Lung Cancer Clinical Trials Research Articles

On Bayesian inference for proportional hazards models using noninformative priors.

In this article, we investigate the properties of the posterior distribution under the uniform improper prior for two commonly used proportional hazards models; the Weibull regression model and the extreme value regression model. We allow the observations to be right censored. We obtain sufficient conditions for the existence of the posterior moment generating function of the regression coefficients. A dataset involving a lung cancer clinical trial and a simulation are presented to illustrate our results.

Statistical analysis of symptoms and quality of life data from a randomised lung cancer clinical trial

Statistical analysis of symptoms and quality of life data from a randomised lung cancer clinical trial

Summary of the proceedings of the United States–Japan lung cancer clinical trials summit: San Francisco, CA, 20–22 November, 1998

a UC Da6is Cancer Center, 4501 X Street, Sacramento, CA 95817, USA b Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, 1100 Fair6iew A6enue North, MP-557, Seattle, WA 98109, USA c Di6ision of Respiratory Diseases, Health Insurance Union, Osaka Central Hospital, 2-8-2 Sonesaki, Kitaku, Osaka 530-0057, Japan d Di6ision of Oncology, Department of Medicine, Uni6ersity of Washington School of Medicine, P.O. Box 356043, Seattle, WA 98195, USA e Department of Internal Medicine, Aichi Cancer Center, Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan f Southwest Oncology Group Operations Office, 14980 Omicron Dri6e, San Antonio, TX 78245, USA

Detection of occult metastases in lung carcinomas: progress and implications for lung cancer staging.

The ability to detect occult regional and systemic metastases in patients with operable lung carcinoma could have a significant impact on the management of the disease. Here, we review the literature, including studies from our own laboratory, regarding the clinical significance of the presence of occult metastases in patients with lung cancer. The accumulated evidence strongly suggests that the detection of occult regional and systemic metastases is an important predictor of disease progression. The use of this method should be considered in the future design of lung cancer clinical trials, at the very least. The detection of occult metastases should have an impact on lung cancer management; to reflect this, we propose a change in the TNM staging system to indicate the presence or absence of occult regional (lymph node) and systemic (bone marrow) metastases. The proposed change is TNnMm, where n and m are occult nodal and bone marrow metastases status.

Summary of the proceedings of the United States-Japan lung cancer clinical trials summit

Summary of the proceedings of the United States-Japan lung cancer clinical trials summit

Summary of the proceedings of the United States-Japan lung cancer clinical trials summit. Maui, Hawaii, 24-25 February 1996.

Summary of the proceedings of the United States-Japan lung cancer clinical trials summit. Maui, Hawaii, 24-25 February 1996.

Clinical trials in lung cancer: nihilism versus enthusiasm.

Clinical trials in lung cancer: nihilism versus enthusiasm.

Ongoing clinical trials in lung cancer

II. Lung Cancer Study Group. Ginsberg R J, Rubenstein LV. Randomized trial of lobectomy versus limited resection for T1N0 non-small cell lung cancer. Ann Thorac StoLe. 1995; 60: 615-23. 12. Ginsberg RJ, Rubinstein L. Lung Cancer Study Group. A randomized comparative trial of lobectomy vs limited resection for patients with T 1 NO non-small cell lung cancer. Lung Cancer 1991: 7: (Suppl): 83. 13. Fernando HC, Goldstraw P. The accuracy ofclinical evaluative intrathoracic staging in lung cancer as assessed by postsurgical patholpgic staging. Cancer 1990; 65: 2503-6.

Diagnostic and therapeutic approaches to lung cancer in Canada and their costs.

Escalating health care costs have made it imperative to evaluate the resources required to diagnose and treat major illnesses in Canadians. For Canadian men, lung cancer is not only the most common malignancy, but also the major cancer killer. As of 1994, lung cancer is expected to overtake breast cancer as the leading cause of cancer deaths in women. This paper presents a detailed description of the methodology used to determine the direct health care costs associated with 'standard' diagnostic and therapeutic approaches for lung cancer in Canada in 1988. Clinical algorithms were developed for each stage of non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). The algorithms were designed to take the form of decision trees for each clinical stage of lung cancer. The proportion of patients assigned to each branch was based upon questionnaire responses obtained from thoracic surgeons and radiation oncologists when presented with clinical scenarios, and information from provincial cancer registries. Direct care costs were derived primarily from one provincial fee schedule (Ontario), and costing information obtained during the conduct of several Canadian clinical trials in lung cancer. Direct costs for diagnosis and initial treatment of NSCLC (excluding relapse and terminal care costs) ranged from $17,889 for the surgery/post-operative radiotherapy arm of stages I and II to $6,333 for the supportive care arm (stage IV). The cost of determining relapse for NSCLC was estimated to be $1,528, and terminal care costs, which included palliative radiotherapy and hospitalisation, were $10,331. Direct costs for diagnosis and initial treatment of SCLC ranged from $18,691 for limited stage disease to $4,739 for the supportive care arm of extensive disease. The cost of diagnosing relapse for SCLC was estimated to be $1,590, and terminal care costs averaged $9,966. This report provides an estimate of the Canadian costs of managing lung cancer by stage and treatment modality. Because the actual costs of all components of care are not available from any combination of sources, these cost estimates must be viewed as an idealised estimate of the cost of lung cancer management. However, we believe that the lung cancer costing model that we have developed provides a level of sophistication which gives a reasonable estimate of the cost per case of treating NSCLC and SCLC.

