Stem cell transplantation for immunodeficiency.
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Bone Marrow Transplantation↗
Biomedical subjects
E Haddad
Publications and source records attributed to E Haddad.
Radiotherapy in the management of epidemic Kaposi's sarcoma: a retrospective study of 643 cases.
PURPOSE: To report to the literature the largest published series of epidemic Kaposi's sarcoma (EKS), treated with radiation therapy, to summarize and discuss our 10 years experience in the treatment of this malignancy. METHODS AND MATERIALS: From June 1986 to December 1996, 643 patients with acquired immunodeficiency syndrome (AIDS)-related epidemic Kaposi's sarcoma were treated with radiation therapy (RT) at the Cancerology Department of Henri Mondor University Hospital. The patients, 640 men and 3 women had an average age of 38.5 years (range 20-68 years). Three hundred eighty-seven patients (60.1 %) had received previous treatment for their Kaposi's sarcoma (KS). In total, 6777 fields were irradiated, as follows: face 1342 (19.8%), eyelid and conjunctiva 362 (5.3%), trunk 1903 (28.1%), upper and lower limbs 2866 (42.3%), genitals 189 (2.8%). and oral cavity 115 fields (1.7%). Radiation therapy consisted of 4 MV or 45-70 kV X-rays, depending on tumor size and location. Doses ranged from 10 to 30 Gy, according to tumor response and toxicity. RESULTS: Objective response (CR and PR) was observed in 92% (5947/6464) of all cases, treated for cutaneous form of EKS. All patients with irradiated oral lesions had an objective response. The overall tolerance was acceptable for the cutaneous lesions. By contrast, in oral lesions, mucosal reactions were often observed after relatively low doses of radiotherapy. CONCLUSIONS: Doses of 15 Gy for oral lesions, 20 Gy for lesions involving eyelids, conjunctiva, and genitals, have been shown to be sufficient to produce shrinkage of the tumor and good palliation of the symptoms. For the cutaneous EKS, we propose 30 Gy given in a local field, using a fractionated scheme with small size applicators. Radiotherapy has its own place in the management of EKS, as an efficient treatment.
Acquired Immunodeficiency Syndrome↗
Prevention of EBV-induced B-lymphoproliferative disorder by ex vivo marrow B-cell depletion in HLA-phenoidentical or non-identical T-depleted bone marrow transplantation.
HLA-mismatched bone marrow transplantation (BMT) is hampered by three major complications: graft rejection, acute graft-versus-host disease (aGVHD) and delayed immune reconstitution. Infusion of anti-LFA1 plus anti-CD2 monoclonal antibodies (MAb), combined with ex-vivo T-cell depletion of the graft, was efficient in preventing graft rejection and aGVHD. Nevertheless, disease-free survival was limited by the high frequency of lethal infections, including EBV-induced lymphoproliferative disease (BLPD), which originates mostly from donor B cells, with an incidence of 5-30%. To decrease the rate of this complication, ex-vivo B-cell depletion was attempted. This study compares a group of 19 patients who received a T- and B-cell-depleted marrow from an HLA-mismatched related donor with a retrospective control group of 19 patients, who had received T-cell-depleted marrow by the same method. The level of T-cell depletion was similar in the two groups. For B-cell depletion, two different methods were compared. The median number of B cells infused in the study group was 0.46/kg. Engraftment and aGVHD incidence were similar in the two groups. No EBV donor-derived BPLD occurred in the study group, compared with seven in the control group, four of whom died because of EBV-BPLD. Event-free survival was significantly different between the two groups. We conclude that ex-vivo B-cell depletion of the graft may be a useful means of preventing EBV-BPLD, and warrants further study on a larger group of patients.
B-Lymphocytes↗
Invasive pulmonary infection due to Scedosporium apiospermum in two children with chronic granulomatous disease.
