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PURPOSE: To investigate the influence of carbogen breathing on chemoradiation and the effects of erythropoietin on transfusions. METHODS AND MATERIALS: From March 1996 to April 2000, 42 (4 Stage III and 38 Stage IV) patients with head and neck cancer were treated with a twice-a-day hyperfractionated schedule. Each fraction consisted of 5 mg/m(2) of carboplatin plus 115 cGy with carbogen breathing. Treatment was given 5 days per week up to total doses of 350 mg/m(2) of carboplatin plus 8050 cGy in 7 weeks. Anemia was treated either by transfusion or by erythropoietin. RESULTS: Forty-one patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Five transfusions were given in the first group, but no transfusion was needed in the erythropoietin group. Local toxicities remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Forty-two complete responses were achieved. At two years actuarial local control, cause-specific survival and overall survival are respectively 85%, 69%, and 68%. At four years estimated probabilities of local control, cause-specific survival and overall survival are also 85%, 69%, and 68%. CONCLUSIONS: These results compare favorably with those of most reported studies. The addition of carbogen breathing appears to improve the results of chemoradiation alone. Erythropoietin therapy avoided transfusions.

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The results of the treatment of metastatic neck nodes is evaluated after a mean follow-up of 24 months (maximum 45 months). Fifty-seven patients with epidermoid carcinoma of the head and neck were treated according to a hyperfractionated chemoradiation schedule including two fractions a day. Each fraction consisted of 10 mg carboplatin + 115 cGy. Two fractions were given each day, five days a week, for a total dose of 700 mg carboplatin + 8050 cGy. Whenever possible, surgical salvage was performed if treated nodes persisted or recurred. Ten patients presented with N0, 8 with N1, 7 with N2a, 4 with N2b, 7 with N2c, and 21 with N3. The classification of the primary tumor was: 3 Tx, 6 T2, 9 T3 and 39 T4. One hundred and eleven nodes were treated (62 with a diameter of 1-3 cm, 26 with a diameter of 3-6 cm and 23 with a diameter over 6 cm). Actuarial node controls were: 100% for N0, 97% for nodes 1-3 cm, 87% for nodes 3-6 cm, 95% for nodes over 6 cm and 97% for the whole group. The actuarial local-regional control was 71% and the disease-free survival was 60%. These results include 5 surgical salvages (11% of N+), 2 of which recurred again (40%), while another 3 (60%) did not recur.

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BACKGROUND: Using chemotherapy as a part of each treatment fraction remains unexplored. This study integrates the concomitant administration of carboplatin with hyperfractionated irradiation by optimizing chemopotentiation through carboplatin administration with each irradiation fraction. METHODS: From February 1993 to August 1996, 52 patients with advanced head and neck cancer were treated on a twice-a-day chemoradiotherapy schedule. Each fraction consisted of 115 cGy preceded by 5 mg/m2 of carboplatin. Treatment was given 5 days a week up to total doses of 350 mg/m2 of carboplatin + 8050 cGy in 7 weeks. RESULTS: All (100%) of patients tolerated the treatment (83% as scheduled). Acute and late toxicities were moderate. Rates of 96% complete response (CR) and 4% partial response (PR) were achieved. At 52 months, local control and cause-specific survival rates are 72% and 59%, respectively. Nodal control rate is 95%. CONCLUSION: These results show potential for improvement upon hyperfractionated radiotherapy alone and compare favorably with those of most reported trials.

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Because of the determinant role of hemoglobin level in blood to the response of treatment (viewpoint admitted whether for irradiation or chemotherapic agents) the AA. have lead an analysis of a group of 36 patients suffering an advanced head and neck cancer (18 months mid-follow up and 30 months maximum) which underwent a program of concomitant radio-chemotherapy hyperfraccionated with carboplatin (the cytostatic) as part of each therapeutic fraction. The results in patients being transfused with an erytrocyte concentrate were compared with those from patients not having had any transfusion. The purpose of this study was the assessment of which are the influence on the prognostic of ENT-cancer resulting of the compulsory necessity of transfunding erytrocyte concentrates aroused by serious anemia presenting during the development of the schedule treatment. In brief, in that kind of patients needing transfusions of red blood cells concentrates because of serious anemia during the treatment (17% of the totality treated) were recorded 50% local failures, 33% metastases and only 17% of the totality were free of neoplasma at the end of the follow-up fixed. Instead between patients not having had transfusions (for treating anemia) the differences registered were 20% failures of loco-regional control and 13% metastases, whereas 67% were free of tumor at the end of the study. The conclusion drawn out is: the important influence on the prognostic of these tumors, when in the course of the scheduled treatment, appear severe anemia making the transfusions compulsory.

