Is meta-analysis a metaphysical or a scientific method?
Explore the source record for details and available documents.
Carcinoma, Non-Small-Cell Lung↗
Biomedical subjects
J P Pignon
Publications and source records attributed to J P Pignon.
Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group.
BACKGROUND: Prophylactic cranial irradiation reduces the incidence of brain metastasis in patients with small-cell lung cancer. Whether this treatment, when given to patients in complete remission, improves survival is not known. We performed a meta-analysis to determine whether prophylactic cranial irradiation prolongs survival. METHODS: We analyzed individual data on 987 patients with small-cell lung cancer in complete remission who took part in seven trials that compared prophylactic cranial irradiation with no prophylactic cranial irradiation. The main end point was survival. RESULTS: The relative risk of death in the treatment group as compared with the control group was 0.84 (95 percent confidence interval, 0.73 to 0.97; P= 0.01), which corresponds to a 5.4 percent increase in the rate of survival at three years (15.3 percent in the control group vs. 20.7 percent in the treatment group). Prophylactic cranial irradiation also increased the rate of disease-free survival (relative risk of recurrence or death, 0.75; 95 percent confidence interval, 0.65 to 0.86; P<0.001) and decreased the cumulative incidence of brain metastasis (relative risk, 0.46; 95 percent confidence interval, 0.38 to 0.57; P<0.001). Larger doses of radiation led to greater decreases in the risk of brain metastasis, according to an analysis of four total doses (8 Gy, 24 to 25 Gy, 30 Gy, and 36 to 40 Gy) (P for trend=0.02), but the effect on survival did not differ significantly according to the dose. We also identified a trend (P=0.01) toward a decrease in the risk of brain metastasis with earlier administration of cranial irradiation after the initiation of induction chemotherapy. CONCLUSIONS: Prophylactic cranial irradiation improves both overall survival and disease-free survival among patients with small-cell lung cancer in complete remission.
Adult↗
Meta-analyses in head and neck squamous cell carcinoma. What is the role of chemotherapy?
Despite more than 70 randomized clinical trials comparing locoregional treatment plus chemotherapy with the same locoregional treatment alone, the effect of chemotherapy on the survival of patients with head and neck squamous cell cancer is uncertain. Indeed, most of the randomized trials have been inconclusive in this regard, and only a few have reported significant results either in favor of or against chemotherapy. This article focuses on four meta-analyses that included a comparison between chemotherapy (neoadjuvant, adjuvant, or concomitant) plus locoregional treatment versus the same locoregional treatment alone and in which survival was the main end-point.
Antineoplastic Agents↗
[Meta-analyses of randomized trials in oncology: pros and cons].
A meta-analysis of trials is a quantitative synthesis of the results of trials addressing the same question. Such a synthesis is useful when the consideration of the results of the trials does not produce a clear answer. To perform a meta-analysis, one must identify all the randomized trials addressing the question, whether their results have been published or not. A meta-analysis can be based on summary data, or it can be based on individual patient data which allows extensive data checking, corrections, and an intent to treat analysis. A meta-analysis provides a test for the efficacy of the treatment under study, and an estimation of this efficacy. It allows also the study of the heterogeneity in efficacy between trials according to their characteristics or between sub-population of patients. Lastly, the results of a meta-analysis may be of help in the design of future trials. The quality of a meta-analysis depends essentially on the completeness of the collection of trials. Apart from this problem, the limits of a meta-analysis are the limits of the trials it includes, the addition of ill designed and ill conducted trials can only lead to a bad meta-analysis. The moderate effect of the treatments available for solid tumours in adults explains the widespread use of meta-analysis in oncology.
Humans↗
Normal serum neuron specific enolase (NSE) value after the first cycle of chemotherapy: an early predictor of complete response and survival in patients with small cell lung carcinoma.
