[Show abstract][Hide abstract] ABSTRACT: The objective of the study was to evaluate the effect of neoadjuvant chemotherapy on the survival of patients with oropharyngeal cancer. Patients with a squamous cell carcinoma of the oropharynx for whom curative radiotherapy or surgery was considered feasible were entered in a multicentric randomized trial comparing neoadjuvant chemotherapy followed by loco-regional treatment to the same loco-regional treatment without chemotherapy. The loco-regional treatment consisted either of surgery plus plus radiotherapy or of radiotherapy alone. Three cycles of chemotherapy consisting of Cisplatin (100 mg/m2) on day 1 followed by a 24-hour i.v. infusion of fluorouracil (1000 mg/m2/day) for 5 days were delivered every 21 days. 2-3 weeks after the end of chemotherapy, local treatment was performed. The trial was conducted by the Groupe d'Etude des Tumeurs de la Tête Et du Cou (GETTEC). A total of 318 patients were enrolled in the study between 1986 and 1992. Overall survival was significantly better (P = 0.03) in the neoadjuvant chemotherapy group than in the control group, with a median survival of 5.1 years versus 3.3 years in the no chemotherapy group. The effect of neoadjuvant chemotherapy on event-free survival was smaller and of borderline significance (P = 0.11). Stratification of the results on the type of local treatment, surgery plus radiotherapy or radiotherapy alone, did not reveal any heterogeneity in the effect of chemotherapy.
British Journal of Cancer 01/2001; 83(12):1594-8. · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Between 1980 and 1985, 914 patients with head and neck squamous cell carcinoma underwent lymph node dissection in our institution. The prognostic value of clinical factors has already been reported (Mamelle et al, 1994, Am J Surg 168: 494-498). We present here a comparison of biological characteristics of pharyngeal tumours in patients who developed distant metastasis and in patients without metastasis, matched on tumour site, node site and size, and year of diagnosis. Tumour differentiation, keratinization, vascular emboli, immunohistochemical expression of p53, c-erb-B2, Rb and bcl2 were first assessed in 31 pairs of patients. Factors of potential interest were then determined in 32 additional pairs of patients. Statistical analysis showed that the risk of distant metastasis was halved in patients with tumours expressing c-erb-B2 compared with patients with c-erb-B2-negative tumours (P = 0.05). The significance of c-erb-B2 expression and its potential value as a prognostic factor is discussed.
British Journal of Cancer 07/1998; 77(11):1932-6. · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We conducted a randomized study in patients with previously untreated advanced (T3) larynx carcinoma to compare total laryngectomy followed by radiotherapy to induction chemotherapy, followed by radiotherapy in good responders, and by total laryngectomy plus radiotherapy in poor responders. A total of 68 patients were included in the study, 36 in the induction chemotherapy group and 32 in the no chemotherapy group. 15 of the 36 patients in the induction chemotherapy group did not have a laryngectomy. Survival and disease-free survival were significantly worse in the induction chemotherapy group than in the no chemotherapy group (P = 0.006 and P = 0.02, respectively). The 2-year survival rates were 69% in the induction chemotherapy group and 84% in the no chemotherapy group. Larynx preservation for patients, selected on the basis of having responded to induction chemotherapy, cannot be considered a standard treatment at the present time.
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to evaluate the efficacy and toxicity of Etanidazole, a hypoxic cell sensitizer, combined with radiotherapy in the treatment of head and neck squamous cell carcinoma.
A total of 374 patients from 27 European centers were included in this trial between 1987 and 1990. Treatment was either conventional radiotherapy alone (between 66 Gy in 33 fractions and 74 Gy in 37 fractions, 5 fractions per week), or the same radiotherapy dose plus Etanidazole 2 g/m2, three times weekly for 17 doses. A minimization procedure, balancing for center, site, and T stage (T1-T3 vs. T4) was used for randomization.
Among the 187 patients in the Etanidazole group, 82% received at least 14 doses of the drug. Compliance to the radiotherapy protocol was 92% in the Etanidazole group and 88% in the control group; the main cause of deviation was acute toxicity, which was observed at an equal rate in the two treatment groups. Fifty-two cases of Grade 1 to 3 peripheral neuropathy were observed in the Etanidazole group vs. 5 cases, all of Grade 1, in the control group (p < 0.001). The 2-year actuarial loco-regional control rates were 53% in the Etanidazole group and 53% in the control group (p = 0.93), and the overall 2-year survival rates were 54% in each group (p = 0.99).