Scedosporium apiospermum is an opportunistic fungus in humans. The incidence of S. apiospermum infection in patients with acquired neutropenia (e.g., patients receiving chemotherapy and bone marrow transplant recipients) is steadily increasing. S. apiospermum has poor in vitro susceptibility to "conventional" antifungal agents, rendering the management of infections complex. Patients with chronic granulomatous disease (CGD) are highly susceptible to fungal infections, which are mostly due to Aspergillus species. We describe two children with CGD and invasive pulmonary infection due to S. apiospermum. Both patients were treated with antifungal therapy including azole derivatives (itraconazole or voriconazole) and surgical resection of infected tissues. These cases highlight that scedosporium infection can closely mimic aspergillus infection and should be considered in any case in which there is a failure to respond to appropriate "conventional" antifungal therapy. We also suggest that the emergence of this pathogen may have been favored by long-term use of amphotericin B in both patients.
Adolescent↗
Treatment of familial hemophagocytic lymphohistiocytosis with bone marrow transplantation from HLA genetically nonidentical donors.
Familial hemophagocytic lymphohistiocytosis (FHL) is a rare genetic disorder associated with the onset early in life of overwhelming activation of T lymphocytes and macrophages invariably leading to death. Allogeneic bone marrow transplantation (BMT) from an HLA-identical related donor is the treatment of choice in patients with this disease. However, fewer than 20% of patients have a disease-free HLA-identical sibling. BMT from HLA-nonidentical related donors has previously met with poor results, with graft rejection a major obstacle in all cases. We describe BMTs from HLA-nonidentical related donors (n = 13) and from a matched unrelated donor (n = 1) performed in two centers in 14 consecutive cases of FHL. Remission of disease was achieved before BMT in 10 patients. Marrow was T-cell-depleted to minimize graft-versus-host disease (GVHD). Antiadhesion antibodies specific for the alpha chain of the leukocyte function-associated antigen-1 (LFA-1, CD11a) and the CD2 molecules were infused pre-BMT and post-BMT to help prevent graft rejection, in addition to a conditioning regimen of busulfan (BU), cyclophosphamide (CP), and etoposide (VP16) or antithymocyte globulin (ATG). Sustained engraftment was obtained in 11 of 17 transplants (3 patients had 2 transplants) and disease-free survival in 9 patients with a follow-up period of 8 to 69 months (mean, 33). Acute GVHD greater than stage I was not observed, and 1 patient had mild cutaneous chronic GVHD that resolved. Toxicity due to the BMT procedure was low. Results obtained using this protocol are promising in terms of engraftment and event-free survival within the limitations of the small sample. We conclude that an immunologic approach in terms of drugs used to obtain disease remission and a conditioning regimen that includes antiadhesion molecules in T-cell-depleted BMT from HLA genetically nonidentical donors is an alternative treatment that warrants further study in FHL patients who lack a suitable HLA genetically identical donor.
Adolescent↗
Frequency and severity of central nervous system lesions in hemophagocytic lymphohistiocytosis.
We have retrospectively assessed the neurological manifestations in 34 patients with hemophagocytic lymphohistiocytosis (HLH) in a single center. Clinical, radiological, and cerebrospinal fluid (CSF) cytology data were analyzed according to treatment modalities. Twenty-five patients (73%) had evidence of central nervous system (CNS) disease at time of diagnosis, stressing the frequency of CNS involvement early in the time course of HLH. Four additional patients who did not have initial CNS disease, who did not die early from HLH complications, and who were not transplanted, also developed a specific CNS disease. Therefore, all surviving and nontransplanted patients had CNS involvement. Initially, CNS manifestations consisted of isolated lymphocytic meningitis in 20 patients and meningitis with clinical and radiological neurological symptoms in nine patients. For these nine patients, neurological symptoms consisted of seizures, coma, brain stem symptoms, or ataxia. The outcome of patients treated by systemic and intrathecal chemotherapy and/or immunosuppression exclusively (n = 16) was poor, as all died following occurrence of multiple relapses or CNS disease progression in most cases. Bone marrow transplantation (BMT) from either an HLA identical sibling (n = 6) or haplo identical parent (n = 3) was performed in nine patients, once first remission of CNS and systemic disease was achieved. Seven are long-term survivors including three who received an HLA partially identical marrow. All seven are off treatment with normal neurological function and cognitive development. In four other patients, BMT performed following CNS relapses was unsuccessful. Given the frequency and the poor outcome of CNS disease in HLH, BMT appears, therefore, to be the only available treatment procedure that is capable of preventing HLH CNS disease progression and that can result in cure when performed early enough after remission induction.