BACKGROUND: Serum neuron specific enolase (NSE) is the most sensitive tumor marker of small cell lung carcinoma (SCLC) at diagnosis. Its prognostic value is still debated. Thus, the authors decided to assess the predictive value, in terms of complete response and survival, of serum NSE measured before and after one cycle of chemotherapy in patients with SCLC. METHODS: Sera from 135 patients with histologically proven limited (n = 63) or metastatic (n = 72) SCLC were obtained. Clinical and biologic parameters with a known or suspected prognostic relevance were reviewed. Serum NSE was measured before chemotherapy (D1-NSE) and 28 days after its initiation (D28-NSE). The prognostic value of the parameters under study was evaluated in univariate and multivariate analyses using the Cox proportional hazards model and logistic regression analysis. RESULTS: The level of serum NSE was raised in 120 patients (88%) prior to therapy. The probability of a normal D28-NSE value was not affected by the baseline D1-NSE value. Disease extension (P = 0.0005), performance status (P = 0.0001), D28-NSE (P = 0.003), and carcinoembryonic antigen (CEA) levels (P = 0.008) were found to be predictive for survival, whereas age, gender, plasma sodium, serum protides, and D1-NSE were not. Median survival and 2-year overall survival were 15.3 months and 21% (95% confidence interval [CI], 13-31%) when D28-NSE was normal and 8.1 months and 15% (95% CI, 8-27%) when it was not (P < 0.03). Only performance status (P = 0.001), disease extension (P = 0.002), and D28-NSE (P = 0.02) were found to be independent prognostic parameters for survival in the multivariate analysis. A simple prognostic index was developed using these 3 variables. Limited disease, a normal D28-NSE value, and a normal CEA value prior to therapy were the only parameters predictive for complete response in the univariate analysis, and D28-NSE (P = 0.01) and disease extension (P = 0.0001) were found to be independent variables in multivariate analysis. A complete response to therapy occurred in 62% with a normal D28-NSE value and in only 34% in the opposite case. CONCLUSIONS: Normal serum D28-NSE is a strong, independent early predictor of both complete response to therapy and survival. This simple tool may be proposed for use in the clinic and in research, in association with an assessment of disease extension and performance status, to predict the outcome of patients with SCLC.
Adult↗
Results of 136 curative hepatectomies with a safety margin of less than 10 mm for colorectal metastases.
BACKGROUND AND OBJECTIVES: It is now established that liver resection is beneficial for metastases from colorectal cancer. Nevertheless, a surgical margin estimated at less than 10 mm at preoperative imaging is considered an absolute contraindication to surgery by some, and a relative contraindication by others. The true impact of the width of the margin on the prognosis is unclear. METHODS: From 1984 to 1996, 196 patients underwent curative hepatectomy for liver metastases and were studied prospectively. Surgery was to be curative (or a complete R0 resection) and mortality was to be avoided. Of these 196 patients, 136 had surgical margins of less than 10 mm. Sixty-eight percent had multiple liver metastases and 15% had extrahepatic metastatic lesions. Clinical and pathological factors were studied specifically and a multivariate analysis was carried out. RESULTS: Overall 5-year survival rate of these 136 patients (taking into account postoperative mortality which attained 1.5%) was 27.8% and the disease-free survival was 22.9%. The surgical margin was 0 mm in 30 cases. The sole prognostic factor was the discovery of unsuspected (resectable) extrahepatic lesions at laparotomy (P < 0.001) ; the width of the free margin had no significant effect. However, in the multivariate analysis of prognostic factors for the entire series (269 hepatectomies), three powerful parameters were identified : (1) the curative nature of resection (P = 0.0007), (2) less than 20% of liver involvement (P = 0.002), and (3) a free margin exceeding 9 mm (P = 0.02). A correlation was found between narrow margins and extensive disease (high number of metastases, bilateral sites, and extended hepatectomy). There was also a greater likelihood of microscopic satellite lesions within 10 mm around the metastases. CONCLUSIONS: The prognostic impact of the width of the surgical margin should not be overestimated. Hepatectomy for liver metastases can procure long-term survival, even in patients with supposedly poor prognostic factors. Resection is justified as long as it is complete and the risks are minimal.
Aged↗
Treatment of unresectable hepatocellular carcinoma with lipiodol chemoembolization: a multicenter randomized trial. Groupe CHC.
