CT-guided interstitial brachytherapy of inoperable non-small cell lung cancer. Combined Nd-YAG laser/HDR brachytherapy versus Nd-YAG laser only in malignant central airway involvement: a prospective randomized study. Palliative endobronchial brachytherapy for central lung tumors. A prospective, randomized comparison of two fractionation schedules. Radiation bronchitis and stenosis secondary to high dose rate endobronchial irradiation. The impact of adjuvant brachytherapy with sublobar resection on pulmonary function and dyspnea in high-risk patients with operable disease: preliminary results from the American College of Surgeons Oncology Group Z4032 trial. Thirty- and ninety-day outcomes after sublobar resection with and without brachytherapy for non-small cell lung cancer: results from a multicenter phase III study. Endobronchial brachytherapy in the treatment of malignant lung tumours Using Numerical Results from Systematic Reviews in Clinical Practice High dose rate brachytherapy for the local control of endobronchial carcinoma following external irradiation. Treatment of endotracheal or endobronchial obstruction by non-small cell lung cancer: lack of patients in an MRC randomized trial leaves key questions unanswered. Medical Research Council Lung Cancer Working Party. Does additional brachytherapy improve the effect of external irradiation? A prospective, randomized study in central lung tumors. High dose rate endobronchial brachytherapy in combination with external beam radiotherapy for stage III non-small cell lung cancer. Optimization of dose and fractionation of endobronchial brachytherapy with or without external radiation in the palliative management of non-small cell lung cancer: a prospective randomized study. High dose rate brachytherapy in patients with local recurrences after radiotherapy of non-small cell lung cancer. A randomised trial of radiotherapy compared with cisplatin chemo-radiotherapy in patients with unresectable squamous cell cancer of the esophagus. Quantitative Synthesis in Systematic Reviews Defining the roles of high dose rate endobronchial brachytherapy and laser resection for recurrent bronchial malignancy. Remote afterloading brachytherapy for the local control of endobronchial carcinoma. The role of intraluminal radiotherapy and concurrent 5-fluorouracil infusion in the management of carcinoma esophagus: a pilot study. Enhancement of local control in locally advanced node-positive nasopharyngeal carcinoma by adjunctive chemotherapy. High dose rate afterloading intraluminal brachytherapy in malignant airway obstruction of lung cancer.
PURPOSE The aim of this study was to assess the technical feasibility , efficacy , and complications of CT-guided interstitial brachytherapy for treating inoperable non-small cell lung cancer ( NSCLC ) . MATERIAL S AND METHODS Twenty one patients were included in this prospect i ve study . The median age was 72.6 years ( 57 - 85 ) . Tumors were treated with brachytherapy that was positioned under CT-fluoroscopy . The treatment planning system ( TPS ) was used preoperatively to reconstruct three dimensional images of the tumor and to calculate the estimated seed number and distribution . The median matched peripheral dose ( MPD ) was 130 Gy ( range , 100 - 160 Gy ) . All procedures were performed under local anesthesia . A follow-up CT was performed 6 weeks later and every 3 months post implantation . RESULTS Follow-up period was 2 - 30 months . The mean diameter of the 21 lung tumors was 4.6 cm ( range , 2.8 - 6.5 cm ) . The response rate of pain relief was 83.3 % ( 10/12 ) . The pain-free duration was 0 - 12 months ( median : 6 months ; 95 % CI : 3 - 9 months ) . Overall responding rate ( CR+PR ) for this group of patients was 71.4 % . Local tumor control rate was 85.7 % . Six ( 28.6 % ) patients died as a result of primary tumor progression ; thirteen ( 61.9 % ) patients died of multi-organ failure or other metastases . Two ( 9.5 % ) patients survived to follow-up . At the time of analysis , the median survival time for all patients was 10 months ( 95 % CI : 6.6 - 13.4 months ) , with 1 year and 2 year survival rates were 42.4 % and 6.5 % , respectively . Median survival time for stage II , stage III , and stage IV was 20 months , 9 months , and 8 months , respectively . No major complications were observed . Minor complications ( 19 % ) included mild pneumothorax ( n=1 ) , hemosputum ( n=1 ) , pleural effusion ( n=1 ) , and localized skin erythema ( n=1 ) . None of these complications required further treatment , although hospital discharge was delayed . No (125)I seeds migrated to other tissues or organs . CONCLUSION Minimally invasive CT-guided interstitial brachytherapy is safe , useful , less complicated and considered as a palliative treatment option for inoperable non-small cell lung cancer BACKGROUND Laser debulking and prosthetic stents are useful modalities in the palliative treatment of initial inoperable or recurrent lung cancer . Recently , endobrochial brachytherapy was introduced to extend the duration of palliation and reduce the number of endoscopic treatments . This trial compares Nd-YAG laser alone and associated to high dose rated (HDR)-brachytherapy . PATIENTS AND METHODS From 1995 to 1998 , 29 consecutive patients , with non-small cell lung cancer ( NSCLC ) and central airway involvement , were r and omized in two groups : group 1 ( 15 patients ) received Nd-YAG laser only ;  group 2 ( 14 patients ) underwent a combined Nd-YAG laser/ HDR brachytherapy treatment . RESULTS There was no mortality or morbidity related to the treatment . The period free from symptoms was 2.8 months for group 1 and increased to 8.5 months in group 2 ( P<0.05 ) . The disease 's progression free period grew from 2.2 months of group 1 to 7.5 months of group 2 ( P<0.05 ) and the number of further endoscopic treatment reduced from 15 to 3 ( P<0.05 ) . CONCLUSION The results confirm the potential of brachytherapy to prolong relief from symptoms , lessen disease progression and reduce costs of treatment . A detailed analysis is presented of both groups AIM OF THE STUDY Remote high dose rate brachytherapy is an effective local treatment modality for central lung tumors and has the potential to improve survival time . Optimal dose and fractionation schemes have not been identified yet . We conducted a prospect i ve r and omized study to compare two treatment schedules in terms of survival time , local tumor control , and possible complications . DESIGN Group 1 received 4 brachytherapies with a dose of 3.8 Gy ( at a 10-mm depth ) on a weekly basis , and group 2 received 2 treatments with 7.2 Gy ( at a 10-mm depth ) at a 3-week interval . At a depth of 5 mm , the calculated doses would be 8 and 15 Gy . This study is still ongoing . Here we report interim results . PATIENTS Ninety-three patients with advanced cancer were included in the study ; 44 were in group 1 and 49 , in group 2 . Both groups were comparable regarding age , sex , tumor stage , Karnofsky performance status , and histologic findings . INTERVENTIONS A mean total irradiation dose of 13.4 + /- 5.2 Gy for group 1 and 13.7 + /- 4.4 for group 2 were applied ( calculated at 10 mm from the source axis , equivalent to 27.9 Gy in group 1 and 28.5 Gy in group 2 at a 5-mm depth ) . RESULTS The 1-year survival rate was 11.4 % in group 1 and 20.4 % in group 2 . No significant difference in survival time was found , but mean survival was longer in group 2 ( 49 weeks ) than in group 1 ( 26 weeks ) . Local control after 3 months was comparable in both groups . Fatal hemoptysis occurred at a similar rate in group 1 ( 22.2 % ) and in group 2 ( 21.1 % ) . CONCLUSION High-dose rate brachytherapy with 2 x 7.2 Gy with a 3-week interval is equivalent to a 4 x 3.8-Gy regimen on a weekly basis . The shorter treatment schedule is more convenient for patients , does not cause more side effects , and provides an equal local tumor control PURPOSE To describe a new clinical entity observed in follow-up bronchoscopies in patients who were treated with high dose rate and medium dose rate remote afterloading brachytherapy of the tracheobronchial tree . METHODS AND MATERIAL S Patients treated by protocol with medium dose rate , 47 patients receiving 1000 cGy at a 5 mm depth times three fractions , high dose rate 144 patients receiving 1000 cGy at a 10 mm depth for three fractions and high dose rate 151 patients receiving 750 cGy at a 10 mm depth for three fractions followed by bronchoscopy .  