Influence of the delay of adjuvant postoperative radiation therapy on relapse and survival in oropharyngeal and hypopharyngeal cancers.

PURPOSE: To determine whether the delay between surgery and the beginning of radiation therapy influences survival or the risk of local-regional relapse in oropharyngeal or hypopharyngeal squamous cell carcinomas. METHODS AND MATERIALS: From 2052 patients referred to the Henri Becquerel Center for the radiation therapy of an oropharyngeal or hypopharyngeal cancer between January 1, 1981 and December 31, 1992, 420 were included in a retrospective study. Exclusion criteria were another cancer, metastasis, incomplete resection, lack of homolateral lymph node resection, or previous chemotherapy. Radiation therapy delivered 45 to 75 Gy on initial location and lymph node. Follow-up was performed until December 31, 1997. A Cox proportional hazard regression analysis was used to evaluate the prognostic factors. RESULTS: The delay between surgery and radiation therapy was not found to be a significant prognostic factor for survival or risk of local-regional relapse. The only parameters found to influence local-regional and survival control were margins' pathologic state (respectively p < 0.0001 and p = 0.015) and T (p < 0.0001) and N (respectively p < 0.0001 and p = 0.0004) stages. In terms of local-regional relapse only, age was a prognostic factor (p = 0.048), and a trend was noted for tumor emboli in vessels or nerves (p = 0.061). CONCLUSION: In patients with oropharyngeal or hypopharyngeal squamous cell carcinoma, the delay between surgical procedure and radiation therapy does not influence survival or risk of local-regional relapse. Radiation therapy might be subjected to complete healing in these patients.

Accelerated fractionation (AF) compared to conventional fractionation (CF) improves loco-regional control in the radiotherapy of advanced head and neck cancers: results of the EORTC 22851 randomized trial.

BACKGROUND AND PURPOSE: A 5 week-hyperfractionated and accelerated radiotherapy regimen without reduction of the total dose was developed to fight tumour repopulation during treatment and tumour hypoxia. The purpose of the study was to try to improve loco-regional control in high risk head and neck carcinoma treated with curative radiotherapy. METHODS AND MATERIALS: From 1985 to 1995, a randomised controlled trial of the EORTC Cooperative Group of Radiotherapy (EORTC 22851) compared the experimental regimen (72 Gy/45 fractions/5 weeks) to standard fractionation and overall treatment time (70 Gy/35 fractions/7 weeks) in T2, T3 and T4 head and neck cancers (hypopharynx excluded). The end-point criteria were local and loco-regional control, overall and disease-free survival, and acute and late toxicities. Five hundred twelve patients were accrued. RESULTS: Patients in the AF (accelerated fractionation) arm did significantly better with regard to loco-regional control (P = 0.02) resulting at 5 years in a 13% gain (95% CI 3-23% gain) in loco-regional control over the CF (conventional fractionation) arm. This improvement is of larger magnitude in patients with poorer prognosis (N2-3 any T, T4 any N) than in patients with more favourable stage. Multivariate analysis confirmed AF as an independent prognostic factor of good prognosis for loco-regional control (P = 0.03). Specific survival shows a trend (P = 0.06) in favour of the AF arm. ACUTE AND LATE TOXICITIES: Acute and late toxicity were increased in the AF arm. Late severe functional irradiation damage occurred in 14% of patients of the AF arm versus 4% in the CF arm. Two cases of radiation-induced myelitis occurred after doses of 42 and 48 Gy to the spinal cord. CONCLUSIONS: This trial shows that accelerated radiotherapy improves loco-regional control in head and neck squamous cell carcinomas. A less toxic scheme should, however, be investigated and documented before using accelerated radiotherapy as a standard regimen of curative radiotherapy for head and neck cancers.

[Motor deficit complicating an isolated aneurysm of the internal iliac artery]. / Déficit moteur compliquant un anévrysme isolé de l'artère iliaque interne.

A 70-year-old man was admitted to the orthopaedic ward for severe sciatic pain and motor deficit. Diagnosis of a unique aneurysm of the right medial iliac artery and compression of the neighbouring elements was based on CT scan, echography and angiography imaging. This observation emphasizes the importance of a through physical examination. Unique aneurysm of the medial iliac artery is rarely observed. Effective treatment and satisfactory results can be obtained with simple ligature.

Clinical staging versus laparotomy and combined modality with MOPP versus ABVD in early-stage Hodgkin's disease: the H6 twin randomized trials from the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group.

