Heart dose exposure as prognostic marker after radiotherapy for resectable stage IIIA/B non-small-cell lung cancer: secondary analysis of a randomized trial.

Background: Heart exposure to ionizing irradiation can cause ischaemic heart disease. The partial heart volume receiving ≥5 Gy (heartV5) was supposed to be an independent prognostic factor for survival after radiochemotherapy for locally advanced non-small-cell lung cancer (NSCLC). But validation of the latter hypothesis is needed under the concurrent risks of lung cancer patients. Patients and methods: The ESPATUE phase III trial recruited patients with potentially operable IIIA(N2)/selected IIIB NSCLC between 01/2004 and 01/2013. Cisplatin/paclitaxel induction chemotherapy was given followed by neoadjuvant radiochemotherapy (RT/CT) to 45 Gy (1.5 Gy bid/concurrent cisplatin/vinorelbine). Operable patients were randomized to definitive RT/CT(arm A) or surgery (arm B) and therefore were treated at two different total dose levels of radiotherapy. HeartV5 and mean heart dose (MHD) were obtained from the 3D radiotherapy plans, the prognostic value was analysed using multivariable proportional hazard analysis. Results: A total of 161 patients were randomized in ESPATUE, heartV5 and MHD were obtained from the 3D radiotherapy plans for 155 of these [male/female:105/50, median age 58 (33-74) years, stage IIIA/IIIB: 54/101]. Power analysis revealed a power of 80% of this dataset to detect a prognostic value of heartV5 of the size found in RTOG 0617. Multivariable analysis did not identify heartV5 as an independent prognostic factor for survival adjusting for tumour and clinical characteristics with [hazard ratio 1.005 (0.995-1.015), P = 0.30] or without lower lobe tumour location [hazard ratio 0.999 (0.986-1.012), P = 0.83]. There was no influence of heartV5 on death without tumour progression. Tumour progression, and pneumonia were the leading causes of death representing 65% and 14% of the observed deaths. Conclusions: HeartV5 could not be validated as an independent prognostic factor for survival after neoadjuvant or definitive conformal radiochemotherapy. Tumour progression was the predominant cause of death. Register No: Z5 - 22461/2 - 2002-017 (German Federal Office for Radiation Protection).

Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study.

BACKGROUND: Adjuvant chemotherapy is beneficial in non-small-cell lung cancer (NSCLC). However, balancing toxicity and efficacy mandates improvement. PATIENTS AND METHODS: Patients with completely resected stages IB-pT3N1 NSCLC were randomly assigned to either four cycles cisplatin (C: 50 mg/m(2) day (d)1 + 8) and vinorelbine (V: 25 mg/m(2) d1, 8, 15, 22) q4 weeks or four cycles cisplatin (75 mg/m(2) d1) and pemetrexed (Px: 500 mg/m(2) d1) q3 weeks. Primary objective was the clinical feasibility rate (no grade (G)4 neutropenia/thrombocytopenia or thrombocytopenia with bleeding, no G3/4 febrile neutropenia or non-hematological toxicity; no premature withdrawal/death). Secondary objectives were drug delivery and efficacy. RESULTS: One hundred and thirty two patients were randomized (stages: 38% IB, 10% IIA, 47% IIB, 5% pT3pN1; histology: 43% squamous, 57% non-squamous). The feasibility rates were 95.5% (cisplatin and pemetrexed, CPx) and 75.4% (cisplatin and vinorelbine, CVb) (P = 0.001); hematological G3/4 toxic effects were 10% (CPx) and 74% (CVb) (P < 0.001), non-hematological toxic effects were comparable (33% and 31%, P = 0.798). Delivery of total mean doses was 90% of planned with CPx, but 66% (cisplatin) and 64% (vinorelbine) with CVb (P < 0.0001). The median number of cycles [treatment time (weeks)] was 4 for CPx (11.2) and 3 for CVb (9.9). Time to withdrawal from therapy differed significantly between arms favoring CPx (P < 0.001). CONCLUSION: Adjuvant chemotherapy with CPx is safe and feasible with less toxicity and superior dose delivery compared with CVb.