Ataxia↗
[Induction chemotherapy followed by concomitant combined radiotherapy and chemotherapy in stage III non-small cell bronchial carcinoma].
PURPOSE: To determine the efficacy and safety of induction chemotherapy followed by concomitant chemoradiotherapy in the treatment of stage III non-small cell lung cancer and whether the response to induction chemotherapy can predict the response to subsequent chemoradiotherapy and survival. MATERIALS AND METHODS: Between December 1987 and June 1993, 46 patients with previously untreated stage III non-small cell lung cancer received every 21 days induction chemotherapy (ICT) including three cycles of 5-fluorouracil (600 mg/m2/d in short infusion from d1 to d5), cisplatin (15 mg/m2/d from d1 to d5), etoposide (50 mg/m2/d from d1 to d5) and hydroxyurea (1,500 mg/d from d1 to d5). The first 21 patients also received bleomycin (3 mg/m2/d from d1 to d5). All patients received concomitant chemotherapy and had chest radiotherapy (CCRT). Patients received irradiation (65 Gy/33-6 fractions/7 weeks) on d25 after the third cycle of chemotherapy. Concomitant chemotherapy was composed of cisplatin (20 mg/m2) and 5-fluorouracil (500 mg/m2) that were administered each Monday and Thursday during radiotherapy. Maintenance chemotherapy consisted of thiotepa (10 mg/m2) and methotrexate (10 mg/m2) that were administered every 2 weeks for 6 months. RESULTS: Pulmonary toxicity was observed in four out of 21 patients who had received bleomycin and subsequently developed pulmonary fibrosis, leading to death for two of them. ICT alone produced five complete responses (11%) and 13 partial responses (28%). The combination of chemotherapy and radiotherapy led to 19 complete responses (41%) and 14 partial responses (30%). Eighteen of the 18 responders (100%) to ICT responded to subsequent CCRT, of whom 13 (72%) became complete responders. Fifteen of the 28 non-responders to ICT (53%) responded to CCRT, six of them being complete responders (21%) (P < 0.001). The median overall survival rate was 17 months when considering all patients, 25 months in patients responding to ICT and 13 months in non-responders. The 2-year survival rates were 28, 55 and 11%, respectively (P < 0.05). ICT did not influence the rate of subsequent metastatic events. However, locoregional reprogression was lower in responders to ICT. The number of metastatic events was not significantly related to response to ICT. By contrast, the rate of local failure was higher when there was resistance to ICT (75% versus 39%). Out of the 19 complete responders to CCRT (13 responders to ICT and six non-responders to ICT), four developed secondary locoregional reprogression (21%) and six developed metastatic disease (31%). In complete responders to CCRT, the rate of locoregional failure was 15% in responders to ICT (2/13) and 33% (2/6) in non-responders to ICT. Four out of the 13 responders to CCRT after response to ICT (31%) and two out of the six complete responders to CCRT developed metastatic disease after non-response to ICT. CONCLUSION: There is a statistically significant relationship not only between the response to ICT and the response to CCRT, but also between the response to ICT and the local outcome and survival.
Adenocarcinoma↗
Detection of donor-derived Langerhans cells in MHC class II immunodeficient patients after allogeneic bone marrow transplantation.
