The role of post-operative radiotherapy in non-small-cell lung cancer: a multicentre randomised trial in patients with pathologically staged T1-2, N1-2, M0 disease. Medical Research Council Lung Cancer Working Party. Adjuvant radiotherapy in non-small cell lung cancer with pathological stage I: definitive results of a phase III randomized trial. Effects of postoperative mediastinal radiation on completely resected stage II and stage III epidermoid cancer of the lung. LCSG 773. Postoperative adjuvant therapy for stage IB non-small-cell lung cancer. Effects of postoperative mediastinal radiation on completely resected stage II and stage III epidermoid cancer of the lung. Postoperative radiotherapy for radically resected N2 non-small-cell lung cancer (NSCLC): randomised clinical study 1988-1992. Postoperative radiotherapy in radically resected non-small cell lung cancer. Postoperative radiation therapy in lung caner: a controlled trial after resection of curative design. A study of postoperative radiotherapy in patients with non-small-cell lung cancer: a randomized trial. Postresection irradiation for T2 N0 M0 non-small cell carcinoma: a prospective, randomized study. A controlled study of postoperative radiotherapy for patients with completely resected nonsmall cell lung carcinoma Beta blockade during and after myocardial infarction: an overview of the randomized trials.
The role of post-operative radiotherapy for patients with non-small-cell lung cancer ( NSCLC ) is unclear despite five previous r and omised trials . One deficiency with these trials was that they did not include adequate TNM staging , and so the present r and omised trial was design ed to compare surgery alone ( S ) with surgery plus post-operative radiotherapy ( SR ) in patients with pathologically staged T1 - 2 , N1 - 2 . M0 NSCLC . Between July 1986 and October 1993 , 308 patients ( 154 S , 154 SR ) were entered from 16 centres in the UK . The median age of the patients was 62 years , 74 % were male , > 85 % had normal or near normal levels of general condition , activity and breathlessness , 68 % had squamous carcinoma , 52 % had had a pneumonectomy , 63 % had N1 disease and 37 % N2 disease . SR patients received 40 Gy in 15 fractions starting 4 - 6 weeks post-operatively . Overall there was no advantage to either group in terms of survival , although definite local recurrence and bony metastases appeared less frequently and later in the SR group . In a subgroup analysis , in the N1 group no differences between the treatment groups were seen , but in the N2 group SR patients appeared to gain a one month survival advantage , delayed time to local recurrence and time to appearance of the bone metastases . There is , therefore , no clear indication for post-operative radiotherapy in N1 disease , but the question remains unresolved in N2 disease BACKGROUND AND PURPOSE To evaluate the benefits and the drawbacks of post-operative radiotherapy in completely resected Stage I ( a and b ) non-small cell lung cancer ( NSCLC ) . MATERIAL S AND METHODS Patients with pathological Stages Ia and Ib NSCLC have been r and omized into two groups : Group 1 ( G1 ) received adjuvant radiotherapy , Group 0 ( G0 ) the control group did not receive any adjuvant therapy .  Local control , toxicity and survival have been evaluated . RESULTS Between July 1989 and June 1997 , 104 patients with pathological stage I NSCLC have been enrolled in this study . Fifty-one patients were r and omized to G1 and 53 to G0 . Six patients have been excluded from the study due to incomplete follow-up data . Regarding local control , one patient in the G1 group had a local recurrence ( 2.2 % ) while in the G0 12 local recurrences have been observed ( 23 % ) . Seventy-one percent of patients are disease-free at 5 years in G1 and 60 % in G0 ( P=0.039 ) . Overall 5-year survival ( Kaplan-Meier ) showed a positive trend in the treated group : 67 versus 58 % ( P=0.048 ) . Regarding toxicity in G1 , six patients experienced a grade 1 acute toxicity . Radiological evidence of long-term lung toxicity , with no significant impairment of the respiratory function , has been detected in 18 of the 19 patients who have been diagnosed as having a post-radiation lung fibrosis . CONCLUSIONS Adjuvant radiotherapy gave good results in terms of local control in patients with completely resected NSCLC with pathological Stage I. Overall 5-year survival and disease-free survival showed a promising trend . Treatment-related toxicity is acceptable Among patients with lung cancer approximately 44 % have disease limited to the chest . Patients with early lesions treated surgically have better survival rates than those with more advanced primary disease or nodal involvement . Postoperative irradiation should reduce local or regional recurrence and hopefully reduce systemic relapse OBJECTIVE Although surgical resection alone is considered adequate treatment in stage IB non-small-cell lung cancer ( NSCLC ) , long-term survival is not satisfactory and the recurrence rate is quite high . The validity of postoperative chemotherapy at stage IB in terms of disease-free and overall survival was assessed in a r and omised trial . METHODS The trial was design ed as a r and omised , two-group study with postoperative adjuvant chemotherapy versus surgery alone as control group . All patients had stage IB disease ( pT2N0 ) assessed after a radical surgical procedure .  