BACKGROUND/AIMS: Lipiodol chemoembolization is a widely used method of treatment in patients with unresectable hepatocellular carcinoma, but its efficacy is still debated. The aim of our study was to assess the efficacy of lipiodol chemoembolization in patients with unresectable hepatocellular carcinoma. METHODS: Seventy-three patients with unresectable hepatocellular carcinoma, but without severe liver disease or portal vein occlusion, were randomly assigned to receive either repeated lipiodol chemoembolization (lipiodol, cisplatin (2 mg/kg), lecithin, and gelatin sponge injected into the hepatic artery) plus tamoxifen (40 mg) or tamoxifen alone. The main end-point was survival. RESULTS: The 37 patients in the lipiodol chemoembolization group received 104 courses (median 3 per patient). By 1 September 1996, 58 patients had died: 30 in the lipiodol chemoembolization group and 28 in the tamoxifen group. There was no difference in survival between the two groups (p=0.77). The relative risk of death in the lipiodol chemoembolization plus tamoxifen group as compared to the tamoxifen group was 0.92 (95% confidence interval 0.55 to 1.56). At 1 year, survival was 51% and 55%, respectively. An objective tumoral response was more frequently observed in the lipiodol chemoembolization group than in the tamoxifen group (24 versus 5.5%, respectively, p=0.046). Lipiodol chemoembolization caused two deaths and induced signs of liver failure in 51% of the patients assigned to this treatment. CONCLUSION: In our randomized study, lipiodol chemoembolization did not improve the survival of patients with unresectable hepatocellular carcinoma treated with tamoxifen.
Adult↗
Resection of liver metastases from colorectal cancer: the real impact of the surgical margin.
AIMS: The benefit of liver resection for metastatic colorectal cancer is now established. Nevertheless if the surgical margin on pre-operative imaging is considered to be less than 10 mm, this is considered an absolute contraindication to surgery by some, and a relative contraindication by others, so its real impact on prognosis is not clear. METHODS: From 1984 to 1996, 269 patients underwent hepatectomy for liver metastases and were prospectively studied. The only two objectives of this surgery were to be curative (or achieve complete R0 resection), and to avoid mortality. Of the 269, 187 patients had surgical margins inferior to 10 mm. Sixty per cent had multiple liver metastases, and 37% had extrahepatic metastatic sites. Their clinical and pathological factors were specifically studied. RESULTS: The crude 5-year survival of these 187 patients (including the 2% post-operative mortality) was 24.7%, and the disease-free survival was 18.8%. The surgical margin was 0 mm in 60 cases and was histologically invaded in 20 cases. The most important prognostic factor was whether the resection was considered palliative (R1-R2 resection according to UICC criteria) (P < 0.0001). When the cases with invaded margins were excluded, there was not prognostic difference between the 107 patients with a margin of 0-4 mm and the 143 patients with a margin greater than 4 mm. However, a surgical margin greater than 9 mm appears to be a second prognostic factor (P = 0.001), when these 187 patients are compared to others. The reasons behind this are that there is a close relationship between narrow margins and extensive disease (high number of metastases, bilateral localization and extended hepatectomy), and also an increased possibility of microscopic satellite lesions within 10 mm around the metastases. CONCLUSION: The real prognostic impact of the surgical margin must not be overestimated. Hepatectomy for metastases can provide long-term survival in patients with supposed poor prognostic factors. Resection is justified so long as it is complete and with minimal risk. An experienced, specialized centre can be a prognostic determinant.
Aged↗
Individual patient data meta-analysis in cancer.
As in many areas of health care, treatments for cancer may differ only moderately in their effects on major end points, such as death. But, such differences are worth knowing about, particularly in common diseases in which they could represent a substantial benefit to public health. Large-scale randomized evidence allows moderate differences to be investigated reliably, and one way to achieve this is by meta-analyses of updated and centrally collected individual patient data from all relevant trials. This paper illustrates why this form of research can often be important in cancer. It also offers the first list of such projects, as a source of information on current and past research in this area.
Humans↗
Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors.