RESULTS Incidence of this entity was 9 % for the first group , 12 % for the second , and 13 % for the third group . Reactions were grade 1 consisting of mild mucosal inflammatory response with a partial whitish circumferential membrane in an asymptomatic patient ; grade 2 , thicker complete white circumferential membrane with cough and /or obstructive problems requiring intervention ; grade 3 , severe inflammatory response with marked membranous exu date and mild fibrotic reaction ; and grade 4 a predominant fibrotic reaction with progressive stenosis . Variables associated with a slightly increased incidence of radiation bronchitis and stenosis included : large cell carcinoma histology , curative intent , prior laser photoresection , and /or concurrent external radiation . Survival was the strongest predictor of the reaction . CONCLUSION Radiation bronchitis and stenosis is a new clinical entity that must be identified in the bronchial brachytherapy patients and treated appropriately BACKGROUND Z4032 was a r and omized study conducted by the American College of Surgeons Oncology Group comparing sublobar resection alone versus sublobar resection with brachytherapy for high-risk operable patients with non-small cell lung cancer ( NSCLC ) . This evaluates early impact of adjuvant brachytherapy on pulmonary function tests , dyspnea , and perioperative ( 30-day ) respiratory complications in this impaired patient population . METHODS Eligible patients with stage I NSCLC tumors 3 cm or smaller were r and omly allocated to undergo sublobar resection with ( SRB group ) or without ( SR group ) brachytherapy . Outcomes measured included the percentage predicted forced expiratory volume in 1 second ( FEV1 % ) , percentage predicted carbon monoxide diffusion capacity ( DLCO% ) , and dyspnea score per the University of California San Diego Shortness of Breath Question naire . Pulmonary morbidity was assessed per the Common Terminology Criteria for Adverse Events version 3.0 . Outcomes were measured at baseline and 3 months . A 10 % change in pulmonary function test or 10-point change in dyspnea score was deemed clinical ly meaningful . RESULTS Z4032 permanently closed to patient accrual in January 2010 at 224 patients . At 3-month follow-up , pulmonary function data are currently available for 148 ( 74 SR and 74 SRB ) patients described in this report . There were no differences in baseline characteristics between arms . In the SR arm , 9 patients ( 12 % ) reported grade 3 respiratory adverse events , compared with 12 ( 16 % ) in the SRB arm ( P = .49 ) . There was no significant change in percentage change in DLCO% or dyspnea score from baseline to 3 months within either arm . In the case of FEV1 % , percentage change from baseline to 3 months was significant within the SR arm ( P = .03 ) , with patients reporting improvement in FEV1 % at month 3 . Multivariable regression analysis ( adjusted for baseline values ) showed no significant impact of treatment arm , tumor location ( upper vs other lobe ) , or surgical approach ( video-assisted thoracoscopic surgery vs thoracotomy ) on 3-month FEV1 % , DLCO% , and dyspnea score . There was no significant difference in incidence of clinical ly meaningful ( 10 % pulmonary function or 10-point dyspnea score change ) change between arms . Twenty-two percent of patients with lower-lobe tumors and 9 % with upper-lobe tumors demonstrated 10 % decline in FEV1 % ( odds ratio , 2.79 ; 95 confidence interval , 1.07 - 7.25 ; P = .04 ) . CONCLUSIONS Adjuvant intraoperative brachytherapy in conjunction with sublobar resection did not significantly worsen pulmonary function or dyspnea at 3 months in a high-risk population with NSCLC , nor was it associated with increased perioperative pulmonary adverse events . Lower-lobe resection was the only factor significantly associated with clinical ly meaningful decline in FEV1 % OBJECTIVE Sublobar resection ( SR ) is commonly used for patients considered high risk for lobectomy . Nonoperative therapies are increasingly being reported for patients with similar risk because of perceived lower morbidity . We report 30- and 90-day adverse events ( AEs ) from American College of Surgeons Oncology Group Z4032 , a multicenter phase III study for high-risk patients with stage I non-small cell lung cancer . METHODS Data from 222 evaluable patients r and omized to SR ( n = 114 ) or SR with brachytherapy ( n = 108 ) are reported . AEs were recorded using the Common Terminology Criteria for Adverse Events , Version 3.0 , at 30 and 90 days after surgery . Risk factors ( age , percent baseline carbon monoxide diffusion in the lung [ DLCO% ] , percent forced expiratory volume in 1 second [ FEV1 % ] , upper lobe vs lower lobe resections , performance status , surgery approach , video-assisted thoracic surgery vs open and extent , and wedge vs segmentectomy ) were analyzed using a multivariable logistic model for their impact on the incidence of grade 3 or higher ( G3 + ) AEs . Respiratory AEs were also specifically analyzed . RESULTS Median age , FEV1 % , and DLCO% were similar in the 2 treatment groups . There was no difference in the location of resection ( upper vs lower lobe ) or the use of segmental or wedge resections . There were no differences between the groups with respect to " respiratory " G3 + AEs ( 30 days : 14.9 % vs 19.4 % , P = .35 ; 0 - 90 days : 19.3 % vs 25 % , P = .31 ) and " any " G3 + AEs ( 30 days : 25.4 % vs 30.6 % , P = .37 ; 0 - 90 days : 29.8 % vs 37 % , P = .25 ) . Further analysis combined the 2 groups . Mortality occurred in 3 patients ( 1.4 % ) by 30 days and in 6 patients ( 2.7 % ) by 90 days . Four of the 6 deaths were thought to be due to surgery . When considered as continuous variables , FEV1 % was associated with " any " G3 + AE at days 0 to 30 ( P = .03 ; odds ratio [ OR ] = 0.98 ) and days 0 to 90 ( P = .05 ; OR = 0.98 ) , and DLCO% was associated with " respiratory " G3 + AE at days 0 to 30 ( P = .03 ; OR = 0.97 ) and days 0 to 90 ( P = .05 ; OR = 0.98 ) . Segmental resection was associated with a higher incidence of any G3 + AE compared with wedge resection at days 0 to 30 ( 40.3 % vs 22.7 % ; OR = 2.56 ; P < .01 ) and days 0 to 90 ( 41.5 % vs 29.7 % ; OR = 1.96 ; P = .04 ) . The median FEV1 % was 50 % , and the median DLCO% was 46 % . By using these median values as potential cutpoints , only a DLCO% of less than 46 % was significantly associated with an increased risk of " respiratory " and " any " G3 + AE for days 0 to 30 and 0 to 90 . CONCLUSIONS In a multicenter setting , SR with brachytherapy was not associated with increased morbidity compared with SR alone . SR/SR with brachytherapy can be performed safely in high-risk patients with non-small cell lung cancer with low 30- and 90-day mortality and acceptable morbidity . Segmental resection was associated with increased " any " G3 + AE , and DLCO% less than 46 % was associated with " any " G3 + AE and " respiratory " G3 + AE at both 30 and 90 days A prospect i ve study was made to assess the short-term clinical and endoscopic response to high-dose-rate endobronchial brachytherapy ( HDREB ) in patients with malignant endobronchial tumours . From July 1995 to May 2000 , 288 HDREB sessions were carried out on 81 patients . The mean patient age was 61.57 yrs ( range 34–82 ) ; males were predominant ( 87.65 % ) . Tumours were primary in 76 patients ( 93.82 % ) and metastatic in five patients ( 6.18 % ) . The inclusion criteria were malignant endobronchial tumour and either palliative treatment for incurable disease or intent-to-cure treatment for residual malignancy on the bronchial resection surface after surgery or an inoperable tumour . The exclusion criteria were as follows : impediments to catheter placement , expected survival < 2 months , Karnofsky index < 60 , or absence of informed consent . The clinical response of a symptom was categorised as complete ( disappearance of the symptom ) , partial ( less than complete ) or absent . The endoscopic response was considered to be complete if lesions disappeared and biopsy findings remained negative 1 month after the last radiation session ; partial if lesions improved to some extent , but the biopsy findings were positive ; and absent if there was no change in relation to baseline . The technique consisted of delivering high-dose irradiation from an Ir192 source to a target volume using one or two endobronchial catheters inserted under optical or video bronchoscopic guidance . Four sessions were scheduled at weekly intervals and 500 cGy was applied per session over a length of 1–9 cm , measured 0.5–1 cm from the centre of the source . In total , 85 % of the symptoms analysed ( haemoptysis , cough , dyspnoea , expectoration , and stridor ) disappeared with HDREB , which was categorised as a complete response . The endoscopic response was complete in 56.79 % of patients , partial or less than complete in 40.74 % and absent in 2.46 % . One major complication occurred ( bronchial fistula 1.2 % ) , but no lethal haemoptysis . Minor complications ( pneumonitis , bronchospasm and bronchial stenosis ) each occurred in one patient ( 1.2 % ) . High-dose-rate endobronchial brachytherapy is a good palliative treatment for endoluminal lung neoplasms , effectively alleviating symptoms and endoscopic evidence in many cases with an acceptable rate of complications . High-dose-rate endobronchial brachytherapy  can be carried out as an intent-to-cure procedure in highly selected cases As professionals , we want to use the best treatments ; as patients , we want to be given them . Knowing whether an intervention works ( or does not work ) is fundamental to clinical decision making . However , clinical decision making involves more than simply taking published results of research directly to the bedside . Physicians need to consider how similar their patients are to those in the published studies , to take the values and preferences of their patients into account , and to consider their own experience with a given test or treatment . Evidence from clinical research is becoming increasingly important in medical- practice decisions as more and better evidence is published . But when is the evidence strong enough to justify changing a practice ? Individual studies that involve only small numbers of patients may have results that are distorted by the r and om play of chance and thus lead to less than optimal decisions . As is clear from other papers in this series , systematic review s identify , critically appraise , and review all the relevant studies on a clinical question and are more likely to give a valid answer . They use explicit methods and quality st and ards to reduce bias . Their results are the closest we can come to reaching the truth given our current state of knowledge . The questions about an intervention that a systematic review should answer are the following : 1 . Does it work ? 2 . If it works , how well does it work in general and compared with placebo , no treatment , or other interventions that are currently in use ? 3 . Is it safe ? 4 . Will it be safe and effective for my patients ? Whereas the critical appraisal and qualitative synthesis provided by review articles can be interpreted directly , the numerical products of quantitative review s can be more difficult to underst and and apply in daily clinical practice . This paper provides guidance on how to interpret the numerical and statistical results of systematic review s , translate these results into more underst and able terms , and apply them directly to individual patients . Many of these principles can also be used to interpret the numerical results of individual clinical studies . They are particularly relevant to systematic review s , however , because such review s contain more information than do primary studies and often exert greater influence than do individual studies . Making Sense of the Numerical Results of Clinical Studies Although the results of clinical studies can be expressed in intuitively meaningful ways , such results do not always easily translate into clinical decision making . For example , results are frequently expressed in terms of risk , which is an expression of the frequency of a given outcome . ( Risks are probabilities , which can vary between 0.0 and 1.0 . A probability of 0.0 means that the event will never happen , and a probability of 1.0 means that it always happens . ) Consider a hypothetical study of the recurrence of migraine headaches in a control group receiving placebo and a treatment group receiving a new antimigraine preparation , drug M ( a secondary prevention trial ) . Suppose that at the end of the trial , migraines recurred in 30 % of the control group ( the risk for recurrence was 0.30 ) but in only 5 % of the drug M group ( risk of 0.05 ) ( Table 1 ) . Table 1 . Numerical Expression of Hypothetical Clinical Trial Results The outcomes of the study are clear enough for the two groups when they are examined separately . But clinicians and patients are more interested in the comparative results , that is , the outcome in one group relative to the outcome in the other group . This overall ( comparative ) result can be expressed in various ways . For example , the relative risk , which is the risk in the treatment group relative to that in the control group , is simply the ratio of the risks in the two groups . In other words , relative risk is the risk in the treatment group divided by that in the control group , 0.05 0.30 , or 0.17 . The comparison can also be expressed as the reduction in relative risk , which is the ratio between the decrease in risk ( in the treatment group ) and the risk in the control group , 0.25 0.30 , or 0.83 ( Table 1 ) . ( The relative risk reduction can also be calculated as 1 relative risk ) . Although the clinical meaning of relative risk ( and relative risk reduction ) is reasonably clear , relative risk has the distinct disadvantage that a given value ( for example , 0.17 ) is the same whether the risk with treatment decreases from 0.80 to 0.14 , from 0.30 to 0.05 , from 0.001 to 0.00017 , and so forth . The clinical implication s of these changes clearly differ from one another enormously and depend on the specific disease and intervention . An important alternate expression of comparative results , therefore , is the absolute risk reduction . Absolute risk reduction is determined by subtracting the risk in one group from the risk in the other ( for example , the risk in the treatment group is subtracted from the risk in the placebo group ) . In the case of our migraine study , the absolute risk reduction would be 0.30 0.05 , which equals 0.25 , or 25 percentage points . In contrast , for a study in which the risk decreased from 0.001 to 0.00017 , the absolute risk reduction would be only 0.00083 , or 0.083 percentage points , which is a trivial change in comparison ( Table 1 ) . This arithmetic emphasizes the difficulty of expressing the results of clinical studies in meaningful