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ContextLung cancer is the leading cause of cancer death. Most patients are diagnosed with advanced disease, resulting in a very low 5-year survival. Screening may reduce the risk of death from lung cancer.ObjectiveTo conduct a systematic review of the evidence regarding the benefits and harms of lung cancer screening using low-dose computed tomography (LDCT). A multisociety collaborative initiative (involving the American Cancer Society, American College of Chest Physicians, American Society of Clinical Oncology, and National Comprehensive Cancer Network) was undertaken to create the foundation for development of an evidence-based clinical guideline.Data sourcesMEDLINE (Ovid: January 1996 to April 2012), EMBASE (Ovid: January 1996 to April 2012), and the Cochrane Library (April 2012).Study selectionOf 591 citations identified and reviewed, 8 randomized trials and 13 cohort studies of LDCT screening met criteria for inclusion. Primary outcomes were lung cancer mortality and all-cause mortality, and secondary outcomes included nodule detection, invasive procedures, follow-up tests, and smoking cessation.Data extractionCritical appraisal using predefined criteria was conducted on individual studies and the overall body of evidence. Differences in data extracted by reviewers were adjudicated by consensus.ResultsThree randomized studies provided evidence on the effect of LDCT screening on lung cancer mortality, of which the National Lung Screening Trial was the most informative, demonstrating that among 53,454 participants enrolled, screening resulted in significantly fewer lung cancer deaths (356 vs 443 deaths; lung cancer−specific mortality, 274 vs 309 events per 100,000 person-years for LDCT and control groups, respectively; relative risk, 0.80; 95% CI, 0.73-0.93; absolute risk reduction, 0.33%; P = .004). The other 2 smaller studies showed no such benefit. In terms of potential harms of LDCT screening, across all trials and cohorts, approximately 20% of individuals in each round of screening had positive results requiring some degree of follow-up, while approximately 1% had lung cancer. There was marked heterogeneity in this finding and in the frequency of follow-up investigations, biopsies, and percentage of surgical procedures performed in patients with benign lesions. Major complications in those with benign conditions were rare.ConclusionLow-dose computed tomography screening may benefit individuals at an increased risk for lung cancer, but uncertainty exists about the potential harms of screening and the generalizability of results.

Background: In advanced non-small cell lung cancer (NSCLC), small biopsy specimens from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are often the only available material from cancer tissue for the analysis of programmed death ligand-1 (PD-L1) expression. We aim to assess the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PD-L1 expression at ≥ 1% and ≥ 50% on EBUS-TBNA samples compared with their corresponding surgically resected tumor.Methods: We retrospectively reviewed all patients who underwent EBUS-TBNA followed by surgical resection of NSCLC between July 2006 and September 2016. Demographic information and periprocedural/surgical data were collected. The archived specimens were retrieved and assessed for PD-L1. A positive PD-L1 stain was defined using two separate cutoff points: ≥ 1% and ≥ 50% of tumor cell positivity. EBUS-TBNA aspirates were compared with the surgically resected specimen to calculate the sensitivity, specificity, PPV, and NPV.Results: Sixty-one patients were included. For PD-L1 ≥ 1%, the sensitivity, specificity, PPV, and NPV were 72%, 100%, 100%, and 80%, respectively. For PD-L1 ≥ 50%, the sensitivity, specificity, PPV, and NPV were 47%, 93%, 70%, and 84%, respectively. The concordance rates for PD-L1 ≥ 1% and ≥ 50% were 87% and 82%, respectively.Conclusions: A PD-L1 cutoff of ≥ 1% on EBUS-TBNA has a strong correlation with resected tumor specimen. For PD-L1 ≥ 50%, there is a significant decrease in the sensitivity and PPV of EBUS-TBNA specimen when compared with resected tumor. When analyzing for PD-L1 expression using a cutoff of ≥ 50%, EBUS-TBNA specimens may misclassify the status of PD-L1. [ABSTRACT FROM AUTHOR]