Chemotherapy consisted of treatment with cisplatin ( 100 mg/m(2 ) on day 1 ) and etoposide ( 120 mg/m(2 ) on days 1 - -3 ) for a total of six cycles . RESULTS Between January 1988 and December 1994 , 66 patients were included in the study . Thirty-three belonged to the adjuvant chemotherapy group and 33 to the control group . Groups were homogeneous for conventional risk factors . There was no clinical significant morbidity associated to chemotherapy . Patients were followed for a minimum period of 5 years . The rates of locoregional recurrence and distant metastases were 18 and 30 % , respectively , in the adjuvant chemotherapy group and 24 and 43 % , respectively , in the control group . The 5-year disease-free survival rates were 59 % in the adjuvant group and 30 % in the control group ( P = 0.02 ) . The difference in the Kaplan -- Meier survival between the groups was significant as assessed using the log-rank test ( P = 0.04 ) . CONCLUSIONS Our results suggest that adjuvant chemotherapy may reduce recurrences and prolong overall survival in patients at stage IB NSCLC deemed radically operated . Despite being difficult to accept , the use of adjuvant chemotherapy might have better long-term results We r and omly assigned 230 patients with resected Stage II or III epidermoid ( squamous-cell ) lung cancer to receive postoperative adjuvant radiotherapy or no adjuvant treatment . Careful intraoperative staging had been performed in all patients . Before r and omization , patients were stratified according to stage , weight loss , age , and institution . Prognostic variables , such as stage , weight loss , age , nodal-disease status , and tumor status , were equally distributed between the two groups . The mean time from r and omization to analysis was 3.5 years among the 210 eligible patients . There was no evidence that radiotherapy improved survival , and although recurrence rates appeared to be somewhat reduced among patients assigned to radiotherapy , these decreases were not statistically significant . However , radiotherapy did produce a striking and significant reduction in recurrences to the ipsilateral lung and mediastinum . Moreover , overall recurrence rates were reduced by radiotherapy in patients with N2 disease ( P less than 0.05 ) , although even this subgroup had no evidence of improved survival . We conclude that radiotherapy can reduce local recurrences after resection of epidermoid carcinoma of the lung , but that it does not increase survival rates In the period 1988 - 1992 , 74 consecutive radically resected patients with NSCLC were r and omised to postoperative radiotherapy or surgery alone in order to evaluate the influence of postoperative radiotherapy on survival . There were 61 males and 13 females , aged 35 - 80 years , median 59 years . Their distribution by stage was as follows : pT1N2 = 19 , pT2N2 = 54 , pT3N2 = one patient ; histology : 32 squamous , 32 adeno and 10 large cell carcinomas ; surgery : atypical resection in six , lobectomy in 27 , bilobectomy in ten , and pneumonectomy in 31 patients . In 27 patients , only one lymph node in a single mediastinal lymph node site was affected ; in 31 patients more than one lymph node in one site ; in 16 patients more sites were affected . In 35/74 patients radiotherapy of hilar and mediastinal sites with 3000 cGy in 2 weeks was performed . On December 31 , 1994 , 19 patients ( 26 % ) were still alive ; 39/55 patients died of the following causes : locoregional failure-10(26 % ) , distant metastases- 25 ( 64 % ) , other tumor-unrelated causes-four patients ( 10 % ) . Five-year survival rates did not show statistically significant differences between the irradiated and surgically treated patients only with respect to sex , pTNM stage , histology and frequency of locoregional failure . The number of metastatic mediastinal lymph nodes was the only significant prognostic factor ( P < 0.005 ) in both r and omised groups PURPOSE To evaluate the value of adjuvant postoperative external-beam radiation ( EBR ) in patients with radically resected non-small cell lung cancer ( NSCLC ) pT1 - 3 pN0 - 2 compared to patients with resected NSCLC without adjuvant EBR . MATERIAL S AND METHODS In 155 patients ( 121 male , 34 female ; mean age , 59 years ) 105 lobectomies , 12 bilobectomies , and 38 pneumonectomies with radical lymph node dissection of the contralateral [ corrected ] side were performed . Postoperative