PURPOSE: Fluorouracil (5-FU) continuous infusion is superior to 5-FU bolus in patients with advanced colorectal cancer, but the survival difference between the two treatments is small and, therefore, the difference in toxicity profile is crucial in choosing a treatment for individual patients. MATERIALS AND METHODS: We conducted a meta-analysis of all randomized trials that compared 5-FU bolus with 5-FU CI, based on individual data from 1,219 patients, to compare the toxicity of the two schedules of 5-FU administration and to identify predictive factors for toxicity. The toxicities considered were World Health Organization (WHO) grade 3 to 4 anemia, thrombopenia, leukopenia, neutropenia, nausea/vomiting, diarrhea, mucositis, and hand-foot syndrome. RESULTS: Hematologic toxicity, mainly neutropenia, was more frequent with 5-FU bolus than with 5-FU CI (31% and 4%, respectively; P < .0001). Hand-foot syndrome was less frequent with 5-FU bolus than with 5-FU CI (13% and 34%, respectively; P < .0001). There was no difference between the two treatment groups in terms of other nonhematologic toxicities. Independent prognostic factors were age, sex, and performance status for nonhematologic toxicities, performance status, and treatment for hematologic toxicities, and age, sex, and treatment for hand-foot syndrome. CONCLUSION: Based on a large data set, this study confirmed and quantified the toxicity profile of the two schedules of administration of 5-FU and allowed the identification of clinical predictors of toxicity.
Colorectal Neoplasms↗
[What are the real indications for hepatectomies in metastases of colorectal origin?].
AIM: To ascertain the real impact of classical contraindications (relative or absolute according to various authors) represented by: a high number of liver metastases (LM), the presence of associated extra-hepatic localizations (EHL), and a surgical margin less than 10 mm. METHODS: A prospective study was conducted in 269 consecutive hepatectomized patients. Inclusion criteria were only the resection of all tumoral tissue, and lack of major operative risk. Fifty-nine patients had at least 4 LM, 62 had an associated EHL, and 187 had a surgical margin < 10 mm. Altogether, 83% of the patients did not match the classical selection criteria. Sixty-two parameters were registered. A uni- and multivariate study of prognostic factors was performed. RESULTS: Although 18% of the resections were palliative (R1 or R2 according to the UICC classification), and the hospital mortality was 3.3% (2.2% during the first postoperative month), global and disease-free 5-year survival rates were 34.4% and 23.3%, respectively. The number of LM had no prognostic implication. A surgical margin > 9 mm improved significantly the prognosis. Between 0 and 9 mm, it had no important prognostic impact if the cut surface was histologically disease-free. A margin < 10 mm was greatly associated with a high number of LM, a bilateral localization of LM, and extended hepatectomy. Among the EHL, only those discovered during laparotomy had a significant adverse impact on prognosis. CONCLUSION: Fundamental principles of the indications of hepatectomy for colorectal LM are to resect all the lesions and to avoid major operative risk. In complex cases, the most frequent, these principles can only be completely followed in a specialized center.
Adolescent↗
[Meta-analysis or large randomized trial, that is the question].
Explore the source record for details and available documents.
Humans↗
Prophylactic cranial irradiation for small-cell lung cancer.
Explore the source record for details and available documents.
Brain Neoplasms↗
Preliminary results of a phase II study of high-dose radiation therapy and neoadjuvant plus concomitant 5-fluorouracil with CDDP chemotherapy for patients with anal canal cancer: a French cooperative study.
