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J L Lefebvre

Publications and source records attributed to J L Lefebvre.

At least 37 records · Page 2Linked to original sources
PubMed1997

Epithelioid sarcoma of the tongue.

A case of epithelioid sarcoma in the tongue is reported. The patient, a 35 year old woman, presented with a non-ulcerated painful lesion of the tongue. Microscopically, the tumour was characterised by multiple coalescent nodules with central geographic necrosis infiltrating the lingual muscle. The tumour cells were epithelioid with abundant eosinophilic cytoplasm and atypical nuclei. Immunohistochemically, the tumour cells stained for vimentin, keratin, and epithelial membrane antigen. These morphological and immunohistochemical appearances led to the diagnosis of epithelioid sarcoma of the tongue. Seven years later, the patient died with metastatic dissemination to the scalp, lungs, and brain. No case of epithelioid sarcoma arising in the tongue has been described previously.

Adult↗
PubMed1997

[Cystic adenoid carcinomas (cylindromas) and olfactory esthesio-neuromas of the nasal cavities and paranasal sinuses. Experience of the ORL Group of the National Federation of Cancer Centers].

In 1991, a retrospective study was conducted by the French Cancer Centers Group. It concerned 752 cancers of the nasal cavities and paranasal sinuses, among which 61 were adenoid cystic carcinomas and 64 esthesioneuroblastomas. Local aggressiveness and high metastatic potential of adenoid cystic carcinomas were confirmed: 27 local relapses, 26 metastases, overall 5-year survival rate at 55%. Concerning esthesioneuroblastomas, the 5-year survival rate was 56% for patients treated with surgery and radiotherapy (7/27 went through combined surgical approaches), and 26% for those treated with radiotherapy alone. Two main factors of poor prognosis can be emphasized: a) intracranial extension: 5-year survival rate at 18% vs 59%, b) immediate node metastases: 5-year survival rate at 11% vs 63%.

Adult↗
PubMed1996

Larynx preservation in pyriform sinus cancer: preliminary results of a European Organization for Research and Treatment of Cancer phase III trial. EORTC Head and Neck Cancer Cooperative Group.

BACKGROUND: As a general rule, surgery whenever possible, followed by irradiation is considered to be the standard treatment for cancer of the hypopharynx, thus sacrificing natural speech. In most patients, surgery includes removal of the larynx. PURPOSE: A prospective, randomized phase III study was conducted by the European Organization for Research and Treatment of Cancer (EORTC) starting in 1990 to compare a larynx-preserving treatment (induction chemotherapy plus definitive, radiation therapy in patients who showed a complete response or surgery in those who did not respond) with conventional treatment (total laryngectomy with partial pharyngectomy, radical neck dissection, and postoperative irradiation) in previously untreated and operable patients with histologically proven squamous cell carcinomas of the pyriform sinus or aryepiglottic fold, but free of other cancers. METHODS: Patients were randomly assigned to one of two treatment arms: 1) immediate surgery with postoperative radiotherapy (50-70 Gy) or 2) induction chemotherapy (cisplatin [100 mg/m2] given as a bolus intravenous injection on day 1, followed by infusion of fluorouracil [1000 mg/m2 per day] on days 1-5). An endoscopic evaluation was performed after each cycle of chemotherapy. After two cycles, only partial and complete responders received a third cycle. Patients with a complete response after two or three cycles of chemotherapy were treated thereafter by irradiation (70 Gy); nonresponding patients underwent conventional surgery with postoperative radiation (50-70 Gy). Salvage surgery was also performed when patients relapsed after chemotherapy and irradiation. The trial was designed to test the equivalence of the two treatment arms; i.e., the induction chemotherapy treatment would be judged equivalent to immediate surgery if the relative risk of death for induction chemotherapy compared with immediate surgery was significantly less than 1.43 using a one-sided hypothesis test at the .05 level of significance. RESULTS: Two hundred two patients entered the trial and were randomly assigned; only 194 were eligible for treatment (94 in the immediate-surgery arm and 100 in the induction-chemotherapy arm). In the induction-chemotherapy arm, complete response was seen in 52 (54%) of 97 patients with local disease (primary tumor) and in 31 (51%) of 61 patients with regional disease (involvement of the neck). Treatment failures at local, regional, and second primary sites occurred at approximately the same frequencies in the immediate-surgery arm (12%, 19%, and 16%, respectively) and in the induction-chemotherapy arm (17%, 23%, and 13%, respectively). In contrast, there were fewer failures at distant sites in the induction-chemotherapy arm than in the immediate-surgery arm (25% versus 36%, respectively; P = .041). The median duration of survival was 25 months in the immediate-surgery arm and 44 months in the induction-chemotherapy arm and, since the observed hazard ratio was 0.86 (logrank test, P = .006), which was significantly less than 1.43, the two treatments were judged to be equivalent. The 3- and 5-year estimates of retaining a functional larynx in patients treated in the induction-chemotherapy arm were 42% (95% confidence interval = 31%-53%) and 35% (95% confidence interval = 22%-48%), respectively. CONCLUSIONS AND IMPLICATIONS: Larynx preservation without jeopardizing survival appears feasible in patients with cancer of the hypopharynx. On the basis of these observations, the EORTC has now accepted the use of induction chemotherapy followed by radiation as the new standard treatment in its future phase III larynx preservation trials.