Background: Support for early detection of lung cancer has emerged from the National Lung Screening Trial (NLST), in which low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20 % relative to chest x-ray. The US Preventive Services Task Force (USPSTF) recently recommended annual screening for the high-risk population, concluding that the benefits (life years gained) outweighed harms (false positive findings, abortive biopsy/surgery, radiation exposure). In making their recommendation, the USPSTF noted that the moderate net benefit of screening was dependent on the resolution of most false-positive results without invasive procedures. Circulating biomarkers may serve as a valuable adjunctive tool to imaging. Results: We developed a broad-based proteomics discovery program, integrating liquid chromatography/mass spectrometry (LC/MS) analyses of freshly resected lung tumor specimens (n = 13), lung cancer cell lines (n = 17), and conditioned media collected from tumor cell lines (n = 7). To enrich for biomarkers likely to be found at elevated levels in the peripheral circulation of lung cancer patients, proteins were prioritized based on predicted subcellular localization (secreted, cell-membrane associated) and differential expression in disease samples. 179 candidate biomarkers were identified. Several markers selected for further validation showed elevated levels in serum collected from subjects with stage I NSCLC (n = 94), relative to healthy smoker controls (n = 189). An 8-marker model was developed (TFPI, MDK, OPN, MMP2, TIMP1, CEA, CYFRA 21-1, SCC) which accurately distinguished subjects with lung cancer (n = 50) from high risk smokers (n = 50) in an independent validation study (AUC = 0.775). Conclusions: Integrating biomarker discovery from multiple sample types (fresh tissue, cell lines and conditioned medium) has resulted in a diverse repertoire of candidate biomarkers. This unique collection of biomarkers may have clinical utility in lung cancer detection and diagnoses. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer deaths in males and the second leading cancer cause of death in females. The 5-year survival of all lung cancer patients in the United States is 16%. Only 15% of new lung cancers are stage I at the time of diagnosis, and over 50% of patients have stage IV lung cancer at diagnosis. Most lung cancers are not diagnosed until the patient presents with signs or symptoms of disease, and these are usually due to advanced-stage disease. If we are going to increase the cure rate for lung cancer, then more cases must be detected while the patient is asymptomatic and before the cancer has spread. Screening of high-risk individuals with low-dose computed tomography (LDCT) may help in diagnosing the lung cancer at earlier stages. Screening with LDCT in high-risk individuals is becoming the standard of care in the United States and, along with smoking cessations, offers the best opportunity for decreasing a substantial number of lung cancer deaths. In this article, recent manuscripts about lung cancer screening with LDCT have been reviewed. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: EarlyCDT®-Lung may enhance detection of early stage lung cancer by aiding physicians in assessing high-risk patients through measurement of biological markers (i.e., autoantibodies). The test's performance characteristics in routine clinical practice were evaluated by auditing clinical outcomes of 1613 US patients deemed at high risk for lung cancer by their physician, who ordered the EarlyCDT-Lung test for their patient. Methods: Clinical outcomes for all 1613 patients who provided HIPAA authorization are reported. Clinical data were collected from each patient's treating physician. Pathology reports when available were reviewed for diagnostic classification. Staging was assessed on histology, otherwise on imaging. Results: Six month follow-up for the positives/negatives was 99%/93%. Sixty-one patients (4%) were identified with lung cancer, 25 of whom tested positive by EarlyCDT-Lung (sensitivity=41%). A positive EarlyCDT-Lung test on the current panel was associated with a 5.4-fold increase in lung cancer incidence versus a negative. Importantly, 57% (8/14) of non-small cell lung cancers detected as positive (where stage was known) were stage I or II. Conclusions: EarlyCDT-Lung has been extensively tested and validated in case–control settings and has now been shown in this audit to perform in routine clinical practice as predicted. EarlyCDT-Lung may be a complementary tool to CT for detection of early lung cancer. [Copyright &y& Elsevier]

