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• W4249552602 abstract "Lung cancer is the leading cause of cancer mortality worldwide, accounting for ∼1.3 million deaths each year. Overall incidence and epidemiology data are summarised in the ESMO Clinical Practice Guidelines (CPG) on ‘metastatic non-small-cell lung cancer (NSCLC)’ [1.Peters S. Adjei A.A. Gridelli C. et al.Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2012; 23: vii56-vii64Abstract Full Text Full Text PDF PubMed Scopus (396) Google Scholar]. A high proportion of NSCLC patients present with symptoms in advanced disease stage. The aim of lung cancer screening is to reduce lung cancer-related mortality by detecting more patients in earlier—potentially curable—stages. Historical randomised, controlled trials (RCTs) on the use of periodical chest X-ray and/or sputum cytology were negative, and screening based on these techniques is therefore not recommended [I, C]. Low-dose computed tomography (LDCT)—more sensitive for the detection of small nodules—was studied in more recent RCTs. The National Lung Screening Trial (NLST) compared LDCT with chest X-ray in 53 454 current or former heavy smokers (≥30 pack-years or ≤15 years since smoking cessation) aged between 55 and 74 years. In this high-risk group, a 20% reduction in lung cancer related deaths, from 425 to 326 (P = 0.004), was reported. All-cause mortality was reduced by 6.7% [2.Aberle D.R. Adams A.M. Berg C.D. et al.Reduced lung-cancer mortality with low-dose computed tomographic screening.N Engl J Med. 2011; 365: 395-409Crossref PubMed Scopus (6433) Google Scholar]. LDCT screening thus reduces lung cancer-related mortality [I, A]. It is, however, not ready for large-scale population-based implementation because of remaining questions surrounding the definition of the at-risk population, timing, interval and method of computed tomography (CT) (particularly 2D versus 3D nodule interpretation [3.Van Klaveren R.J. Oudkerk M. Prokop M. et al.Management of lung nodules detected by volume CT scanning.N Engl J Med. 2009; 361: 2221-2229Crossref PubMed Scopus (660) Google Scholar]), how to handle (false) positive findings and, especially, cost-effectiveness when compared with, e.g. smoking cessation alone [4.Aberle D.R. Abtin F. Brown K. Computed tomography screening for lung cancer: Has it finally arrived? Implications of the national lung screening trial.J Clin Oncol. 2013; 31: 1002-1008Crossref PubMed Scopus (104) Google Scholar]. Further analyses and results of several ongoing European trials are eagerly awaited. Other potential methods of screening, such as exhaled breath or blood biomarkers lack validation and are therefore not recommended in clinical practice [II, C]. Bronchoscopy is the appropriate test for centrally located tumours, where a pathological diagnosis will be obtained in ∼90% of cases by means of forceps biopsy, bronchial brushing or washing [III, A]. For the pathological classification, we refer to the diagnostic paragraph in the CPG ‘metastatic non-small-cell lung cancer (NSCLC)’ [1.Peters S. Adjei A.A. Gridelli C. et al.Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2012; 23: vii56-vii64Abstract Full Text Full Text PDF PubMed Scopus (396) Google Scholar]. Peripheral lesions, especially solitary pulmonary nodules, are a diagnostic challenge. Typical calcification patterns usually point to a benign aetiology. Likewise, a solid nodule that has been stable for at least 2 years upon comparison with prior imaging results is very likely to be benign. Factors such as age, smoking history, size, borders or density can be of help in risk assessment, but do not replace evaluation by an experienced multidisciplinary team. Teams are strongly encouraged to follow existing guidelines of pulmonary or imaging societies for initial solitary pulmonary nodule management [III, A]. Examples are the recently revised American College of Chest Physicians (ACCP) guidelines [5.Gould M.K. Donington J. Lynch W.R. et al.Evaluation of individuals with pulmonary nodules: When is it lung cancer?: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.Chest. 