Bcl-2 expression predicts radiotherapy failure in laryngeal cancer

Early stage laryngeal cancer can be effectively cured by radiotherapy or conservative laryngeal surgery. In the UK, radiotherapy is the preferred first line treatment. However, up to 25% of patients with T2 tumours will demonstrate locally persistent or recurrent disease at the original site, requiring salvage surgery to achieve a definitive cure. Patients experiencing treatment failure have a relatively poor prognosis. A retrospective analysis was conducted consisting of 124 patients with early stage (T1-T2, N0) laryngeal squamous cell carcinoma. In total, 62 patients who failed radiotherapy were matched for T stage, laryngeal subsite and smoking history to a group of 62 patients successfully cured by radiotherapy. Using immunohistochemistry the groups were compared for expression of apoptotic proteins: bcl-2, bcl-X(L), bax, bak and survivin. Radioresistant laryngeal cancer was associated with bcl-2 (P < 0.001) and bcl-X(L) (P = 0.005) expression and loss of bax expression (P = 0.012) in pretreatment biopsies. Bcl-2 has an accuracy of 71% in predicting radiotherapy outcome. The association between expression of bcl-2, bcl-X(L) and bax with radioresistant cancer suggests a potential mechanism by which cancer cells avoid the destructive effects of radiotherapy. Predicting radioresistance, using bcl-2, would allow the clinician to recommend conservative laryngeal surgery as an alternative first line treatment to radiotherapy.     

Overexpression of Bcl-2 in squamous cell carcinoma of the larynx: a marker of radioresistance

Squamous cell carcinoma of the larynx can be treated using radiotherapy or surgery, either alone or in combination. Radiotherapy is preferred for early-stage tumours, as it spares the larynx and therefore preserves speech and swallowing. Unfortunately, approximately 15% of tumours treated this way will prove to be radioresistant, as manifest by tumour recurrence within the original radiotherapy field over the ensuing 12 months. By causing extensive DNA damage, radiotherapy aims to induce apoptosis and tumour regression. Our hypothesis was that defects in the mechanisms that recognise DNA damage, induce cell cycle arrest or control apoptosis, either alone or in combination, may be responsible for radioresistance. We therefore undertook an immunohistochemic analysis of pretreatment biopsies of radioresistant (n = 8) and radiosensitive (n = 13) laryngeal tumours. To minimise the impact of confounding factors, strict inclusion criteria were observed; all tumours were of the glottic subsite and all recurrences developed within 12 months of radiotherapy at the site of the original tumour. The expression of key proteins involved in DNA damage recognition (p53), cell cycle arrest (ATM, p16 and p21/WAF1) and apoptosis (Bcl-2 and BAX) were studied. Ki-67 was also assessed as a marker of cell proliferation to exclude low mitotic rate as a cause of radioresistance. A statistically significant correlation was observed between overexpression of Bcl-2 and radioresistance (p = 0.003, Fisher's exact test). We hypothesise that overexpression of the anti-apoptotic protein Bcl-2 allows tumour cells with extensive radiation-induced DNA damage to continue proliferating; the absence of an appropriate apoptotic response manifests clinically as radioresistance.     

Tumour vascularity is a significant prognostic factor for cervix carcinoma treated with radiotherapy: independence from tumour radiosensitivity.

The aim of the study was to investigate the relationship between intrinsic radiosensitivity and vascularity in carcinoma of the cervix given radiotherapy, and assess whether more refined prognostic information can be gained by combining the two parameters. A retrospective study was carried out on 74 patients with locally advanced carcinoma of the cervix. Formalin-fixed, paraffin-embedded tumour biopsies were stained with anti-factor VIII using immunohistochemistry. Vascularity was scored using the intra-tumour microvessel density (IMD), or 'hot-spot', technique. For the same patients, the measurement of intrinsic radiosensitivity (SF2) had been made previously on the same pretherapy samples. Patients were stratified by the median IMD and SF2 scores. Women with radioresistant and highly vascular tumours had poorer 5-year survival (P = 0.0005, P = 0.035 respectively) and local control (P = 0.012, P = 0.077 respectively) than those with radiosensitive and poorly vascular tumours. No significant correlation was seen between IMD and SF2. Multivariate analysis (including tumour stage and patient age) showed that only SF2 and IMD were significant prognostic factors for survival. Patients with both a radioresistant and highly vascular tumour had a 5-year survival level of 18% compared to 77% for those patients with a radiosensitive and poorly vascularized tumour. Tumour angiogenesis and cellular radiosensitivity are independent prognostic factors for cervix carcinoma treated with radiotherapy. Allowing for tumour radiosensitivity increases the prognostic significance of vascularity measurements in cervix tumours.     