Adult↗
PubMed1996

Phase II study on mitoxantrone in adenoid cystic carcinomas of the head and neck. EORTC Head and Neck Cancer Cooperative Group.

BACKGROUND: Based on activity in a case report, mitoxantrone was studied in a phase II study in adenoid cystic carcinoma. PATIENTS AND METHODS: Patients with symptomatic and/or rapidly progressive metastatic or recurrent adenoid cystic carcinoma were eligible for this study. They were treated with mitoxantrone given intravenously by bolus injection at a dose of 14 mg/m2, cycles repeated every 3 weeks. RESULTS: Thirty-six chemotherapy-naive patients entered on trial, 4 were ineligible. A median of 6 cycles per patient were given. Leucocytopenia (in 97% of patients) was the most important side effect and tended to be cumulative. Other side effects were mainly mild to moderate and consisted of nausea (62%), vomiting (29%), alopecia (53%) and mucositis (41%). Four of 32 patients had a partial response (12%; 95% CI 4%-29%) lasting 3-13 months, 22 patients (69%) had a stable disease. CONCLUSION: Mitoxantrone at this dose and schedule has modest activity in adenoid cystic carcinomas.

Adult↗
PubMed1996

Current status of larynx preservation trials.

Over the past 15 years, larynx preservation has been extensively assessed but only in the light of induction chemotherapy. From these evaluations, it appeared that the use of induction chemotherapy was safe and adequate for patient selection: irradiation with or without salvage surgery for induction chemotherapy responders and surgery with or without postoperative irradiation for induction chemotherapy nonresponders. Neither the ultimate local control nor survival worsened, and at least, half the patients retained their larynxes. Such results should not lead researchers to forget other larynx-preserving possibilities. Irradiation alone and, moreover, irradiation with modified fractionation or chemotherapy permits cure and preservation of function in many larynx and hypopharynx cases. Conversely, subtotal surgery may, in very selected cases, reach a similar goal. Finally, the new advances in imaging and biology could lead to fine tuning of patient selection. These advances could have the additional advantage of permitting use, thereafter, of chemotherapy as a real treatment and not as simply a selection parameter.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[Current knowledge on the action of retinoids in carcinoma of the head and neck].

The retinoids are a pharmacologic class based on the vitamin A or retinol. The most known related derivatives are the all-trans (ATRA), 13 and 9 Cis retinoic acids. The antitumor and differenciative activities have been demonstrated in: in vitro, in vivo and clinical studies. In head and neck cancers, the clinical phase III trials in chemoprevention of second primary tumors have shown discordant results related to the type of retinoic acid. Nuclear retinoic acid receptors are members of the steroid-thyroid and vitamin D3 superfamily of nuclear receptors which regulate differenciation proliferation and apoptosis in cooperation with mediated proteins of the apoptosis (especially p53 protein). A thorough knowledge on the earlier mechanisms involved in carcinogenesis of squamous cell carcinomas would lead to futur reversal therapy with the reversal of pathologic to normal tissues by the restauration of mechanisms of the physiologic control. This futur clinical trial research could provide cancer prevention and control by the induction of cellular differentiation rather than proliferation (retinoids) and/or the expression of tumor-suppressor genes (p53 protein transfection). Finally, the retinoids treatment should be performed in control studies because of the toxicity at high doses.