PURPOSE: To compare (1) clinical staging and irradiation alone versus staging laparotomy and treatment adaptation in patients with a favorable prognosis (H6F); (2) two combined modalities in patients with an unfavorable prognosis (H6U). PATIENTS AND METHODS: The H6F trial (n = 262) consisted of randomization to clinical staging plus subtotal nodal irradiation (STNI) or to staging laparotomy plus treatment adaptation (adjuvant chemotherapy [CT] only in the 33% with negative laparotomy). The H6U trial (n = 316) consisted of no laparotomy, randomization to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), and mantle irradiation. RESULTS: In the H6F trial, 6-year freedom from progression (FFP) rates (78% v 83%; P = .27) were similar in clinical and laparotomy stagings, respectively. Survival rates were 93% and 89%, due to laparotomy-related deaths. In the H6U trial, the ABVD arm had superior results (6-year FFP rate, 88% v 76%; P = .01), but they were not significant for survival (91% v 85%; P = .22). CT discontinuation due to hematologic intolerance occurred more often with MOPP (14.5% v 7.3%). Decrease of the pulmonary vital capacity ([VC] < 70% of the theoretic value) was observed more frequently after ABVD than after MOPP (12% v 2%; P = .08), with two lethal pulmonary insufficiencies occurring in the ABVD arm. No modification of the isotopic left ventricular ejection fraction (LVEF) occurred. Gonadal toxicity was less in the ABVD arm. CONCLUSION: Early-stage patients benefit from treatment adaptation to initial characteristics in terms of tumor control and late toxicities. Staging laparotomy before STNI may be deleted even in favorable patients at no cost to survival or FFP. In unfavorable patients, ABVD achieved better results than MOPP, at lower hematologic and gonadal cost. Therefore, despite its pulmonary toxicity, ABVD is the best choice to design improved CT regimens associated with mantle irradiation.

Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomized trial of the EORTC cooperative group of radiotherapy.

EORTC protocol 22791 compared once daily fractionation (CF) of 70 Gy in 35-40 fractions in 7-8 weeks, to pure hyperfractionation (HF) of 80.5 Gy in 70 fractions in 7 weeks using 2 fractions of 1.15 Gy per day, in T2-T3 oropharyngeal carcinoma (excluding base of tongue), N0,N1 of less than 3 cm. From 1980 to 1987, 356 patients were entered. In the final analysis (June 1990), the local control was significantly higher (p = 0.02 log-rank) after HF compared with CF. At 5 years, 59% of patients are local disease-free in the HF arm compared to 40% in the CF arm. The superiority of HF was demonstrated in patients staged T3N0,T3N1 but not in T2. The Cox model confirmed that the treatment regimen was an independent significant prognostic factor for locoregional control (p = 0.007 log-rank). This improvement of locoregional control was responsible for a trend to an improved survival (p = 0.08 log-rank). There was no difference in late normal tissue damage between the two treatment modalities.

Results of postoperative radiation therapy in medullary carcinoma of the thyroid: a retrospective study by the French Federation of Cancer Institutes--the Radiotherapy Cooperative Group.

Between 1971 and 1989, 59 patients received external radiation therapy with a curative intent. There were 25 females and 34 males, ranging in age from 19 to 87. No patients had distant metastasis at the onset of treatment. The majority of patients had a total thyroidectomy (55/59), generally combined with neck dissection. Residual tumour was left in 11 cases, and 44 patients had positive cervical nodes. Using megavoltage radiotherapy, the whole neck and the upper mediastinum area were most often irradiated through a large anterior Y-shaped field without laryngeal shielding. The mean dose to the tumoral bed was 54 Gy. Dysphagia was observed in 32 patients (11, 17 and 5 scores were grade 1, 2 and 3, respectively). Dyspnea occurred in five cases and in two of these cases, it was considered to be severe. Local recurrences were noted in 18 (30%) patients, most of them occurring within the fields of irradiation. Parameters such as age, sex, total dose, irradiated volumes or cervical node enlargement did not modify the local control rate. The same conclusions can be drawn for distant failures. Thirty five patients are still alive and among them, 24 have no evidence of disease. The average length of survival is 70.5 months and is shortened by the occurrence of distant failures except in patients with bone metastases.

The predictive value of cell kinetic measurements in a European trial of accelerated fractionation in advanced head and neck tumors: an interim report.