Studies have shown that fluorescence in situ hybridization (FISH) testing increases lung cancer detection on cytology specimens in peripheral nodules. The goal of this study was to determine whether a predictive model using clinical features and routine cytology with FISH results could predict lung malignancy after a nondiagnostic bronchoscopic evaluation. Patients with an indeterminate peripheral lung nodule that had a nondiagnostic bronchoscopic evaluation were included in this study (N = 220). FISH was performed on residual bronchial brushing cytology specimens diagnosed as negative (n = 195), atypical (n = 16), or suspicious (n = 9). FISH results included hypertetrasomy (n = 30) and negative (n = 190). Primary study end points included lung cancer status along with time to diagnosis of lung cancer or date of last clinical follow-up. Hazard ratios (HRs) were calculated using Cox proportional hazards regression model analyses, and P values b .05 were considered statistically significant. The mean age of the 220 patients was 66.7 years (range, 35-91), and most (58%) were men. Most patients (79%) were current or former smokers with a mean pack year history of 43.2 years (median, 40; range, 1-200). After multivariate analysis, hypertetrasomy FISH (HR = 2.96, P b .001), pack years (HR = 1.03 per pack year up to 50, P = .001), age (HR = 1.04 per year, P = .02), atypical or suspicious cytology (HR = 2.02, P = .04), and nodule spiculation (HR = 2.36, P = .003) were independent predictors of malignancy over time and were used to create a prediction model (C-statistic = 0.78). These results suggest that this multivariate model including test results and clinical features may be useful following a nondiagnostic bronchoscopic examination. [ABSTRACT FROM AUTHOR]

The article presents the conducted nested case-control study on airflow obstruction and the presence of radiographic evidence of emphysema as risk factors for lung cancer. In the study, lung cancer patients from the Mayo Clinic in Minnesota are matched to six control subjects for age, sex and smoking history and quantitative computed tomography (CT) scan analysis of emphysema was conducted. The results of the study showed that airflow obstruction is proved to be an independent risk factor for lung cancer.

The article presents a study that documents the development of lung cancer discovered in high-risk patients who receive yearly screening chest computed tomography (CT) scans. The study examined eighteen lung cancers by at least four serial CT scans among 14 women and 4 men with an age range of 53 to 79 years. The results suggest that though factors preferred lesser fast-growing cancers in women, lung cancers are not restricted to exponential development.

Respiratory illnesses are a huge and rising burden to health-care systems and societies worldwide. Research is crucial to tackle the enormous problem of chest diseases. However the vast number of research questions and available research approaches often creates confusion and risks dilution of resources by spreading them too diffusely. Clear research directions will help to use research funds efficiently to provide treatment advances that benefit patient care. This paper presents the visions of leading experts on future research directions, focusing on what should rather than what is going to be done. These opinions provide a guide for new investigators and a platform for intellectual debates through which coordinated research efforts can help progress towards respiratory health. [ABSTRACT FROM AUTHOR]

The article presents the study conducted by the North Central Cancer Treatment regarding the difference between the prognostic factors of overall survival and progression-free survival on patients with small lung cancer (SCLC). A pooled analysis has been administered to 688 patients with limited-stage disease SCLC and extensive-stage disease SCLC to improve the understanding of these conditions. The result shows that these factors include baseline creatinine levels and metastatic sites.

Objective: Patients with schizophrenia sometimes receive substandard medical care. This study explored such disparities among lung cancer patients with underlying schizophrenia. Methods: This retrospective study focused on patients with pre-existing schizophrenia (or in some instances schizoaffective disorder) and a lung cancer diagnosis made between 1980 and 2004. ‘Disparity’ was defined as a patient's having been prescribed less aggressive therapy for a potentially curable cancer based on state-of-the-art treatment standards for the time and for the cancer stage. Qualitative methods were used to assess healthcare providers' decision-making. Results: 29 patients were included. The median age was 59 years; 38% were men. Twenty-three had non-small cell lung cancer and 6 small cell lung cancer; 17 had potentially curable cancers. Five of 17 had a ‘disparity’ in cancer care: (1) no cancer therapy was prescribed because of chronic obstructive pulmonary disease; (2) no cancer therapy was prescribed because of infection; (3) no chemotherapy was prescribed because the patient declined it; radiation was provided; (4) no chemotherapy was prescribed because of the patient's schizophrenia symptoms; radiation was administered; and (5) no surgery was performed because of disorientation from a lobotomy; radiation was prescribed. Comments from healthcare providers suggest reflection and ethical adjudication in decision-making. Conclusion: Schizophrenia was never the sole reason for no cancer treatment in patients with potentially curable lung cancer. This study provides the impetus for others to begin to assess the effect of schizophrenia on lung cancer management in other healthcare settings. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article focuses on computed tomography (CT) screening of lung cancer. According to the authors, none of the existing CT screening trials have shown lung cancer mortality benefit associated with screening. Among the cited problems with CT screening include large number of false positive results and increased risk of cancer due to radiation.