T-cell dependent immune response is initiated by dendritic cells, which are the only leucocytes able to prime naive CD4-positive T cells. Langerhans cells (LC) are dendritic cells characterized by their localization within the epidermis, their dendritic shape, and their expression of specific markers such as major histocompatibility complex (MHC) class II molecules, CD1a and S100 protein. We retrospectively studied the phenotype of LC in the skin of eight children with MHC class II deficiency (bare lymphocyte syndrome) after allogeneic bone marrow transplantation (BMT). The presence of donor-derived MHC class II positive LC within the epidermis was studied by immunohistochemistry on skin biopsies performed for the determination of graft-versus-host disease. MHC class II positive LC were undetectable in the epidermis of a child who did not engraft and of three children 13-18 d after HLA-mismatched BMT, despite engraftment. However, donor-derived MHC class II positive LC were detected in four children 9-43 d after HLA-identical BMT. Our results demonstrate that LC can differentiate or expand very quickly, as early as within 9 d after BMT.
Biopsy↗
The majority of myeloid-antigen-positive (My+) childhood B-cell precursor acute lymphoblastic leukaemias express TEL-AML1 fusion transcripts.
The t(12:21) translocation fuses the TEL and AML1 genes and has been found in up to 28% of paediatric B-cell precursor acute lymphoblastic leukaemias (BCP-ALL). The AML1 gene is a transcription factor which regulates expression of several myeloid differentiation associated genes. A molecular analysis of TEL-AML1, E2A-PBX1, MLL-AF4, BCR-ABL expression and an immunophenotypic study of CD13/CD33 myeloid antigen expression have been performed prospectively on tumour cells from 96 paediatric BCP-ALL patients. Percentages of CD13 or CD33 expressing leukaemic cells were found to be higher in TEL-AML1 positive cases (n = 22) than in TEL-AML1 negative (n = 74) cases (P<0.001). In 22/96 cases (23%) >10% of neoplastic cells were found to express at least one of the two markers. In 14 of these cases (63%), TEL-AML1 expression was detected, whereas t(4;11), t(11;19) and t(9;22) translocations were found by molecular methods in only three cases (14%). In four cases (18%) no molecular marker was found. These data show that TEL-AML1 expression is significantly associated with myeloid antigen expression by leukaemic cells and suggests that the prognostic significance of myeloid antigen expression in paediatric ALLs should be re-evaluated in the light of molecular cytogenetic markers.
Antigens, Differentiation, Myelomonocytic↗
Hepatic GVHD after HLA-haploidentical bone marrow transplantation in children with severe combined immunodeficiency: the effect of ursodeoxycholic acid.
We describe two children with a severe combined immune deficiency (SCID) with B cells. Following a T-cell-depleted haploidentical bone marrow transplantation (BMT), they both developed a chronic graft-versus-host disease (GVHD) of the skin and a severe persisting hyperbilirubinaemia and elevated liver enzymes. The diagnosis of a vanishing bile duct syndrome was confirmed by liver biopsies. Because corticosteroids and cyclosporin A induced only a partial response, ursodeoxycholic acid (UDCA) was added to their treatment schedule. Serum bilirubin and liver enzymes returned to normal within months. A control liver biopsy showed normal and proliferating bile ducts without cholestatic damage. We conclude that UDCA was well tolerated and may be of value as an additional treatment for hepatic GVHD in SCID.
Adrenal Cortex Hormones↗
Applications in in ovo technology.