[Glandular papilloma of the right main bronchus. Detection of an exon 2 mutation of the KRAS gene (c.35G>A)]. / Glanduläres Papillom des rechten Hauptbronchus. Nachweis einer Exon-2-Mutation des KRAS-Gens (c.35G>A).

Benign epithelial tumors of the tracheobronchial system and the lungs are exceedingly rare. These entities encompass squamous and glandular papillomas (as well as their mixed forms) and adenomas (alveolar adenoma, papillary adenoma, salivary gland-like pleomorphic and mucinous adenomas and mucinous cystadenomas). These tumors are considered to be biologically benign neoplasms; however, they can pose considerable diagnostic difficulties, especially during frozen section evaluation, as they can mimic malignant tumors and in particular they can resemble well differentiated papillary adenocarcinomas. As a result of the extreme rarity of these tumors only a few descriptive diagnostic series exist and a systematic investigation including molecular data does not exist. This article presents the case of a 64-year-old patient with a glandular papilloma of the right main bronchus including the immunohistochemical and molecular work-up as well as a review of the current literature.

ßV-tubulin expression is associated with outcome following taxane-based chemotherapy in non-small cell lung cancer.

BACKGROUND: Tubulin-binding agents (TBAs) are effective in non-small cell lung cancer (NSCLC) treatment. Both ßIII- and ßV-tubulins are expressed by cancer cells and may lead to resistance against TBAs. METHODS: Pre-treatment samples from 65 locally advanced or oligometastatic NSCLC patients, who underwent uniform induction chemotherapy with paclitaxel and platinum followed by radiochemotherapy with vinorelbine and platinum were retrospectively analysed by immunohistochemistry. Protein expression of ßIII- and ßV-tubulin was morphometrically quantified. RESULTS: Median pre-treatment H-score for ßIII-tubulin was 110 (range: 0-290), and 160 for ßV-tubulin (range: 0-290). Low ßIII-tubulin expression was associated with improved overall survival (OS) (P=0.0127, hazard ratio (HR): 0.328). An association between high ßV-tubulin expression and prolonged progression-free survival (PFS, median 19.2 vs 9.4 months in high vs low expressors; P=0.0315, HR: 1.899) was found. Further, high ßV-tubulin expression was associated with objective response (median H-score 172.5 for CR+PR vs 120 for SD+PD patients, P=0.0104) or disease control following induction chemotherapy (170 for CR+PR+SD vs 100 for PD patients, P=0.0081), but not radiochemotherapy. CONCLUSION: Expression of ßV-tubulin was associated with treatment response and PFS following paclitaxel-based chemotherapy of locally advanced and oligometastatic NSCLC patients. Prolonged OS was associated with low levels of ßIII-tubulin. Prospective evaluation of ßIII/ßV-tubulin expression in NSCLC is warranted.

Lung segment geometry study: simulation of largest possible tumours that fit into bronchopulmonary segments.

BACKGROUND: Segmental resection in stage I non-small cell lung cancer (NSCLC) has been well described and is considered to have similar survival rates as lobectomy but with increased rates of local tumour recurrence due to inadequate parenchymal margins. In consequence, today segmentectomy is only performed when the tumour is smaller than 2 cm. METHODS: Three-dimensional reconstructions from 11 thin-slice CT scans of bronchopulmonary segments were generated, and virtual spherical tumours were placed over the segments, respecting all segmental borders. As a next step, virtual parenchymal safety margins of 2 cm and 3 cm were subtracted and the size of the remaining tumour calculated. RESULTS: The maximum tumour diameters with a 30-mm parenchymal safety margin ranged from 26.1 mm in right-sided segments 7 + 8 to 59.8 mm in the left apical segments 1-3. CONCLUSIONS: Using a three-dimensional reconstruction of lung CT scans, we demonstrated that segmentectomy or resection of segmental groups should be feasible with adequate margins, even for larger tumours in selected cases.