Apoptosis↗
PubMed1996

[An improved quality of life self-questionnaires specific for head and neck tumors].

The assessment of quality of life is an element that is now taken into account in the evaluation of therapies in oncology and especially for treatments connected with important sequellae. The lack of a specific tool measuring the quality of life of patients with head and neck cancers (H&N), validated in French, leads us to develop and to validate a self-questionnaire. The construction of this questionnaire has been realised following a strict procedure (identification of aspects to explore, formulation and selection of items) conducting to a specific module of 17 questions with 4 modes of reply. The validation of the questionnaire has been undertaken on 116 patients that filled the specific module H&N and the general self-questionnaire QLQ-C30 of the EORTC. The acceptability is excellent since only 4% of the patients have refused to participate to this study and that the number of missing data is very low. The value of the Cronbach alpha coefficient with the global score equal to 0.85, reflects a good reliability of the questionnaire. Global score correlation of the module H&N with the different scales (functional and symptoms) of the QLQ-C30 are coherent. Global scores are correlated to the nature of the treatment (p < 0.001), to the evolution of the disease (p = 0.01), to the tumour site (p = 0.015) but not to the code WHO neither to the performance of a laryngectomy. The whole results indicate that we have a specific tool, reliable, and validated. Associated to a general quality of life questionnaire, this specific tool will be useful to complete the evaluation of therapies, especially during of comparative clinical trials.

Activities of Daily Living↗
PubMed1995

European School of Oncology Advisory report to the European Commission for the Europe Against Cancer Programme: oral carcinogenesis in Europe.

A European School of Oncology Advisory Group has reviewed current knowledge on the epidemiology, treatment and prevention of cancer of the oral cavity. While the major factors in the aetiology of such cancers are thought to be well understood, i.e. tobacco and alcohol consumption, current increases in the occurrence of the disease, especially in young adults throughout Europe, are cause for concern. The reasons for such increases are not clearly evident and the Advisory Group has suggested further work which is required to be carried out to understand the aetiology. In treatment of the disease there have been no major improvements in survival for patients in recent decades and the importance of examining new radiotherapy modalities and defining the role of chemotherapy is emphasized. Primary prevention of oral cancer could be achieved by stopping smoking tobacco, limiting alcohol consumption to a minimum (2-3 drinks per day) and increasing intake of fruits and vegetables. To supplement these actions, while neither population screening programmes nor screening trials could be recommended by the Advisory Group, initial chemoprevention trials have produced some promising results and this represents an interesting area which is the focus of much current research.

Europe↗
PubMed1995

[Hypercalcemia and squamous cell carcinoma of the upper respiratory-digestive tracts. Incidence and prognosis].

We performed a retrospective analysis on all head and neck cancers with hypercalcemia seen between January 1988 and June 1993 at the Centre Oscar-Lambret, cancer center of northern France. Hypercalcemia, non albumin-corrected, higher than 2.60 mmol/l was observed in 173 of 3,394 consecutive patients (5%). Median age of patients with hypercalcemia was 53 years and 97% of these patients were males. All patients with hypercalcemia had advanced or recurrent and/or metastatic squamous cell carcinoma of head and neck (SCCHN); 31 of them were not pretreated. There was no significant difference in histology between patients with or without hypercalcemia, but hypercalcemia was most commonly associated with lesions of the oropharynx (p = 0.00001). The median of calcemia was of 2.83 mmol/l (2.61-4.70). Gastrointestinal and neurologic symptoms respectively occurred in 24% and in 14% of patients and bone metastases in 25% of patients. Median survival after the first determination of hypercalcemia was of 7 weeks (0-128) for the overall group of 173 patients and of 12 weeks (1-128) for those 31 patients with hypercalcemia at initial diagnosis. Prognosis associated factors were: efficacy of antitumour treatment, performance status and hypercalcemia superior or not to 3 mmol/l. We concluded that hypercalcemia in head and neck cancer is usually a late manifestation associated with advanced, recurrent and/or metastatic disease and carries a poor prognosis. The prolongation of survival can be obtained in some patients if an effective antitumour treatment is feasible.