2013; 143: e93S-e120SAbstract Full Text Full Text PDF PubMed Scopus (790) Google Scholar], or the Fleishner Society recommendations for small solid nodules [6.Macmahon H. Austin J.H. Gamsu G. et al.Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society.Radiology. 2005; 237: 395-400Crossref PubMed Scopus (1290) Google Scholar] or for sub-solid nodules [7.Naidich D.P. Bankier A.A. MacMahon H. et al.Recommendations for the management of subsolid pulmonary nodules detected at CT: a statement from the Fleischner Society.Radiology. 2013; 266: 304-317Crossref PubMed Scopus (732) Google Scholar]. In nodules considered suspect, a pre-treatment pathological proof, preferably obtained by biopsy, is recommended [III, A]. Appropriate techniques are peripheral sampling by bronchoscopy [directed by either radial endobronchial ultrasound (EBUS) or navigational CT], tru-cut biopsy under CT guidance or video-assisted thoracoscopy (VATS) biopsy. However, in some patients with clinical stage I/II lesions, diagnostic samples may not be accessible and resection or stereotactic ablative radiotherapy (SABR) may be selected if there is a high likelihood of malignancy based on assessment of clinical and imaging findings by an experienced multidisciplinary group [III, A]. The overall staging and risk assessment is summarised in the CPG ‘metastatic non-small cell lung cancer (NSCLC)’ [1.Peters S. Adjei A.A. Gridelli C. et al.Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2012; 23: vii56-vii64Abstract Full Text Full Text PDF PubMed Scopus (396) Google Scholar]. After distant metastases have been ruled out, a more detailed locoregional staging is mandatory to distinguish early stages (I/II) from potentially resectable stage IIIA and from unresectable stage III, according to the seventh TNM staging system [8.Goldstraw P. Crowley J. Chansky K. et al.The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours.J Thorac Oncol. 2007; 2: 706-714Abstract Full Text Full Text PDF PubMed Scopus (2847) Google Scholar] [III, A]. This is a multidisciplinary process involving imaging, endoscopic and surgical techniques [9.Vansteenkiste J. Dooms C. De Leyn P. Early stage non-small-cell lung cancer: challenges in staging and adjuvant treatment: evidence-based staging.Ann Oncol. 2010; 21: vii189-vii195Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar]. Accuracy is vital to avoid erroneous interpretations leading to a false stage III or stage IV diagnosis in early-stage patients and vice versa. Absence of suspect mediastinal lymph node (LN) metastasis on both CT and positron emission tomography (PET) images has a high negative predictive value, and these patients can in general proceed to surgery, except in the case of a centrally located tumour or hilar LNs [I, A]. In these cases the probability of mediastinal LN disease is increased and may also be obscured on imaging [10.Silvestri G.A. Gonzalez A.V. Jantz M.A. et al.Methods for staging non-small cell lung cancer: diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.Chest. 2013; 143: e211S-e250SAbstract Full Text Full Text PDF PubMed Scopus (951) Google Scholar]. In patients with mediastinal LNs on imaging, The ACCP makes the distinction between discrete (non-bulky) LNs (i.e. discrete nodes seen on CT, well enough defined to measure their size) and extensive (bulky) LN infiltration (i.e. nodes can no longer be distinguished or measured, multiple nodes are matted together and the boundary between them is obscured, mediastinal vessels may be encircled) [10.Silvestri G.A. Gonzalez A.V. Jantz M.A. et al.Methods for staging non-small cell lung cancer: diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.Chest. 