Reliability and validity of the functional assessment of cancer therapy—lung (FACT-L) quality of life instrument

The FACT-L (version 3) is a 44-item self-report instrument which measures multidimensional quality of life. Available in eight languages, it is currently being used in several Phase II and III lung cancer clinical trials. Reliability and validity of the 33-item version 2 of the FACT-General (FACT-G) have previously been published. This paper reports further validation data on the FACT-G with a subsample of lung cancer patients from the original publication and, more importantly, presents data on the Lung Cancer Subscale (LCS). The nine LCS questions were administered along with the FACT-G to 116 patients with lung cancer. Internal consistency (coefficient alpha) was improved from 0.53 to 0.68 by dropping two questions which were uncorrelated with the others. A subset of 41 patients was tested again at 2 months to evaluate sensitivity to change in performance status rating (PSR) and to obtain estimates of a clinically meaningful change score for the FACT-G and the 7-item LCS. Using a linear test for trend, sensitivity to change in performance status rating (PSR) was obtained with the Total score ( P = 0.03), the Physical Well Being (PWB) subscale ( P = 0.02), the Functional Well Being (FWB) subscale ( P = 0.05), and the LCS ( P = 0.03). A 21-item Trial Outcome Index (TOI), combining scores on PWB, FWB and LCS, was highly reliable (coefficient a = 0.89) and sensitive to change in PSR F(1,38) = 4.84 ( P = 0.01). This TOI is probably the most relevant and precise indicator of patient-reported quality of life available for lung cancer patients who complete the FACT-L while participating in an oncology clinical trial. The FACT-L may also be of benefit in evaluating quality of life in patients with lung diseases other than cancer.

The EORTC QLQ-LC13: a modular supplement to the EORTC core quality of life questionnaire for use in lung cancer clinical trials : Bengt Bergman, Dept of Pulmonary Medicine, Göteborg University, and Stein Kaasa, Palliative Care Unit, Dept of Oncology, Tronheim University Hospital, for the EORTC Study Group on Quality of Life

The EORTC QLQ-LC13: a modular supplement to the EORTC core quality of life questionnaire for use in lung cancer clinical trials : Bengt Bergman, Dept of Pulmonary Medicine, Göteborg University, and Stein Kaasa, Palliative Care Unit, Dept of Oncology, Tronheim University Hospital, for the EORTC Study Group on Quality of Life

The EORTC QLQ-LC13: a modular supplement to the EORTC core quality of life questionnaire (QLQ-C30) for use in lung cancer clinical trials

The EORTC Study Group on Quality of Life has developed a modular system for assessing the quality of life of cancer patients in clinical trials composed of two basic elements: (1) a core quality of life questionnaire, the EORTC QLQ-C30, covering general aspects of health-related quality of life, and (2) additional disease- or treatment-specific questionnaire modules. Two international field studies were carried out to evaluate the practicality, reliability and validity of the core questionnaire, supplemented by a 13-item lung cancer-specific questionnaire module, the EORTC QLQ-LC13. In this paper, the results of an evaluation of the QLQ-LC13 are reported. The lung cancer questionnaire module comprises both multi-item and single-item measures of lung cancer-associated symptoms (i.e. coughing, haemoptysis, dyspnoea and pain) and side-effects from conventional chemo- and radiotherapy (i.e. hair loss, neuropathy, sore mouth and dysphagia). It was administered to patients with non-resectable lung cancer recruited from 17 countries. In total, 883 and 735 patients, respectively, completed the questionnaire prior to and once during treatment. The symptom measures discriminated clearly between patients differing in performance status. All item scores changed significantly in the expected direction (i.e. lung cancer symptoms decreased and treatment toxicities increased) during treatment. With one exception (problems with a sore mouth), the change of toxicity measures over time was related specifically to either chemoor radiotherapy. However, the single item on neuropathy did not measure adequately the full range of symptoms. The hypothesised scale structure of the questionnaire was partially supported by the data. The multi-item dyspnoea scale met the minimal standards for reliability (Cronbach α coefficient >0.70), while the pain items did not form a scale with reliability estimates acceptable for group comparisons. In conclusion, the results from international field testing lend support to the EORTC QLQ-LC13 as a clinically valid and useful tool for assessing disease- and treatment-specific symptoms in lung cancer patients participating in clinical trials, when combined with the EORTC core quality of life questionnaire. In a few areas, however, the questionnaire module could benefit from further refinements. In addition, its performance over a longer period of time still needs to be investigated.

