes tion on the histological state of the in continuity ( radical mastectomy ) , the axillary nodes based on pectoral node addition of immediate post-operative radibiopsy ( Forrest et al. , 1974 ) . cal radiotherapy to skin flaps and regional The failure of the type of local therapy node areas does not confer any advantage to influence the results of treatment of in survival or local recurrence rates primary breast cancer is due to the fact compared with a watching policy , in that dissemination has taken place by which the use of radiotherapy is delayed the time the patient first discovers her until indicated by local recurrence ( Cole , lesion . At least 7000 of women with 1964 ; Easson , 1968a ; Fisher et al. , so-called early ( clinical stage I and II ) 1970 ) . disease will die from metastases within 2 . If immediate radical radiotherapy 20 years ( Easson , 1968b ; Brinkley and is to be given post-operatively , there is Haybittle , 1975 ) . In these women surno advantage in performing surgical provival is unlikely to be influenced by cedures which are more extensive than the extent or type of local treatment . a simple ( total ) mastectomy ( Brinkley Conversely , for those whose disease is and Haybittle , 1966 , 1971 ) . truly confined to the breast , removal 3 . Simple mastectomy and immediate of the breast alone should result in cure . radical radiotherapy give results as good It is our belief that histological evidence as those from radical surgery alone ( Kaae of the state of the axillary nodes is cur and Johansen , 1968 ; Hamilton , Langl and s rently the best guide to these two types and Prescott , 1974 ) . of disease . Also , there is increasing evidence that We are convinced that , except as when a simple mastectomy is performed , methods to obtain axillary node histology 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 PURPOSE This guideline presents evidence -based recommendations for stereotactic body radiation therapy ( SBRT ) in challenging clinical scenarios in early-stage non-small cell lung cancer ( NSCLC ) . METHODS AND MATERIAL S The American Society for Radiation Oncology convened a task force to perform a systematic literature review on 4 key questions addressing : ( 1 ) application of SBRT to operable patients ; ( 2 ) appropriate use of SBRT in tumors that are central ly located , large , multifocal , or unbiopsied ; ( 3 ) individual tailoring of SBRT in " high-risk " clinical scenarios ; and ( 4 ) SBRT as salvage therapy after recurrence . Guideline recommendations were created using a predefined consensus-building methodology supported by American Society for Radiation Oncology-approved tools for grading evidence quality and recommendation strength . RESULTS Although few r and omized trials have been completed for SBRT , strong consensus recommendations based on extensive , consistent publications were generated for several questions , including recommendations for fractionation for central tumors and surgery versus SBRT in st and ard-risk medically operable patients with early-stage NSCLC . Lower quality evidence led to conditional recommendations on use of SBRT for tumors > 5 cm , patients with prior pneumonectomy , T3 tumors with chest wall invasion , synchronous multiple primary lung cancer , and as a salvage therapy after prior radiation therapy . These areas of moderate- and low- quality evidence highlight the importance of clinical trial enrollment as well as the role of prospect i ve data registries . CONCLUSIONS SBRT has an important role to play in treating early-stage NSCLC , particularly for medically inoperable patients with limited other treatment options . Shared decision-making with patients should be performed in all cases to ensure the patient underst and s the risks related to SBRT , the side effects , and the alternative treatments available
In general , single-agent chemotherapy is not recommended for the adjuvant treatment of breast cancer in any patient population .
Anthracycline-taxane-based polychemotherapy regimens are , overall , considered superior to earlier-generation regimens and have the most significant impact on patient survival outcomes .
Regimens with varying anthracycline and taxane doses and schedules are options ; in general , paclitaxel given every 3 weeks is inferior .
Evidence does not support the use of bevacizumab in the adjuvant setting ; other systemic therapy agents such as metformin and vaccines remain investigatory .
BACKGROUND The Program in Evidence -Based Care ( pebc ) of Cancer Care Ontario recently created an evidence -based consensus guideline on the systemic treatment of early breast cancer .
The evidence for the guideline was compiled using a systematic review to answer the question " What is the optimal systemic therapy for patients with early-stage , operable breast cancer , when patient and disease factors are considered ? "
The question was addressed in three parts : cytotoxic chemotherapy , endocrine treatment , and human epidermal growth factor receptor 2 (her2)-directed therapy .