2013; 143: e211S-e250SAbstract Full Text Full Text PDF PubMed Scopus (951) Google Scholar]. Except for those with bulky LN disease, nodal tissue confirmation is recommended [11.De Leyn P. Lardinois D. Van Schil P.E. et al.ESTS guidelines for preoperative lymph node staging for non-small cell lung cancer.Eur J Cardiothorac Surg. 2007; 32: 1-8Crossref PubMed Scopus (420) Google Scholar] [I, A]. For that purpose, endoscopic techniques such as endobronchial (EBUS) or oesophageal ultrasound (EUS)-guided sampling by expert teams are preferred as a first step to confirm LN disease, as they are less invasive and less costly than mediastinoscopy [I, A]. For patients with suspect LNs on imaging and negative EBUS/EUS results, an additional mediastinoscopy is recommended [12.Annema J.T. van Meerbeeck J.P. Rintoul R.C. et al.Mediastinoscopy vs. endosonography for mediastinal nodal staging of lung cancer: A randomized trial.JAMA. 2010; 304: 2245-2252Crossref PubMed Scopus (479) Google Scholar]. Figure 1 provides a practical schematic for rational locoregional staging. In patients scheduled for radical treatment (surgery alone, surgical or non-surgical combined modality treatment), risk assessment is an integral aspect to allow joint decision-making with the patient, even if data supporting its relevance in decision-making are limited [III, A]. If pulmonary function tests point to a forced expiratory volume in 1 s (FEV1) and diffusing capacity for carbon monoxide (DLCO) >80%, patients can proceed to surgery without further pulmonary evaluation [13.Brunelli A. Charloux A. Bolliger C.T. et al.ERS/ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy).Eur Respir J. 2009; 34: 17-41Crossref PubMed Scopus (582) Google Scholar] [III, A]. When either FEV1 or DLCO is <80%, additional ergospirometry helps to assess the risk for postoperative complications or mortality. Patients with a maximal oxygen consumption (VO2max) >20 ml/kg/min may proceed to surgery as far as pneumonectomy, while those with a VO2max <10 ml/kg/min have a very high postoperative risk [13.Brunelli A. Charloux A. Bolliger C.T. et al.ERS/ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy).Eur Respir J. 2009; 34: 17-41Crossref PubMed Scopus (582) Google Scholar] [III, A]. For the others, more formal lung function testing—including segment counting used to estimate postoperative lung function—is needed, as the risk of postoperative shortness of breath is important to both the patient and clinician. As a guide, a predicted postoperative FEV1 and DLCO >40% is acceptable [14.Lim E. Baldwin D. Beckles M. et al.Guidelines on the radical management of patients with lung cancer.Thorax. 2010; 65: iii1-iii27Crossref PubMed Scopus (375) Google Scholar]. The risk of in-hospital death can also be also estimated using a validated scoring method such as the Thoracoscore [15.Falcoz P.E. Conti M. Brouchet L. et al.The Thoracic Surgery Scoring System (Thoracoscore): risk model for in-hospital death in 15,183 patients requiring thoracic surgery.J Thorac Cardiovasc Surg. 2007; 133: 325-332Abstract Full Text Full Text PDF PubMed Scopus (202) Google Scholar] [III, A]. There have been a number of risk models to predict adverse cardiac outcomes, but they do not seem to discriminate well in patients undergoing thoracic surgery [16.Brunelli A. Cassivi S.D. Fibla J. et al.External validation of the recalibrated thoracic revised cardiac risk index for predicting the risk of major cardiac complications after lung resection.Ann Thorac Surg. 2011; 92: 445-448Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar]. It is best practice to evaluate and optimise any co-morbidities [chronic obstructive pulmonary disease (COPD), heart failure, ischaemic heart disease, diabetes, renal insufficiency, coagulation disorders] before planned surgery [14.Lim E. Baldwin D. Beckles M. et al.Guidelines on the radical management of patients with lung cancer.Thorax. 2010; 65: iii1-iii27Crossref PubMed Scopus (375) Google Scholar] [III, A]. Surgery remains the cornerstone of treatment of early-stage NSCLC for patients willing to accept the procedure-related risks [III, A]. Those not willing to accept these risks should be informed about other radical options such as SABR. Current randomised trials comparing surgery with stereotactic body radiotherapy in patients with stage I disease will be relevant for future guideline and policy recommendations. Based on data from the LSCG 821 trial, lobectomy is the current treatment of choice (given sufficient lung function) [I, A]. More limited resections (segmentectomy and wedge resection) are associated with increased local recurrence [17.Ginsberg R.J. Rubinstein L.V. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group.Ann Thorac Surg. 1995; 60: 615-622Abstract Full Text PDF PubMed Scopus (2223) Google Scholar]. The optimum extent of resection for small lesions (<2 cm), adenocarcinoma in situ and minimally invasive adenocarcinoma are the subject of investigations in randomised trials and cohort studies, respectively. In terms of LN management, randomised trials have not solved the controversial issue of LN sampling versus systematic nodal dissection. These two options do not differ in terms of complication rates, but data are conflicting with respect to survival outcome [18.Wu Y.I. Huang Z.F. Wang S.Y. et al.A randomized trial of systematic nodal dissection in resectable non-small cell lung cancer.Lung Cancer. 2002; 36: 1-6Abstract Full Text Full Text PDF PubMed Scopus (278) Google Scholar, 19.Darling G.E. Allen M.S. Decker P.A. et al.Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non-small cell carcinoma: results of the American College of Surgery Oncology Group Z0030 Trial.J Thorac Cardiovasc Surg. 2011; 141: 662-670Abstract Full Text Full Text PDF PubMed Scopus (504) Google Scholar]. The extent of LN dissection is therefore nowadays mainly dictated by staging requirements for guaranteed ‘R0 resection’ status. This is stipulated by the International Association for the Study of Lung Cancer (IASLC) as a minimum of six nodes/stations, three of which should be mediastinal including the sub-carinal station, with negativity of the highest resected node [20.Goldstraw P. International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology. Editorial Rx Press, Florida2009Google Scholar] [III, A]. Minimal access surgery (VATS lobectomy) is increasingly carried out. A systematic review reported improved 5-year survival and reduced systemic recurrences in patients who received VATS lobectomy [21.Yan T.D. Black D. Bannon P.G. McCaughan B.C. Systematic review and meta-analysis of randomized and non-randomized trials on safety and efficacy of video-assisted thoracic surgery lobectomy for early-stage non-small cell lung cancer.J Clin Oncol. 2009; 27: 2553-2562Crossref PubMed Scopus (566) Google Scholar], and another meta-analysis reported lower in-hospital complications [22.Cao C. Manganas C. Ang S.C. et al.Video-assisted thoracic surgery versus open thoracotomy for non-small cell lung cancer: A meta-analysis of propensity score-matched patients.Interact Cardiovasc Thorac Surg. 2013; 16: 244-249Crossref PubMed Scopus (138) Google Scholar]. It is important to appreciate, however, that most of the comparative studies included were non-randomised; and hence, there is a possibility of selection bias influencing good outcomes for VATS lobectomy. To date there have not been any RCTs sufficiently powered to detect important differences between the two techniques in either overall or disease-free survival. Either open thoracotomy or VATS access can thus be utilised as appropriate to the expertise of the surgeon [III, A]. There is a broad evidence base supporting the use of adjuvant cisplatin-based doublet chemotherapy after surgery for stages II and III NSCLC, originating from 23 randomised trials published between 1992 and 2005 [I, A]. Five ensuing meta-analyses have been undertaken, summarising the beneficial effects as a hazard ratio ranging between 0.74 and 0.87 [23.Lim E. Harris G. Patel A. et al.Preoperative versus postoperative chemotherapy in patients with resectable non-small cell lung cancer: systematic review and indirect comparison meta-analysis of randomized trials.J Thorac Oncol. 2009; 4: 1380-1388Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar]. Individual patient data meta-analysis affirmed the beneficial effects of cisplatin-based chemotherapy per subgroup of patients with lung cancer, and it is recommended for stages II–III [24.Pignon J.P. Tribodet H. Scagliotti G.V. et al.Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group.J Clin Oncol. 2008; 26: 3552-3559Crossref PubMed Scopus (1679) Google Scholar] [I, A]. Most studies used a two-drug combination with cisplatin and an attempted cumulative cisplatin dose of at least 300 mg/m², delivered in three to four cycles. The most frequently used regimen across trials is cisplatin–vinorelbine. Efficacy in stage IB remains controversial since the results are inconsistent in this subgroup [II, B]. Data suggest that there is no overall survival (OS) benefit, except for patients with tumours >4 cm in the CALGB 9633 study [25.Strauss G.M. Herndon 2nd, J.E. Maddaus M.A. et al.Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups.J Clin Oncol. 2008; 26: 5043-5051Crossref PubMed Scopus (766) Google Scholar], or patients with tumours >5 cm in the JBR.10 study [26.Winton T. Livingston R. Johnson D. et al.Vinorelbine plus cisplatin vs. observation in resected non-small cell lung cancer.N Engl J Med. 2005; 352: 2589-2597Crossref PubMed Scopus (1618) Google Scholar]. Currently, adjuvant chemotherapy is not recommended in stage IA, with reports of potential harm, although the number of patients in this subgroup was small [II, B]. As lung cancer patients often have smoking-induced cardiopulmonary co-morbidity, the indication of adjuvant chemotherapy after thoracic surgery needs to be assessed individually according to the risk-benefit ratio. Age per se is not a contra-indication for adjuvant chemotherapy [27.Pepe C. Hasan B. Winton T.L. et al.Adjuvant vinorelbine and cisplatin in elderly patients: National Cancer Institute of Canada and Intergroup Study JBR.10.J Clin Oncol. 2007; 25: 1553-1561Crossref PubMed Scopus (200) Google Scholar]. Patients must be well recovered following surgery. In contrast, data regarding neo-adjuvant chemotherapy are scarce. With 10 trials—some small-sized—addressing this question, the most recent published in 2011 [28.Scagliotti G.V. Pastorino U. Vansteenkiste J.F. et al.Randomized phase III study of surgery alone or surgery plus preoperative cisplatin and gemcitabine in stages IB to IIIA non-small cell lung cancer.J Clin Oncol. 2012; 30: 172-178Crossref PubMed Scopus (181) Google Scholar], results are largely dominated by the MRC LU22 study which reported a favourable hazard ratio of 0.88 (P = 0.07) [29.Gilligan D. Nicolson M. Smith I. et al.Preoperative chemotherapy in patients with resectable non-small cell lung cancer: results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review.Lancet. 2007; 369: 1929-1937Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar]. When the results of adjuvant versus neo-adjuvant chemotherapy were compared using indirect comparison meta-analysis [23.Lim E. Harris G. Patel A. et al.Preoperative versus postoperative chemotherapy in patients with resectable non-small cell lung cancer: systematic review and indirect comparison meta-analysis of randomized trials.J Thorac Oncol. 2009; 4: 1380-1388Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar] (Table 1), or directly as in the NATCH trial [30.Felip E. Rosell R. Maestre J.A. et al.Preoperative chemotherapy plus surgery versus surgery plus adjuvant chemotherapy versus surgery alone in early-stage non-small cell lung cancer.J Clin Oncol. 2010; 28: 3138-3145Crossref PubMed Scopus (258) Google Scholar], no clinically important differences in OS were discerned. Induction chemotherapy can be given with the intent of tumour down-staging allowing complete resection, but this has not been evaluated in a formal randomised setting [III, B]. However, indirect data from the MRC LU22 study suggest that 31% of patients are down-staged as a result of preoperative chemotherapy, even though, in this study, all tumours were considered suitable for resection at baseline [29.Gilligan D. Nicolson M. Smith I. et al.Preoperative chemotherapy in patients with resectable non-small cell lung cancer: results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review.Lancet. 