Brachytherapy boost in loco-regionally advanced nasopharyngeal carcinoma: a prospective randomized trial of the International Atomic Energy Agency.

BACKGROUND: The purpose was to determine whether a brachytherapy boost improves outcomes in patients with advanced nasopharyngeal carcinoma treated with standard chemo-radiotherapy. METHODS: Patients with nasopharyngeal carcinoma WHO grades I-III and TNM stages III or non-metastatic stage IV were eligible for this phase III study. Patients were randomized to either arm (A) induction chemotherapy, followed by external beam radiotherapy (EBRT) with concomitant cisplatin (n = 139) or arm (B), the same schedule plus a brachytherapy boost to the nasopharynx (n = 135). The EBRT doses given were 70 Gy to the primary tumour and positive lymph nodes and 46 Gy to the negative neck. The additional brachytherapy boost in arm (B) was given by either low dose-rate (LDR - 11 Gy) or high dose-rate (HDR - 3 fractions of 3.0 Gy) brachytherapy. The primary endpoint was 3-year overall survival (OS) and secondary endpoints were: local control, regional control, distant metastasis and grade 3-4 adverse events. RESULTS: 274 patients were randomized between September 2004 and December 2008. The two arms were comparable with regard to age, gender, stage and grade. 273 patients completed treatment. Median follow-up was 29 months (0.2-67 months). The effect of treatment arm, country, age, gender, WHO pathology, stage (T3-4, N2-3 versus other) and chemotherapy on overall survival (OS), disease-free survival (DFS) and local recurrence-free survival (LRFS) was studied. Stage significantly affected OS (p = 0.024) and DFS (p = 0.018) while age significantly affected OS (p = 0.014). None of the other factors studied were significant. The 3-year LRFS was 60.5% and 54.4% in arms A and B respectively (p = 0.647). The 3-year regional control rate in the neck was 59.7% and 54.3% respectively (p = 0.7). Distant metastasis developed in 59.7% of patients in arm A and 55.4% in arm B (p = 0.377). Patients with T1/T2 N + had a 3 year LRFS of 51.8% in Arm A (62 patients) versus 57.9% in Arm B (67 patients) (p = 0.343). The grade 3-4 toxicity rate was 21.6% (30/139) and 24.4% (33/135) respectively (p = 0.687). CONCLUSIONS: The addition of a brachytherapy boost to external beam radiotherapy and chemotherapy did not improve outcome in loco-regionally advanced nasopharyngeal carcinoma.

[Hodgkin disease, clinical stages IA-IIB: evaluation of the value of cisplatin. Preliminary results]. / Maladie de Hodgkin, stades cliniques IA-IIB: évaluation de l'intérêt du cisplatine. Résultats préliminaires.

Cisplatinum is highly effective in numerous solid tumors and was evaluated in Hodgkin's disease clinical stages (CS) I/II. Sixty-five patients (43 male, 22 female; median age 25, with 12 patients under 16: CS IA-IIA 41, IB 5, IIB 19) were randomly assigned to one of the following arms (PAF87 protocol): 3 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine with methylprednisolone) cycles (ABVD arm) or 3 ABVD plus cisplatinum cycles (ABVD-Plt arm) followed by radiotherapy (RT); extended field (40 Gy) RT with a short paraaortic field including the spleen (30 Gy) was then administered in the ABVD arm; extended field (30 Gy) without lombosplenic port prophylaxis. RT was administered in ABVD-Plt arm when patients were in complete remission (CR) after chemotherapy (CT). Median follow-up was 35 months (6-62 months). During CT, 1 patient (ABVD-Plt) died from viral meningo-encephalitis; five patients (1 ABVD, 4 ABVD-Plt) stopped treatment because of emesis, of whom three receiving only 1.5-2.5 (ABVD-Plt) cycles, are still in CR after 13-60 months. Fifty-five patients (27 ABVD-Plt) were in CR after CT. Among the 27 ABVD-Plt patients, all in CR after RT, two died (one from myocardial infarction and one from immunoblastic lymphoma); one patient from the ABVD arm died from gastro-intestinal hemorrhage in 1st CR. No ABVD-Plt patient relapsed; 1 ABVD patient relapsed in non-irradiated area. At five years, actuarial survival/relapse-free survival was 96.1/90% and 88.2/100% for ABVD and ABVD-Plt patients, respectively.

Advanced Hodgkin disease (clinical stages IIIB and IV): low relapse rate after brief chemotherapy followed by high-dose total lymphoid irradiation.

From January 1980 to September 1986, 50 patients with Hodgkin disease, clinical stages (CS) IIIB (26 cases) and IVB (24 cases) were treated by three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy, followed by high-dose (40 Gy) (sub)total lymphoid irradiation, including the spleen. Ten patients (2 CS IIIB, 8 CS IVB) were in failure, and seven (4 CS IIIB, 3 CS IVB) died during their first complete remission (2 from treatment-related complications, 1 from unknown cause, 4 from insufficient supportive care and/or a shortage of health supplies); three patients (CS IIIB) relapsed (2 alive in second complete remission, 1 deceased). After 7 years, actuarial survival and relapse-free duration were, respectively, 64% for the 50 patients and 89% for the 40 patients in complete remission. Unfavourable outcome was observed in patients with pelvic nodal involvement. The low relapse rate (none in CS IVB) was the most striking result after brief chemotherapy followed by total lymphoid irradiation.

Hodgkin's disease, clinical stages IA to IIIB: combined modality therapy (3 MOPP followed by curative and prophylactic radiotherapy including the spleen). Six-year results.

From January 1980 to September 1985, 82 patients with IA to IIIB clinical stage (CS) Hodgkin's disease were treated by three MOPP chemotherapy (CT) cycles followed by extended field radiotherapy (RT) including the spleen (30-40 Gy). 2 patients died during the treatment (medullary aplasia, pulmonary edema). 6 were in failure after three MOPP cycles; they received other CT; 3 died and 3 are alive in remission (survival: 2.5 to 3.5 yr). 74 were in complete remission (CR) after completion of treatment. 4 patients relapsed (all alive after re-treatment) and 4 died in first CR (tuberculosis, hepatitis, myeloma, unknown cause). At 6 yr, actuarial survival and relapse-free survival are respectively 89.8% for the 82 patients and 93% for those in CR. These good results are due to: the administration of CT before RT, limited to three cycles; identification of failures after CT; inclusion of the spleen in RT ports in all cases; and a short lumbo-aortic port in CS I and II.