Concomitant chemoradiotherapy followed, where feasible, by surgery for cancer of the esophagus.

PURPOSE: To conduct a multicenter phase II study of a concomitant combination of chemotherapy and radiotherapy followed by surgery, where feasible, in patients with nonmetastatic esophageal tumor, stratified on operability at diagnosis. METHODS: Each cycle consisted of fluorouracil (5FU) 800 mg/m2/d by continuous intravenous (IV) infusion on days 1 to 5, cisplatin (CDDP) 50 mg/m2/d IV bolus on days 1 and 8, hydroxyurea (HU) 1.5 or 2 g/d orally on days 8 to 12 and concomitant radiotherapy 20 Gy in 10 fractions over 12 days. All patients were to receive two cycles on days 1 and 22. If feasible, surgery was performed 3 to 6 weeks after cycle two completion. Otherwise, a third cycle was administered. RESULTS: Eighty-eight patients were included between September 1990 and September 1993. Of the 47 operable patients, 41 (87%) underwent surgery and 38 (81%) had a complete resection. No residual primary tumor was found in the surgical specimen in 17 cases (36%), and only microscopic foci in 13 (28%). Two-year overall and disease-free survival probabilities were 51% (95% confidence interval [CI]; 37 to 65) and 43% (95% CI, 28 to 57), respectively. Among the 41 inoperable patients, 12 (29%) became operable. Seven (17%) had complete resection, two incomplete resection, and three exploratory surgery. Two-year overall and disease-free survival probabilities were 29% (95% CI, 15 to 43) and 27% (95% CI, 13 to 40), respectively. Five deaths occurred during chemoradiotherapy, six postoperatively and four in patients with evidence of cancer. Five late complications (one myelopathy) were observed. CONCLUSION: Despite a high histologic response rate in initially operable patients, overall survival was similar to that observed in other preoperative chemoradiation series because of substantial toxicity.

Split course interstitial brachytherapy with a source shift: the results of a new iridium implant technique versus single course implants for salvage irradiation of base of tongue cancers in 55 patients.

Between January 1973 and December 1984, 55 patients with prior irradiation of the oropharynx underwent salvage irradiation for recurrent (26 patients) or second cancers (29 patients) of the base of tongue. The initial irradiation had delivered from 45 to 80 Gy to the base of tongue. One of two techniques of Iridium implantation was used for salvage. Single course implants, delivering 60 Gy, were used until June 1981 in a total of 31 patients. After June 1981, split course implants with a source shift were used in 24 patients in the hope of decreasing treatment complications. The first and second course of the split course implants delivered 35 and 30 Gy, respectively, at a 1-month interval. The active lines of the second implant were placed parallel to and between the position of the lines of the first implant. This shift in the source position resulted in a more uniform dose within the treated volume with a 60% reduction in the high dose sleeves. The overall 3-year survival was 19% (28% T less than or equal to 3 cm). The overall local failure rate was 45.5% (25/55). The difference between the local failure rate after single course implants (52%) and after split course implants (37.5%) was not statistically significative. The response observed after the first course of a split course implant proved to be a reliable indication of the probability of achieving local control after a full course of treatment: 2/14 failures (14%) if the response was greater than or equal to 75% versus 7/10 (70%) if the response was less than 75% (p less than 0.01). The only complication noted in the 40 patients achieving immediate local control after either implant technique was mucosal necrosis. The introduction of split course implants was followed by a two and a half fold decrease in the incidence of necrosis: 43% (9/21) in the single course group and 16% (3/19) in the split course group (p = 0.05). Interstitial brachytherapy offers an effective and reasonable option for salvage therapy in patients with recurrent and second cancers occurring in the base of tongue even when the tumor arises in a zone that has previously received high dose irradiation. The use of split course implants with a shift in the position of the active lines at the time of the second implant significantly decreases the risk of radionecrosis.

[Brain metastasis of choriocarcinoma in males. Apropos of a case. Review of the literature]. / Métastases cérébrales du choriocarcinome chez l'homme. A propos d'un cas. Revue de la littérature.