By mid-August 1995, 55% of broiler embryos in North America were vaccinated for Marek's disease using the INOVOJECT system, with 201 INOVOJECT machines placed with 16 of the top 25 poultry producers, providing the industry with the capacity to inject in excess of 400 million eggs per month or about 5 billion eggs per annum. In ovo administration of a bursal disease antibody-infectious bursal disease virus (BDA-IBDV) complexed vaccine to specific-pathogen-free (SPF) embryos was safer and more potent than conventional IBDV vaccine alone because it delayed the appearance of bursal lesions, produced no early mortality, produced higher geometric mean antibody titers against IBDV, and generated protective immunity against challenge. In ovo administration of a BDA-IBDV complexed vaccine to broiler embryos generated antibody titers against IBDV sooner than conventional virus vaccinates, and generated protective immunity against challenge Direct DNA injection of plasmid DNA encoding beta-galactosidase into breast muscle in ovo and posthatch was an effective means to achieve both gene transfer and expression, with potential for the development of gene vaccines using plasmids encoding protective antigens from poultry pathogens. In ovo administration of 800 U chicken myelomonocytic growth factor (cMGF), a chicken hematopoietic cytokine for cells of the monocytic-granulocytic lineages, significantly reduced mortality associated with Escherichia coli exposure within the hatcher when compared to PBS controls (6.1 vs 12.4, P < or = 0.05), but not when compared to a yeast expression control. A procedure was developed enabling injection prior to the onset of incubation without compromising embryo viability. This in ovo injection process has opened up the window of embryo development during incubation for intervention, as illustrated by the 100% male phenotype produced in chicks hatching from eggs injected with aromatase inhibitor prior to incubation. These data illustrate some of the in ovo applications presently in use by the poultry industry, and under development or in research at EMBREX.
Animals↗
In vivo infusion of anti-LFA-1 and anti-CD2 antibodies prevents graft failure after HLA partially incompatible bone marrow transplantation in children with high risk acute lymphoblastic leukaemia.
Bone marrow transplantation (BMT) from matched sibling donors is the therapy of choice for children with high-risk acute lymphoblastic leukaemia in children. It is however not available to more than two-thirds of patients who lack a matched donor. Here, we review the outcome of 28 patients with high-risk ALL who were transplanted in France with alternative marrow sources such as HLA-phenoidentical unrelated volunteers and HLA-partially incompatible relatives. For these patients, we tested the possibility to prevent T-depleted marrow graft rejection by infusing in vivo two monoclonal antibodies directed against adhesion receptors i.e., LFA-1 and CD2. Two previous multicenter trials in children transplanted with partially incompatible bone marrow for inborn errors of metabolism showed their efficacy in this setting. Twenty eight patients were enrolled in this study and followed for a median of 4.4 years. Bone marrow engraftment occurred in 81% of the evaluable patients. Post-transplantation leukaemic relapse was the most frequent cause of death in this group of patients, and occurred in 39% of patients. The second most frequent complication was infectious disease, while an EBV-induced B-lymphocyte proliferative disorder occurred in four patients. In conclusion, T-cell-depletion combined with infusion of anti-LFA-1 and anti-CD2 antibodies is efficient in preventing graft failure and GVHD in this group of children with high-risk leukaemia undergoing partially incompatible BMT. The overall DFS is not improved in contrast to what has been previously observed in patients with immunodeficiencies transplanted with a similar rejection prophylaxis. Other approaches are therefore needed aiming either at preserving donor T-cell mediated immunity or accelerating immune reconstitution.
Antibodies, Monoclonal↗
A child who was feverish for 2 years.
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Buttocks↗
Efficacy of cyclosporine A in the treatment of macrophage activation syndrome in juvenile arthritis: report of five cases.
OBJECTIVES: To evaluate the efficacy of cyclosporine A in the treatment of macrophage activation syndrome (MAS) occurring in children with juvenile arthritis. STUDY DESIGN: MAS developed in two boys and three girls with systemic juvenile arthritis (four) and polyarticular juvenile arthritis (one). In three children whose condition was life-threatening, increased parenteral administration of corticosteroids failed to improve their condition; therefore cyclosporine A (2 to 5 mg/kg per day) was added. In two other patients with less severe clinical manifestations, cyclosporine A alone (2 to 8 mg/kg per day) was given. RESULTS: After the introduction of cyclosporine A, rapid improvement was obtained in all patients and apyrexia occurred within 24 to 48 hours. The biologic abnormalities disappeared more slowly (up to 5 weeks for liver enzymes). CONCLUSIONS: These observations underline the usefulness of cyclosporine A in this complication. The use of this drug may circumvent the need for increased doses of corticosteroids in some patients. The mechanism of action of cyclosporine A remains speculative, but these results indicate indirectly that T-helper lymphocytes may play a role in the pathogenesis of MAS.