ways . Relative risk and relative risk reduction clearly give a quantitative sense of the effects of an intervention in proportional terms but provide no clue about the size of an effect on an absolute scale . In contrast , although it tells less about proportional effects , absolute risk says a great deal about whether an effect is likely to be clinical ly meaningful . Despite this benefit , even absolute risk is problematic because it is a dimensionless , abstract number ; that is , it lacks a direct connection with the clinical situation in which the patient and physician exist . However , another way of expressing clinical research results can provide that clinical link : the number needed to treat ( NNT ) . Number Needed To Treat The NNT for a given therapy is simply the reciprocal of the absolute risk reduction for that treatment [ 1 , 2 ] . In the case of our hypothetical migraine study ( in which risk decreased from 0.30 without treatment with drug M to 0.05 with treatment with drug M , for a relative risk of 0.17 , a relative risk reduction of 0.83 , and an absolute risk reduction of 0.25 ) , the NNT would be 1 0.25 , or 4 . In concrete clinical terms , an NNT of 4 means that you would need to treat four patients with drug M to prevent migraine from recurring in one patient . To emphasize the difference between the concepts embodied in NNT and relative risk , recall the various situations mentioned above , in all of which the relative risk was 0.17 but in which the absolute risk decreased from 0.80 to 0.14 in one case and from 0.001 to 0.00017 in another . Note that the corresponding NNTs in these two other cases are 1.5 and 1204 , respectively : that is , you would need to treat 1.5 and 1204 patients to obtain a therapeutic result in these two situations compared with 4 patients with drug M ( Table 1 ) . The NNT can be calculated easily and kept as a single numerical reminder of the effectiveness ( or , as we will see , the potential for harm ) of a particular therapy . As we suggested , the NNT has the crucial advantage of direct applicability to clinical practice because it shows the effort that is required to achieve a particular therapeutic target . The NNT has the additional advantage that it can be applied to any beneficial outcome or any adverse event ( when it becomes the number needed to harm [ NNH ] ) . The concept of NNT always refers to a comparison group ( in which patients receive placebo , no treatment , or some other treatment ) , a particular treatment outcome , and a defined period of treatment . In other words , the NNT is the number of patients that you will need to treat with drug or treatment A to achieve an improvement in outcome compared with drug or treatment B for a treatment period of C weeks ( or other unit of time ) . To be fully specified , NNT and NNH must always specify the comparator , the therapeutic outcome , and the duration of treatment that is necessary to achieve the outcome . Important Qualities of the Number Needed To Treat The NNT is treatment specific . It describes the difference between treatment and control in achieving a particular clinical outcome . Table 2 shows NNTs from a selection of systematic review s and large r and omized , controlled trials . Table 2 . Numbers Needed To Treat from Systematic Review s and R and omized , Controlled Trials A very small NNT ( that is , one that approaches 1 ) means that a favorable outcome occurs in nearly every patient who receives the treatment and in few patients in a comparison group . Although NNTs close to 1 are theoretically possible , they are almost never found in practice . However , small NNTs do occur in some therapeutic trials , such as those comparing antibiotics with placebo in the eradication of Helicobacter pylori infection or those examining the use of insecticide for head lice ( Table 2 ) . An NNT of 2 or 3 indicates that a treatment is quite effective . In contrast , such prophylactic interventions as adding aspirin to streptokinase to reduce 5-week vascular mortality rates after myocardial infa rct ion may have NNTs as high as 20 to 40 and still be considered clinical ly effective . Limitations of the Number Needed To Treat Although NNTs are powerful instruments for interpreting clinical effects , they also have important limitations . First , an NNT is generally expressed as a single number , which is known as its point estimate . As with all experimental measurements , however , the true value of the NNT can be higher or lower than the point estimate determined through clinical studies . The 95 % CIs of the NNT are useful in this regard because they provide an indication that BACKGROUND : External irradiation is an established palliative treatment for patients with inoperable lung cancer . However , persistent or recurrent symptoms due to local disase are common following external irradiation . The impact of high dose rate ( HDR ) brachytherapy in the palliative management of patients with local sequelae of residual or recurrent endobronchial lung carcinoma following external irradiation  was investigated . METHODS : A prospect i ve cohort of 29 patients ( 19 men , mean age 65 years ) underwent HDR brachytherapy for inoperable lung cancer . All patients had completed external irradiation at least one month before entry into the study ( mean ( SD ) dose 4400 ( 1481 ) cGy , completed 12.9 ( 21.3 ) months previously ) . Patients underwent outpatient bronchoscopic placement of 1 - 3 HDR brachytherapy catheters for delivery of 750 - 1000 cGy of intraluminal irradiation every two weeks on 1 - 3 occasions . Prospect i ve evaluation before and four weeks after completion of HDR brachytherapy included assessment of indices of level of function , symptoms , extent of atelectasis ( chest radiography ) , and bronchoscopic determination of degree of endobronchial obstruction . RESULTS : One hundred and eighteen catheters were placed in 81 treatments . Eleven of the 26 patients who underwent repeat bronchoscopy showed a reduction in the degree of endobronchial obstruction ; five of 18 patients had radiographic improvement in the extent of atelectasis . Positive response rates ranged from 25 % for signs and symptoms related to pneumonitis to 69 % for haemoptysis . Performance status improved in 24 % of patients . Two patients died before completion of the study protocol . Short term complications included one episode of non-fatal , massive haemoptysis , five of minor haemoptysis , and one pneumothorax . CONCLUSIONS : HDR brachytherapy may improve the degree of endobronchial obstruction , atelectasis , symptoms , and level of function with minimal short term complications in patients with recurrent or residual symptomatic disease following external irradiation Symptoms of endotracheal or endobronchial obstruction caused by non-small cell lung cancer ( NSCLC ) may be relieved with external beam radiotherapy ( XRT ) or endobronchial treatment . The comparative roles of these two methods need to be established . Patients with predominantly intraluminal obstruction of the trachea , a main bronchus or a lobar bronchus by unresectable NSCLC were r and omized to XRT versus the clinician 's choice of endobronchial treatment with brachytherapy , laser resection or cryotherapy , according to local availability and practice . Clinicians ' assessment s included symptoms of obstruction , WHO performance status , lung function tests and adverse effects of treatment . Patients completed a Rotterdam Symptom Checklist  at all assessment s and a daily diary card to record the severity of major symptoms during the first 4 weeks . To show a difference of 15 % in the relief of breathlessness rates at 4 months ( from 65 % to 80 % ) , 400 patients were required . In spite of our many previously successful lung cancer trials , and initial interest