[Lung cancer staging: what is the actual role of mediastinoscopy?]. / Staging des Lungenkarzinoms: Welche Rolle spielt die Mediastinoskopie heute?

Today several methods for invasive mediastinal staging of lung cancer are available. Whereas mediastinoscopy and anterior mediastinotomy had been the gold standard in every situation several years ago, today EBUS-TBNA has been developed as an alternative to mediastinoscopy concerning the status of lymph node positions 2 L / R, 4 L / R and 7. Actually mediastinoscopy is accepted as the gold standard only in special situations such as negative cytology of suspicious lymph nodes after EBUS-TBNA and mediastinal evaluation after neoadjuvant treatment.

Effects of minimally invasive surgery and functional physiotherapy on motor function of children with cerebral palsy: A non-randomised controlled trial.

PURPOSE: This non-randomised controlled trial investigated whether a combined programme of functional physiotherapy and minimally invasive orthopaedic surgery improves the level and degree of capacity and performance of gross motor function in children with spastic cerebral palsy (CP). METHODS: Fifty-two children with spastic CP aged 5-7 years, Gross Motor Function Classification System (GMFCS) levels II-IV, were allocated to two equal groups: experimental group (selective percutaneous myofascial lengthening [SPML] procedure and 9-month functional strengthening physiotherapy programme) and control (standard physiotherapy) groups. At baseline and at the end of the 9-month intervention, the capacity and performance of gross motor function were assessed with the Gross Motor Function Measure (GMFM) D and E subcategories and Functional Mobility Scale (FMS), respectively. The level of gross motor function was measured with the GMFCS. RESULTS: There was a statistically significant difference in the post-intervention improvements in the GMFM D (experimental mean difference = 19.63 ± 10.46; control mean difference = 2.40 ± 4.62) and E (experimental mean difference = 19.33 ± 11.82; control mean difference = 4.20 ± 6.26) between experimental and control group (p < 0.001). There was a significant improvement in the GMFCS level and each FMS distance for the experimental group (p < 0.001), but not for the control group (p > 0.05). CONCLUSION: SPML procedure combined with functional physiotherapy improves gross motor function in children with spastic CP, by raising the degree and level of motor independence.

[Role of mediastinoscopy and repeat mediastinoscopy today]. / Heutige Rolle der Mediastinoskopie und der Remediastinoskopie.

For patients with lung cancer preoperative evaluation of the mediastinal lymph nodes is important to estimate local operability and/or to consider the necessity of neoadjuvant treatment. Cervical mediastinoscopy is generally accepted as a safe and highly accurate procedure in the staging of lung cancer. Nodes accessible to CM are the levels of the superior (level 2R and 2L) and inferior (level 4R and 4L) paratracheal and subcarinal (level 7) nodal stations. Additionally extended CM and left parasternal mediastinotomy allow the exploration of the aortopulmonary window (level 5) and anterior mediastinal nodes (level 6). In locally advanced lung cancer repeat mediastinoscopy was used after induction chemotherapy or chemoradiation to reexplore the upper mediastinum in order to select patients with a higher probability to undergo complete resection. Operative mortality of both investigations is less than 0.5%; the preoperative complication rate is very low (less than 4%). Because of the higher sensitivity, specificity, and accuracy, mediastinoscopy and repeat mediastinoscopy are superior to new methods like FDG-PET, FDG-PET/CT, EBUS-FNA, and EUS-FNA.

Solitary pulmonary nodule with growth and contrast enhancement at CT: inflammatory pseudotumour as an unusual benign cause.

Small (< or =10 mm) pulmonary nodules are frequently detected at modern chest CT. As most of these nodules are benign, non-invasive classification is required--usually based on assessment of growth and perfusion. Absence of growth and no evidence of perfusion, as demonstrated by lack of enhancement at contrast-enhanced CT or MRI, strongly suggest a benign nodule. On the other hand, growth with a doubling of the nodule's volume between 20 days and 400 days or enhancement suggest a malignant nature of the lesion. We present an example of a nodule with strong contrast enhancement and a doubling time of approximately 260 days, which histologically represented a benign inflammatory pseudotumour.

