Preoperative radiotherapy for esophageal carcinoma.

BACKGROUND: The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. OBJECTIVES: This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery and whether or not any pre-defined patient subgroups benefit more or less from preoperative radiotherapy SEARCH STRATEGY: MEDLINE and CancerLit searches were supplemented by information from trial registers and by hand searching relevant meeting proceedings and by discussion with relevant trialists, organisations and industry. The search strategy was run again in MEDLINE, EMBASE and the Cochrane Library on 30th April 2001, two years after original publication. No new trials were found. The search strategy was re-run August 2002 and August 2003 on MEDLINE, EMBASE , CancerLit and The Cochrane Library, and July 2004 and 2005 on MEDLINE, EMBASE and the Cochrane Library. No new relevant trials were identified on any of these occasions. SELECTION CRITERIA: Trials were eligible for inclusion in this meta-analysis provided they randomized patients with potentially resectable carcinoma of the esophagus (of any histological type) to receive radiotherapy or no radiotherapy prior to surgery. Trials must have used a randomization method which precluded prior knowledge of treatment assignment and completed accrual by December 1993, to ensure sufficient follow-up by the time of the first analysis (September 1995). DATA COLLECTION AND ANALYSIS: A quantitative meta-analysis using updated data from individual patients from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials. This approach was used to assess whether preoperative radiotherapy improves overall survival and whether it is differentially effective in patients defined by age, sex and tumour location. MAIN RESULTS: With a median follow-up of 9 years, in a group patients with mostly squamous carcinomas, the hazard ratio (HR) of 0.89 (95% CI 0.78-1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p=0.062). No clear differences in the size of the effect by sex, age or tumor location were apparent. AUTHORS' CONCLUSIONS: Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients (90% power, 5% significance level) would be needed to reliably detect such an improvement (from 15 to 20%).

Familial relative risk of colorectal cancer: a population-based study.

This study aimed to assess the familial relative risk for colorectal cancer (CRC) and its variation according to age and gender. A population-based family study was carried out in France, from 1993 to 1998, including 761 families. Familial CRC risks were estimated from a cohort analysis of the relatives. No obvious decrease in CRC risk was found with increasing age, except when either the proband, or the relative, were in the youngest age class. The effect of the relatives' and probands' ages on the CRC risk differed according to their gender. The cumulative risk of CRC increased at an earlier age in male relatives of probands younger than 60 years of age, than in female relatives. This result suggests that mechanisms specific to females, possibly interacting with genetic factors, explain the difference in the cumulative risks between families with male and female probands.

Prognosis of rectal cancer in France.

We studied changes in the prognosis of cancer of the rectum (excluding the rectosigmoid junction) from 1978 to 1986 in the French department of Calvados on the basis of the 616 cases in the cancer registry. Taken as whole, survival has improved slightly with time (P < 0.01), but the improvement is only significant for men (P < 0.02), patients under 70 years (P < 0.01) and patients living in urban areas (P < 0.05). With regard to tumour characteristics, the improvement was significant only for patients with Dukes' stage C tumours at surgery (P < 0.02). To determine the reasons for the improvement in survival, the year of diagnosis and all other prognostic factors were studied in a multivariate model. Diagnostic conditions such as age and tumour stage did not vary from 1978 to 1986; in contrast, the rates of tumour resection and adjuvant radiation therapy increased, possibly explaining at least part of the improvement, particularly for patients with Dukes' stage C tumours.

Contribution of cervical ultrasound and ultrasound fine-needle aspiration biopsy to the staging of thoracic oesophageal carcinoma.