from clinicians in 24 UK centres , who estimated they could r and omize 200 patients per year into the present trial , only 75 patients were r and omized from seven centres over 3.5 years . Intake to the trial was therefore ab and oned in November 1996 although an independent Data Monitoring and Ethics Committee had concluded in April 1996 that the scientific case for the trial was still strong ; there were no competing trials ; there were no design problems ; and much had been done to promote the trial . The main reasons given by centres for the slow intake were : lack of referrals of untreated patients ; patients being referred specifically for endobronchial treatment ; patients having already received XRT ;  emergency endobronchial relief of obstruction being necessary ; and XRT and endobronchial treatment being considered complementary and not as alternatives . The relative advantages and disadvantages of XRT versus endobronchial treatment remain to be determined . The lack of recruitment to this trial raises the issue of innovative techniques not being given the chance of proving their worth compared with traditional treatments PURPOSE Endobronchial brachytherapy has become more widely used to increase the total local dose of irradiation ( " boost " ) applied for the treatment of lung cancer . Apart from treatment for local stenosis , endobronchial brachytherapy in combination with external irradiation ( EI ) has the potential to improve local tumor control and perhaps prolong survival , but the real benefit has not been proven yet . To evaluate the possible effects of external irradiation with an additional boost of high dose rate ( HDR ) brachytherapy , we conducted a prospect i ve r and omized study . METHODS AND MATERIAL S Design -two groups were compared : Group 1 was treated with external radiotherapy alone ( planned dose 60 Gy ) ; Group 2 received an additional boost of HDR brachytherapy of scheduled 4.8 Gy each ( at 10 mm from the source axis ) before and after external irradiation . Patients -98 patients with advanced inoperable lung cancer were included in the study , 42 in Group 1 and 56 in Group 2 . Both groups were comparable with respect to age , sex , tumor stage , Karnofsky performance status ( KPS ) , and histology . RESULTS A mean total external irradiation dose of 50.5 + /- 14.1 Gy in Group 1 and 50 + /- 12.5 Gy in Group 2 was applied . Group 2 received an additional dose of 7.44 + /- 2.6 Gy ( at 10 mm depth ) through brachytherapy . The median survival time in both groups was comparable ( 28 weeks and 27 weeks , respectively ) . In patients with squamous cell carcinoma ( 68 patients ) Group 2 showed an advantage in median survival with borderline significance ( 40 vs. 33 weeks , p = 0.09 ) . Group 2 showed also a better local tumor control in all patients ; patients with squamous cell carcinoma had a significantly longer period of local tumor control . Fatal hemoptysis was the cause of death in 6 ( 14.2 % ) patients in Group 1 and 11 ( 18.9 % ) in Group 2 ( p = 0.53 ) . CONCLUSIONS High dose rate brachytherapy in patients with inoperable lung cancer increased local control in our r and omized study when used in combination with external irradiation .  Survival time was also longer , but with no clear statistical significance . This applied especially to patients with squamous cell carcinomas . There was no statistically significant difference in the incidence of fatal hemoptysis between the two groups INTRODUCTION A phase-II study was planned to test the effect of external beam radiotherapy in combination with endobronchial brachytherapy on the local control and survival of stage-III non-small cell lung cancer patients . MATERIAL S AND METHODS Thirty patients with stage-III non-small cell lung cancer have been treated with 60 Gy external beam radiotherapy and 3 x 5 Gy HDR endobronchial brachytherapy to control tumor and to prolong survival . RESULTS Therapy regimen was found to be very effective for the palliation of major symptoms , palliation rates were 42.8 % for cough , 95.2 % for hemoptysis , 88.2 % for chest pain and 80.0 % for dyspnea . There was a 76.7 % tumor response ( 53.3 % complete , 23.3 % partial ) verified by chest CT scans and bronchoscopy . However , median locoregional disease free survival was 9+/-4 months ( 95 % CI : 1 - 17 ) and it was only 9.6 % at 5 years . Major side effects were radiation bronchitis ( 70.0 % ) , esophagitis ( 6.6 % ) in the acute period and bronchial fibrosis ( 25 % ) , esophagial fibrosis ( 12.5 % ) and fatal hemoptysis ( 10.5 % ) in the late period . Median survival was 11+/-4 months ( 95 % CI : 4 - 18 ) , and 5-year actuarial survival was 10 % . Locoregional disease free survival ( P=0.008 ) and the overall survival was longer ( P<0.001 ) in the patients younger than 60 , survival was also improved in the patients with complete response ( P=0.019 ) . There were no major complications during catheterisation ; early side effects were quite tolerable but severe late complications were around 10 % . CONCLUSIONS It is concluded that endobronchial brachytherapy in combination with external irradiation provides a good rate of response , however does not eradicate locoregional disease and does not prolong survival except for some subgroups such as younger patients AIMS Endobronchial brachytherapy ( EBBT ) is an established modality for the palliation in advanced non-small cell lung cancer . We compared three different schedules using EBBT with or without external radiation ( XRT ) in this setting . MATERIAL S AND METHODS Forty-five patients were r and omized to three treatment arms . Arm A received XRT to a dose of 30 Gy/10 fr/2 weeks and two sessions of EBBT 8 Gy each . Arm B received the same XRT and a single session of EBBT 10 Gy at 1 cm . Arm C received only a single fraction of brachytherapy to a dose of 15 Gy at 1 cm without XRT .  Symptomatic response rates , duration of symptom palliation , obstruction scores , quality of life outcomes and complications were assessed and compared . RESULTS The overall symptomatic response rates were 91 % for dyspnea , 84 % for cough , 94 % for hemoptysis and 83 % for obstructive pneumonia . There was no significant difference between the arms . The median time to symptom relapse was 4 - 8 months for all symptoms and the median time to symptom progression was 6 - 11 months . The results were comparable between groups except for hemoptysis , where a shorter palliation was seen in Arm C that achieved statistical significance ( P < 0.01 ) . Quality of life showed significant improvement , with maximum benefit in Arm A. Complication rates were low . Only one patient died of fatal hemoptysis . CONCLUSION EBBT is thus a safe and effective palliative tool in advanced non-small cell lung cancer , either alone or in conjunction with XRT . The difference between the treatment arms were not statistically significant in most categories , but patients treated with XRT and two endobronchial sessions of 8 Gy had the most consistent benefit in terms of all the parameters studied Thirty-one patients with recurrences of locally advanced Stage III lung cancer were treated with high dose rate brachytherapy .  All patients had previously received a full course external beam irradiation .  