2007; 369: 1929-1937Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar].Table 1Comparison of 5-year survival rates with surgery alone, surgery followed by adjuvant chemotherapy or neo-adjuvant chemotherapy followed by surgery. Data adapted from Lim et al. [23.Lim E. Harris G. Patel A. et al.Preoperative versus postoperative chemotherapy in patients with resectable non-small cell lung cancer: systematic review and indirect comparison meta-analysis of randomized trials.J Thorac Oncol. 2009; 4: 1380-1388Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar].Stage5-year survivalPostoperative chemotherapyPreoperative chemotherapyReportedExpected95% CIExpected95% CIIA7378.476.4–80.378.173.7–81.8IB5463.259.8–66.462.755.2–69.0IIA4858.554.6–62.057.949.4–64.9IIB3850.545.9–54.749.839.7–58.2IIIA2540.134.5–45.339.327.0–49.4Reproduced with permission from Lim et al. [23.Lim E. Harris G. Patel A. et al.Preoperative versus postoperative chemotherapy in patients with resectable non-small cell lung cancer: systematic review and indirect comparison meta-analysis of randomized trials.J Thorac Oncol. 2009; 4: 1380-1388Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar]. Open table in a new tab Reproduced with permission from Lim et al. [23.Lim E. Harris G. Patel A. et al.Preoperative versus postoperative chemotherapy in patients with resectable non-small cell lung cancer: systematic review and indirect comparison meta-analysis of randomized trials.J Thorac Oncol. 2009; 4: 1380-1388Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar]. Several predictive factors for the use of adjuvant cisplatin-based chemotherapy have been described, such as immunohistochemistry staining for the DNA repair component Excision Repair Cross Complementation Group 1 (ERCC1) [31.Olaussen K.A. Dunant A. Fouret P. et al.DNA repair by ERCC1 in non-small cell lung cancer and cisplatin-based adjuvant chemotherapy.N Engl J Med. 2006; 355: 983-991Crossref PubMed Scopus (1547) Google Scholar]. They should guide neither the indication of adjuvant therapy nor the choice of therapy [IV, B], since ERCC1 findings could not be validated in recent analyses [32.Friboulet L. Olaussen K.A. Pignon J.P. et al.ERCC1 isoform expression and DNA repair in non-small cell lung cancer.N Engl J Med. 2013; 368: 1101-1110Crossref PubMed Scopus (306) Google Scholar], and none of these markers has been prospectively validated in large cohorts. The same holds true for molecular analyses for, for example, EGFR, KRAS or ALK mutations. Actually, randomised study data suggested a worse survival with postoperative use of the EGFR-tyrosine kinase inhibitor gefitinib compared with placebo in the adjuvant setting, even in the subgroup with EGFR-mutated tumours [33.Goss G.D. Lorimer I. Tsao M.S. et al.A phase III randomized, double-blind, placebo-controlled trial of the epidermal growth factor receptor inhibitor gefitinb in completely resected stage IB-IIIA non-small cell lung cancer (NSCLC): NCIC CTG BR.19.J Clin Oncol. 2010; 28 (Suppl: LBA7005): 18sCrossref Scopus (212) Google Scholar]. Hence, at present, targeted agents should not be used in the adjuvant setting [II, A]. In patients unfit for surgery, SABR is the treatment of choice for peripherally located stage I NSCLC (if SABR is not available, a hypofractionated radiotherapy schedule with a high biologically equivalent dose is advised) [III, A]. SABR has led to improved population-based survival in elderly patients [34.Haasbeek C.J. Palma D. Visser O. et al.Early-stage lung cancer in elderly patients: a population-based study of changes in treatment patterns and survival in the Netherlands.Ann Oncol. 