This study was performed to evaluate the use of cervical ultrasonography and ultrasound-guided fine-needle aspiration for pretherapeutic staging of oesophageal cancer. 50 patients with a thoracic-oesophageal cancer (upper third = 8, middle = 36, lower = 6), previously untreated, underwent cervical ultrasonography to detect supraclavicular lymph node metastases (LN). An ultrasound fine-needle aspiration biopsy was attempted in 12 cases of suspected LN. 26 patients were operated on, of which 13 had surgical exploration of the neck. All patients were followed after treatment with special attention to the supraclavicular area. 14 patients (28%) were ultrasonography positive, 5 of 8 in the upper third, 9 of 42 in the two other thirds. Of the 12 patients where a fine-needle biopsy was attempted, 9 showed neoplastic cells (75%). 5 patients had cervical metastatic LN at surgery, and 5 other patients demonstrated supraclavicular LN metastases during the follow-up. There was one false positive and six false negatives from cervical ultrasonography and two false negatives of UGFAB (ultrasound-guided fine-needle aspiration biopsy). The sensitivity and the specificity of the cervical ultrasonography were 68 and 97%, respectively. The pretherapeutic staging was modified: 7 patients initially stage II-III were regraded to stage IV. Cervical ultrasonography is a reliable method of assessment of supraclavicular LN in thoracic oesophageal carcinoma.

Prospective randomised study of split-course radiotherapy versus cisplatin plus split-course radiotherapy in inoperable squamous cell carcinoma of the oesophagus.

Between 1983 and 1989, 211 patients with inoperable squamous cell carcinoma of the oesophagus were randomised in a study comparing split-course irradiation (two courses of 20 Gy in five fractions of 4 Gy, separated by a rest of 2 weeks) (arm A) and the same split-course irradiation in combination with cisplatin (CDDP) (3-4 days before each of the two courses of radiotherapy, repeated every 3-4 weeks, for a total of six cycles) (arm B). The Cox's regression model with retrospective stratification was used to compare the two arms to correct for the imbalance at randomisation of the T classification. The median overall survival was 7.9 (95% confidence interval (CI) 7.3-9.4) months in arm A and 9.6 (95% CI 8-13.5) months in arm B. The difference in overall survival was only borderline significant (P=0.048) with a reduction of the instantaneous rate of death of 24%. The 1 and 2 year overall survival rate were respectively 29% (95% CI 21-37%) and 15% (95% CI 8-22%) in arm A and 45% (95% CI 36-54%) and 20% (95% CI 13-27%) in arm B; thereafter, the survival curves became similar. The median progression free survival (PFS) was 5.0 (95% CI 4.6-5.7) versus 6.9 (95% CI 5.3-8.7) months (P=0.028) and the median time to local progression was 6.2 (95% CI 5.1-7.6) months versus 10.9 (95% CI 8.1-15.5) months (P=0.018), respectively, in arms A and B. Haematological toxicities were slightly more commonly observed in the combined group (1% versus 6%). This study shows that split-course irradiation in combination with CDDP is very well tolerated and should be preferred to radiotherapy alone.

Palliative therapy of inoperable oesophageal carcinoma with radiotherapy and methotrexate: final results of a controlled clinical trial.

Between May 1976 and January 1982, 170 patients were entered in a randomized study comparing a combined treatment consisting of methotrexate followed by irradiation versus radiotherapy alone in patients with non metastatic inoperable oesophageal cancer. Methotrexate was administered subcutaneously in 4 days to a total dose of 24 mg/m2. Radiotherapy was performed, in both groups, at a dose of 56.25 Gy in 25 fractions (5 weeks). The administration of methotrexate did not lead to an increased intolerance to radiotherapy but severe hematological toxicities were observed in 7.8% of the cases. No difference in the duration of survival was detected. Initial performance status of the patients and their weight loss prior to entry on trial were the factors that were most predictive of the patient's prognosis.

Preoperative radiotherapy in esophageal carcinoma: a meta-analysis using individual patient data (Oesophageal Cancer Collaborative Group).

PURPOSE: The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery. METHODS AND MATERIALS: This quantitative meta-analysis included updated individual patient data from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials. RESULTS: With a median follow-up of 9 years, the hazard ratio (HR) of 0.89 (95% CI 0.78-1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p = 0.062). No clear differences in the size of the effect by sex, age, or tumor location were apparent. CONCLUSION: Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients would be needed to reliably detect such an improvement (15-->20%).

Localized squamous-cell cancer of the esophagus: retrospective analysis of three treatment schedules.