staging was done according to the TNM system and was as follows : pT1 ( n=38 ) , pT2 ( n=89 ) , pT3 ( n=28 ) ; pN0 ( n=39 ) , pN1 ( n=67 ) and pN2 ( n=49 ) . Histopathologic study revealed 68 squamous cell carcinomas , 53 adenocarcinomas , 21 large cell carcinomas , 6 adenosquamous cell carcinomas , and 7 bronchioloalveolar cell carcinomas . All patients were r and omly assigned into two treatment groups : 72 patients with no further treatment ( control group ) , and 83 patients ( EBR group ) with adjuvant postoperative EBR of the bronchial stump and mediastinum ( 50 to 56 Gy , 8 or 23 MV photons , 2 Gy/d , 5 d/wk ) beginning 4 to 6 weeks after surgery . RESULTS The overall 5-year survival rate ( median observation time , 43 months ) of all patients was 24.1 % ( EBR group , 29.7 % ; control group , 20.4 % ; p>0.05 , not significant ) . The relative risk of the EBR group was 0.85 with a two-sided confidence interval of 0.66 to 1.09 . The overall 5-year recurrence-free survival was 20.6 % ( EBR , 27.1 % ; control group , 15.6 % ; p=0.07 ) . The relative risk of the EBR group was 0.80 with a confidence interval of 0.63 to 1.01 . The rate of local recurrences at the bronchial stump and /or mediastinum was significantly smaller in the EBR group ( n=5 ) than in the control group ( n=17 ) ( p<0.01 ) . Multivariate analysis ( chi2 test ) demonstrated an independent influence of postoperative EBR on the incidence of local recurrences . The incidence of distant metastases was slightly but not significantly higher in patients without EBR ( 38 patients ) compared to those who had EBR ( 32 patients ) . CONCLUSION High-dose postoperative EBR to the mediastinum significantly reduces the risk of local recurrence at the bronchial stump and /or mediastinum . Age , sex , histologic subtype , tumor size , surgical approach , or extent of lymph node involvement had no prognostic value -- only postoperative EBR had an independent influence on the risk of local recurrence . The effect of postoperative EBR was on the verge of significance with respect to recurrence-free survival and showed the same tendency in overall survival , however with an attenuated relative risk Abstract Postoperative supervoltage radiotherapy was tested in a controlled clinical trial in an attempt to improve the survival for patients with bronchogenic carcinoma .  Radiation therapy began 3 to 4 weeks after surgery ; three fields were used giving a dose of 6,000 rad in six weeks to the mediastinum from a Co 60 unit . Between 1966 and 1975 , 224 patients were included in this study . All had a resection of curative design . 175 patients were evaluable . No increase in survival time was noticed in the irradiated group . The 5 year survival rate was lower in this group ( 24 % versus 43 % for the control group ) but the difference was not statistically significant . For squamous cell carcinoma , the analysis showed a detrimental effect of radiation therapy in the T 2 group ( PURPOSE To study the value of postoperative radiotherapy for non-small-cell lung cancer ( NSCLC ) with positive regional lymph metastases ( NI or N2 ) after radical surgery . MATERIAL S AND METHODS From February 1982 to October 1995 , 366 patients with NSCLC and N1 or N2 disease were r and omized into  postoperative radiotherapy ( S + R ) ( 183 patients ) and no further treatment ( S alone ) ( 182 patients ) . Postoperative radiotherapy ( RT ) was administrated 3 - 4 weeks after radical operation . Irradiated fields covered the bronchial stump , ipsilateral hilum , and most of the mediastinum . The midplane dose was 6000 cGy/30 fractions/6 weeks , with the spinal cord limited to 4000 cGy/20 fractions/4 weeks or less . One hundred thirty-four patients in S + R group and 162 patients in S alone group were evaluated . Clinical data were comparable in both arms , except for the numbers of N2 patients . RESULTS The 3-year and 5-year overall survival rates were 51.9 % and 42.9 % in the S + R group and 50.2 % and 40.5 % in the S alone Group ( p = 0.56 ) . The 3-year and 5-year disease-free survival rates were 50.7 % + /- 4.7 % and 42.9 % + /- 5.2 % in the S + R group vs. 44.4 % + /- 4.3 % and 38.2 % + /- 4.5 % in the S alone group ( p = 0.28 ) , respectively . In the patients with NI or T3 - 4 tumors , there was a trend toward improved survival in the S + R group , especially in the patients with T3 - 4N1M0 . These patients demonstrated 20 % improvement in overall survival ( p = 0.092 ) and greater than 20 % better disease-free survival ( p = 0.057 ) . Postoperative RT reduced local recurrence but had no impact on distant metastases . CONCLUSION Postoperative RT significantly reduced local relapses , but did not improve overall survival , due to a high frequency of distant metastases in this patient group BACKGROUND Stage I nonirradiated T2 N0 non-small cell lung carcinoma has a postoperative prognosis not very different from stage II irradiated T1 N1 carcinoma . The hypothesis was that more locoregional malignant sites are overlooked in T2 N0 M0 than in T1 N0 M0 tumors , considering the better prognosis of this last group , and that T2 N0 cancer might benefit from postresection irradiation . METHODS From 1985 to 1991 , 163 non-small cell lung carcinomas were classified T2 N0 M0 and r and omized for irradiation or nonirradiation after operation . After revision of all the cases , 132 were included in this study : 60 were irradiated and 72 were not irradiated .  