The value of cell kinetic measurements in head and neck tumors in predicting which patients will benefit from accelerated fractionation radiotherapy regimens is being tested in a multicenter European trial (EORTC trial 22851). This paper reports on the first analysis of the correlation of kinetics with outcome in this trial. A proportion of patients in both the accelerated arm (72 Gy in 5 weeks, 1.6Gy per fraction, 45 fractions) and the conventional arm (70-72 Gy in 7-8 weeks, 1.8-2.0 Gy per fraction, 35-40 fractions) were given an i.v. injection of 100 mg/m2 IUdR (iododeoxyuridine) before treatment, and a tumor biopsy was taken several hours later. The potential doubling time of the tumor (Tpot) was obtained from a flow cytometric analysis of tumor cell nuclei using an anti-IUdR antibody. From a total of 260 patients entered in the trial, 53 have undergone kinetic analysis. Adequate IUdR labeling was seen in 47 patients (88.7%), from which the mean value for Tpot was found to be 4.5 +/- 2.5 days (+/- S.D.). Of the IUdR labeled patients, 30 have now been followed up for at least 1 year, 17 with conventional and 13 with accelerated radiotherapy. These patients were split into those with fast and those with slowly growing tumors, the dividing line being the median Tpot value of 4.6 days. After conventional 7-week radiotherapy, 2 of 6 patients with "fast" growing tumors obtained local control compared with 8 of 11 with "slow" growing tumors. A small difference in local control was seen been fast and slow tumors in the accelerated arm (5/9 vs. 3/4). These preliminary data support the hypothesis that patients with fast growing tumors do poorly with conventional radiotherapy and that pretreatment kinetic measurements can select patients at risk. The predictive power of the method must await the final analysis of trial results.

[The inhibiting effect of anticholera vaccination carried out simultaneously or at short intervals on yellow fever immunization. Is it real or assumed? Results of a retrospective study]. / L'effet inhibiteur de la vaccination anticholérique simultanée ou rapprochée sur l'immunisation contre la fièvre jaune est-il réel ou supposé? Résultats d'une étude rétrospective.

121 serum samples from African adults previously immunised with 17 D yellow fever vaccine alone (control group) or simultaneous yellow fever and cholera vaccines were tested for yellow fever antibodies by seroneutralization and haemagglutination inhibition assays. Comparison of the rates of seroconversion and antibody titers between the groups vaccinated the same day or into a short (less than or equal to 10 days) or a long time interval with both vaccines and the control group gave no significant difference. The association of cholera and yellow fever vaccines do not influence the long-term efficiency of yellow fever vaccination.

Prognostic value of response after three MOPP cycles in Hodgkin's disease--stage III and IV.

Sixty-eight patients with Hodgkin's disease stage III and IV were evaluated after three out of six MOPP cycles. At that time, 46 (68%) were classified as early responders and 22 as slow responders. The criteria of response were: disappearance of B symptoms, decrease in the size of the largest lymph nodes (by more than 50%) and significant reduction (more than 20%) of mediastinal enlargement. Out of 43 early responders, 38 were in complete remission after six MOPP cycles and only five out of 22 slow responders. Such an early response is only related to the absence of B symptoms at the time of diagnosis (p less than 0.05). The survival curves of early responders and slow responders were significantly different (p less than 0.02). A rapid erythrocyte sedimentation rate (ESR) (greater than 50 mm) was the most frequently abnormal sign found in the group not responding after three MOPP cycles (p less than 0.0001). Such a significant prognostic value of early response is observed for stage III but not for stage IV patients. We conclude that early clinical response after three MOPP cycles is a good prognostic factor which must be kept in mind in the formulation of the therapeutic regimen for Hodgkin's disease stage III and IV.

[Diagnosis and evaluation of the extent of cancer of the prostate]. / Diagnostic et bilan d'extension du cancer de la prostate.

Diagnosis is suggested by the functional symptoms and digital rectal examination and must be confirmed by histological examination. The second step is to evaluate the patient's condition, the extent of the cancer and the consequences on the urinary system; the choice of the treatment depends on this evaluation. The most common tumors are adenocarcinomas with a histological grading strongly correlated to the lymphatic involvement and frequency of metastases. Lymphatic involvement is closely related to the local clinically demonstrable involvement, histological grade, serum acid phosphatase concentrations and results of lymphography. Upon diagnosis of cancer of the prostate more than half the patients already harbour metastases, usually of the bone. This percentage is correlated to the size of the primary tumor, involvement of the seminal vesicles, histological grade and lymphatic involvement. The authors propose a series of investigations adapted to each case.

The use of various immunochemical, biochemical and biological methods for the analysis of rabies virus production in tissue cultures.

For the preparation of rabies vaccines, virus was grown in cultures of primary cells (bovine fetal kidney) or heteroploid cell lines (Hak and Vero). Comparative analysis of concentrated and/or purified antigen has shown a good correlation between the protective capacity (as determined by the NIH test for potency) on one hand, and hemagglutinating titer, optical absorbance at 280 nm and glycoprotein content (evaluated by the Enzyme-Immuno Assay - EIA) on the other. Furthermore, the evaluation of the respective content of glycoprotein and nucleoprotein (EIA) before and after impairment of viral membrane can be done to know if the rabies glycoprotein is anchored in an intact membrane or not (soluble glycoprotein). In addition, a good correlation has been obtained for the virus harvest between the NIH-test and the EIA-glycoprotein titer. In the light of the easy and rapid application of Enzyme-Immunoassay it is suggested that this technique be used for the analysis and evaluation of expected potency of virus harvest during rabies vaccine production.