2012; 23: 2743-2747Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar], and the convenience of this outpatient therapy over three to eight visits has also led to a reduction in the proportion of untreated patients. The SABR dose should be to a biologically equivalent tumour dose of ≥100 Gy, prescribed to the encompassing isodose. A systematic review comparing outcomes of SABR and surgery in patients with severe COPD revealed a higher 30-day mortality following surgery but similar OS at 1 and 3 years [35.Palma D. Lagerwaard F. Rodrigues G. et al.Curative treatment of stage I non-small-cell lung cancer in patients with severe COPD: Stereotactic radiotherapy outcomes and systematic review.Int J Radiat Oncol Biol Phys. 2012; 82: 1149-1156Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar]. Analysis of SABR outcomes in 676 patients found a median OS of 40.7 months, and actuarial 5-year rates of initial local, regional and distant recurrence of 10.5%, 12.7% and 19.9%, respectively [36.Senthi S. Lagerwaard F.J. Haasbeek C.J. et al.Patterns of disease recurrence after stereotactic ablative radiotherapy for early stage non-small-cell lung cancer: a retrospective analysis.Lancet Oncol. 2012; 13: 802-809Abstract Full Text Full Text PDF PubMed Scopus (338) Google Scholar]. A systematic review of SABR in centrally located tumours found local control rates of >85% with biologically equivalent doses ≥100 Gy [37.Senthi S. Haasbeek C.J. Slotman B.J. Senan S. Outcomes of stereotactic ablative radiotherapy for central lung tumours: a systematic review.Radiother Oncol. 2013; 106: 276-282Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar]. The risk of high-grade toxic effect was <9% when the biologically equivalent normal tissue dose was ≤210 Gy. Prospective trials of SABR versus primary resection are now underway. For tumours with a size >5 cm and/or central location, far less data are available for SABR. These patients are preferentially treated with radical radiotherapy using more conventional daily or accelerated schedules [38.Mauguen A. Le Péchoux C. Saunders M.I. et al.Hyperfractionated or accelerated radiotherapy in lung cancer: an individual patient data meta-analysis.J Clin Oncol. 2012; 30: 2788-2797Crossref PubMed Scopus (202) Google Scholar] [III, A]. Adding chemotherapy to radiotherapy for patients with stage II-N1 disease may be considered [V, C]. Although this was not properly assessed in clinical studies, there may be a similar benefit as for resected patients with stage II-N1 disease. There is no indication that postoperative radiotherapy (PORT) improves outcome in patients with completely resected N0 or N1 disease, with a meta-analysis in fact demonstrating a detrimental effect on survival in these cases [39.PORT meta-analysis trialists group Postoperative radiotherapy for non-small cell lung cancer.Cochrane Database Syst Rev. 2005; : CD002142PubMed Google Scholar]. For patients in whom unsuspected mediastinal nodal metastases are discovered during surgery, PORT has not been shown to improve OS in prospective randomised studies. PORT in completely resected early-stage NSCLC is therefore not recommended [I, A]. It can however be indicated after incomplete surgery [III, B]. Chemotherapy is an integral part in the treatment of locally advanced NSCLC (LA-NSCLC) as it improves survival in all subgroups of patients, whether treated with surgery or radiotherapy, as shown in meta-analyses based on individual patient data [40.Arriagada R. Auperin A. Burdett S. et al.Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data.Lancet. 2010; 375: 1267-1277Abstract Full Text Full Text PDF PubMed Scopus (457) Google Scholar, 41.Pignon J.P. Stewart L.A. Randomized trials of radiotherapy alone versus combined chemotherapy and radiotherapy in stages IIIa and IIIb non-small cell lung cancer: a meta-analysis.Cancer. 1996; 77: 2413-2414Crossref PubMed Scopus (40) Google Scholar] [I, A]. The optimal chemotherapy regimen has not been investigated in randomised studies which were specifically designed for this purpose. In the absence of such trials, no strict recommendation can be given as to the best combination. Of the six randomised studies in the meta-analyses, five used cisplatin-based schedules and only one carboplatin. In the carboplatin study, a weekly infusion was used, but this relates to only 91 patients out of a total of 1205 in the meta-analysis. Cisplatin-based schedules are" @default.
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• W4249552602 title "Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up" @default.
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