BACKGROUND AND PURPOSE: A retrospective study comparing chemotherapy and radiation, esophagectomy alone versus preoperative radiochemotherapy and surgery in localized squamous-cell esophageal carcinoma. MATERIALS AND METHODS: Between 1989 and 1995, 139 patients (40 stage I, 77 stage IIA and 22 stage IIB according to the UICC 78 TNM classification) were treated in two different institutions. They were divided into three groups according to the treatment proposed: E group (treatment by esophagectomy; n = 30), RCT+E group (treatment by preoperative radiochemotherapy and esophagectomy; n = 46), RCT group (treatment by radiochemotherapy; n = 63). Factors like age, tumor localization and stage were similar in all groups. An intention to treat analysis was made. RESULTS: The E group showed no postoperative mortality, while in the RCT+E group, the surgery mortality was 12.8%. The mortality after RCT was 1.7%. After preoperative radiochemotherapy, a pathological complete response was observed in 25% of cases and the curative resection rate was higher (82% after RCT + E versus 60% after E). The 5-year survival difference between the three groups was not relevant (E group, 12.6%; RCT group, 25.8%; RCT + E group, 38.7%). The median survival was 29, 24 and 28.5 months, respectively. The event-free survival was identical for the E group and the RCT group. For patients treated by radiochemotherapy, local and/or distant relapses were significantly reduced by esophagectomy (relapses occurred in 51% of patients in the RCT + E group versus 75% in the RCT group, P = 0.017). Palliative care (dilatations, prosthesis, gastrostomy or jejunostomy) to improve dysphagia was necessary for 38% of patients treated by exclusive radiochemotherapy versus 11% of patients treated by surgery (P = 0.001). CONCLUSIONS: Treatments by esophagectomy or radiochemotherapy were not significantly different. Preoperative radiochemotherapy and surgery lead to a higher survival rate than exclusive radiochemotherapy, however, with a high postoperative mortality rate. This study suggests the relevance of a prospective randomized trial to compare RCT+E and RCT alone.

Cancer of the esophagus and associated lesions: detailed pathologic study of 100 esophagectomy specimens.

One hundred surgical specimens from patients with esophageal cancers were studied in detail. The characteristics of the cancers were similar to those described in the literature. Subserial sectioning of the specimens permitted determination of the type, number, and extent of noncancerous mucosal lesions and their exact location in relation to the carcinomas. Ninety-five per cent of the resected esophagi contained at least one focus of intraepithelial neoplasia, for the most part adjacent to the invasive carcinoma; in 14 per cent of the cases, intraepithelial carcinomas were detected at some distance from the invasive carcinomas. The invasive carcinomas involved an average of 20 per cent of the mucosal surface and the intraepithelial neoplasias, 5 per cent. The noncancerous mucosal lesions were analyzed, and their extent was evaluated. Esophagitis, parakeratosis, atrophy, dyskeratosis of the epithelium, and hyperplasia and metaplasia of the mucosal gland ducts were encountered. The exact significance of these lesions in esophageal carcinogenesis is not known. The mucosal abnormalities associated with preoperative irradiation are defined. The results of iodine and toluidine blue testing are presented.

Tobacco type and risk of squamous cell cancer of the oesophagus in males: a French multicentre case-control study.

BACKGROUND: The association between tobacco smoking and oesophageal cancer is well established. However, some major questions remain unanswered such as the importance of kind of tobacco and smoke inhalation. The aim of this study was to investigate the effect of each kind of tobacco on the risk of squamous cell cancer of the oesophagus in men and to test whether the effect of kind of tobacco is similar whatever the sub-site of cancer. Tobacco consumption was assessed by the number of years of consumption and time since quitting. METHODS: We conducted a multicentre case-control study in three university hospitals in France (Caen, Dijon, and Toulouse). From 1991 to 1994, 208 cases and 399 controls, all male, were selected. During the interview, the subject's entire tobacco history was recalled, noting each type of tobacco consumed throughout life. RESULTS: Strong tobacco, dark tobacco and non-filter-tipped cigarettes were associated with an increase in risk whatever the adjustments, whilst light, filter-tipped cigarettes and mild tobacco were not. Hand-rolled cigarettes were more strongly associated with risk than manufactured cigarettes. The effect of hand-rolled cigarettes appeared stronger for the lower third whilst those of strong cigarettes and dark tobacco appeared stronger for the upper third of the oesophagus. The effect of inhaling was confined to the upper third. CONCLUSIONS: Our results, emphasizing the role of dark tobacco, hand-rolled cigarettes, strong cigarettes and non-filter-tipped cigarettes are in line with previous publications. Moreover, they suggest that the mechanism underlying the tobacco effect could be different according to the sub-site of cancer.