Summary: This article discusses the strengths and weaknesses of using sputum cytology, plain chest radiograph and computerized tomography (CT) as screening modalities for lung cancer and provides recommendations for screening. [Copyright &y& Elsevier]

The article presents the medical literature of non-small cell lung cancer (NSCLC)-stage IIIB and provides specific treatment guidelines that can serve as a useful tool for the clinician who deals directly with locally advanced NSCLC. This type of lung cancer includes patients with T4 tumors. The optimal treatment for stage IIIB NSCLC depends on several variables, including the extent of disease, age, comorbid risk factors, and patient performance status. Chemoradiotherapy is recommended.

The article presents a medical research study that examined whether computed tomography screening increases the frequency of lung cancer diagnosis and resection and if it reduces the risk of a diagnosis of advanced lung cancer or death from lung cancer. Asymptomatic current and former smokers were screened annually for lung cancer via computed tomography. The authors found that low-dose computed tomography screening can increase the frequency of lung cancer diagnosis and treatment, but that a reduction in advanced lung cancer or death from cancer may not be a result of the screening. The authors conclude that asymptomatic individuals should not be screened outside of clinical research studies. [ABSTRACT FROM AUTHOR]

The article investigates the role of monoclonal antibodies, tyrosine kinase and direct protein inhibitors in the treatment of non-small lung cancer. Results indicated that the addition monoclonal antibody bevacizumab to chemotherapy has improved the survival of patients with non-small cell lung carcinoma.

The article compares the efficiency of cytology and fluorescence in situ hybridization (FISH) for detection of lung cancer in bronchoscopic specimens. FISH and cytology have been performed on 123 washing and 78 brushing specimens. FISH and cytology for patients with negative results at the time of initial bronchoscopy are 83% and 100%. This outcome suggests that FISH is significantly more sensitive than conventional cytology for identifying lung cancer.

Background: Lung cancer is the most common cause of cancer death in the world. Nonetheless, public policy organizations have consistently recommended against screening for lung cancer, with the result that screening is not widely practiced. The Como Conference was undertaken to consider the need for a change in the existing recommendations against screening. Purpose: The primary objective of the Como Conference was to consider whether there is sufficient scientific evidence to advise screening for lung cancer among asymptomatic individuals outside the context of a clinical trial. Methodological issues that are relevant to the proper interpretation of early detection trials were carefully considered. Advantages and problems associated with technological advances in CT scans and digital chest radiographs (CXRs) were fully explored. Economic issues relevant to screening were also considered. Recommendations: It is recommended that physicians assume responsibility for informing high-risk individuals regarding options for screening for lung cancer. Targeted high-risk individuals include middle-aged or elderly men and women who are current or former cigarette smokers of > 20 to 30 pack-years without serious medical comorbidities. It is recommended that such persons be informed that symptomatic lung cancer is usually advanced and incurable, while surgery for early lung cancer offers a far better chance of cure. They should also be informed about advances in imaging technology, as they relate to CT scans and CXRs. Conclusions: Whenever possible, high-risk individuals should be encouraged to enroll in ongoing trials. For subjects who, though eligible, do not have access to such trials, a process of shared decision-making between physicians and at-risk individuals is strongly recommended. After discussion of the existing state of knowledge, high-risk individuals should be made aware that it is reasonable for them to choose to undergo testing for lung cancer. [ABSTRACT FROM AUTHOR]