Antirheumatic Agents↗
Molecular detection of t(8;21)/AML1-ETO in AML M1/M2: correlation with cytogenetics, morphology and immunophenotype.
The t(8;21) identifies a subgroup of acute myeloid leukaemia (AML) with a relatively good prognosis which may merit different treatment. It is associated predominantly, but not exclusively, with AML M2, and corresponds to rearrangements involving the AML1 and ETO genes. AML1-ETO positive, t(8;21) negative cases are well recognized but their incidence is unknown. In order to determine optimal prospective AML1-ETO RT-PCR screening strategies, we analysed 64 unselected AML M1 and M2 cases and correlated the results with other biological parameters. Molecular screening increased the overall detection rate from 8% to 14%. AML1-ETO was found in 3% (1/32) of AML M1 and 25% (8/32) of M2, including three patients without a classic (8;21) but with chromosome 8 abnormalities. It was more common in younger patients. Correlation with morphology enabled development of a scoring system which detected all nine AML1-ETO-positive cases with a false positive rate of 7% (4/55). Although certain AML1-ETO-positive cases demonstrated characteristic immunological features (CD19 and CD34 expression, CD33 negativity), each of these markers was insufficiently specific to permit prediction in an individual case. We conclude that initial routine prospective molecular screening for AML1-ETO in all AMLs, combined with standardized morphological and immunological analysis, is desirable in order to produce improved prognostic stratification and to determine whether screening can ultimately be restricted to appropriate subgroups.
Adolescent↗
Isoform-dependent effects of halothane in human skinned striated fibers.
BACKGROUND: Reports of the effects of halothane on isoform contractile proteins of striated muscles are conflicting. To determine whether halothane affects cardiac and skeletal contractile proteins differently, the authors examined the effects of two doses of halothane (0.44 and 1.26 mM, equivalent to 0.75 and 2.25 vol%, respectively) on the Ca++ sensitivity and maximal force in human skinned cardiac, type I (slow twitch), and type II (fast twitch) skeletal muscle fibers. METHODS: Left ventricular muscle strips and skeletal muscle biopsy specimens were obtained from eight and ten patients undergoing cardiac and orthopedic surgery, respectively. Sarcolemma and sarcoplasmic reticulum were destroyed with ethylene glycol bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid plus Brij 58. Ca++ sensitivity was studied by observing the isometric tension developed by skinned fibers challenged with increasing concentrations of Ca++. Muscle fiber type was determined in each skeletal fiber by the difference in strontium-induced tension measurements. RESULTS: Halothane shifted the Ca++ tension curves toward higher Ca++ concentrations and increased the Ca++ concentrations for half-maximal activation in both cardiac and type I skeletal muscle fibers (from 1.96 microM and 1.06 microM under control conditions to 2.92 microM and 1.71 microM in presence of 0.75 vol% halothane, respectively) without changing the slope of this relationship (Hill coefficient). In contrast, no significant effect was observed in type II fibers. Halothane also decreased the maximal activated tension in the three groups of fibers with a lesser effect in type II fibers. CONCLUSIONS: Halothane decreases Ca++ sensitivity and maximal force in human skinned cardiac and type I fibers at 20 degrees C. It is concluded that the negative inotropic effects of halothane depend on contractile proteins isoforms.
Anesthetics, Inhalation↗
[Place of iridium 192 implantation in irradiation of T1-T2 squamous cell carcinoma of the velopharyngeal arch].