Adding Etanidazole to conventional radiotherapy did not afford any benefit for patients with head and neck carcinoma. This study failed to confirm the hypothesis of a benefit for patients with N0-N1 disease, which had been suggested by the results of a previous study (10).
International Journal of Radiation OncologyBiologyPhysics 09/1997; 39(2):275-81. · 4.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We studied 1771 patients treated for a thyroid cancer in two institutions. None of these patients had been treated with external radiotherapy and 1497 had received (131)I. The average (131)I cumulative activity administered was 7.2 GBq, and the estimated average dose was 0.34 Sv to the bone marrow and 0.80 Sv to the whole body. After a mean follow-up of 10 years, no case of leukaemia was observed, compared with 2.5 expected according to the coefficients derived from Japanese atomic bomb survivors (P = 0.1). A total of 80 patients developed a solid second malignant neoplasm (SMN), among whom 13 developed a colorectal cancer. The risk of colorectal cancer was found to be related to the total activity of (131)I administered 5 years or more before its diagnosis (excess relative risk = 0.5 per GBq, P = 0.02). These findings were probably caused by the accumulation of (131)I in the colon lumen. Hence, in the absence of laxative treatment, the dose to the colon as a result of (131)I administered for the treatment of thyroid cancer could be higher than expected from calculation of the International Commission on Radiological Protection (ICRP). When digestive tract cancers were excluded, the overall excess relative risk of second cancer per estimated effective sievert received to the whole body was -0.2 (P = 0.6).
British Journal of Cancer 02/1997; 75(5):734-9. · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study the predictive value of pretreatment potential doubling time and labeling index, as measured by flow cytometry in patients with head and neck squamous cell carcinoma treated with conventional radiotherapy.
70 patients with a squamous cell carcinoma of the oropharynx and 4 patients with another involved head and neck site were entered in this prospective study. The duration of the S phase (TS), the labeling index (LI), and the potential doubling time (Tpot) were obtained by flow cytometry measurements of a tumor biopsy obtained after i.v. injection of 200 mg bromodeoxyuridine to the patient. The treatment consisted of 70 Gy in 7 weeks, 2 Gy per fraction and five fractions per week.
The mean and median LI were 7.7% (standard deviation, SD: 5.0) and 6.3%, respectively. The mean and median TS were 9.3 h (SD: 3.6) and 8.3 h, respectively. The mean and median Tpot were 5.6 days (SD: 5.4) and 4.6 days, respectively. No significant relationship was found between the Tpot or LI and the tumor stage (T), nodal status (N), histological grade, and the site of the primary within the oropharynx. The only parameter significantly associated with an increased risk of local relapse was the tumor stage (p < 0.001). The mean Tpot for the group of tumors that relapsed locally was 5.3 days (SD: 3.3), compared to 6.1 days (SD: 4.08) for those who did not relapse locally (NS). Two parameters were significantly associated with a decrease in disease-free (DFS) and overall survival, namely the tumor stage (p < 0.005, and p < 0.001, respectively, for DFS and overall survival) and nodal involvement (p = 0.02 and (p < 0.005, respectively, for DFS and overall survival). The TS, LI, DNA index, and Tpot were not significantly associated with local relapse, DFS, and survival, either in the univariate or in the multivariate analysis.
The method used to evaluate tumor cell kinetics did not provide clinically relevant kinetic parameters for this type of cancer. The classic prognostic factors (tumor stage and nodal status) were strongly associated with clinical outcome.
International Journal of Radiation OncologyBiologyPhysics 06/1996; 35(3):471-6. · 4.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite the five million children who have been screened for neuroblastoma in Japan through detection of catecholamine metabolites, it is still uncertain whether screening for this disease is beneficial. The Japanese study has clearly indicated that screening at 6 months or earlier leads to heavy overdiagnosis. It is shown in this paper that screening at a later age may give the same reduction in mortality with possibly less overdiagnosis. However, it is estimated that, even with two screens at 12 and 18 months, the reduction in mortality would not greatly exceed 25%, under realistic hypotheses on the length of the preclinical phase of the disease. The evaluation of the efficacy of this screening strategy would need the recruitment of half a million children per year over 5-7 years and the follow-up of an equal number of controls. Such a trial would improve our knowledge of the natural history of the disease and might help to answer some questions raised recently regarding its biological heterogeneity.