All treatments were performed under topical anaesthesia and took 6 - 14 min depending on the strength of the Iridium-192 source . The high dose rate brachytherapy was calculated as 10 Gy at one cm from the source axis for each session and this was repeated every 2 weeks to a maximum of three sessions . All treatments were well tolerated and no immediate treatment related complications were observed . Response evaluation 6 weeks after high dose rate brachytherapy showed that there was a partial response in 22 patients and nine patients were non-responders . Median survival was 7 and 3 months , respectively . All non-responders had initially presented with a T4N3 tumor . Ten patients died because of fatal pulmonary hemorrhages 2 - 24 weeks after brachytherapy and three others died because of a bronchial fistula . Endobronchial brachytherapy appears to be a valuable treatment alternative for local palliation . However , the relatively high number of complications at follow-up warrants further investigation to establish the optimal benefit to be derived from high dose rate brachytherapy treatment of locally advanced Stage III tumors BACKGROUND AND PURPOSE Following our phase II experience , a r and omised trial was undertaken to evaluate the efficacy of adding chemotherapy to radiotherapy in patients with unresectable squamous cell cancer of the esophagus . PATIENTS AND METHODS Patients r and omised to the RT group received 50 Gy/25 fx/5 weeks of teletherapy followed 1 - 2 weeks later with 12 Gy/2 fx of high-dose-rate intra-lumenal brachytherapy spaced a week apart . Following the first 3 years of recruitment , due to unexpected late morbidity , brachytherapy was excluded and the protocol modified to 66 Gy/33 fx/6.5 weeks . The CRT group received identical radiotherapy with concurrent weekly cisplatin at 35 mg/m(2 ) for 6 - 7 cycles . RESULTS Between April 1999 and December 2005 , 125 patients were r and omised to a RT ( n=60 ) or CRT group ( n=65 ) . Radiotherapy treatment was completed in 78 % ( 47/60 ) of the RT group and 89 % ( 58/65 ) of the CRT group ( P=0.10 ) . Six or more cycles of cisplatin could be delivered in 63 % ( 41/65 ) , which result ed in RTOG grade 3 neutropenia of 3 % . Late morbidity in the form of ulcers ( 5 % vs. 15 % odds ratio 0.29 , 95 % CI 0.08 - 1.11 , P=0.08 ) and strictures ( 13 % vs. 28 % , odds ratio 0.40 , 95 % CI 0.16 - 1.01 , P=0.05 ) was observed in the RT and CRT groups , respectively . At a median follow up of 23 months of all patients alive ( range 6 - 82 months ) and with 95/125 events , the median , 1 , 2 and 5 year projected survival was 7.1 months , 32.3 % , 22.8 % and 13.7 % vs. 13.4 months , 57.6 % , 38.9 % and 24.8 % for the RT and CRT groups , respectively ( hazard ratio 0.65 , 95 % CI 0.44 - 0.98 , P=0.038 ) . CONCLUSIONS The addition of concurrent cisplatin to radiotherapy result ed in a modest improvement in survival and was associated with manageable additional acute and late morbidity A quantitative systematic review , or meta- analysis , uses statistical methods to combine the results of multiple studies . Meta-analyses have been done for systematic review s of therapeutic trials , diagnostic test evaluations , and epidemiologic studies . Although the statistical methods involved may at first appear to be mathematically complex , their purpose is simple : They are trying to answer four basic questions . Are the results of the different studies similar ? To the extent that they are similar , what is the best overall estimate ? How precise and robust is this estimate ? Finally , can dissimilarities be explained ? This article provides some guidance in underst and ing the key technical aspects of the quantitative approach to these questions . We have avoided using equations and statistical notations ; interested readers will find implementations of the described methods in the listed references . We focus here on the quantitative synthesis of reports of r and omized , controlled , therapeutic trials because far more meta-analyses on therapeutic studies than on other types of studies have been published . For practical reasons , we present a stepwise description of the tasks that are performed when statistical methods are used to combine data . These tasks are 1 ) deciding whether to combine data and defining what to combine , 2 ) evaluating the statistical heterogeneity of the data , 3 ) estimating a common effect , 4 ) exploring and explaining heterogeneity , 5 ) assessing the potential for bias , and 6 ) presenting the results . Deciding Whether To Combine Data and Defining What To Combine By the time one performs a quantitative synthesis , certain decisions should already have been made about the formulation of the question and the selection of included studies . These topics were discussed in two previous articles in this series [ 1 , 2 ] . Statistical tests can not compensate for lack of common sense , clinical acumen , and biological plausibility in the design of the protocol of a meta- analysis . Thus , a reader of a systematic review should always address these issues before evaluating the statistical methods that have been used and the results that have been generated . Combining poor- quality data , overly biased data , or data that do not make sense can easily produce unreliable results . The data to be combined in a meta- analysis are usually either binary or continuous . Binary data involve a yes/no categorization ( for example , death or survival ) . Continuous data take a range of values ( for example , change in diastolic blood pressure after antihypertensive treatment , measured in mm Hg ) . When one is comparing groups of patients , binary data can be summarized by using several measures of treatment effect that were discussed earlier in this series [ 3 ] . These measures include the risk ratio ; the odds ratio ; the risk difference ; and , when study duration is important , the incidence rate . Another useful clinical measure , the number needed to treat ( NNT ) , is derived from the inverse of the risk difference [ 3 ] . Treatment effect measures , such as the risk ratio and the odds ratio , provide an estimate of the relative efficacy of an intervention , whereas the risk difference describes the intervention 's absolute benefit . The various measures of treatment effect offer complementary information , and all should be examined [ 4 ] . Continuous data can be summarized by the raw mean difference between the treatment and control groups when the treatment effect is measured on the same scale ( for example , diastolic blood pressure in mm Hg ) , by the st and ardized mean difference when different scales are used to measure the same treatment effect ( for example , different pain scales being combined ) , or by the correlation coefficients between two continuous variables [ 5 ] . The st and ardized mean difference , also called the effect size , is obtained by dividing the difference between the mean in the treatment group and the mean in the control group by the SD in the control group . Evaluating the Statistical Heterogeneity of the Data This step is intended to answer the question , Are the results of the different studies similar ( homogeneous ) ? It is important to answer this question before combining any data . To do this , one must calculate the magnitude of the statistical diversity ( heterogeneity ) of the treatment effect that exists among the different sets of data . Statistical diversity can be thought of as attributable to one or both of two causes . First , study results can differ because of r and om sampling error . Even if the true effect is the same in each study , the results of different studies would be expected to vary r and omly around the true common fixed effect . This diversity is called the within- study variance . Second , each study may have been drawn from a different population , depending on the particular patients chosen and the interventions and conditions unique to the study . Therefore , even if each study enrolled a large patient sample , the treatment effect would be expected to differ . These differences , called r and om effects , describe the between- study variation with regard to an overall mean of the effects of all of the studies that could be undertaken . The test most commonly used to assess the statistical significance of between- study heterogeneity is based on the chi-square