Lung cancer is the number one cancer killer in North America. Currently, screening for lung cancer is not recommended. Therefore, patients will not receive a diagnosis until they present with symptomatic disease, which is usually advanced stage disease. Previous trials of screening with chest roentgenograms and sputum cytology have failed to show a decrease in lung cancer mortality. Some reports of screening with low-dose spiral CT scans have detected lung cancers at a smaller size (average size, 1.5 cm) than those usually detected by chest radiographs (mean size, 3.0 cm). Spiral CT scanning has been shown to detect between 58% and 85% of non-small cell lung cancers (NSCLCs) while they are in stage IA, and this compares favorably to the current medical practice, in which only 15% are detected as localized disease (Surveillance, Epidemiology, and End Results study data). This article summarizes the spiral CT screening data, and reviews some of the data related to screening with sputum cytology, sputum methylation, and autofluorescence bronchoscopy. Last, there is a brief discussion of some promising future strategies, with emphasis and data from studies presented at this Aspen Lung Conference. [ABSTRACT FROM AUTHOR]

Objective: To compare the survival of patients with medically inoperable or unresectable stage III non-small cell lung cancer treated with thoracic radiotherapy alone or in combination with chemotherapy.Design: Randomized, prospective phase III trial.Setting: Multi-institutional cooperative oncology group.Patients: A total of 121 patients were enrolled in the study, of whom 7 (5.8%) were ineligible. All patients were ambulatory and had measurable or evaluable disease. Before they were randomized, patients were stratified by ECOG performance score, histologic type, maximum tumor diameter, and NCCTG institution.Interventions: Radiotherapy consisted of a total of 5000 cGy in 5 weeks with a 1000 cGy boost in 5 fractions to a small tumor field. Combined modality therapy was MACC which is intravenous methotrexate, intravenous doxorubicin, intravenous cyclophosphamide, and oral lomustine (CCNU), on day 1 and 28. Chemotherapy was followed by identical thoracic radiotherapy 4 weeks after the second cycle of chemotherapy. Four weeks after thoracic radiotherapy was completed, patients received another two cycles of identical chemotherapy. Patients who had progression of disease after chest irradiation only were treated with MACC chemotherapy.Main Results: Major clinical responses were observed in 31 of 56 (55%; 95% Cl, 42% to 68%) patients treated with combination therapy and 37 of 58 (64%; Cl, 51% to 76%) treated with radiation only (P greater than 0.2). The median time to progression was 192 days with radiotherapy only compared with 199 days for combined modality therapy (P greater than 0.2). The median survival time was 313 days compared with 317 days, respectively (P greater than 0.2). The 1-, 2-, and 5-year survival rates after thoracic radiation only were 45% (Cl, 32% to 58%), 16% (Cl, 6% to 25%), and 7%. With chemoradiotherapy, the survival rates were 46% (Cl, 33% to 60%), 21% (Cl, 11% to 32%), and 5%, respectively. Myelosuppression was significantly greater for the combined modality therapy arm (P = 0.002).Conclusion: Chemotherapy with MACC, in combination with thoracic radiotherapy, did not result in significant survival advantage compared with radiation alone (P greater than 0.2) in patients with medically inoperable or unresectable stage III non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

A reply from Drs. Peter B. Bach, James R. Jett and colleagues is presented in response to letters to the editor about their article "Computed tomography screening and lung cancer outcomes."