Changing pattern of oesophageal cancer incidence in France.

BACKGROUND: Data from several Western countries suggest a rapid increase in the incidence of adenocarcinoma of the oesophagus, as well as variations in the sex ratio and the subsite distribution of oesophageal cancer. Although France has a high incidence rate of oesophageal cancer in males, no information was available on trends in its occurrence. The purpose of this study was to report changes in the pattern of oesophageal cancer incidence in three regions of France. METHODS: Data from the three population-based cancer registries of Calvados, Côte d'Or and Haute-Garonne were used to study time trends of oesophageal cancer by sex, age, subsite and histological type between 1978 and 1987. Annual incidence rates have been standardized by the direct method using the world standard population. To test the trend in cancer incidence, either an exponential curve of the form y = aekt was fitted to the annual incidence rates by means of a regression technique, or incidence rates were compared between two 5-year periods after age standardization by Mantel-Haenszel test. RESULTS: The mean annual variation of oesophageal cancer in males was -2.9% in Calvados (P < 0.05), + 0.5% in Côte d'Or (NS) and + 12.4% in Haute-Garonne (P < 0.05). The corresponding figures in females were + 7.9% (NS), + 19.6% (P < 0.05) and + 50.7% (NS). The significant variations in males (decrease in Calvados and increase in Haute-Garonne) were confined to the oldest age group (> or = 65 years). With regard to subsite, incidence in males increased in Haute-Garonne for the upper and the middle third, while there was a significant decrease in Calvados only for the middle third. For histological type, no increase in adenocarcinoma was noticed in males while there was a slight increase in incidence in females (statistically significant in Calvados). CONCLUSIONS: In France, the incidence of oesophageal cancer has decreased in the high-risk region (Calvados) in males, while there was a slight increase in the three studied regions in females. The important rise in incidence of oesophageal adenocarcinomas observed in some Western countries has yet to be seen in France.

Potentiation of cisplatin and carboplatin cytotoxicity by amphotericin B in different human ovarian carcinoma and malignant peritoneal mesothelioma cells.

An in vitro study of the combined cytotoxicity of either cisplatin (CDDP) or carboplatin and amphotericin B (AmB) was undertaken on a set of different ovarian carcinoma (IGROVI, IGROVI-C10, OAW42) and peritoneal malignant mesothelioma (CFB-CARP1) cell lines and ascitic cells freshly obtained from ovarian cancer patients so as to investigate the possibility of overcoming their resistance to platinum compounds. Growth-inhibition curves obtained 6 days after a 2-h period of exposure to the drugs showed that AmB at 5-10 mg/l allowed a 5- to 10-fold decrease in the 50% growth-inhibitory concentrations (IC50) of CDDP and carboplatin on either sensitive or resistant cells. Intracellular platinum assays with IGROVI cells showed that AmB acted by increasing dramatically the platinum uptake at a proportion that accounted for the increase in cytotoxicity. In the subline IGROVI-C10, a 10-fold resistant subline of IGROVI, AmB at 10 mg/l allowed recovery to the level of sensitivity seen in the parental cell line in the absence of AmB but not to the level observed in the presence of AmB. Acquisition of resistance mechanisms that are independent of the regulation of platinum uptake might be involved in this cell line. Thus, AmB might act by increasing the intracellular concentration of platinum without modifying the resistance mechanism involved downstream. However, in our models an increase in the intracellular level of platinum was always sufficient for the recovery of chemosensitivity in vitro. We also show that the phosphodiesterase inhibiting methylxanthines act synergistically with AmB. The latter drugs are weakly toxic and could also attenuate the nephrotoxicity of AmB.