Quality of life assessment — results and comparison of two cell lung cancer clinical trials (EORTC - German cooperative group BMFT) : H Flechtner, (1) R Holle, (2) N Aaronson, (3) M Heim (1): (1)= Oncology Centre Mannheim, Theod. Kutz. Ufer, 6800 Mannheim, FRG, (2)= University of Heidelberg, FRG, (3)= The Netherlands Cancer Inst., NL

Quality of life assessment — results and comparison of two cell lung cancer clinical trials (EORTC - German cooperative group BMFT) : H Flechtner, (1) R Holle, (2) N Aaronson, (3) M Heim (1): (1)= Oncology Centre Mannheim, Theod. Kutz. Ufer, 6800 Mannheim, FRG, (2)= University of Heidelberg, FRG, (3)= The Netherlands Cancer Inst., NL

Chapter 19 Some considerations for the therapeutic use of monoclonal antibodies in lung cancer

Abstract Ten years after the revolutionary work of Kohler and Milstein 1 clinical trials in lung cancer employing monoclonal antibodies are just beginning 2 . Clinical investigators are familiar with the critical issues in the design of clinical trials of chemotherapy. The design of monoclonal antibody trials will borrow heavily from that experience and yet will break new ground. In this review we will consider the issues governing the development of clinical trials strategies.

Use of the yearly event-specific conditional probability in the analysis of two randomized clinical trials in lung cancer: Different patterns of locoregional and metastatic relapses: Jacques Benichou, Claude Chastang, Guy Decroix, and The Groupe d'Etude et de Traitement de Biostatistique et d'Informatique Médicale du CHU Lariboisier̀e Saint Louis, Départment de Biostatistique et d'Informatique Médicale du CHU Lariboisier̀e Saint Louis, Paris,

Use of the yearly event-specific conditional probability in the analysis of two randomized clinical trials in lung cancer: Different patterns of locoregional and metastatic relapses: Jacques Benichou, Claude Chastang, Guy Decroix, and The Groupe d'Etude et de Traitement de Biostatistique et d'Informatique Médicale du CHU Lariboisier̀e Saint Louis, Départment de Biostatistique et d'Informatique Médicale du CHU Lariboisier̀e Saint Louis, Paris,

A method for predicting accrual, cost, and paper flow in clinical trials

We consider a mathematical model for accrual and costs associated with randomized clinical trials. A model that predicts the cost as a function of time can be constructed from the design assumptions of the trial and estimates of per patient costs of recruitment, treatment, and follow-up. Our notion of cost is a general one and includes personnel and paper flow as well as money. Costs associated with accrual and follow-up are distinguished in order to more accurately model per patient expenses. We assume that the investigator will specify these expenses in the same fashion that accrual and survival rates are estimated for statistical design. The size of the patient population to be followed can then be modeled and used to estimate cost. Although relatively simple cost equations result for the assumptions of constant accrual and exponential survival, very general assumptions can be incorporated into the model. The model has the advantages of predicting the time course of costs, allowing for different accrual and follow-up costs, and being amenable to revision during the conduct of a trial. Examples of cost modeling in a lung cancer clinical trial and cost minimization are offered.

Effect of Categorizing a Continuous Covariate on the Comparison of Survival Time

Abstract The variance of the estimated hazard ratio between two groups when there is one categorized continuous gamma-distributed covariate is derived using exponential and Weibull regression models and asymptotic theory. Categorizing a continuous covariate increases the variance of the estimated hazard ratio and decreases the efficiency of the analysis. The efficiency of categorization is studied as a function of the strength of the relation between survival time and the covariate, the choice of cut points used in categorizing, and the number of categories. An application of the results to an advanced lung cancer clinical trial is given.

Effect of Categorizing a Continuous Covariate on the Comparison of Survival Time

Abstract The variance of the estimated hazard ratio between two groups when there is one categorized continuous gamma-distributed covariate is derived using exponential and Weibull regression models and asymptotic theory. Categorizing a continuous covariate increases the variance of the estimated hazard ratio and decreases the efficiency of the analysis. The efficiency of categorization is studied as a function of the strength of the relation between survival time and the covariate, the choice of cut points used in categorizing, and the number of categories. An application of the results to an advanced lung cancer clinical trial is given.

A multidimensional approach to the measurement of quality of life in lung cancer clinical trials

A multidimensional approach to the measurement of quality of life in lung cancer clinical trials

Age as a criterion for eligibility in a lung cancer clinical trial.

The results of a clinical trial can be generalized only if the study sample is representative of the population with the disease entity under study. A prerequisite for patient participation in a clinical trial is that all the eligibility criteria be met. In many cooperative group trials, it is common practice to use age as a criterion for eligibility on the premise that advanced age is an unfavorable prognostic factor. In this paper, we evaluate the bias introduced in a sample when this practice was followed in a lung cancer protocol. Of 653 lung cancer cases reviewed, 77 met the eligibility criteria; an additional 23 patients were ineligible for the trial solely on the basis of age. There was no significant difference in survival between these two groups of patients. This indicates that age is not an unfavorable prognostic factor for patients with lung cancer and should not be used as a criterion for eligibility in a clinical trial.