Background Small cell lung cancer (SCLC) is a lethal disease for which there have been only small advances in diagnosis and treatment in the past decade. Our goal was to revise the evidence-based guidelines on staging and best available treatment options. Methods A comprehensive literature search covering 2004 to 2011 was conducted in MEDLINE, Embase, and five Cochrane databases using SCLC terms. This was cross-checked with the authors' own literature searches and knowledge of the literature. Results were limited to research in humans and articles written in English. Results The staging classification should include both the old Veterans Administration staging classification of limited stage (LS) and extensive stage (ES), as well as the new seventh edition American Joint Committee on Cancer/International Union Against Cancer staging by TNM. The use of PET scanning is likely to improve the accuracy of staging. Surgery is indicated for carefully selected stage I SCLC. LS disease should be treated with concurrent chemoradiotherapy in patients with good performance status. Thoracic radiotherapy should be administered early in the course of treatment, preferably beginning with cycle 1 or 2 of chemotherapy. Chemotherapy should consist of four cycles of a platinum agent and etoposide. ES disease should be treated primarily with chemotherapy consisting of a platinum agent plus etoposide or irinotecan. Prophylactic cranial irradiation prolongs survival in those individuals with both LS and ES disease who achieve a complete or partial response to initial therapy. To date, no molecularly targeted therapy agent has demonstrated proven efficacy against SCLC. Conclusion Evidence-based guidelines are provided for the staging and treatment of SCLC. LS-SCLC is treated with curative intent with 20% to 25% 5-year survival. ES-SCLC is initially responsive to standard treatment, but almost always relapses, with virtually no patients surviving for 5 years. Targeted therapies have no proven efficacy against SCLC. [ABSTRACT FROM AUTHOR]

Randomized controlled trials of smoking interventions have not been well-documented for lung cancer screening populations. In this study, we randomly assigned 171 current smokers who were undergoing low-dose fast spiral chest CT (SCTS) for lung cancer screening to receive either standard written self-help materials or a written list of Internet resources for smoking cessation. At the 1-year follow-up, more of the subjects receiving Internet-based resources reported making a stop attempt (68% versus 48%, P=0.011). However, there were no statistically significant differences in 7-day point prevalence quit rates (5% versus 10%) or advancement in motivational readiness to stop smoking (27% versus 30%), respectively, between the groups. Clearly, more investigation is warranted into how to tailor smoking interventions for cancer screening participants. [Copyright &y& Elsevier]

Summary: Purpose: This study assessed whether maintenance therapy with carboxyaminoimidazole (CAI), compared to placebo, prolonged overall survival in stage IIIB/IV NSCLC patients who had tumour regression or stable disease after treatment with one chemotherapy regimen. Methods: After completion of chemotherapy, patients were randomized to receive daily oral CAI at 250mg or placebo. Treatment continued until patient refusal, disease progression or unacceptable adverse event (AE). Quality of life (QOL) was assessed by UNISCALE and Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L). Results: Registration was halted early for slow accrual (targeted 360, randomized 186: 94 CAI, 92 placebo). All patients were off active treatment at time of analyses. Non-haematologic AEs (primarily grade 1, 2) observed significantly more often in the CAI group included fatigue (54.5% versus 29.3%), anorexia (31.1% versus 13.0%), nausea (62.2% versus 30.4%), vomiting (32.2% versus 14.1%), neurosensory (60.0% versus 44.6%) and ataxia (33.3% versus 16.3%). Patients discontinued treatment for AEs, death on study or refusal more often in the CAI group (36.0% versus 8.7%, p <0.0001). No significant differences in survival or time to progression were observed (median: CAI versus placebo: 11.4 months versus 10.5 months, log rank p =0.54; 2.8 months versus 2.4 months, log rank p =0.50). More patients receiving CAI reported a clinically significant (10-point) decline in QOL particularly on the functional (58% versus 37%, p =0.05) construct of FACT-L and UNISCALE (72% versus 51%, p =0.04). Conclusion: The addition of CAI following chemotherapy does not provide clinical benefit or improvement in QOL over placebo in advanced NSCLC. [Copyright &y& Elsevier]