Factors affecting compliance with colorectal cancer screening in France: differences between intention to participate and actual participation.

This study aimed to identify the social, cultural and psychological characteristics influencing behaviour in a cancer mass screening campaign in a French population. The intention to take a screening test and actually doing it was studied, in particular. A self reported-questionnaire was mailed in December 1992 to a random sample of people living in Caen (western France), and aged from 45-74 years. The sample was formed by random selection from electoral registers. The study was population based, in the Caen area, department of Calvados, France. The questionnaire comprised 26 open and close questions. Starting in February 1993, the occult blood screening test (haemoccult IIR) for colorectal cancer was offered by general practitioners (GPs), occupational health doctors and pharmacists in the Caen area to all those aged 45-74 years. From 1 February 1993 to 30 June 1994, the data on the mass screening campaign were centralized and the study population divided into those who took the screening test and those who did not. Of the 1,129 persons contacted, 645 (57.1%) returned the questionnaire. After exclusions, 585 questionnaires were used for analysis. The results show that whether a person will actually take a screening test cannot be predicted from their intention to do so. The sociodemographic and cultural characteristics influencing the intention to take the test differ from those influencing execution of the test. Among the variables tested here, the following four sociodemographic and cultural characteristics were independently predictive of actually taking the screening test for colorectal cancer: compliance with the health insurer's advice; low or medium sociodemographic status, living with a partner (or widowhood); and not knowing someone with cancer. The analysis of the quantitative and qualitative differences between the intention to take the test and actually doing it could elucidate the reasons underlying refusal. Poor screening compliance has multiple causes. A record of intention to take a screening test alone is not appropriate. This type of study should no longer be carried out to determine the mechanisms underlying behaviour towards secondary prevention.

Involvement of general practitioners in mass screening. Experience of a colorectal cancer mass screening programme in the Calvados region (France).

Good compliance with screening programmes is essential and experience from ongoing studies points to the importance of involving general practitioners (GPs). The aim of this study was to evaluate factors influencing the participation of GPs in a screening programme, as well as acceptance of the test by the population. Fifty GPs were randomly chosen among the 117 practices of three districts in Calvados (France) where haemoccult test-based mass screening for colorectal cancer was underway. Each GP was asked to fill in a personal questionnaire as well as a detailed record for each patient between 45 and 74 years seen in the practice during a 1-week period. The GPs offered the test to 95% of the patients. The overall refusal rate was 7.8%, and was higher in women than in men (9.9% vs 5.9%; P < 0.05). Manual workers had a lower refusal rate than other occupational groups (2.5% vs 8.5%; P < 0.05). The GP's motivation was an important factor in patient compliance: the refusal rate was 5.4% in the case of highly motivated GPs, against 20.0% when the GP was poorly motivated (P < 0.01). GP motivation was higher in urban than in rural areas (P < 0.05) but did not depend on sex, age or the duration or type of practice. According to the GPs, motivating factors were the perceived need for screening, involvement in planning the campaign, and regular feedback. Conversely, a lack of time and the possibility of false-negative results were the most important impediments. This study demonstrates that patient compliance is closely linked to practitioner motivation.(ABSTRACT TRUNCATED AT 250 WORDS)

Recent time trends in cancer of the oesophagus and gastric cardia in the region of Calvados in France, 1978-1995: a population based study.