Radiobiological characterization of head and neck and sarcoma cells derived from patients prior to radiotherapy

The radiobiological parameters of 33 tumor cell lines were studied in biopsy samples obtained from patients prior to radiotherapy. Epithelial tumor cells derived from head and neck cancer patients were more radioresistant than tumor cell lines derived from patients with sarcoma regardless of method of analysis. The presence of radioresistant tumor cell lines was associated with local failure in some patients. However, the presence of radiosensitive tumor cells did not necessarily predict local control. Our data suggest radiocurability is complex and inherent radiobiological parameters of tumor cells may be only one factor in radiotherapy outcome.     

Significance of Cox-2 expression in rectal cancers with or without preoperative radiotherapy

PURPOSE: Radiotherapy has reduced local recurrence of rectal cancers, but the result is not satisfactory. Further biologic factors are needed to identify patients for more effective radiotherapy. Our aims were to investigate the relationship of cyclooxygenase-2 (Cox-2) expression to radiotherapy, and clinicopathologic/biologic variables in rectal cancers with or without radiotherapy. METHODS AND MATERIALS: Cox-2 expression was immunohistochemically examined in distal normal mucosa (n = 28), in adjacent normal mucosa (n = 107), in primary cancer (n = 138), lymph node metastasis (n = 30), and biopsy (n = 85). The patients participated in a rectal cancer trial of preoperative radiotherapy. RESULTS: Cox-2 expression was increased in primary tumor compared with normal mucosa (p < 0.0001), but there was no significant change between primary tumor and metastasis. Cox-2 positivity was or tended to be related to more p53 and Ki-67 expression, and less apoptosis (p < or = 0.05). In Cox-2-negative cases of either biopsy (p = 0.01) or surgical samples (p = 0.02), radiotherapy was related to less frequency of local recurrence, but this was not the case in Cox-2-positive cases. CONCLUSION: Cox-2 expression seemed to be an early event involved in rectal cancer development. Radiotherapy might reduce a rate of local recurrence in the patients with Cox-2 weakly stained tumors, but not in those with Cox-2 strongly stained tumors.     

The role of Ki67 proliferation assessment in predicting local control in bladder cancer patients treated by radical radiation therapy.

PURPOSE: To assess whether tumour proliferation as measured by Ki67 immunostaining has any predictive value for local control in bladder cancer patients treated by radiotherapy. PATIENTS AND METHODS: Fifty-five patients suffering from infiltrating bladder carcinoma recommended for radical radiotherapy (66 Gy/6-7 weeks) were included in this study. Paraffin-embedded pre-treatment tumour sections were stained with the Ki67 antibody. The percentage of Ki67-positive nuclei was correlated with established prognostic factors, local control and survival. RESULTS: The Ki67 index was not related to local control in our patients when the median was selected as the cut-off value. Patients with tumours with a very low (<27%) Ki67 index had better local control at 5 years (69%) than patients with tumours with greater (>27%) Ki67 expression indices (31.5%) (P<0.05; log-rank test). CONCLUSIONS: Ki67 immunostaining was a feasible method to estimate tumour proliferation. Patients with very low proliferating tumours seemed to achieve better local control after fractionated radiotherapy compared to other patients. Further studies are needed with a greater number of patients to accurately define the role of Ki67 expression in predicting tumour repopulation during fractionated radiotherapy.     

CDC25A, VAV1, TP73, BRCA1 and ZAP70 gene overexpression correlates with radiation response in colorectal cancer

