Phase I clinical study of the new amino acid-linked nitrosourea, S 10036, administered on a weekly schedule.

Diethyl-1-[3-(2-chloroethyl)-3-nitrosoureido]ethylphosphonate (S 10036) is a new nitrosourea that has been evaluated in a clinical trial because of its activity in the National Cancer Institute panel screen and its rational chemical approach. A Phase I study was conducted in 22 evaluable patients with advanced cancers. The drug was given as a slow i.v. infusion over a period of 60 min on days 1, 8, 15, and 22 followed by a 4-week rest period. The dose levels ranged from 25 to 200 mg/m2/week for 4 consecutive weeks using a modified Fibonacci scheme. Thrombocytopenia was the only acute dose-limiting toxicity and started at a dose of 100 mg/m2/week and above. Hematological toxicity was delayed, cumulative, and dose related. Nausea and vomiting were moderate to severe and dose related. Three responses (one complete and two partials) have been noted. Phase II studies of S 10036 are planned at a dose of 100 mg/m2/week for 4 consecutive weeks ("induction therapy") for patients without prior therapy and 100 mg/m2/week for 3 consecutive weeks for those with prior chemotherapy or radiotherapy. Because of the cumulative toxicity, the recommended dose for the second cycle of S 10036 chemotherapy ("maintenance therapy") is 100 mg/m2/week every 3 weeks.

Pathology of the membranous labyrinth: comparison of T1- and T2-weighted and gadolinium-enhanced spin-echo and 3DFT-CISS imaging.

PURPOSE: To assess the value of unenhanced T1-weighted images, T2-weighted images, gadolinium-enhanced T1-weighted images, and three-dimensional Fourier transformation-constructive interference in steady state (3DFT-CISS) images in depicting lesions of the membranous labyrinth. METHODS: Six patients were studied using 1-T MR; both enhanced (gadolinium-tetraazacyclododecane tetraacetic acid) and unenhanced images were obtained and different sequences compared to determine which provided the most information. RESULTS: A combination of gadolinium-enhanced T1-weighted and 3DFT-CISS images could depict all membranous labyrinth pathology. Unenhanced T1-weighted images were necessary to exclude spontaneous hyperintensity in the membranous labyrinth. Gadolinium-enhanced T1-weighted images were needed to detect enhancing pathology such as labyrinthitis and tumors inside the membranous labyrinth. In these cases, 3DFT-CISS images allowed immediate differentiation between inflammation and tumor. In temporal bone tumors involving the bony and membranous labyrinth, unenhanced and enhanced T1-weighted images often sufficed to suggest the correct diagnosis. Only 3DFT-CISS images were able to demonstrate small structures (as fistulas) and to help us confirm or rule out obliteration of the labyrinthine fluid spaces. 3DFT-CISS images were necessary to detect small congenital malformations of the membranous labyrinth when only MR was performed. Uncalcified obliteration of the labyrinth fluid spaces could be reliably detected only on 3DFT-CISS images. Here also gadolinium-enhanced T1-weighted images had to be obtained because enhancement of the soft tissues inside the membranous labyrinth had been observed. CONCLUSION: The CISS sequence and enhanced T1-weighted sequence formed the best sequence combination for diagnosis of membranous labyrinth lesions; additional, unenhanced T1-weighted images can help one differentiate labyrinthitis, proteinaceous fluid, subacute hemorrhage, or tumor inside the labyrinth.

Constructive interference in steady state-3DFT MR imaging of the inner ear and cerebellopontine angle.

PURPOSE: To assess the value of a three-dimensional Fourier transformation MR technique "CISS" (constructive interference in steady state) in imaging the inner ear. SUBJECTS: We studied 50 normal inner ears (40 axial, 10 coronal) and 10 pathologic inner ears in 60 patients. RESULTS: The cochlea, semicircular canals, and vestibulum were visualized in detail. Cranial nerve VII and the cochlear, superior vestibular, and inferior vestibular branch of cranial nerve VIII were identified in 90%, 94%, 80%, and 88% of the cases, respectively. A vascular loop was recognized inside the internal auditory canal in 6%, and in the porus in 30%, of the cases. The high signal of the cerebrospinal fluid and labyrinthine fluids (perilymph and endolymph) on the CISS images made excellent delineation of tumors in the cerebellopontine angle and internal canal possible and allowed detection of tumoral labyrinth involvement. The thin sections, high resolution of the images, and capability of producing multiplanar and three-dimensional reconstructions often offered additional information. CONCLUSIONS: The CISS sequence allows detailed study of the normal and pathologic inner ear and promises to be highly valuable in the demonstration of the vascular loop.