Prophylactic cranial irradiation in locally advanced non-small-cell lung cancer after multimodality treatment: long-term follow-up and investigations of late neuropsychologic effects.

PURPOSE: Relapse pattern and late toxicities in long-term survivors were analyzed after the introduction of prophylactic cranial irradiation (PCI) into a phase II trial on trimodality treatment of locally advanced (LAD) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Seventy-five patients with stage IIIA(N2)/IIIB NSCLC were treated with induction chemotherapy, preoperative radiochemotherapy, and surgery. PCI was routinely offered during the second period of study accrual. Patients were given a total radiation dose of 30 Gy (2 Gy per daily fraction) over a 3-week period starting 1 day after the last chemotherapy cycle. RESULTS: Introduction of PCI reduced the rate of brain metastases as first site of relapse from 30% to 8% at 4 years (P =.005) and that of overall brain relapse from 54% to 13% (P <.0001). The effect of PCI was also observed in the good-prognosis subgroup of 47 patients who had a partial response or complete response to induction chemotherapy, with a reduction of brain relapse as first failure from 23% to 0% at 4 years (P =.01). Neuropsychologic testing revealed impairments in attention and visual memory in long-term survivors who received PCI as well as in those who did not receive PCI. T2-weighted magnetic resonance imaging revealed white matter abnormalities of higher grades in patients who received PCI than in those who did not. CONCLUSION: PCI at a moderate dose reduced brain metastases in LAD-NSCLC to a clinically significant extent, comparable to that in limited-disease small-cell lung cancer. Late toxicity to normal brain was acceptable. This study supports the use of PCI within intense protocols for LAD-NSCLC, particularly in patients with favorable prognostic factors.

Preoperative chemotherapy followed by concurrent chemoradiation therapy based on hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non-small-cell lung cancer: mature results of a phase II trial.

PURPOSE: To evaluate the feasibility and efficacy of an intensive multimodality approach with combination chemotherapy, hyperfractionated accelerated chemoradiotherapy, and definitive surgery in prognostically unfavorable subgroups of locally advanced non-small-cell lung cancer stages IIIA and IIIB (LAD-NSCLC). PATIENTS AND METHODS: Following staging, including mediastinoscopy, 94 patients with inoperable LAD-NSCLC were treated preoperatively with chemotherapy (three courses of split-dose cisplatin and etoposide [PE]) followed by concurrent chemoradiotherapy (one course of PE combined with 45 Gy hyperfractionated accelerated radiotherapy). After repeat mediastinoscopy, patients underwent surgery 4 weeks postradiation. RESULTS: Of 94 consecutive patients (52 stage IIIA [> or = two lymph node levels involved] and 42 stage IIIB [no pleural effusion, no supraclavicular nodes]), 62 (66%) completed induction and underwent surgery. Complete resection (R0) was achieved in 50 (53% of all patients) and pathologic complete response (PCR) in 24 (26%). After a median follow-up of 43 months, the median survival time was 20 months for IIIA, 18 months for IIIB, and 42 months for R0 patients. Calculated survival rates at 4 years were 31%, 26%, and 46%. Two patients died of sepsis preoperatively and four died postoperatively of pleural empyema (n = 1), stump insufficiency (n = 2), and cardiac failure (n = 1). Other toxicities were acceptable-mainly hematologic during chemotherapy or chemoradiotherapy and esophagitis during chemoradiotherapy. CONCLUSION: This intensive multimodality treatment is feasible and demonstrates high efficacy in prognostically unfavorable LAD-NSCLC subgroups with high R0 rates and improved long-term survival compared with historical controls

[Operative and interventional therapy of lung metastases]. / Lungenmetastasen--Welche Chancen hat lhr Patient jetzt noch?