Radiotherapy is increasingly used in adjuvant approaches for colorectal cancer (CRC) to reduce local recurrence and improve survival. However, the principal limitation is the large variability in response among different individuals due to tumor heterogeneity. In the present study, we compared gene expression profiles between radiosensitive and radioresistant colorectal cancer cell lines to identify radiation-related molecules that can be used to evaluate the effects of radiation. The CRC cell line SW620 was irradiated with a high-energy photo beam. Following radiation treatment, RNA was extracted from non-irradiated and irradiated cells, respectively, and gene expression analysis was performed by oligonucleotide microarray and the DAVID bioinformatics method. To further confirm the results, an additional 4 CRC cell lines, COLO205, T84, HCT116, SW480 and SW403 were purchased from ATCC. The radiosensitivities of each were determined by the survival fraction at 2 Gray (SF2) of the surviving cells using the ATPLite assay, and the gene expression profiles after irradiation among the radiosensitive and radioresistant cell lines were analyzed by membrane arrays. The relationships between gene expression and patient clinicopathological features were also analyzed using membrane arrays and RT-PCR. The results from oligonucleotide microarray analysis show that 1601 genes were up-regulated (gene expression ratio of post- to pre-radiation treatment>2). By bioinformatic database analysis, 30 up-regulated genes were identified as involved in DNA damage response pathways, immune response pathways and the complement and coagulation cascades pathway. Fifteen genes showed differential gene expression profiles between radiosensitive (HCT116 and SW620) and radioresistant CRC cell lines (SW403 and SW480). In 110 CRC tissues, we detected five genes CDC25A, VAV1, TP73, BRCA1 and ZAP70 from 15 overexpressed genes that significantly related to prognostic factors (tumor size, advanced stage, invasive depth, lymph node metastasis and differentiation). These findings suggest that CDC25A, VAV1, TP73, BRCA1 and ZAP70 may be novel markers for predicting the effectiveness of radiotherapy in CRC patients.     

VEGF表达预测鼻咽癌放疗效应的价值

[目的]探讨血管内皮生长因子（VEGF）预测鼻咽癌（NPC）放疗效应的价值。[方法]应用免疫组化法检测50例放射敏感和30例放射抵抗的鼻咽部低分化鳞状细胞癌在接受放疗前的肿瘤组织中VEGF的表达情况,分析VEGF的表达与放疗效应的关系。[结果]VEGF在NPC中总的阳性表达率为58．75％（47／80）。在50例放射敏感的NPC组织中,33例f66．00％1VEGF阳性表达,在30例放射抵抗的NPC组织中,14例（46．67％）VEGF阳性表达;两组比较,差异无统计学意义（χ2=2．892,P=0．105）。根据VEGF阳性表达预测NPC放疗抵抗,其预测鼻咽癌放疗效应的敏感性46．67％,特异度34．00％,准确率38．75％。ROC曲线下面积为0．625（95％CI：0．491～0．760;P=0．062）。[结论]放疗前鼻咽部低分化鳞状细胞癌肿瘤组织中VEGF表达对预测放疗效应的价值有限。     

Retrospective analysis of results of treatment of 91 oral cavity cancers from 1982 to 1992]

PURPOSE: To analyse retrospectively the results of different treatment regimens of carcinomas of the floor of the mouth and tongue. MATERIALS AND METHODS: Between 1982 and 1992, 61 patients with carcinoma of the floor of the mouth and 30 with tongue cancer (25 stage I, nine stage II, 28 stage III, 29 stage IV) were treated in the radiotherapy department of Poitiers. Nine patients with stage I tumours were treated with 70 Gy low-dose rate brachytherapy only, without nodal dissection. Stages II and III were treated with combined surgery with neck dissection; and radiotherapy of stage II with nodal metastasis and for all stage III cases. Stage IV cases were treated either surgically if possible, or with combined chemotherapy and radiation. RESULTS: The five-year overall survival rate was 87.3% for stage I, 68.5% for stage II, 45.3% for stage III, and 0% for stage IV patients. Most relapses appeared in the first two years after treatment. Eight patients (32%) with stage I cancer developed nodal relapses, isolated in five cases. Complications of radiotherapy were acceptable. Four cases of osteonecrosis were observed after radiotherapy. All of these appeared simultaneously with a local relapse. CONCLUSION: These results are comparable with reports in the literature. The remarkable observation of our study is the high incidence of nodal recurrences after local treatment of stage I tumours. Therefore, local treatment is insufficient for early-stage tumours. The question of neck dissection for the early stage is discussed.     

Potential role of microvessel density in predicting radiosensitivity of T1 and T2 stage laryngeal squamous cell carcinoma treated with radiotherapy.