British Journal of Cancer 07/1995; 71(6):1125-31. · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Because genetic predisposition probably plays an important role in the aetiology of most of childhood cancers, studies of second primaries occurring after these cancers may be particularly informative about possible common genetic mechanisms in both of these cancers. We have studied the incidence of thyroid tumours occurring after cancer in childhood in a cohort of 592 children treated before 1970. Among these children, six later developed a thyroid carcinoma, and 18 developed a thyroid adenoma. Radiation doses received to the thyroid by each of the irradiated children have been estimated using individual radiotherapeutic technical records. Thyroid carcinomas and thyroid adenomas were five times more frequent after irradiation for neuroblastoma than after irradiation for any other first cancer. This ratio did not depend on sex, nor on time elapsed since irradiation, nor on dose of radiation received for the thyroid gland. This result suggests that there is a common mechanism for the occurrence of neuroblastoma and of differentiated thyroid tumour.
British Journal of Cancer 04/1992; 65(3):425-8. · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In a French case-control study of 1010 women with breast cancer and 1950 controls with nonmalignant disease, the variations of the effects of 8 risk factors for breast cancer as a function of age at diagnosis, were analysed by tests of homogeneity and trend. The risks associated with a late age at first full-term pregnancy and with nulliparity were different between age-groups (test of homogeneity: p = 0.03), and the highest risks for these two factors were observed in women 45-54 years old. The risks associated with Quetelet index were also found to vary with age at diagnosis (test for trend: p = 0.008). A high Quetelet index decreased the risk of breast cancer in the younger age-groups; this decrease of risk became progressively less important with advancing age, and no such effect was found in the oldest age-group. Inverse results were observed for a tall stature (test for trend: p = 0.04): a tall stature increased the risk of breast cancer in the younger age-groups, and the figures suggested a reverse effect in the oldest group. No large variation with age was found for the effects of age at menarche, history of breast cancer death in mother or sisters, prior biopsy for benign breast disease, and weight. In conclusion, the relative importance of certain risk factors for breast cancer is closely related to age at diagnosis. Nulliparity and a late age at first birth appear to be major risk factors only for middle-aged women, whereas a low Quetelet index and a tall stature appear to increase the risk of breast cancer only for younger women.
Journal of Clinical Epidemiology 02/1990; 43(3):267-75. · 5.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine whether antibiotic treatment increases the risk of colonization by Pseudomonas aeruginosa, we performed a case-control study comparing antibiotic exposure in cancer patients colonized by P. aeruginosa and in noncolonized controls. Of 88 patients, 76 had been exposed to at least one antibiotic, but colonization was not statistically associated with exposure to any specific antibiotic treatment, administered orally or parenterally, alone or in combination.
Antimicrobial Agents and Chemotherapy 09/1989; 33(8):1400-2. · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Of a cohort of 634 children treated from 1942 to 1969 at the Gustave Roussy Institute for a first cancer and alive 5 years after treatment, 32 later developed second malignant neoplasms (SMN). A case-control study was performed to determine the relationship between the dose of radiotherapy received on a given anatomical site for the treatment of a first cancer, and the risk of SMN development at the same anatomical site. Another aim of the study was to analyse the effects of the association of radiotherapy with chemotherapy on the risk of SMN. The 32 cases of second malignant neoplasms were individually matched with one to nine patients of the cohort (a total of 162) who did not develop a SMN after a first cancer, matching on age, sex, type of first cancer and follow-up duration. The doses of radiotherapy delivered for the treatment of the first cancer were retrospectively estimated at the 26 anatomical sites of SMN. When the SMN was a leukaemia, the mean active bone-marrow dose was estimated as a weighted mean of the doses received by 20 bone sites. As compared to anatomical sites in children who had not received radiotherapy, the sites which had received 50 Gy or more had a relative risk of SMN of 5.8 (P less than 0.05). When taking into account the dose received at the site of the SMN, neither the number of fractions nor the type of radiations were related to the risk of SMN. Children who had received chemotherapy had a relative risk of SMN of 2.7 (95% CI: 1.2-6.4), adjusted for the dose of radiotherapy, as compared to those who had not. The relative risk of SMN did not vary with the dose nor the duration of the chemotherapy. Dactinomycin was found to increase the relative risk of second soft tissue and bone sarcomas. Cyclophosphamide was found to be less carcinogenic than the other alkylants. The relative risk of SMN was equal to 2.0 (n.s.) after radiotherapy of more than 25 Gy, to 4.4 (n.s.) after chemotherapy, and to 21.4 (P less than 0.01) after the combination of these two treatments modalities, as compared to patients treated by surgery alone. This study suggests that the oncogenic effect of radiations might be increased by chemotherapy, and that the combination of the two treatment modalities might be one of the major factors responsible for overall risk of SMN.