distribution [ 6 ] . It provides a measure of the sum of the squared differences between the results observed and the results expected in each study , under the assumption that each study estimates the same common treatment effect . A large total deviation indicates that a single common treatment effect is unlikely . Any pooled estimate calculated must account for the between- study heterogeneity . In practice , this test has low sensitivity for detecting heterogeneity , and it has been suggested that a liberal significance level , such as 0.1 , should be used [ 6 ] . Estimating a Common Effect The questions that this step tries to answers are , 1 ) To the extent that data are similar , what is their best common point estimate of a therapeutic effect , and 2 ) how precise is this estimate ? The mathematical process involved in this step generally involves combining ( pooling ) the results of different studies into an overall estimate . Compared with the results of individual studies , pooled results can increase statistical power and lead to more precise estimates of treatment effect . Each study is given a weight according to the precision of its results . The rationale is that studies with narrow CIs should be weighted more heavily than studies with greater uncertainty . The precision is generally expressed by the inverse of the variance of the estimate of each study . The variance has two components : the variance of the individual study and the variance between different studies . When the between- study variance is found to be or assumed to be zero , each study is simply weighted by the inverse of its own variance , which is a function of the study size and the number of events in the study . This approach characterizes a fixed-effects model , as exemplified by the Mantel-Haenszel method [ 7 , 8 ] or the Peto method [ 9 ] for dichotomous data . The Peto method has been particularly popular in the past . It has the advantage of simple calculation ; however , although it is appropriate in most cases , it may introduce large biases if the data are unbalanced [ 10 , 11 ] . On the other h and , r and om-effects models also add the between- study variance to the within- study variance of each individual study when the pooled mean of the r and om effects is calculated . The r and om-effects model most commonly used for dichotomous data is the DerSimonian and Laird estimate of the between- study variance [ 12 ] . Fixed- and r and om-effects models for continuous data have also been described [ 13 ] . Pooled results are generally reported as a point estimate and CI , typically a 95 % CI . Other quantitative techniques for combining data , such as the Confidence Profile Method [ 14 ] , use Bayesian methods to calculate posterior probability distributions for effects of interest . Bayesian statistics are based on the principle that each observation or set of observations should be viewed in conjunction with a prior probability describing the prior knowledge about the phenomenon of interest [ 15 ] . The new observations alter this prior probability to generate a posterior probability . Traditional meta- analysis assumes that nothing is known about the magnitude of the treatment effect before r and omized trials are performed . In Bayesian terms , the prior probability distribution is noninformative . Bayesian approaches may also allow the incorporation of indirect evidence in generating prior distributions [ 14 ] and may be particularly helpful in situations in which few data from r and omized studies exist [ 16 ] . Bayesian analyses may also be used to account for the uncertainty introduced by estimating the between- study variance in the r and om-effects model , leading to more appropriate estimates and predictions of treatment efficacy [ 17 ] . Exploring and Explaining Heterogeneity The next important issue is whether the common estimate obtained in the previous step is robust . Sensitivity analyses determine whether the common estimate is influenced by changes in the assumptions and in the protocol for combining the data . A comparison of the results of fixed- and r and om-effects models is one such sensitivity analysis [ 18 ] . Generally , the r and om-effects model produces wider CIs than does the fixed-effects model , and the level of statistical significance may therefore be different depending on the model used . The pooled point estimate per se is less likely to be affected , although exceptions are possible [ 19 ] . Other sensitivity analyses may include the examination of the residuals and the chi-square components [ 13 ] and assessment of the effect of deleting each study in turn . Statistically significant results that depend on a single study may require further exploration . Cumulative Meta- Analysis Endobronchial therapy is commonly used in the palliative management of malignant disease , but the optimal combinations of treatment modalities ( laser , brachytherapy , external beam radiotherapy ) have not been defined . We have undertaken a prospect i ve analysis of symptom response , duration of response , and prognostic factors for 117 patients treated with brachytherapy at a single centre , to identify hypotheses suitable for prospect i ve r and omised studies . All but one patient had received previous treatment . The percentage of patients with scores of 0 or 1 ( none or mild ) for each symptom pre-treatment and at 3 months were as follows : cough 62 % to 77 % ( 43 % improving by at least one grade , N.S. ) ; dyspnoea 32 % to 56 % ( 50 % improvement by at least one grade , P = 0.0063 ) ; haemoptysis 78 % to 97 % ; performance status 65 % to 84 % ( 54 % by at least one grade , P = 0.0417 ) . An actuarial risk of fatal haemoptysis at 2 years of 20 % was associated with prior laser resection ( P = 0.048 ) . Death before 2 months was associated with dyspnoea scores of 3 or 4 . Suggestions for r and omised studies are made to address some of the uncertainties revealed by the analysis PURPOSE The study was design ed to , ( a ) st and ardize endobronchial brachytherapy and , ( b ) to evaluate the relief of obstructive signs and symptoms . METHODS Patients with endobronchial carcinoma were treated on a protocol ( n = 342 ) with remote afterloading brachytherapy . Group 1 patients were treated with medium dose rate and received 1000 cGy at 5 mm depth for three fractions ( n = 47 ) . Group 2 were treated with high dose rate , 1000 cGy to a 10 mm depth for three fractions ( n = 144 ) and Group 3 received 750 cGy delivered to a 10 mm depth for three fractions ( n = 151 ) . Each group was divided into curative , palliative , and recurrent categories . Neodymium yttrium aluminum garnet photoresection was used in 24 % of patients prior to brachytherapy  .  RESULTS Evaluation consisted of symptom index scoring with weighted responses of hemoptysis 99 % , obstructive pneumonia 99 % , cough 85 % , and dyspnea 86 % . Obstruction improvement was 80 % overall , curative 87 % , palliative 84 % , and recurrent 70 % of mean pretreatment scores . Survival 10 % alive , 88 % expired , and 2 % lost to follow-up . Cause of death was intrathoracic carcinoma 41 % , metastatic carcinoma 38 % , intercurrent disease 9 % , and unknown cause 13 % . Survival from diagnosis and first treatment was , respectively , for curative 10.8 and 9.5 months , palliative 14 and 5.6 months , and recurrent 25.6 and 6.2 months . Significant complications were fatal hemoptysis 7 % , and radiation bronchitis and stenosis 11 % . CONCLUSION Endoluminal brachytherapy provides excellent palliation of the endobronchial portion of neoplastic disease Fifty patients with carcinoma of the esophagus were entered in a r and omized pilot study to test the efficacy of intraluminal radiotherapy ( ILRT ) and concurrent 5-fluorouracil ( 5-FU ) infusion .  