All were followed up . The study was closed in October 1995 . Statistical analysis was then performed considering volume , location , cell type , survival , and recurrence in the two groups . RESULTS One hundred thirteen patients were followed up during a minimum of 5 years : the survival was 44.2 % . There was no significant difference considering cell type or irradiation . There was no recurrence-free survivor beyond 5 years with a tumor invading the visceral pleura . At the close of the study ( follow up , 4 years 3 months to 10 years 1 month ) , 49 of 132 patients were alive . The median survival was 3 years 11 months . Fifty-nine patients had died of local ( 21 ) or distant ( 40 ) recurrences ( 2 patients had both local and distant recurrence ) . There was again no significant difference considering cell type or irradiation , either in the survival or in the mode of recurrence . CONCLUSIONS Stage I T2 N0 M0 non-small cell lung carcinoma tends to manifest distant metastasis . Prospect i ve studies of stratified systemic adjuvant therapy should improve the present moderate result of radical resection in this group of tumors Postoperative radiotherapy is commonly used to treat patients with completely resected nonsmall cell lung carcinoma , but its effect on overall survival has not been established Long-term beta blockade for perhaps a year or so following discharge after an MI is now of proven value , and for many such patients mortality reductions of about 25 % can be achieved . No important differences are clearly apparent among the benefits of different beta blockers , although some are more convenient than others ( or have slightly fewer side effects ) , and it appears that those with appreciable intrinsic sympathomimetic activity may confer less benefit . If monitored , the side effects of long-term therapy are not a major problem , as when they occur they are easily reversible by changing the beta blocker or by discontinuation of treatment . By contrast , although very early IV short-term beta blockade can definitely limit infa rct size , more reliable information about the effects of such treatment on mortality will not be available until a large trial ( ISIS ) reports later this year , with data on some thous and s of patients entered within less than 4 hours of the onset of pain . Our aim has been not only to review the 65-odd r and omized beta blocker trials but also to demonstrate that when many r and omized trials have all applied one general approach to treatment , it is often not appropriate to base inference on individual trial results . Although there will usually be important differences from one trial to another ( in eligibility , treatment , end-point assessment , and so on ) , physicians who wish to decide whether to adopt a particular treatment policy should try to make their decision in the light of an overview of all these related r and omized trials and not just a few particular trial results . Although most trials are too small to be individually reliable , this defect of size may be rectified by an overview of many trials , as long as appropriate statistical methods are used . Fortunately , robust statistical methods exist -- based on direct , unweighted summation of one O-E value from each trial -- that are simple for physicians to use and underst and yet provide full statistical sensitivity . These methods allow combination of information from different trials while avoiding the unjustified direct comparison of patients in one trial with patients in another . ( Moreover , they can be extended of such data that there is no real need for the introduction of any more complex statistical methods that might be more difficult for physicians to trust . ) Their robustness , sensitivity , and avoidance of unnecessary complexity make these particular methods an important tool in trial overviews
BACKGROUND The role of postoperative radiotherapy in the treatment of patients with completely resected non-small cell lung cancer was not clear .
A systematic review and quantitative meta- analysis was therfore undertaken to evaluate the available evidence from r and omised trials .
OBJECTIVES To evaluate the effect of post-operative radiotherapy ( PORT )  on survival and recurrence in patients with completely resected non-small cell lung cancer .
To investigate whether or not pre-defined patient sub-groups benefit more or less from PORT .