Denta Scan: CT software program used in the anatomic evaluation of the mandible and maxilla in the perspective of endosseous implant surgery.

A radiological technique, using a new CT software program for the evaluation of alveolar process height and width, is presented. Irradiation is kept within acceptable limits when this technique is used. Measurements obtained with this technique were compared with those obtained on panoramic radiographs in 40 "half-jaws" (21 maxillar and 19 mandibular). We found that new indications for implantation emerge in the mandibular region because 'Denta Scan' can sometimes show possibilities to place implants on the buccal side of the canal (2 of 19 mandibular cases) when no possibilities are present above the canal on both the panoramic radiographs and Denta Scan images. In the maxillar region Denta Scan avoids unnecessary interventions by demonstrating the insufficient width of the alveolar ridge, often missed on panoramic radiographs (4 of 21 maxillar cases). Moreover the use of Denta Scan allows the use of implants with optimal length and diameter (23 of the 40 cases), giving better long-term results.

Vertebral artery dissection without ischemic events in the vertebro-basilar system.

A case of extracranial vertebral artery dissection is reported, presenting with headache and pulsatile tinnitus, without ischemic events in the vertebrobasilar system.

[10-year experience in the chemotherapy of epidermoid carcinomas of the upper aerodigestive system (5 protocols - 458 patients)]. / Dix ans d'expérience de la chimiothérapie des carcinomes épidermoïdes des voies aéro-digestives supérieures (5 protocoles - 458 malades).

The authors report protocols and results observed with various palliative chemotherapy, used successively against epidermoid carcinomas of head and neck area. This study was followed up during the last ten years by a group of physicians working in 8 specialized oncological centers. The poor prognosis and efficiency of antimitotic drugs in head and neck carcinomas require analyse of a great number of patients files. The cooperative work of several teams allows for more rapidly significant results. Each protocol was closed after a two year period. The protocols were dropped one after another, in order to provide a greater efficiency and a lower toxicity. It was possible to confirm the limited efficiency of "heavy" protocols and the most useful association. The members of this group now pursue a randomised study comparing the results obtained with cis-platyl used alone or in addition to three other drugs. The aim of this study is to assess which is more efficient and less toxic.

[Randomized trial of vincristin-methotrexate-bleomycin and cis-platin or detorubicin for advanced head and neck cancer (author's transl)]. / Etude randomisée d'une association de vincristine-méthrotréxate-bléomycine et cis-plastine ou détorubicine dans les cancers avancés des voies aérodigestives supérierures et de l'oesophage.

In a randomized multicenter trial, 151 patients, with advanced epidermoid carcinoma of the head, neck and oesophagus, were treated with an association of vincristin, methotrexate, bleomycin and cis-platin (group I) or detorubicin (group II). Prognostic factors were equally distributed for the both groups. Partial or complete responses were obtained in 22 patients of group I (29 p. cent) and 9 in group II (12 p. cent, p less than 0.05). Objective response rates were higher in untreated patients or those in good condition but the difference was not statistically significant. Five probably treatment induced deaths (3 p. cent) were observed. Treatment was stopped in 2 patients (15 p. cent) for haematological, general or digestive toxicity. This trial confirms the efficacy of vincristin, methotrexate, bleomycin and cis-platin for advanced head and neck carcinomas.

[Palliative chemotherapy of epidermoid carcinoma of the upper respiratory and digestive tracts with a combination of carboplatin and 5-fluorouracil]. / Chimiothérapie palliative des carcinomes épidermoïdes des voies aéro-digestives supérieures par une association de carboplatine et de 5 fluoro-uracile.