Almost every third patient succumbing to a malignant disease has metastases in the lungs. However, these are often asymptomatic and are detected fortuitously during a routine examination. Today, the surgical removal of lung metastases is associated with a risk of less than 1%, but only one-third of the patients meet the criteria for such a procedure. The long-term outcome after resection of lung metastases depends in particular on the nature of the primary tumor, the number of metastases, the duration of the period between the occurrence of the primary and development of metastases, and the completeness of the resection. In the case of inoperable metastases, interventional measures may suffice to achieve local tumor control. For the treatment of lung metastases, radiofrequency ablation in particular is currently being investigated.

[Tracheal injuries, fistulae from bronchial stump and bronchial anastomoses and recurrent laryngeal nerve paralysis : management of complications in thoracic surgery]. / Tracheaverletzungen, Insuffizienz von Bronchusstumpf/-anastomose und Rekurrensparese : Management der Komplikationen in der Thoraxchirurgie.

BACKGROUND: Complications cannot always be avoided and their treatment is an integral component of a high quality medical treatment. Complications of the central airways are rare but necessitate supportive treatment by an experienced thoracic surgeon. OBJECTIVE: The reader should become acquainted with measures to prevent complications, to recognize and treat complications early and should understand the necessity for an interdisciplinary approach. MATERIAL AND METHODS: A selective literature research was supplemented by personal experiences and complemented with prospectively collected photographs. RESULTS: There are risk constellations for the appearance of all the mentioned complications which the surgeon needs to know in order to be able to take measures for early detection of complications. Iatrogenic tracheal injuries and bronchial stump fistulae are rare (< 5 %) whereas recurrent laryngeal nerve palsy after left-sided pneumonectomy occurs in up to 30 % of cases. DISCUSSION: After the occurrence of complications at the latest, it is very important to include experienced thoracic surgeons and other specialists when necessary to protect the patient from further damage.

HER2 expression and markers of phosphoinositide-3-kinase pathway activation define a favorable subgroup of metastatic pulmonary adenocarcinomas.

OBJECTIVES: Pulmonary adenocarcinomas (ADC) can be sub-grouped based on dominant oncogenic drivers. EGFR mutations define an entity of metastatic ADC with favorable prognosis and high susceptibility to EGFR tyrosine kinase inhibition. In contrast, the clinical impact of additional ERBB family members in ADC is less defined. To this end we prospectively studied HER2 expression, gene amplification, and mutation in relation to outcome of patients with advanced or metastatic ADC. MATERIALS AND METHODS: Diagnostic tumor biopsies from 193 sequential patients with stage III/IV ADC were prospectively studied for HER2 expression by immunohistochemistry (IHC). Cases with IHC scores 2+ or 3+ were analyzed by HER2 chromogenic in situ hybridization (CISH), and sequencing of HER2 exons 20 and 23. Additional prospectively determined biomarkers included PTEN, cMET, pAKT, and pERK expression, KRAS, EGFR, BRAF and PIK3CA mutations, and ALK fluorescence ISH (FISH). RESULTS AND CONCLUSION: HER2-IHC was feasible in 176 (91.2%) cases. Of 53 (30%) cases with IHC scores 2+/3+, 45 (85%) could be studied by CISH and 34 (64%) by sequencing. The lower number of HER2-mutational analyses resulted from exhaustion of tumor tissue and DNA following mutational analysis of KRAS, EGFR, BRAF and PIK3CA. HER2 amplification was detected in 4 cases (2.3%), while no mutation was found. HER2 expression correlated with expression of pAKT and cMET. Expression of HER2 and pAKT was associated with favorable overall survival in stage IV disease. HER2-expressing ADC more frequently harbored KRAS mutations, while HER2 expression was absent in all 4 cases with BRAF mutation. HER2-IHC was not predictive of HER2 gene amplification or mutation, which both were rare events in prospectively studied patients with advanced or metastatic ADC. Expression of HER2 and pAKT define a population of patients with stage IV ADC with a distinct disease course, who could benefit from specifically tailored pharmacotherapies.