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Considering the limited results achieved up to now in the treatment of advanced ENT-cancer, with the classic customary procedures, the AA. suggest a new therapeutic schedule (within the concurrent radio-chemotherapy context) in which the selected cytotoxic drug, the carboplatin, is a part of each therapeutic fraction. A group of 36 patients suffering advanced ENT-cancer (2 cases stage III and 34 stage IV) were studied between Mars 1993 and September 1995, and the outcomes assessed after a 18 months mean follow-up (30 months maximum). There were 11% surgically rescued cases, being the full dosage administered twice daily 8.050 cGy plus 700 mg carboplatin. Tolerance was very good, so 100% of the patients received a complete treatment. Initial response was also fine resulting 93% full remissions on primaries, 96% on neck adenopathies (6% surgical rescues). Regarding the actuarial control after 30 months were controlled 88% of neck adenopathies, control loco-regional amounted for 69%, control on primaries 63% and actuarial survival amounted 55%. The AA. drawn out 10 conclusions, underlining the good tolerance of the therapeutic sketch proposed, because the antineoplastic results are by far better than those experienced with whichever modality of management of tumors of these sites and staging.

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To evaluate the effect of thymostimulin in a treatment schedule of concurrent hyperfractionated chemoradiation therapy, with the cytostatic forming part of each therapeutic fraction, the authors included in this protocol 36 patients with advanced head and neck carcinomas randomized into two groups. Group A received 115 cGy + 5 mg/m2 of carboplatin per fraction in two daily fractions for a total dose of 8.050 cGy + 700 mg of carboplatin, while group B received the same treatment associated with thymostimulin, with the following schedule: 1.5 mg/kg/day in the week before chemoradiation + 1.5 mg/kg twice a week during treatment + 1 mg/kg twice a week for two years or until recurrence. The results were evaluated upon reaching 18 months of follow-up (30 maximum). A smaller decrease in lymphocyte levels was observed in group B, but no differences were seen in toxicity between the groups. Patients included in the B group had a slightly longer disease-free-survival interval, but 17% of recurrences and 11% of distant metastases were observed in the A group, whereas 22% of recurrences and 22% of distant metastases were seen in the B group. The number of complete remissions (94%) was the same in both groups.

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Possible ototoxicity related with a hyperfractionated concurrent chemo-radiation schedule was studied in 36 patients with head and neck cancer. The schedule consisted of two daily fractions, each consisting of 5 mg/m2 of carboplatin plus 115 cGy. Therapy was given 5 days a week for 7 weeks up to a total dose of 700 mg carboplatin and 8050 cGy. Tonal audiograms and superliminal tests were carried out before treatment, at conclusion, six months post-treatment, and every year thereafter. After a mean follow-up of 18 months (maximum 30 months), no treatment-related sensorineural hearing loss was observed. However, recruitment disappeared in post-treatment superliminal tests in 37% of patients who presented sensorineural deafness with recruitment, although it reappeared in audiograms recorded six months later. We attributed this to transient demyelinization. After treatment, a previous tympanosclerosis reactivated in 1 case and effusive otitis media occurred in 8 patients. Previous effusive otitis media disappeared in 1 patient (nasopharyngeal tumor).

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We studied four generations of a Canary Islands family presenting a tardive heredodegenerative hearing loss, associated with IgA mesangial glomerulonephritis, of probable autosomal dominant heredity. With respect to the family, we revised Alport's syndrome, for possible transmission associated with X chromosome, as well as heredodegenerative hearing loss associated with renal pathology of autosomic transmission currently described; we differentiate these hearing losses from our case study, and we discuss the pathogeny of the auditive affection in the said hereditary syndromes. Lastly, we stress the autoimmune hypothesis because of the IgA nephropathy association in the family case, and we list the characteristics of the syndrome described.

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The AA. present a review of the embryologic development of both external and middle ear and its relationship with the phylogenesis. They consider the trascendence of this linkage in the shaping and in the physiology of the conductive apparatus of the sound and even admit the possibility of determine diseases like the cholesteatoma.

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The AA. present a review of the embryologic development of the internal ear linked with evolutive phylogenic events, which will determine the morphogenesis of this organ, of ancestral origin. The significance of those phenomena in order to bring about several physiological attributes as the possibility of vestibular hearing and even to set off pathologic conditions like the otosclerosis are considered.

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Before an acoustic neuroma case, with a buds evolution, coincident with influenza, actually the most significant explorations are revised, a protocol is proposed, and discussing the convenience to repeat specific explorations after a year when the first explorations have been iniciativelly negatives; being insinuated the possibility that some virus infections could act as a stimulus in the speed of neuromas growth.

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