We have reviewed the results of 165 T1 and T2 squamous cell carcinomas of the faucial arch treated by definitive irradiation including or not iridium 192 brachytherapy to ascertain whether a significant relationship exists between iridium implantation, local control, complications and survival. From March 1971 to November 1990, 58 T1 and 107 T2 (NO: 107/165; N1: 30/165; N2: 9/165; N3: 19/165) biopsy proven squamous cell carcinomas of the tonsillar region (104/165) and the soft palate and uvula (61/165) were treated in the Henri Mondor Hospital by definitive irradiation with curative intent. From 1971 to 1981 (period 1), only guide gutter technique was available, so that implants were reserved for small tumors: patients were either managed by definitive telecobaltherapy to tumor site and neck node areas (group I; n = 48; mean dose: 70 Gy; confidence interval: +/- 5.5, 5 fractions of 1.8 Gy per week) or by exclusive iridium implant (group 2; n = 11; all T1NO; 64 Gy +/- 4.8) or by a combination of external beam radiation therapy to tumor site and neck nodes areas and iridium implant (group 3; n = 40). In 1981 (period 2), a new plastic tube technique, which enables implantation of larger areas, was introduced and all patients (group 4; n = 66) were then managed by external radiation therapy (group 3 + 4: 47 Gy +/- 4.3) followed by an iridium implant (31 Gy +/- 10.5). Clinically positive neck nodes either received additional external dose with electrons or were excised. Overall 5-year survival (Kaplan Meier) was 23%, 50.5%, and 60% in groups 1, 2 and 3 + 4, respectively (p < 0.001, log rank). Five-year local control was 58%, 100%, and 91%, respectively (p < 0.001). Five-year necrosis rate was 10%, 25% and 30%, respectively (NS). Comparison of results between the two periods of the study (group 1 + 2 + 3 vs group 4) shows that these two groups are statistically comparable according to site and size of tumor and N status and that both local control (77% vs 94% at 5 years; p < 0.01) and disease free survival (56% vs 71%; p = 0.03) were improved after 1980, while there was a trend to an increase in overall survival (42% vs 53% at 5 years; p = 0.08); nodal control (86% vs 95% at 5 years) and necrosis rate (11% vs 20% at 5 years) were not modified. Multivariate analysis showed that both local control (p < 0.0001) and overall survival (p < 0.0001) were improved when tumor was implanted. We recommend then to treat T1 and T2 squamous cell carcinomas of the faucial arch by external radiation therapy to tumor site and neck areas (45 Gy/25 fractions/5 weeks) followed by a 30 Gy iridium implant and, for patients with clinically positive nodes, either a further 25-30 Gy electron beam irradiation to the nodes or neck node dissection.
Adult↗
[Comparison of concomitant radiotherapy and chemotherapy with radiotherapy alone in advanced cancers of the head and neck: results of a randomized trial].
From April 1987 to October 1992, 67 patients with inoperable squamous cell carcinoma of the head and neck region were included in a randomized trial. All patients had induction chemotherapy with cisplatin (100 mg/m2, D1) and fluorouracil (1 g/m2, from D1 to D5) every three weeks for a total of three cycles. Patients were randomized to concurrent external radiation therapy (70 Gy/39 fractions/8 weeks) and chemotherapy with cisplatin (50 mg/m2 in short infusion, D1, D15, D29, D43) and fluorouracil (5 mg/kg, intra-muscular, every Monday, Wednesday and Friday) (experimental group) versus radiotherapy alone with the same modalities (control group). The followup for living patients was 14 to 60 months with a median of 42 months. Analysis of preliminary results has shown that: 1) early and late side effects are similar in both groups; 2) after completion of treatment, the percentage of patients in complete remission was 71% (20/28) in the experimental group and 43% (12/28) in the control group; this difference was statistically significant among non responders to induction chemotherapy (1/15 versus 13/20, P = 0.001), but non significant among responders (11/13 versus 7/8) and 3) there were no differences between both randomized groups in term of 3-year overall survival and of 3-year loco-regional control. Results are discussed taking into account a review of literature.
Antineoplastic Combined Chemotherapy Protocols↗