The incidence of oesophageal cancer differs from country to country, and even between areas of the same country. Many studies in recent years have shown an upward trend of a particular histologic type: adenocarcinoma of the oesophagus. It is difficult to precisely locate adenocarcinomas situated at the junction between the oesophagus and the gastric cardia. Clear criteria to define and classify such tumours are essential in order to analyse their evolution. The present study describes the changing incidence of cancers of the oesophagus and gastric cardia according to histologic type from 1978 to 1995 in Calvados, the highest-risk French region with two different topographic classifications of adenocarcinomas: one based on Misumi's criteria and the other based on local extension of cancer. In total, 1835 cancers of the oesophagus and gastric cardia were diagnosed in this period. Incidence rates for oesophageal and gastric cardia cancers standardized on the world population were 24.4/10(5) and 2.4/10(5) in men and 1.4/10(5) and 0.4/10(5) in women, respectively. The time trend in the incidence of squamous cell cancers was downward in men -0.74 (P < 10(-6)) and stable in women +0.04 (P = 0.65). Regarding adenocarcinomas, with the classification based on Misumi's categories, there was a slight but significant upward trend for oesophageal adenocarcinoma in men [mean annual variation of +0.09 (P < 10(-5))] while the tendency was downward and significant for gastric cardia adenocarcinoma [mean annual variation of -0.09 (P < 10(-4))]. When adenocarcinomas of the oesophagus and those of the gastric cardia with oesophageal involvement are taken together (second classification), there was an upward trend which was not significant in men and was significant in women. There was no such upward trend in adenocarcinomas limited to the gastric cardia and/or involving the stomach. Because of the difficulties in determining accurate localization routinely in population-based studies, it seems sensible to preclude classification biases in recommending the grouping together of gastric cardia adenocarcinomas with oesophageal adenocarcinomas, at least with those among the latter occurring in the lower third of the oesophagus.

Incidence of digestive cancers and occupational exposure to asbestos.

While the role of exposure to asbestos in the development of several cancers such as mesotheliomas and bronchopulmonary cancers is now well established, the possible relationship between digestive cancers, other than peritoneal mesotheliomas, and occupational exposure to asbestos is still controversial. The great majority of the studies are based on mortality data. The aim of the study was to analyse the relationship between digestive cancer incidence and occupational exposure to asbestos in a population of subjects for whom precise occupational exposure data and precise incidence data were available. The population consisted of salaried and retired workers from a company using asbestos to manufacture fireproof textiles and friction materials. There were 1454 men (79.9%) and 366 women (20.1%). A cumulative exposure index and a mean exposure concentration in fibres/ml for each subject were calculated with the aid of an in-house job-exposure matrix. The number of cases of digestive cancer observed was compared with the expected and Standardized Incidence Ratio (SIR) was estimated. Precise occupational exposure data allowed us to study the dose-response relationship between asbestos exposure and risk of digestive cancer using Cox model. Fifty-six digestive cancers occurred in the study population over the 18-year follow-up period for 48.4 expected (SIR = 1.16 [0.87-1.50]). Comparing with incidence in the county, SIR was not significant for any of the digestive localization, but for peritoneum. However, even after taking into account the potential confounders via the Cox model, there was a significant dose-response relationship between the occurrence of digestive cancers and the mean exposure concentration, even after exclusion of peritoneum cancers. Our study provides initial evidence suggesting a relationship between occupational exposure to asbestos and the risk of digestive cancer: first, it is a study of incidence although the risk evidenced is not significant; secondly, a dose-effect relationship is demonstrated in the whole population. However, these preliminary results require confirmation by more powerful studies focusing on larger series.

Cancer incidence and mortality in France in 1975-95.

The aims of the European Network of Cancer Registries (ENCR) are to improve the quality, comparability and availability of cancer registry data in Europe. This paper on cancer incidence and mortality in France presents the most recent available data, with short-term projections to 1995, and a commentary based, where possible, on epidemiological research carried out in France. Cancer incidence in men in France increased throughout the study period 1975 to 1995, from 92,000 new cases in 1975 to about 135,000 in 1995. This increase was partly due to the ageing of the French population, but incidence rates have also increased, particularly from 1975 to 1985. The trend appears to be levelling off in the 1990s, with an incidence rate in 1995 of about 482 per 100,000 (this and subsequent rates quoted are standardized to the European Standard Population). Among women, the all-cancer incidence rates also increased during the 1970s and 1980s. Although the rate of increase was less pronounced than in men, the trend is continuing in the 1990s. The estimated age standardized rate in 1995 was 309 per 100,000, representing 104,000 new cases. The main components of these changes in the last decade were, for men, increases in large bowel and prostate cancer, which have been partly compensated for by decreases in oral cavity, larynx and stomach cancer. For women the trend was dominated by the continuing increase in breast cancer with increases also in large bowel and lung cancers. Of the numerically important cancers in women, only stomach cancer has shown a clear decline. The situation in 1995 was that breast cancer remained the predominant cancer affecting women in France, accounting for almost one third of all new cases of cancer diagnosed and one fifth of cancer deaths. The next most frequent cancers in women were those of the large bowel. Regrettably, incidence rates of both breast and bowel cancer are increasing in women. For men in France the most frequent cancers in 1995 were those of the prostate, large bowel and lung, all of which increased in incidence since 1975. Although it is estimated that there will be more newly diagnosed cases of prostate cancer than lung cancer in 1995, the latter will cause many more deaths, particularly of young men.