Curative radiotherapy is the first choice of therapy for T1 and T2 stage laryngeal squamous cell carcinoma (LSCC) patients to preserve their phonation. Patients with recurrent tumors who undergo salvage surgery require prolonged nasal feeding. Therefore, clinical interest has been focused on elucidating a predictive factor indicating which tumors are likely to be radiosensitive before radiotherapy. We analyzed the relations between radiosensitivity and clinicopathological factors (gender, tumor location, histological factors, and clinical tumor-node-metastasis stage), expression of apoptosis-related proteins (p53, bax, bcl-2), apoptotic index using the terminal deoxynucleotidyltransferase-mediated nick end labeling method, expression of cell proliferation-related proteins (Ki-67-labeling index and epidermal growth factor receptor overexpression) and microvessel density (MVD, vessels/field = 0.391 mm2) in biopsy specimens from 31 LSCC patients given radiotherapy (total radiotherapy dose of 52-70 Gy over 4-6.5 weeks). Univariate analysis revealed that tumors with a high MVD (> or =35 vessels/field) showed better radiosensitivity than those with a low MVD (<35 vessels/field, P = 0.008) and that a high Ki-67-labeling index (> or =40%) was weakly associated with radiosensitivity (P = 0.056). Multivariate analysis and Kaplan-Meier analysis showed that MVD alone had significant predictive power for radiosensitivity in T1 and T2 stage LSCCs after radiotherapy (P = 0.012, 0.0003, respectively). No significant association between clinicopathological factors, or of overexpression of p53, bax, bcl-2, epidermal growth factor receptor, or apoptotic index, with radiosensitivity was found. These results indicate that MVD is a potentially useful clinical factor predicting radiosensitivity for patients with early stage LSCCs before treatment.     

喉癌单纯放疗后原发灶复发的救援治疗

目的：探讨对喉癌单纯放疗后原发灶复发进行挽救治疗的疗效。方法：回顾52例1990年-1995年于中山大学肿瘤防治中心进行单纯放疗的喉癌患者，其中17例治疗后原发灶复发的患者进行总结。5例患者进行姑息性化疗，另外12例患者行手术挽救，6例行喉部分切除术，6例行喉全切除术。应用SPSS10．0统计软件进行分析。结果：单纯放射治疗后原发灶复发经再次挽救治疗后总体三年和五年累计生存率分别为56．3％和37．5％。其中进行姑息化疗的患者经挽救后的生存时间介于8～26个月，进行手术挽救的患者三年和五年累计生存率分别为75％和50％，Kaplan—Meier分析表明两者之间存在显著差异(Log Rank=8．14，P=0．0043)。另外，进行手术挽救的患者中，喉部分切除术和喉全切除术挽救患者的五年累计生存率均为50％，Kaplan-Meier分析显示两者间无显著差异(Log Rank=0．08，P=0．7782)。12例进行手术挽救的患者中5例(41．7％)出现术后并发症，主要是术后感染(25％)和咽瘘(25％)。结论：喉癌单纯放疗后原发灶复发患者进行手术挽救可以获得较好的疗效。原发灶早期(T1和T2)患者复发后可选择进行喉部分切除术挽救。手术挽救后的并发症主要是术后感染和咽瘘。     

Prognostic factors in the management of metastatic epidural spinal cord compression

The results of 51 patients with metastatic spinal cord compression were analyzed. There were seven paralyzed patients, three received radiotherapy (RT) alone and four received laminectomy (L) + RT. No patient regained any motor function. Of six ambulatory patients, half received RT and half L + RT. All remained ambulatory after the treatment. Of 38 paraparetic patients, 20 underwent L + RT. Their complete, partial and nonresponse (CR, PR, NR respectively) rates were 25%, 60% and 15%, respectively. This result was clearly better than 18 other patients treated by RT alone of which only 22% regained ambulation (CR = 22%) while 67% were NR and 11% had a PR. In this series combined modality therapy appears better in paraparetic patients. Five patients with radiosensitive tumors all had CR/ PR whether treated by RT or L + RT. Patients with epithelial tumors treated by L + RT had a PR (CR + PR) of 71% while RT alone gave only 25%. On the basis of this analysis we conclude: (1) ambulatory patients respond satisfactorily to RT alone; (2) paraparetic patients with radiosensitive tumors do well with RT alone while such patients with epithelial tumors merit L + RT; but (3) paraplegic patients rarely benefit from either modality; (4) pain control appears a useful measure of minimally adequate radiation dose in individual patients.     