A 22 year-old male patient had a choriocarcinoma of the mediastinum metastatic to the brain, liver, lung and skin. He was treated with five cycles of chemotherapy containing cisplatinum, vinblastine, VP16 and bleomycin and he achieved a partial remission. Then he developed a progressive disease exclusively located to the brain and he died of an intracranial hemorrhage. The autopsy showed the mediastinum and the lung being free of residual trophoblastic tumor. Pure choriocarcinoma is rare in males, but brain metastases are frequently present in this case. Therapeutic guidelines are uncertain, so they must refer to the experience obtained in gestational choriocarcinoma. Two groups of patients are individualized both in male germ cell tumors and in placental choriocarcinoma: one group of patients with brain metastases at diagnosis, with a better prognosis, and one group of patients with brain metastases occurring in the course of the disease, with a poor outcome. The risk of intratumoral hemorrhage is common to all varieties of choriocarcinoma brain metastases and is not lowered by greater effectiveness of the chemotherapy. Brain metastases found at the moment of the choriocarcinoma diagnosis require chemotherapy and radiotherapy and in some selected cases, a surgical removal.

[Esophageal cancer: did combined treatments improve prognosis?]. / Cancer de l'oesophage: les traitements combinés ont-ils amélioré le pronostic?

Prognosis of esophageal cancer is very poor. Five-year survival does not exceed 20% after radical surgery, the best available treatment. Unfortunately, only 40% of the patients are amenable to surgery because of poor general status and/or locoregional extension. Adjuvant treatment did not yield survival improvement. Preoperative radiotherapy (three randomized trials) or postoperative radiotherapy (one randomized trial) showed only a decrease of regional relapses, perhaps only for the nodes negative patients. Neoadjuvant chemotherapy obtains some interesting response rate (20-60%), but there has been no evidence yet for survival improvement. Recently, promising results were presented after combination of radiotherapy and chemotherapy. In this paper, we review the present status of combined treatment for esophageal cancer. Our multicentric group (OSOF) is now completing a phase II trial, that should soon form the basis for a phase III prospective study.

[Salvage treatment with a view to recovery in a group of 1700 otorhinolaryngologic cancers treated by radiotherapy]. / Etude des traitements de rattrapage à visée curative réalisés dans une population de 1,700 cancers ORL irradiés.

Results after radiotherapy, alone or combined with surgery, applied prior to 1982 in 1700 patients with localized ENT tumors showed 669 (39%) of T and/or N failures and isolated second ENT localizations. Therapeutic recovery operation was performed in 263 of these 669 cases (39%). For the 324 cases of isolated T failures, 31% had recovery treatment, with a level varying between 15% for base of tongue and 55% for laryngeal tumors. Frequency of treatments varied with initial TNM (18% for T3-T4 and 47% for T1-T2) and initial treatment (26% after combined radiotherapy-surgery and 32% after radiotherapy alone). Surgery had been the main treatment (74%) followed by curietherapy (19%). Overall control rate was 55.5%. The 3 year survival rate for all isolated T failures treated was 31%, with survival medians of between 8 and 44 months as a function of initial localization. For the 156 cases of isolated N failures, 62% had recovery treatment, results varying according to whether it was a case of immediate N failure or a lymph node recurrence. The local control rate was 62.5% globally, the 3 year survival for isolated N failures treated 17.5%. For the 115 T + N failures, recovery treatment was attempted in only 9 cases (7%) but all patients died within 2 years of evolution of the local and regional disease. For the 74 second ENT localizations, 80% had recovery treatment with a global local control of 73% and a 3 years survival of 35%. Recovery treatment for therapeutic ends is therefore a frequently practised procedure (39% of cases).(ABSTRACT TRUNCATED AT 250 WORDS)

[Radiotherapy with neoadjuvant chemotherapy]. / La radiothérapie avec chimiothérapie première (néo-adjuvante).