The role of bronchoscopy in pulmonary complications due to mustard gas inhalation.

Over the last five years we have repetitively treated a group of 21 Iranian soldiers who developed pulmonary complications as a result of severe inhalation injury due to mustard gas during the Iran-Iraq war. Early respiratory manifestations included hemorrhagic inflammation of the tracheobronchial tree accompanied by severe erosions. Secondary complications consisted of chronic infections, suppurative bronchitis, and extensive stenotic process of the entire tracheobronchial tree with life-threatening sequelae. After a delay of up to 15 months, scars, ulcers, and strictures developed in the central airways. Progressive deterioration of gas exchange was common. At this point, bronchoscopy, both diagnostic and therapeutic, was invaluable in evaluating the conditions in these patients since many required multiple therapeutic bronchoscopies. Repeated bougienage of the stenotic tracheobronchial lesions and laser photoresection of scarring tissue was life-saving. The recurrence rate of stenosis was very high, with intervals of less than six months on the average. One pneumonectomy was necessary, with the excised lung showing bronchiectasis and chronic pneumonia. To this date we have performed 146 therapeutic bronchoscopies. In four patients, silicone stents had to be implanted. One patient received brachytherapy and external beam radiation therapy in an effort to prevent continued scarring and life-threatening stenoses of the tracheobronchial tree. Our experience demonstrates the extreme usefulness of bronchoscopy in the diagnosis and treatment of pulmonary complications due to inhalation of poisonous gases.

Management of malignant esophagotracheal fistulas with airway stenting and double stenting.

Prognosis of inoperable or recurrent esophageal carcinoma is, at best, poor. Once an esophagotracheal fistula has developed, the overall condition of the patient declines rapidly. Aspiration pneumonia and severe coughing are common. The introduction of esophageal tubes does not always seal the fistula sufficiently and may compromise the airway causing stridor and dyspnea. In 30 patients (25 male, 5 female; age 23 to 74 years; mean, 56 years) with very large fistulas and airway problems, we inserted an airway stent (Dynamic) (n = 12) or an esophageal tube combined with a Dynamic airway stent (n = 18) with the aim of sealing the fistula and restoring patency of the airway and GI passage. The tracheobronchial Dynamic stent was chosen because its slightly concave, flexible posterior silicone membrane adapts ideally to the convex esophageal tube. The stents were well tolerated and significantly improved the quality of life. Of 30 patients, 16 could breathe and swallow unimpaired until shortly before their death. Moderate complaints persisted in five patients, dysphagia in eight patients, and dyspnea in one patient. Mean survival time in the double stent group was significantly greater (110 days) than in the airway stent-only group (24 days) or comparable groups in the literature treated with esophageal tubes only. We conclude that carefully selected patients can benefit from double stenting of esophagus and airways.

Video-assisted thoracoscopy in the treatment of pleural empyema: stage-based management and outcome.

OBJECTIVE: Despite modern diagnostic methods and appropriate treatment, pleural empyema remains a serious problem. Our purpose was to assess the feasibility and efficacy of the video-assisted thoracoscopic surgery in the management of nontuberculous fibrinopurulent pleural empyema after chest tube drainage treatment had failed to achieve the proper results. METHODS: We present a prospective selected single institution series including 45 patients with pleural empyema who underwent an operation between March 1993 and December 1996. Mean preoperative length of conservative management was 37 days (range, 8-82 days). All patients were assessed by chest computed tomography and ultrasonography and underwent video-assisted thoracoscopic debridement of the empyema and postoperative irrigation of the pleural cavity. RESULTS: In 37 patients (82%), video-assisted thoracoscopic debridement was successful. In 8 cases, decortication by standard thoracotomy was necessary. There were no complications during video-assisted thoracic operations. The mean duration of chest tube drainage was 7. 1 days (range, 4-140 days). At follow-up (n = 35) with pulmonary function tests, 86% of the patients treated by video-assisted thoracic operation showed normal values; 14% had a moderate obstruction and restriction without impairment of exercise capacity, and no relapse of empyema was observed. CONCLUSIONS: Video-assisted thoracoscopic debridement represents a suitable treatment for fibrinopurulent empyema when chest tube drainage and fibrinolytics have failed to achieve the proper results. In an early organizing phase, indication for video-assisted thoracic operation should be considered in due time to ensure a definitive therapy with a minimally invasive intervention. For pleural empyema in a later organizing phase, full thoracotomy with decortication remains the treatment of choice.