Classification of sensitivity or resistance of cervical cancers to ionizing radiation according to expression profiles of 62 genes selected by cDNA microarray analysis

To identify a set of genes related to radiosensitivity of cervical squamous cell carcinomas and to establish a predictive method, we compared expression profiles of 9 radiosensitive and 10 radioresistant tumors obtained by biopsy before treatment, on a cDNA microarray consisting of 23,040 human genes. We identified 121 genes whose expression was significantly greater in radiosensitive cells than in radioresistant cells, and 50 genes that showed higher levels of expression in radioresistant cells than in radiosensitive cells. Some of these genes had already known to be associated with the radiation response, such as aldehyde dehydrogenase 1 (ALDH1) and X-ray repair cross-complementing 5 (XRCC5) (P<.05, Mann-Whitney test). The validity of the total of 171 genes as radiosensitivity related genes were certified by permutation test (P<.05). Furthermore, we selected 62 genes on the basis of a clustering analysis, and confirmed the validity of these genes with cross-validation test. The cross-validation test also indicates the possibility of making prediction of radiosensitivity for discriminating radiation-sensitive from radiation resistant biopsy samples by predicting score (PS) values calculated from expression values of 62 genes in 19 samples, because the prediction successfully and unequivocally discriminated the radiosensitive phenotype from the radioresistant phenotype in our test panel of 19 cervical carcinomas. The extensive list of genes identified in these experiments provides a large body of potentially valuable information for studying the mechanism(s) of radiosensitivity, and selected 62 genes opens the possibility of providing appropriate and effective radiotherapy to cancer patients.     

Image-guided hypofractionated small volume radiotherapy of non-small cell lung cancer - feasibility and clinical outcome

Purpose: Local hypofractionated stereotactic radiation treatment (hfSRT) of early stage non-small cell lung cancer (NSCLC) represents a highly effective treatment alternative in medically inoperable patients. Method: Between June 2007 and December 2010, 65 patients with NSCLC were treated with image-guided hypofractionated radiotherapy. The Union Internationale Contre le Cancer (UICC) stage distribution was: IA, n = 19; IB, n = 15; IIB, n = 5; IIIA, n = 10; IIIB, n = 6; and IV, n = 10. The fractionation schedule used was 3 × 12.5 Gy (n = 36) prescribed to the encompassing 67% isodose line for peripheral primary tumours, and 8 × 6 Gy (n = 26) or 8 × 5 Gy (n = 3) prescribed to the encompassing 80% isodose line for centrally located tumours. Results: Mean follow-up was 13.8 months (range 1-41 months). Until now 6 patients developed a local recurrence, 2 of them in combination with mediastinal lymph node failure. The 1-year actuarial local control rate was 93% and overall survival 79%. Pneumonitis was seen in 14 patients (21.5%) (Common Terminology Criteria for Adverse Events (CTCAE) grade I: n = 12, and II: n = 2) after a median time period of 9.5 months. No patient developed pneumonitis of CTCAE grade III or higher. Conclusion: Image-guided hfSRT is effective and feasible in patients with non-operable NSCLC, even in higher stages, whenever local control is crucial and there are contraindications against systemic therapy.     

Prediction of radiosensitivity in human esophageal squamous cell carcinomas with heme oxygenase-1: a clinicopathological and immunohistochemical study

The lack of an accurate system to predict the response to radiotherapy for individual cancer lesions remains a major clinical problem. The aim of this study was to establish whether heme oxygenase-1 (HO-1) may be useful in predicting radiosensitivity of esophageal cancers. We evaluated biopsy specimens from 13 esophageal squamous cell cancer patients. Of these, 8 patients had tumors responding to radiotherapy, and the remainder were considered radioresistant. Expression of HO-1 was assayed using a standard immunoperoxidase technique. Clinicopathological parameters were also analyzed as factors potentially contributing to radiosensitivity. Seven of 13 patients (53.8%) showed cytoplasmic staining for HO-1 in cancer tissues. The local treatment failure rate was 0% for HO-1 positive patients, as opposed to 83.3% for HO-1-negative patients (p=0.012). In contrast, tumor size, stage, and histologic grade were not significantly different between radiotherapy responders and non-responders to radiation therapy. No relationship was observed between HO-1 expression and clinicopathologic features. The results of the current study suggest that expression of HO-1 may be a useful indicator of radiosensitivity for esophageal cancer patients.     