Adult↗
PubMed1994

A phase II study of pirarubicin in patients with advanced recurrent head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous carcinoma (HNSCC) is a chemotherapy-sensitive tumour, but this sensitivity is not reflected in an impact on survival. The study of new drugs is therefore indicated. Pirarubicin (4'-O-tetrahydropyranyl-doxorubicin) has a higher preclinical index than doxorubicin, with low cardiotoxicity in animal models. PATIENTS AND METHODS: Twenty-six patients with squamous cell carcinoma of the head and neck and documented progression after or during previous chemotherapy were entered into the study. Two patients were ineligible for evaluation. Pirarubicin was given at a dose of 70 mg/m2 every 3 weeks. RESULTS: Partial remission was seen in 1 of the 24 evaluable patients. The predominant toxicity was bone marrow depression, with leucopenia in 62% of the patients. One patient died due to a gastrointestinal haemorrhage during a period with WHO grade IV thrombocytopenia. CONCLUSION: On the basis of these results, pirarubicin cannot be recommended as second-line treatment in patients with recurrent and metastatic HNSCC. Its possible relevance for first-line treatment cannot be judged from these data.

Adult↗
PubMed1994

Management of early oral cavity cancer. Experience of Centre Oscar Lambret.

From 1974 to 1983, 579 patients presenting with early oral cancer (excluding lip tumours) were treated at Centre Oscar Lambret. Of these, 429 were treated locally by brachytherapy with local control achieved in 82% of the cases (90% after salvage surgery). Treatment-related complications occurred in 19% of the cases, requiring surgical management in 13 patients. In contrast, only 51% of the 35 patients treated by external radiotherapy and brachytherapy were controlled, resulting in a poor 5-year survival (14%). Results for the 24 patients treated surgically were similar to those of brachytherapy alone. Finally, for T1 T2 N0 patients, the advantages of an elective neck dissection are not clear and could be clarified by a randomised trial. Indeed, this retrospective study failed to find a significant difference in the incidence of death due to an uncontrolled neck evolution whatever the neck management.

Adult↗
PubMed1993

Composite resection with mandibulectomy in the treatment of posterolateral oral cavity and lateral oropharynx squamous cell carcinoma.

From 1972 to 1987, 403 patients underwent a composite resection consisting of segmental mandibulectomy and neck dissection for the treatment of bucco-pharynx squamous cell carcinoma (303 patients had postoperative radiotherapy [XRT], 29 patients had preoperative XRT, and 100 patients had tissue salvage performed after XRT). Of the 303 patients who received preoperative XRT, 32 were clinically staged T2, 149 were staged T3, and 122 were staged T4; 194 of the 303 patients were staged N0. In the 100 patients who experienced relapse and who required "salvage surgery," the restaging found 20 patients staged T2, 39 staged T3, and 41 staged T4; 73 of the 100 patients were staged N0. The patients' mean postoperative stay was 15 days for those who had prior surgery and 21 days for those who had salvage surgery. With a minimum follow-up of 5 years, locoregional recurrences and postoperative death occurred in 86 of 274 patients (31%) in whom surgery and postoperative XRT were performed; in 17 of 29 patients (59%) who had preoperative XRT performed; and in 61 of 100 patients (61%) who had salvage surgery performed. In addition, in terms of functional results, only 61% of patients (206) were able to maintain normal speech function, and only 23% (91) were able to maintain normal oral feeding. Of the 403 patients, the 5-year survival rates were 33% for the overall population, 42% for patients with postoperative XRT, 16% for patients in whom operation was performed after preoperative XRT, and 17% for patients who underwent salvage surgery.

Adult↗
PubMed1991

Experimental studies and preliminary clinical trial of vinorelbine-loaded polymeric bioresorbable implants for the local treatment of solid tumors.