One hundred and thirteen patients with advanced squamous cell cancer of the head and neck were entered into a multicenter trial. Median age was 54 yr (range: 33-74 yr). Median Karnofsky index was 70 (60-100). Thirty-five patients had had prior induction chemotherapy. The first schedule was carboplatin 300 mg/m2, dl and fluoro-uracil 1000 mg/m2/d administered in continuous IV infusion for 96 h every 4 weeks (group 1). The second schedule was carboplatin 350 mg/m2, dl and fluoro-uracil administered at the same dose every 3 weeks (group II). Median number of cycles was 3 (range: 1-16). Seven patients were not eligible. The response rate was 26% (95% confidence limits: 18-34). Nine patients had a complete response. The median duration of response was 6 months (2-16+). The response rates in the 2 groups were not statistically different (21 and 31%) but disease progression was more frequent in group I (61%) than in group II patients (25%). Six early deaths occurred, without sign of drug toxicity. Grade 2 hematological toxicity between or before any cycle was more frequent in group II patients, in particular for leucopenia (13 vs 42%, P less than 0.05). One death was related to granulopenia. Grade 2 or 3 gastric toxicity was observed in 43 patients. No other major toxicity was observed. In our study, combination therapy with carboplatin and fluoro-uracil was found to be moderately active but myelotoxic.

[Randomized placebo trial of myeloprotection with goralatide in patients with squamous cell carcinoma of the upper respiratory and digestive tracts or esophagus, treated with a carboplatin-fluorouracil combination]. / Essai randomisé avec placebo de myéloprotection par le goralatide des patients présentant un carcinome épidermoïde des voies aérodigestives supérieures ou de l'oesophage, traités par l'association carboplatine-5 fluorouracile.

Eighty-four patients with locally advanced, non metastatic squamous cell carcinoma of head and neck or esophagus, were included in a multicentric double-blind randomized trial, comparing goralatide (12.5 or 62.5 micrograms/kg/day, d1-d4) to placebo, associated with carboplatin (400 mg/m2, d1) and 5-fluorouracile (1 g/m2/d continuous IV over 96 hours). Haematological toxicity was analysed on 221 cycles of chemotherapy. All but one patient were evaluable because of early death without haematological toxicity. No significant difference was observed for mean nadir of leukocytes, granulocytes, platelets counts and hemoglobin level. Duration of haematological toxicity was no significantly different for the two groups of patients. Anemia and lymphopenia were more frequent in the goralatide treated patients. Clinical and biological tolerability of goralatide was excellent.

[Predictive value of the hemogram for myelotoxicity induced by the association of carboplatin-fluorouracil on the 4th day of the therapeutic regimen]. / Valeur prédictive de l'hémogramme du 4e jour pour la myélotoxicité induite par l'association carboplatine-5-fluorouracile.

The aim of this study was to determine the value of haematological counts at the 4th day of a chemotherapy cycle, in order to foresee neutro and/or thrombocytopenia during the same chemotherapy cycle. One hundred and ten cycles of chemotherapeutic regimens with carboplatin (400 mg/m2, dl) and 5-fluorouracile (1 g/m2/d, by iv continuous infusion for 96 hours) every 3 weeks, were analyzed for 42 patients with locally advanced but non metastatic squamous cell carcinoma of head and neck, without prior chemotherapy. Lymphocyte counts were significantly decreased at the 4th day but normalized at the 8th day (P < 10(-6)). Decreases of lymphocyte and neutrophil counts at the 4th day were significantly correlated to grade > 2 neutropenia. The positive predictive value of lymphocyte or neutrophil counts is about 50% for some cut-off values but not high enough, with the schedule of chemotherapy in our study, to justify the systematic prophylactic therapy with haematopoietic growth factors.

[An expert system of aiding decision making in breast pathology connected to a clinical data base]. / Conception d'un système expert d'aide à la décision en pathologie mammaire connecté à une base de données cliniques.

The René Huguenin Cancer Center holds a medical file for each patient which is intended to store and process medical data. Since 1970, we introduced computerization: a development plan was elaborated and simultaneously a statistical software (Clotilde--GSI/CFRO) was selected. Thus, we now have access to a large database, structured according to medical rationale, and utilizable with methods of artificial intelligence towards three objectives: improved data acquisition, decision making and exploitation. The first application was to breast pathology, which represents one of the Center's primary activities. The structure of the data concerning patients is by all criteria part of the medical knowledge. This information needs to be presented as well as processed with a suitable language. To this end, we chose a language-oriented object, Mering II, usable with Apple and IBM 4 micro-computers. This project has already allowed to work out an operational model.

[A randomized study comparing cisplatin alone or combined in the palliative treatment of carcinoma of the head and neck. Analysis of a series of 209 patients]. / Etude randomisée comparant le cisplatine seul ou associé dans le traitement palliatif de carcinomes des voies aéro-digestives supérieures. Analyse d'une série de 209 patients.