Neoadjuvant chemotherapy can be used before radiotherapy to combat microscopic metastatic loci and to facilitate irradiation. Improvement in the survival time by impeding the dissemination of metastases seems to be real for breast cancer, but has not been observed to date in randomized studies of ENT cancers. Neoadjuvant chemotherapy in Hodgkin's disease has improved survival time and tolerance to irradiation, allowing a lowering of the total doses used and the volumes irradiated. In breast and ENT cancers, it has become possible, due to tumor regression, to replace mutilating treatments with more conservative ones consisting of radiotherapy alone, without increasing the risk of local relapse. Indeed, it is in this domain that neoadjuvant chemotherapy is the most useful. Two important conditions must be met for its successful application: a) a sufficiently effective regimen must be chosen, in order to prevent tumor growth prior to irradiation (which would aggravate the prognosis); and b) an accurate identification and localization of the tumor before undertaking any treatment so as to not detract from the effectiveness of the radiotherapy.

[Curative radiotherapy of unresectable bronchial cancer. Apropos of 266 cases without metastasis with 4 to 6 years follow-up (oat cell carcinoma excluded)]. / Radiothérapie à visée curative du cancer bronchique inopérable. A propos de 266 cas non métastasés d'emblée, avec délais d'observation de 4 à 10 ans (anaplasiques à petites cellules exclus).

Two hundred and sixty-six patients with inoperable bronchial carcinomas (oat cell excluded) without apparent metastases were treated with curative doses of radiotherapy. The malignancies were: 72% epidermoid epitheliomas, 11.5% adenocarcinomas, 10% large anaplastic cells and 6.5% without histology. According to the TNM classification, 3.5% were T1, 44% were T2 and 52% were T3. Mediastinal invasion was found in 44% of the cases. The mean age of the patients was 65 years (range 31-90 years). The Karnofsky index was less than or equal to 70 in 40% of the subjects. Unoperability was linked to the extent of local involvement in 59% of the cases and to age, general condition or an insufficient forced expiratory volume in 55% of the patients. Sixty to 65 Gy were administered, either classically fractionated or hypofractionated. After irradiation, 43% of the subjects underwent complete radiological remissions. Fifty-five percent of the patients died with local tumor evolution, 40% with isolated local evolution without associated metastases. The overall survival rate at 5 years was 7%; it was 16% for patients with a normal mediastinum and a Karnofsky index greater than 70 (51 cases); if these parameters were inversed, it was 2.5%. The fractionation protocol, the histological type, the use of chemotherapy (48 cases) did not affect the local control rate nor survival. There were almost no complications with this therapy. Patients frequently experienced functional improvement when curative doses of radiotherapy were applied to all the inoperable, non-metastatic cancers and the percentage of survivors at 5 years was non-negligible.

[Value of postoperative radiotherapy in T3 or N+ bronchial cancer. Apropos of 113 cases]. / Intérêt de la radiothérapie post-opératoire dans le cancer bronchique T3 ou N+. A propos de 113 cas.

Post-operative radiotherapy was applied in a series of 113 patients with bronchial cancer (T3 or N+) between 1977 and 1983, lesions being classified T1 in 24 cases, T2 in 44, T3 in 45, N0 in 23, N1 in 51 and N2 in 39, one out of two T3 cases being N+. Pneumonectomy has been performed in 64 cases (58%) and limited surgery in 49 (42%). An incomplete exeresis was carried out in 21% of cases. Radiotherapy dose 45 Gy in cases with macroscopically complete resection and 65 Gy in other cases. Fractioning was conventional (CI) 72 times with 5 sessions of 1.8 Gy per week, and hypofractionated (HFI) 41 times as 5 Gy on D1 and D3 and 6.5 Gy on D15 and D17 for an equivalent dose at 45 Gy in CI and with, in addition, 5 Gy on D29 and D31 for an equivalent dose at 65 Gy in CI. Overall actuarial survival at 5 years was 38%, and 42% for N+, with 54% for N1 (pedicular N+) and 28% for N2 (mediastinal N+). The 3-year actuarial survival for T3 N0 was 53%. Frequency of local and regional recurrence was 18% and was equal for N1 and N2. In contrast, metastases occurred in 33% of N2 and only 12% of N1. No apparent difference was noted in incidence of local and regional recurrence or survival as a function of histopathologic type, operation performed, quality of surgical resection, or irradiation fractioning. No serious complication of radiotherapy was reported.(ABSTRACT TRUNCATED AT 250 WORDS)