Completion pneumonectomy: current indications, complications, and results.

OBJECTIVE: Completion pneumonectomy is reported to be associated with high morbidity and mortality, especially when done in patients with benign disease. We review our 9 years of experience with this operation to evaluate the postoperative outcome and long-term results of various indications. METHODS: Between January 1990 and December 1998, 66 consecutive patients underwent completion pneumonectomy (6.8% of all pneumonectomies), and their cases were retrospectively reviewed. The indication was benign disease in 17 patients and malignant disease in 49 patients. In patients with malignant indications there were 14 local recurrences, 4 second primary tumors, 5 metastatic diseases, and 26 indications because of incomplete initial resection. RESULTS: There were no intraoperative deaths, and the postoperative mortality rate was 7.6%. Complications were encountered in 32 (53%) patients, without any significant difference between benign indication (71%) and malignant indication (47%; P =.0923). Bronchopleural fistula was encountered in 5 (7.6%) patients, and empyema was encountered in 7 (11%) patients. The actuarial 5-year survival was 57% for all patients, 65% for those with benign indications, and 54% for those with malignant indications (60% for local recurrence, 50% for second primary tumor, and 56% for incomplete resection), without any difference between benign and malignant indications (P =.9478). CONCLUSIONS: Completion pneumonectomy can be performed with acceptable mortality and morbidity, even in patients with benign disease. Patients with preoperative infection can be managed with bronchial stump covering and adequate postoperative drainage. Although complications are common, they can successfully be managed with a proper understanding of them.

Therapy of localized non-small cell lung cancer (take home messages).

Surgery remains the mainstay in curative therapy of stage I and II NSCLC and selected patients with stage III disease. The high rate of distant metastases occurring in patients after complete surgical resection demonstrates the need for effective adjuvant systemic therapy. However, outside of trials, (neo)adjuvant chemotherapy is currently not considered as an established standard in localized NSCLC. Postoperative radiotherapy increases local tumor control in completely resected N2 disease and after R1/R2 resections and is generally recommended in these situations. In inoperable patients radiotherapy offers the only chance of cure. Combined radiochemotherapy and the highly accelerated CHART radiotherapy have been shown to be superior to standard radiotherapy. Progress in the treatment of localized NSCLC over the last decades has been only modest and with the exception of favourable subgroups, prognosis of NSCLC remains grim. In the light of the high rate of local and distant metastases multidisciplinary approaches appear necessary in the vast majority of patients.

Preoperative treatment strategies in stage III non-small cell lung cancer.

Recent experience has emphasized the need to include systemic chemotherapy in combined-modality management of locally advanced non-small cell lung cancer stage III. If definitive surgery is planned in these situations, preoperative application of drugs-induction chemotherapy-has many advantages in comparison to postoperative delivery. Patients' compliance to treatment, achievable dose intensities of drugs, possible locoregional downstaging, and frequent postoperative problems following complex resections are some of the arguments favouring preoperative chemotherapy. Despite numerous phase-II investigations, little evidence from randomized phase-III trials has been generated. Early inclusion of radiotherapy prior to definitive resection may help to improve preoperative downstaging. Besides available mature phase-II data, phase-III results from ongoing randomized trials are lacking to define the overall value of such a complex approach. Important issues in the future will aim at individualizing these intensive programs according to findings in clinical prognostic factor analyses and to prospectively validate a prognostic risk stratification. Data from translational and molecular research may further help to develop such evidence-based guidelines.