Purpose: The primary goal was to identify the maximum tolerable dose (MTD) of thoracic radiation therapy (TRT) that can be given with chemotherapy and amifostine for patients with limited-stage small-cell lung cancer (LSCLC).Methods and Materials: Treatment began with two cycles of topotecan (1 mg/m(2)) Days 1 to 5 and paclitaxel (175 mg/m(2)) Day 5 (every 3 weeks) given before and after TRT. The TRT began at 6 weeks. The TRT was given in 120 cGy fractions b.i.d. and the dose escalation (from 4,800 cGy, dose level 1, to 6,600 cGy, dose level 4) followed the standard "cohorts of 3" design. The etoposide (E) (50 mg/day) and cisplatin (C) (3 mg/m(2)) were given i.v. before the morning TRT and amifostine (500 mg/day) was given before the afternoon RT. This was followed by prophylactic cranial irradiation (PCI). The dose-limiting toxicities (DLTs) were defined as Grade > or =4 hematologic, febrile neutropenia, esophagitis, or other nonhematologic toxicity, Grade > or =3 dyspnea, or Grade > or =2 pneumonitis.Results: Fifteen patients were evaluable for the Phase I portion of the trial. No DLTs were seen at dose levels 1 and 2. Two patients on dose level 4 experienced DLTs: 1 patient had a Grade 4 pneumonitis, dyspnea, fatigue, hypokalemia, and anorexia, and 1 patient had a Grade 5 hypoxia attributable to TRT. One of 6 patients on dose level 3 had a DLT, Grade 3 esophagitis. The Grade > or =3 toxicities seen in at least 10% of patients during TRT were esophagitis (53%), leukopenia (33%), dehydration (20%), neutropenia (13%), and fatigue (13%). The median survival was 14.5 months.Conclusion: The MTD of b.i.d. TRT was 6000 cGy (120 cGy b.i.d.) with EP and amifostine. [ABSTRACT FROM AUTHOR]

Summary: Small cell lung cancer is highly sensitive to chemotherapy, and a survival advantage with its use is well established. However, whether chemotherapy also confers such benefits to patients with severe organ dysfunction has not been extensively studied. The goal of this study was to provide further guidance for clinical decision-making. Medical records from small cell lung cancer patients who were seen at a single tertiary care institution between 1994 and 2002 were reviewed. All patients with severe organ dysfunction were identified. The latter was defined as creatinine ≥3mg/dl, total bilirubin ≥3mg/dl, and/or platelet count ≤50×106 per milliliter. An in depth review of treatment and outcome in this patient subgroup was then undertaken. A total of 993 small cell lung cancer patients were seen during this period, and 25 (2.5%) had severe organ dysfunction. Eleven had been treated with chemotherapy, 11 had not, and this information was not retrievable in 3. Cyclophosphamide, etoposide (oral or intravenous), paclitaxel, cisplatin, or carboplatin were prescribed as single agents or in combination; 8 of 11 patients received an initial dose reduction. With chemotherapy, three patients normalized their bilirubin, and one manifested a notable drop. Median survival was 150 days for chemotherapy-treated patients but only 10 days for those who did not receive it. One patient died a few days after chemotherapy; three others were hospitalized immediately thereafter; and two were lost to follow up. In five patients, no notable adverse events were noted in the medical record. These preliminary findings suggest that, even in the presence of severe organ dysfunction, a subgroup of small cell lung cancer patients can tolerate chemotherapy, normalize their laboratory parameters, and go on to live for several months. [Copyright &y& Elsevier]

Purpose: This Phase III study was performed to determine whether twice-daily (b.i.d.) radiotherapy (RT) resulted in better survival than once-daily (q.d.) RT for patients with limited-stage small-cell lung cancer (LD-SCLC).Methods and materials: A total of 310 patients with LD-SCLC initially received three cycles of etoposide and cisplatin. Subsequently, the 261 patients without significant progression were randomized to two cycles of etoposide and cisplatin plus either q.d. RT (50.4 Gy in 28 fractions) or split-course b.i.d. RT (24 Gy in 16 fractions, a 2.5-week break, and 24 Gy in 16 fractions) to the chest. Patients then received a sixth cycle of etoposide and cisplatin followed by prophylactic cranial RT.Results: Follow-up ranged from 4.6 to 11.9 years (median, 7.4 years). The median survival and 5-year survival rate from randomization was 20.6 months and 21% for patients who received q.d. RT compared with 20.6 months and 22% for those who received b.i.d. RT (p = 0.68), respectively. No statistically significant differences were found in the rates of progression (p = 0.68), intrathoracic failure (p = 0.45), in-field failure (p = 0.62), or distant failure (p = 0.82) between the two treatment arms. No statistically significant difference was found in the overall rate of Grade 3 or worse (p = 0.83) or Grade 4 or worse toxicity (p = 0.95). Grade 3 or worse esophagitis (p = 0.05) was more common in the b.i.d. arm. Grade 5 toxicity occurred in 4 (3%) of 130 patients who received b.i.d. RT compared with 0 (0%) of 131 who received q.d. RT (p = 0.04).Conclusion: Although this study did not demonstrate an advantage to split-course b.i.d. RT, the long-term survival was favorable, likely reflecting the positive influences of concurrent combined modality therapy and prophylactic cranial RT. [Copyright &y& Elsevier]