The median age was 65 years , with 80 % having middle third lesions ; in 62 % , the lesions were longer than 5 cm . After external beam therapy of 50 Gy in 5 weeks , patients were r and omized to receive chemotherapy . Significant improvement in dysphagia was recorded in 76 % patients with complete response in 47 cases ranging from 6 to 27 months . The overall survival at 2 years was 15 % with ILRT alone versus 22 % with ILRT plus 5-FU infusion PURPOSE To determine the efficacy of chemotherapy adjunctive to radical radiotherapy ( neoadjuvant + /- adjuvant ) in patients with node-positive nasopharyngeal carcinoma ( NPC ) . METHODS AND MATERIAL S All the node-positive patients given adjunctive chemotherapy between 1984 - 1989 ( n = 209 , CHEMO ) were compared with all the node-positive patients treated by radical radiotherapy alone during the same period ( n = 409 , NCHEMO ) . The CHEMO group had significantly more bulky nodes , lower cervical/supraclavicular nodes , and more advanced overall stages than the NCHEMO group because nodal size ( > or = 24 cm ) was used as a selection criterion for chemotherapy ( 1984 - 1988 departmental protocol and 1988 - 1989 prospect i ve r and omized trial ) . The chemotherapy consisted of two courses of neoadjuvant cisplatin ( 100 mg/m2 D1 ) and 5-fluorouracil ( 5-FU ) ( 1 gm/m2 D1-D3 ) in 191 patients . In addition to the two courses of neoadjuvant , four courses of adjuvant chemotherapy , of the same combination , were given after radical radiotherapy in a further 18 patients . Radical radiotherapy delivered a nasopharyngeal dose of 60 - 62.5 Gy . In addition , parapharyngeal booster external radiotherapy ( 20 Gy ) was given in the presence of parapharyngeal involvement , and intracavitary brachytherapy ( 24 Gy ) was used to treat any local residual tumor diagnosed at 4 - 6 weeks after external radiotherapy . Both crude and actuarial rates were compared ( survival , distant metastases , and local failures ) between CHEMO and NCHEMO for all patients , for individual Ho 's overall stage , for patients with nodes of different sizes ( < or =3 cm , > 3- < or = 6 cm , > 6 cm ) , for individual T-stage and individual N-stage , and for patients belonging to different gender and different age groups ( < 40 years , > or = 40 years ) . Multivariate analyses using the Cox Regression Model were performed to identify significant prognostic factors . RESULTS With a median follow-up of 5.5 years ( range 0.7 to 10 years ) , CHEMO had significantly less local failures overall than NCHEMO ; this was especially true for patients with advanced stages ( III + IV ) . Additionally , in all nodal-size subgroups , in all node-positive T3 , and in node-positive T3-Stage IV , there was a significant reduction in local failures after chemotherapy . There was a trend toward fewer local failures in favor of chemotherapy in Stage III , Stage IV , and T3-Stage III ( 0.05<p < or = 0.1 ) . There was no difference in local failures between CHEMO and NCHEMO in Stage II or in T1 and T2 . The multivariate analyses identified the administration of adjunctive chemotherapy to be of independent significance in determining the local failure rate for all patients , the T3 ( node-positive ) , and the advanced overall stages ( III and IV combined ) . There was no difference in overall survival , relapse-free survival , and distant metastasis rates between CHEMO and NCHEMO among patients belonging to Stages III and IV despite the presence of more advanced nodal diseases in CHEMO . There were very few late local relapses in patients given adjunctive chemotherapy , in contradistinction to the well-known predisposition of NPC to late local relapses after radical radiotherapy . CONCLUSION Adjunctive chemotherapy enhanced local control in node-positive NPC in general , and node positive-T3 and -T3-Stage IV in particular with reduction of late local relapses . The enhancement in local control of the locally advanced NPC could be explained by the significant shrinkage of the primary tumor by the neoadjuvant chemotherapy , leading to an increased safety margin between the tumor volume and the radiation volume . We recommend that adjunctive chemotherapy ( neoadjuvant + /- adjuvant ) should become an integral part of the multimodality curative treatment for patients with node-positive T3 NPC PURPOSE This is a retrospective study to review the palliation rate , survival rate and complications of high dose rate ( HDR ) intraluminal brachytherapy in the treatment of malignant airway obstruction of lung cancer . METHODS AND MATERIAL S A total of 225 high dose rate ( HDR ) brachytherapy treatments were delivered to 76 patients with symptomatic malignant airway obstruction by remote afterloading technique . An average of 7 Gy at a radius of 1 cm from the center of the source was delivered by Iridium-192 ( Ir-192 ) sources . The majority of the patients received 3 fractions at 2 week intervals . Fifty-four patients received HDR brachytherapy as part of their initial treatment ; 20 patients presented as symptomatic endobronchial recurrence . Two patients received YAG laser photoresection to open up the obstruction to allow insertion of the brachytherapy catheter . Fifty-nine patients received concurrent external beam irradiation . Forty-two patients were given 60 - 70 Gy in 6 - 7 weeks with curative intent . Seventeen patients were given 20 - 59 Gy in 2 - 5 weeks as a palliative measure . Nine patients received a radiosensitizer . One patient received concurrent chemotherapy . RESULTS The symptomatic response rates are as follows : dyspnea had an 87 % response rate ( 59 % partial response , 28 % complete response ) , cough had a 79 % response rate ( 47 % partial response , 32 % complete response ) , hemoptysis had a 95 % response rate ( 38 % partial response , 57 % complete response ) , and postobstructive pneumonia had an 88 % response rate ( 53 % partial response , 35 % complete response ) . Sixty-six patients had follow up endoscopic examination ( 1 - 3 months after brachytherapy ) . Their total response rate was 87 % ( 52 % partial response and 35 % complete response ) . There were four acute complications : three cases of massive hemoptysis and one of mild hemoptysis . There are five late complications : three cases of radiation pneumonitis and two of esophagitis . At the time of this study , 55 patients have  died with the maximum survival duration 113 months ( 9.4 years ) from diagnosis date and 18 months from first HDR treatment . Twenty-one patients are still alive with a mean follow-up duration of 20 months from diagnosis date and 7.8 months from the first HDR treatment . CONCLUSION HDR brachytherapy is an excellent modality for palliating symptomatic malignant airway obstruction with an acceptable complication rate ; however , no definitive increase of survival rate was observed . Prospect i ve clinical trials are needed to better define its merit regarding survival . This paper also includes a literature review and discussion of HDR brachytherapy on bronchogenic cancer
BACKGROUND This is an up date d version of the original review published in Issue 2 , 2008 of The Cochrane Library .
Non-small cell lung cancers ( NSCLC ) constitute about 80 % of all lung cancer cases .
Although surgery is the only curative treatment of NSCLC , fewer than 20 % of tumors can be radically resected .
Radiotherapy is one of the main treatment modalities in lung cancer , contributing to both its cure and palliation .
Endobronchial brachytherapy ( EBB ) has been used as one approach to improve local control either alone or in combination with other treatments .
OBJECTIVES To assess the effectiveness of palliative EBB compared with external beam radiation therapy ( EBRT ) or other alternative endoluminal treatments in controlling thoracic symptoms and increasing survival in patients with advanced NSCLC .