Two hundred and nine patients, with locoregional or metastatic recurrences of head and neck epidermoid carcinoma, were randomized to receive a palliative chemotherapy. The chemotherapy regimens were delivered every 3 weeks, and consisted in (1) cisplatin, 80 mg/m2 given alone (CDDP regimen), or (2) in combination with vincristine, 1 mg, methotrexate 10 mg/m2 d 1, 2, 3, and bleomycin 10 mg/m2, d 1, 2 and 3 (1040 regimen). Short-term results were better for patients treated by the 1040 regimen, with a 30% response rate (including 4 complete responses) vs 15% with the CDDP regimen (P = 0.01). A superiority of combination chemotherapy was found for all tumoral sites, but was particularly significant for pulmonary and cutaneous metastases, in previously un irradiated areas (P = 0.001). Tolerance was significantly better with the CDDP regimen (P = 0.001); severe side effects, affecting mainly general status, digestive tract and bone marrow were encountered in 5% of the patients in the CDDP group, vs 21% in the 1040 group, with one death related to pancytopenia. The median duration of remissions was not statistically different in the 2 groups, as well as the 2 years overall survival. Among responders, the survival was slightly better in those treated with CDDP alone; moreover, the quality of long term results was found highly correlated with a good initial general status, and with low levels of side effects. Those results confirm recent data of the literature, and lead to the following conclusions: (1) combination chemotherapy with CDDP give a better response rate than CDDP alone, (2) response rate doesn't influence overall duration of survival, (3) tolerance to treatment is crucial to preserve quality of life, and thus, (4) palliative chemotherapy in head and neck cancer should be efficient but also as short of intensity as possible.

[Cardiac complications of thoracic radiotherapy]. / Complications cardiaques de la radiothérapie thoracique.

The cardiac complications of radiotherapy have been reviewed in the light of 46 case histories collected from 16 treatment centres in France. They are usually found after radiotherapy for Hodgkin's disease and carcinoma of the breast. Although histologically there may be diffuse fibrosis involving the endocardium, myocardium and pericardium, it is pericarditis which is the usual clinical feature. It often occurs late, and takes many forms. The dry constrictive fibrous type of pericarditis is the most severe because of the amount of myocardial fibrosis usually associated with it. It is rare for there to be clinical features of myocardial fibrosis, and if present they are variable: isolated disorders of repolarisation or of conduction, or true cardiomyopathies. Lesions of the coronary arteries are exceptionally rare after radiotherapy, and involve fibrosis of the intima or atherosclerosis.

[Cardiac risks of adriamycin. Early detection of high-risk patients by isotopic cardiac function study]. / Risque cardiaque de l'adriamycine. Repérage précoce des sujets á haut risque par l'étude fonctionnelle cardiaque isotopique.

Adriamycin is known to be effective in the treatment of breast cancer. Serial radionuclide determinations of the left ejection fraction can provide advanced warning of adriamycin cardiotoxicity, prior to clinical signs of the left ventricular dysfunction. Patients at high risk of congestive heart failure can be detected. Depending on the results of the second course of chemotherapy, guidelines and criteria can be laid down to predict the appropriate time for drug discontinuation.

[Randomized trial of initial chemotherapy with cisplatin alone or in combination in 241 advanced carcinomas of the upper respiratory and digestive tract]. / Essai randomisé de chimiothérapie initiale par cisplatine seul ou associé dans 241 carcinomes étendus des voies aéro-digestives supérieures.

Two hundred and forty-one patients, with advanced squamous cell carcinoma of head and neck, were randomized to receive three courses of induction chemotherapy. The chemotherapy regimens were delivered every 3 weeks, and consisted in 1) cisplatin, 80 mg/m2 given alone (CDDP regimen), or 2) in combination with vincristine, 1 mg, d 1, methotrexate 10 mg/m2 d 1, 2, 3, and bleomycin 10 mg/m2, d 1, 2, and 3 (MOB-P). Tolerance was significantly better with the CDDP regimen (p less than 0.05); severe side effects, affecting mainly digestive tract, and bone marrow, were encountered in 7% of the patients in the CDDP group, vs 15% in the MOB-P group, without death related to pancytopenia. Short-term results were better for patients treated by the MOB-P regimen, with a 42% response rate (including 9 complete responses) vs 22% with the CDDP regimen (p = 0.01). A superiority of combination chemotherapy was more significant for primary sites than regional lymph nodes. The relapse-free survival was not statistically different in the 2 groups, as well as the 2 years overall survival. Among responders, the survival was found highly correlated with a good initial general status (p less than 0.01), and with the highest total doses of cisplatin (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