British Journal of Cancer 06/1989; 59(5):792-6. · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The risk of subsequent second malignant neoplasm was studied in a cohort of 634 patients, treated for a childhood cancer at the Gustave Roussy Institute between 1942 and 1969, and in complete remission five years after diagnosis. The most frequent types of first primary cancers (FPC) were Wilms' tumours (28% of the children), neuroblastomas (16%), lymphomas (12%) and soft tissue sarcomas (11%). Median follow-up duration after FPC was 19 years. Thirty-two patients (obs = 32) developed a total of 35 second cancers. Bone, thyroid, connective tissues and skin were the most frequent types of second cancer, with six patients for each type. The average annual incidence of second cancer was 0.36%. The average annual incidence for the periods 5-9, 10-14, 15-19, 20-24 and 25+ years after FPC was respectively 0.16%, 0.34%, 0.36%, 0.71% and 1.18%. The cumulative incidence of second cancer for the periods 5-20, 5-25 and 5-30 years after FPC was, respectively, 4.3% (95% CI: 2.8-6.6%), 7.8% (95% CI: 5.1-11.8%) and 13.0% (95% CI: 8.2-20.0%). The expected number of cancers in the cohort, computed from Danish cancer incidence data, was exp = 2.2. When compared to this expected number, the average annual excess incidence of second cancer, defined as obs-exp divided by the number of person years of observation, was 0.33%. This rose from 0.15% for the period 5-9 years after FPC to 1.09% for the period beginning 25 years after FPC. The standardised incidence ratio of second cancer (i.e. obs/exp) was 15 (95% CI: 10-21), and was fairly constant in the period extending from 15 to 20 years after FPC diagnosis. Obs/exp was equal to 25 for the patients who had had chemotherapy and equal to 9 for those who had not. Cyclophosphamide seemed less carcinogenic than the other alkylating agents. Obs/exp was similar for the patients who had received radiotherapy and for those who had not. The risk of cancer increased with age in the reference population and increased faster in the cohort, because the standardised incidence ratio is constant over a long period.
British Journal of Cancer 04/1989; 59(3):448-52. · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Between 1982 and 1985, a case-control study of nulliparous women, aged 25-45, was conducted to analyse the relationships between the risk of breast cancer and causes of nulliparity, including contraceptive methods. Fifty-one cases of breast cancer diagnosed less than 3 months before interview were matched with 95 controls on age at diagnosis, year of interview, and medical center. The causes of nulliparity related to female sterility or subfertility (mechanical or hormonal disorders) were not found to be associated with a significantly higher risk of breast cancer. The causes related to fertilization failure, i.e. no sexual partner, rare sexual intercourse (less than once per month), or partner with abnormal semen, were found to lead to an increased risk. Detailed analysis of contraceptive methods showed that the risk of breast cancer increased (p = 0.02) with a longer duration of use of barrier methods (withdrawal or condom). Conversely, the risk significantly decreased (p = 0.004) with a longer duration of use of non-barrier methods (oral contraceptives, IUD, cap, local spermicides, vaginal douche, safe period, or no method), i.e. methods allowing a direct exposure to human semen.
Journal of Clinical Epidemiology 02/1989; 42(12):1227-33. · 5.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Colonization of central catheter tips has been associated with catheter-related infections. This colonization is defined as the presence of over 15 CFU in a semiquantitative catheter tip culture performed after catheter removal. Using a simple pour-plate technique, we determined the microbial concentrations in samples of blood collected via the hubs of 205 central catheters while they were in position in 179 cancer patients. All catheters were removed within three days of blood collection via the hub and cultured semiquantitatively. We then compared the results for the hub blood cultures and catheter tip cultures. Cultures from 18% of the hub samples and 29% of the tips were positive. When a cutoff limit of 1,000 CFU/ml was used for the blood cultures, the sensitivity was 20% and the specificity was 99% for estimating catheter tip colonization. These values did not seem to be related to the underlying disease, the site of catheter insertion, or the antibiotic treatment administered at catheter removal. We conclude that, if positive, cultures of blood sampled via the catheter hub can be useful in assessing the risk of catheter colonization in cancer patients.