36例喉癌并发原发肺癌的临床分析

目的 探讨喉癌患者以肺癌为表现的第二原发癌的发病情况,治疗方法及预后。方法 总结2182例喉癌患者中出现的36例第二原发肺癌,回顾分析喉癌的治疗（分为单一放疗、单一手术、手术＋放疗）对发生第二原发肺癌的影响,及第二原发肺癌的治疗情况和预后。随访患者均超过5年,随诊率为100％。生存率用寿命表法计算。结果 36例第二原发肺 癌、占喉癌患者总例数的1．7％（36／2182）;占喉癌第二原发癌的45．0％（36／80）,而同期15541例肺癌患者中,则没有在喉部发生第二原发癌者。第二原发肺癌多在喉癌确诊后平均44个月（1－14年）时发现。36例中,鳞癌32例,腺癌2例,小细胞未分化癌1例,大细胞未分化癌1例。第二原发肺癌平均生存23个月,2年生存率41．7％,5年生率为1例,大细胞未分化癌1例。第二原发肺癌平均生存23个月,2年生存率为41．7％,5年生存率为8．3％。结论 喉癌的第二原发癌以肺癌为最多,而肺癌很少出现第二原发喉癌。喉癌的治疗方法对肺癌的方法与否及发生时机影响不大,手术＋放疗优于单一手术及单一放疗。     

以手术为主与以放疗为主治疗Ⅲ、Ⅳ期喉癌的疗效比较

目的 对比以手术为主和以放疗为主综合治疗方法在Ⅲ、Ⅳ期喉癌治疗中的疗效,探索Ⅲ、Ⅳ期喉癌合理的治疗方法.方法 回顾性分析Ⅲ、Ⅳ期喉癌103例(Ⅲ期39例,Ⅳ期64例)的临床资料.根据治疗方法分为手术±放疗组(S±R组,46例)和放疗或放化疗±挽救手术组(R±S组,57例).分析对比两组的总生存(OS)率、无复发生存(RFS)率和喉保留率.多因素分析影响Ⅲ、Ⅳ期喉癌患者生存率和喉保留率的独立因素.结果 S±R组2年OS率、RFS率分别为74.7％(34/46)、72.4％(33/46),优于R±S组的46.4％(26/57)、40.9％(23/57)(P＜0.05).R±S组的喉保留率高于S±R组[32.6％(15/46)比93.0％(53/57),P＜ 0.05].影响预后的独立因素为治疗方法和T分期,影响喉保留率的独立因素为治疗方法.结论 手术±放疗治疗Ⅲ、Ⅳ期喉癌的生存率优于放疗或放化疗±挽救手术,而前者喉保留率则低于后者.Ⅲ、Ⅳ期喉癌应以手术±放疗为首选治疗方法,生活质量的改善宜通过喉功能保留手术和发音重建的方法来实现.     

Induction of plasminogen activator inhibitor type-1 (PAI-1) by hypoxia and irradiation in human head and neck carcinoma cell lines

Background  

Squamous cell carcinoma of the head and neck (SCCHN) often contain highly radioresistant hypoxic regions, nonetheless, radiotherapy is a common treatment modality for these tumours. Reoxygenation during fractionated radiotherapy is desired to render these hypoxic tumour regions more radiosensitive. Hypoxia additionally leads to up-regulation of PAI-1, a protein involved in tumour progression and an established prognostic marker for poor outcome. However, the impact of reoxygenation and radiation on PAI-1 levels is not yet clear. Therefore, we investigated the kinetics of PAI-1 expression and secretion after hypoxia and reoxygenation, and determined the influence of ionizing radiation on PAI-1 levels in the two human SCCHN cell lines, BHY and FaDu.     

The impact of surgical adjuvant thoracic radiation for different stages of non-small cell lung cancer: the experience from a single institution

A retrospective analysis is performed of 223 patients receiving radiotherapy after complete surgery or microscopic-positive resection margins for non-small cell lung cancer. All patients received a total dose of 55 Gy. For 98 stage II (T1, T2N1), a 5-year survival rate of 37% was found. First failure analysis showed 15% (15/98) local and 39% (38/98) distant failures. Patients with hilar-positive lymph nodes had a 5-year survival rate of 32%, compared with 41% for lobar-positive nodes due to more distant failures. Patients with squamous histology had a better survival than non-squamous tumours. There were 48 patients with pN2 tumours. First failure analysis gave 23% (11/48) local and 39.5% (19/48) distant failures resulting in 35% 5-year survival. Patients with pT3N0 with microscopic-positive resection margins and pT3N1 tumours had 5-year survival rates of 21.5 and 17%. Postoperative radiotherapy should be advised in cases of positive hilar nodes, and in all cases of mediastinal-positive nodes. A combination schedule with chemotherapy seems necessary.