BACKGROUND: Chemotherapy (5-fluorouracil-mitomycin C) concomitant with radiotherapy (RT) increases local control and colostomy-free survival in advanced anal canal carcinomas (ACC). The purpose of this prospective trial was to analyse the toxicity of and response to an induction chemotherapy combining 5-fluorouracil (5-FU) and CDDP administered concomitantly with irradiation. PATIENTS AND METHODS: Thirty patients (24 F/6 M, mean age 60, range 38-74) with an advanced ACC > 40 mm and/or with node involvement were prospectively treated (1 T1, 16 T2, 8 T3, 5 T4, 10 N1, 1 N2, 8 N3) from November 1994 to January 1996. Two induction and two concomitant cycles of 5-FU (800 mg/ m2 D1-4 infusion) and CDDP (80 mg/i.v./m2 at D1) were delivered. RT consisted of 45 Gy (1.8 Gy/fr, 5 fr/w) on pelvis +/- inguinal nodes or 30 Gy (3 Gy/fr, 4 fr/w) by direct perineal field. A boost (15-20 Gy) was delivered six weeks later. RESULTS TOXICITY: one patient died of a pulmonary embolism on D4. The remaining 29 received the entire treatment, with reduced 5-FU doses in 11 patients because of acute toxicity. The RT boost was delayed for one patient (aplasia). In 109 cycles, 3 grade 4 and 17 grade 3 toxicities were observed; there were no toxic deaths. Tumor response: the complete response (CR) and partial response (PR) rates were, respectively, 11% and 61% after induction chemotherapy, 59% and 31% after concomitant radiochemotherapy and 96% and 0% two months after completion of the treatment. No tumor progression was observed. CONCLUSION: the treatment was well tolerated and there was good compliance. After induction chemotherapy, most of the patients were in PR, with some even in CR. After completion of the treatment all but one were in CR. The tumor response and the long term results of 50 patients will be analysed before initiation of a randomised trial is considered.
Adult↗
Review article: critical review of meta-analyses of randomized clinical trials in hepatogastroenterology.
BACKGROUND: This review attempts to identify meta-analyses performed in hepatogastroenterology, and to assess their quality and to identify simple criteria of good quality. METHODS: Meta-analyses of randomized clinical trials in hepatogastroenterology published as full papers before 1993 were included. A quality score was defined as the sum of 27 items evaluated in each publication and coded 2 if adequate, 1 if partial and 0 if missing. Quality criteria were identified by discriminant analysis through three groups of meta-analyses defined by their quality score (poor, middle, high). RESULTS: From 1981 to 1992, 62 publications were identified, including 42% in the last 2 years. Nineteen per cent concerned peptic ulcers, 18% oesophageal varices and 6% digestive cancers. They reported 180 meta-analyses. The quality score ranged from 14 to 40, the median was 29. Twenty-five per cent of the studies obtained a score lower than 23 and 25% a score higher than 34. Several stages of meta-analysis were poorly performed: identification and selection of trials, study of trial quality, data extraction and achievement of sensitivity analyses, subgroup and indirect analyses. Some of them led to biases and questions about the validity of results. Five criteria were significantly associated with high quality: presence of a protocol, assessment of trial quality, only randomized trials pooled, achievement of sensitivity analyses, and peer-reviewed publication. CONCLUSIONS: In hepatogastroenterology, there is an exponential increase in publication of meta-analyses but their quality is heterogeneous. In particular, the control of the biases has to be better performed.
Gastrointestinal Diseases↗
Randomized trials of radiotherapy alone versus combined chemotherapy and radiotherapy in stages IIIa and IIIb nonsmall cell lung cancer: a meta-analysis.
Explore the source record for details and available documents.
Antineoplastic Combined Chemotherapy Protocols↗
Prognostic value of clinicopathological parameters in head and neck squamous cell carcinoma: a prospective analysis.
The prognostic weight of histological and biological factors was compared with that of known clinical prognostic factors in a population of 108 consecutive previously untreated patients with head and neck squamous cell carcinoma. Parameters studied were: tumour vascularisation, mitotic index, histological differentiation, nuclear grade, keratinisation, desmoplasia, growth pattern, inflammation, tumour emboli in peripheral vessels, keratins 6, 13, 19 immunohistochemical expression, cytofluorometric ploidy and S-phase. In multivariate analysis (Cox), only age and nodal status had a significant impact on the overall survival, whereas T stage was the only significant factor associated with locoregional failure. The cumulative incidence of metastases was correlated not only with age, T and N stage, but also with histological differentiation. All the other histological and biological factors studied failed to provide further prognostic information. These findings may help to select patients with high metastatic risk.
Age Factors↗
The role of chest irradiation in small cell lung cancer.
Explore the source record for details and available documents.
Carcinoma, Small Cell↗