Journal of Clinical Microbiology 12/1988; 26(11):2297-9. · 4.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Risk factors for candidemia were analyzed in a case-control study of 30 cancer patients with candidemia and 58 controls. In a univariate analysis, previous surgery, neutropenia, central catheterization, chemotherapy, specific antibiotic treatments, and peripheral cultures positive for Candida spp. were associated with a significantly increased risk of candidemia. In a multivariate logistic model, the significant risk factors for candidemia were positive peripheral cultures for Candida spp. (P = 0.02), central catheterization (P = 0.03), and neutropenia (P = 0.05). These results should help to identify cancer patients with a high risk of candidemia, who should be given early systemic antifungal therapy.
Journal of Clinical Microbiology 04/1988; 26(3):429-32. · 4.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: From September 1963 to January 1968, 243 patients with operable breast cancer were included in a randomized trial designed to compare classical radical mastectomy (RM) alone to extended mastectomy (EM), i.e. RM plus internal mammary dissection. One hundred and seventeen patients underwent RM, and 126 EM. After a mean follow-up time of 20 years, no significant differences were observed between the two treatment groups for overall survival, for the relapse-free survival rates, nor for distant metastasis, or locoregional recurrence rates. From a regression model, significant interactions were found between risk of death, EM, and both nodal status and site of the tumour. When compared to RM, EM significantly decreased the risk of death for patients with internal or medial tumour and positive axillary nodes (P = 0.05). No beneficial effect of EM was observed for any of the other patients; on the contrary, EM seemed to increase the risk of death for the patients with external tumour and negative axillary nodes (P = 0.07).
European Journal of Surgical Oncology 09/1987; 13(4):309-14. · 2.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Small cell lung carcinoma is the most frequent cancer in man. In France, the geographic distribution is not homogenous and the frequency is time-dependent. The main risk factors are smoking and some professional exposures.
Bulletin du cancer 02/1987; 74(5):501-9. · 0.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We assessed the results of treatment in 283 patients with lung or bone metastases from differentiated thyroid carcinoma who were followed for up to 40 yr (median, 44 months) after the discovery of the metastases. The survival rates from the time of discovery of the metastases were 53% at 5 yr, 38% at 10 yr, and 30% at 15 yr; 156 patients died. Multivariate analysis revealed that only 4 variables had an independent prognostic significance for survival. They were extensive metastases, older age at discovery of the metastases, absence of radioiodine uptake by the metastases, and moderately differentiated follicular cell type. The site of metastases (lung or bone) was not a prognostic factor for survival after treatment of metastatic disease. Remission was achieved in 79 patients after metastases were found. The only predictive factor for 5-yr disease-free survival after treatment of metastases was the initial extent of disease. Our results suggest that the aim of management should be to detect and treat metastases in patients with thyroid cancer as early as possible.
[Show abstract][Hide abstract] ABSTRACT: In a French case-control study of 1,010 breast cancer cases and 1,950 controls with nonmalignant diseases, the risk of breast cancer was found to be positively associated with frequency of cheese consumption and the level of fat in the milk consumed. A negative association was found between frequency of yogurt consumption and the risk of breast cancer. No association was found between the consumption of butter and the risk of breast cancer. The positive association between a daily consumption of alcohol and the risk of breast cancer previously reported was not altered when dairy produce consumption was taken into account.
JNCI Journal of the National Cancer Institute 10/1986; 77(3):633-6. · 14.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: HLA complex is made up of numerous loci whose alleles are codominant. Several associations between HLA antigens and diseases have been identified. Analysis of these associations require statistical methods taking into account the number of tests and the existence of alleles which have not yet been identified. Statistical methods for the estimation and the comparison of alleles frequencies are presented for genotypic, phenotypic and marginal data. An example concerning patients with medullary thyroid carcinoma illustrates these methods.
Revue d Épidémiologie et de Santé Publique 02/1986; 34(1):1-9. · 0.69 Impact Factor