Influence of rural environment on diagnosis, treatment, and prognosis of colorectal cancer.

STUDY OBJECTIVE: Several studies have shown that residential location (urban or rural) influences the incidence of colorectal cancer. The aim was to investigate the influence of rural environment on colorectal cancer history and survival in a well defined population. DESIGN: Patients with colorectal cancer diagnosed in the department of Calvados (France) were classified by place of residence (urban/rural) and information on clinical symptoms, tumour extension, treatment, and survival was collected. SETTING: The study was population based, in the department of Calvados in France. PATIENTS: During 1978-1984, 1445 colorectal cancers were collected by the Digestive Tract Cancer Registry of Calvados, 1047 with an urban place of residence (544 males and 503 females) and 284 with a rural place of residence (134 males and 150 females). MEASUREMENTS AND MAIN RESULTS: In both sexes, rural patients with colorectal cancers were treated less frequently in a specialised health care centre (40.0%) than patients from an urban population (53.4%). The difference was mainly but not entirely explained by distance from the specialised health care centre. In females in the rural population, cancers were diagnosed more frequently at the stage of severe clinical symptoms (22.1%) and metastases (18.8%) than they were in the urban population (15.5% and 12.3%). In addition among females a rural environment appeared to confer a worse prognosis (relative risk = 1.3). CONCLUSIONS: Our findings suggest an inequality between rural and urban populations, especially for women. The loneliness of rural women leads to a delay in diagnosis and worse survival. In health education campaigns on colorectal cancer, efforts must be made to provide medical information to rural women in order to reduce the delay in diagnosis and improve survival.

Adjuvant radiotherapy and chemotherapy in resectable gastric cancer. A randomized trial of the gastro-intestinal tract cancer cooperative group of the EORTC.

One hundred and fifteen patients with curative and palliative surgery for gastric cancer were randomized to receive radiotherapy alone (1) or in combination with short-term (ST) 5-FU (2), long-term (LT) 5-FU (3), ST and LT 5-FU (4). The ST 5-FU was given at a daily dose of 575 mg/m2, every 4-6 h during the first 4 days of treatment before starting irradiation. The LT 5-FU was given at a dosage of 750 mg/m2 every 2 weeks for 18 months or until progression. The median survival times for treatment 1 to 4 was respectively 12, 10, 15 and 18 months. There was a statistically significant overall difference between the four treatments (P = 0.041). However, when the comparisons were adjusted for the most significant prognostic factors, the difference in survival disappeared. Moreover, no difference was found between treatments in terms of time progression. Nevertheless, among 22 patients with residual tumour, the three who were still alive without disease progression (with survivals of 19+, 49+ and 90+ months at the time of this analysis) had been treated with radiotherapy combined with ST and LT 5-FU.

Adjuvant therapy for resectable oesophageal cancer: results of a pilot study.

119 operable patients with an epidermoid oesophageal carcinoma were treated preoperatively with a combination of chemotherapy (cisplatin 80 to 100 mg/m2: 2 cycles) and radiotherapy (two courses of 18.5 Gy). The response rate was evaluated on resected specimens. The toxicity was moderate. The pathological study of the 101 resected specimens showed no residual tumor (CR) in 24 patients and partial response (PR) in 46. The response rate (CR + PR) was better in stage I (89%) than in stages II and III. A controlled study is needed to evaluate the effectiveness of this protocol as regards survival.