Vinorelbine is a new 5' nor Vinca alkaloid, active by i.v. route, in various types of cancer disease such as non-small cell lung cancer and advanced breast cancer. In order to evaluate the possibility of using this drug for local treatment of cancer, Vinorelbine-loaded bioresorbable polymeric implants were prepared using a copolymer of D,L-lactic and glycolic acids (PLA 37.5 GA 25). According to the manufacturing process, the 1.2-mm-diameter cylindrical rods obtained had a drug content of 1, 5, or 20% (w/w) and released half of their content within about 6 days in vitro. In vivo release in rats was slower, half of the drug being released after about 14 days. A dose-dependent antitumoral effect was observed in mice (solid P388 leukemia model) when implants were administered into or in contact with the tumor. At highest drug loads and when administered soon after tumor implantation, Vinorelbine implants were more effective than i.v. administration (median survival time of treated animals related to untreated controls, greater than 360 versus 188). In dogs, results of toxicity experiments revealed that administration of implants in vital organs must be avoided. On the contrary, s.c. administration was well tolerated. A transient local necrosis was observed in the days following implantation, but normal skin was recovered after about 10 weeks. Thus, a clinical trial was conducted on patients with head and neck cancer; implantation of 20% loaded polymeric implants into the tumor sites succeeded in 8 of 9 patients. The sole failure was attributed to the unusual hardness of the tumor tissue. Except for a local transient inflammatory reaction (easily treated with nonsteroidal antiinflammatory agents), no other sign of toxicity was detected, and patients tolerated the device well. Fourteen days after implantation, patients underwent their planned surgery, and the implants were recovered. Residual drug content varied from 24 to 55%. In all cases, there was a clearly delimited necrotic area around the implant, ranging from 0.5 to 3.5 cm in diameter. In the smallest tumors, necrosis was also observed in the normal tissue inside this area. These results invite further studies to evaluate such drug-loaded polymeric implants.

Adult↗
PubMed1991

Comparison of surgery and radiotherapy in T1 and T2 glottic carcinomas.

We retrospectively studied 356 patients who received treatment for T1 and T2 glottic carcinomas. Two hundred and thirty patients were treated with surgery (200 by cordectomy, 15 by vertical partial laryngectomy, and 15 by subtotal laryngectomy). Radiotherapy was used to treat 126 patients. There were 206 T1 and 24 T2 lesions in the surgically treated group and 107 T1 and 19 T2 lesions in the radiotherapy group. Sixty-four patients received radiotherapy because it was the treatment of choice (scheduled radiotherapy) and 62 patients received radiotherapy because they had medical contraindications for surgery (default radiotherapy). Actuarial survival rates at 5 years were 84% for patients who underwent surgery and 78% for patients who underwent scheduled radiotherapy. In the surgically treated group, there were 10 local recurrences in 170 patients with tumors of the true vocal cord, eight recurrences in 36 patients with anterior commissure lesions, and 6 recurrences in 24 patients with tumors extending to the arytenoid. In the scheduled radiotherapy group, there were 7 local recurrences in 38 patients with true vocal cord tumors, 6 recurrences in 20 patients with anterior commissure tumors, and 5 recurrences in 6 patients with tumors extending to the arytenoid. We conclude that survival is similar in these patients whether they receive operative treatment or scheduled radiotherapy. However, in the radiotherapy group, local recurrences were more frequent in patients with tumors extending to the arytenoid. We advocate extended functional surgery for patients with T1 and T2 glottic lesions except for those with small tumors arising from the middle third of the vocal cord.

Carcinoma, Squamous Cell↗
PubMed1991

Hypothyroidism following combined treatment for hypopharyngeal and laryngeal carcinoma.

The development of hypothyroidism following combined treatment for pharyngeal and laryngeal cancer has received little attention in the literature. We prospectively studied 32 patients over 4 years to determine the incidence of such hypothyroidism and to examine the effect of hemithyroidectomy associated with a combined treatment modality. All patients were men with pharyngeal or laryngeal squamous cell carcinomas and no prior history of thyroid disease. Treatment consisted of radical surgery (30 of 32 patients), followed by postoperative radiotherapy (31 patients). The results of thyroid function tests (free triiodothyronine, free thyroxine, and thyroid-stimulating hormone [TSH]) were all normal preoperatively; tests were repeated every 3 months after treatment. Elevation of TSH values in two successive blood samples was required to make a diagnosis of hypothyroidism. Of 12 patients who underwent hemithyroidectomy as part of total pharyngolaryngectomy and postoperative radiotherapy, 7 became hypothyroid a mean of 6 months after treatment. Twenty patients had similar combined treatment but without thyroid resection. Hypothyroidism developed a mean of 10 months after treatment in only four patients in this group (p less than 0.05). We conclude that hypothyroidism frequently develops following combined treatment for pharyngeal and laryngeal cancer even when thyroid resection has not been performed. Patients should be evaluated postoperatively and carefully monitored by means of serial thyroid function tests.

Carcinoma, Squamous Cell↗