Purpose: This Phase III study was performed to determine whether chemotherapy plus b.i.d. or q.d. radiotherapy (RT) resulted in superior survival for patients with Stage III non-small-cell lung cancer (NSCLC).Methods and Materials: Patients with Stage III NSCLC and an Eastern Cooperative Oncology Group performance status of ≤1 were randomized to receive either standard q.d. RT (60 Gy in 30 daily fractions) or split-course b.i.d. RT (30 Gy in 20 fractions b.i.d.) followed by a 2-week break and then 30 Gy in 20 fractions b.i.d. Both arms included etoposide and cisplatin (EP) during RT.Results: Between December 1994 and February 1999, 246 patients were accrued and 234 were deemed eligible and included in the analyses. Of the 234 patients, 123 had Stage IIIa disease and 111 had Stage IIIb disease. The incidence of severe (Grade 3 or greater) acute nonhematologic toxicity (q.d. RT, 53% vs. b.i.d. RT, 65%) and severe (Grade 3 or greater) hematologic toxicities (thrombocytopenia, 41% q.d. RT vs. 39% b.i.d. RT; neutropenia, 80% q.d. RT vs. 81% b.i.d. RT) was not significantly different between the treatment arms. Five patients (3 in q.d. RT group and 2 in b.i.d. RT group) died as a result of acute toxicity. The follow-up ranged from 2 to 73 months (median 43). No significant differences were found between the q.d. and b.i.d. RT arms in terms of time to progression (p = 0.9; median 9.4 and 9.6 months, respectively), overall survival (p = 0.4; median 14 and 15 months and 2-year survival rate 37% and 40%, respectively), and cumulative incidence of local failure (p = 0.6; 2-year rate 45% and 41%, respectively).Conclusion: This program of split-course b.i.d. RT plus EP was not superior to standard q.d. RT plus EP. The toxicity, tumor control, and survival rates were similar with either b.i.d. or q.d. RT. Our future efforts will concentrate on new combinations of systemic therapy and innovative methods of administering increasing doses of RT. [Copyright &y& Elsevier]

Purpose: We undertook an analysis of quality-adjusted survival using the Q-TWiST (Quality Time Without Symptoms or Toxicity) methodology and developed a new graphic representation called a quality-adjusted life-years plot, which presents a complete and concise Q-TWiST analysis on a single plot.Methods and Materials: The Q-TWiST plot incorporates the time without symptoms or toxicity and several combinations of utility coefficients for toxicity and relapse days into the same plot. In addition, the plot includes threshold lines, to judge whether a particular combination of utility coefficients reaches a significance level.Results: The differential in toxicity incidence and severity between the two thoracic radiation treatment arms was inconsequential. Sensitivity analyses were run using Q-TWiST plots. For all combinations of the various toxicity definitions and utility coefficients, the median Q-TWiST was greater for the once-daily thoracic radiation treatment arm than for the twice-daily treatment arm, without achieved significance.Conclusion: This work refines the results previously reported for this Phase III clinical trial in patients with limited-stage small-cell cancer, and there was no significant difference in survival after adjusting for toxicity and progression. Furthermore, the new methods developed for this trial allow for a more detailed and parsimonious presentation of survival and toxicity data for all oncology clinical trials. [Copyright &y& Elsevier]

The author reflects on the report on lung cancer screening by the International Early Lung Cancer Action Project (IELCAP) group published in "The New England Journal of Medicine." According to the author, observational studies such as the IELCAP can provide important information but cannot prove efficacy of screening through mortality reduction. He said that the improved survival reported by the IELCAP group may simply be a reflection of bias from screening.