[Retrospective study of 139 cases of epidermoid carcinoma of the upper respiratory and digestive tracts treated by induction chemotherapy with cisplatin-5FU. Influence of the result on the therapeutic protocol]. / Etude rétrospective de 139 carcinomes épidermoïdes des voies aéro-digestives supérieures (VADS) traités par chimothérapie d'induction cisplatyl-5FU. Influence du résultat sur le protocole thérapeutique.

A retrospective study of 139 untreated staged III and IV epidermoid carcinomas of the upper aero digestive tract is reported concerning oropharynx, oral cavity, hypopharynx and larynx, all of them received as a first treatment, chemotherapy using a five days course of Cisplatinium (20 mg/m2/D) and 5FU (1,000 mg/m2/D). The aim of the trial was to determine: a) a free of disease survival and a global survival rate's increase, b) a more conservative treatment. The results of chemotherapy were clinically evaluated in two groups: Responders (a total or a more than 50% response), and no responders. The results were: on the tumor site: 64% responders (25% total response)--more in smaller lesion; on the lymphatic nodes: 54% responders (more in N1-N2). The results vary in inverse ratio to the stage of the lesion; usually, 2 cycles of chemotherapy are used but in case of efficiency: 2 to 6 cycles are provided increasing to 20% the rate of the total responders; toxicity of the drugs was neligible: 6 cases, 3 of them were renal insufficiency. The global survival rate at 3 months reaches 56.7%. The median line of survival reaches 32 months in responders reverse 15 months (NR); but there are no significant difference between the two groups concerning the recurrences, or the metastasis. The local treatment (after chemotherapy) decided in the 137 patients was surgery, in 40 cases and radiotherapy, in 97 cases (conservative treatment; 80%).(ABSTRACT TRUNCATED AT 250 WORDS)

A semi-automated program for volume measurement in focal hepatic lesions: a first clinical experience.

The value of a semi-automated program for volumetric measurements was tested in 53 patients with liver lesions. Three different radiologists performed 10 measurements on a liver lesion in each patient. The variances of the measurements were calculated. There was no difference in intra- and interoperator variance of the measurements. If the diameter of the liver lesion exceeded the slice thickness, the different measurements became more reliable and more reproducible. The semi automation of the volume measurements makes its use in daily clinical practice possible. Volume measurement can be interesting in the follow-up and evaluation of the treatment on tumor reduction. However further and more thorough investigation is needed to test the clinical usefulness of the program.

Giant angiomyolipoma with atypical arteriovenous shunting: CT and angiographic studies.

The advent of both ultrasound and computerized tomography made the pre-operative diagnosis of angiomyolipoma much easier. However, differentiation from retroperitoneal, perinephric space and especially intrarenal liposarcoma remains difficult or impossible. Angiographic findings are atypical and often do not allow differentiation from renal cell carcinoma. Early filling of the renal vein in renal cell carcinoma is sometimes used to distinguish renal cell carcinoma from angiomyolipoma. A case of a giant angiomyolipoma with arteriovenous shunting and early filling of the renal vein is described.

Ultrasonographic findings in peptic ulcer: a report on 24 cases proven endoscopically.

A series of 24 patients is presented who had routine upper abdominal sonography for reason of atypical abdominal pain; in all cases the sonographically suggested diagnosis of a mucosal ulceration was proved by a following endoscopy. The ultrasonic findings were localized thickening of the gastric wall in combination with presence of liquid intragastrically in a fasting patient.

Herniography in adults: review and personal studies.

In 120 adults (87 men, 33 women) with suspicion of a hernia but with normal physical examination, herniography disclosed 125 positive findings correlated with the clinical manifestations. There were no false positive or false negative herniographic diagnoses among 25 patients who underwent surgery. Herniography is a useful examination to evaluate patients with an uncertain or normal physical examination and with clinical manifestations suggestive for hernia. This relatively simple technique and the use of a non-ionic contrast medium are well tolerated.