Avoidance of treatment interruption: an unrecognized benefit of accelerated radiotherapy in oropharyngeal carcinomas?

PURPOSE: To assess the impact of treatment interruption on the potential gain in locoregional control obtained with accelerated radiotherapy (RT) compared with conventionally fractionated RT in patients with oropharyngeal carcinomas. METHODS AND MATERIALS: 152 patients treated with radical RT for oropharyngeal carcinomas between 1979 and 1996 were retrospectively analyzed. According to the American Joint Committee on Cancer (AJCC) staging system, there were 6/30/43/73 stages III/III/IV. Sixty-one patients were treated with a conventional RT schedule (median dose 70 Gy in 35 fractions), and 91 patients with either of two 5/5.5-week accelerated RT schedules (median dose 69.6-69.9 Gy in 41 fractions). Discounting weekends, RT was interrupted for 2 consecutive days or more in 53 patients (median duration 11 days, range 2-97), including 67% of the patients in the conventional RT group and 13% in the accelerated RT group. Median follow-up for surviving patients was 55 months (range 23-230). The Cox proportional hazards model was used for the multivariate analysis of factors influencing locoregional control. RESULTS: In univariate analysis, factors associated with a significant decrease in locoregional control included WHO performance status > or =1, advanced AJCC stages (III and IV), conventional RT fractionation, overall treatment time > or =44 days (median), and RT interruption. In the multivariate analysis, when introduced into the model individually, the three significant therapeutic factors remained significant after adjustment for the forced clinical variables. However, when the three therapeutic factors were introduced together into the model, beside the AJCC stage (P = 0.017), only RT interruption remained a significant independent adverse prognostic factor (P = 0.026). CONCLUSIONS: This multivariate analysis highlights the potential negative impact of treatment gaps on locoregional control in oropharyngeal carcinomas. This suggests that treatment interruption may be an even more important parameter than the type of RT schedule per se. Thus, when assessing the relative merit of two RT schedules, inclusion of the other therapeutic factors in a multivariate model is mandatory in order to avoid misinterpretation of the results.

Feasibility and tolerance of pulsed dose rate interstitial brachytherapy.

PURPOSE: Pulsed dose rate (PDR) treatment is a new approach that associates the physical advantages of high-dose-rate (HDR) technology with the potential radiobiological advantages of low-dose-rate (LDR) brachytherapy. This retrospective study analyzes the feasibility, toxicity, and preliminary oncologic results in a series of 43 patients treated with PDR interstitial brachytherapy. METHODS AND MATERIALS: Twenty-four patients with pelvic, 17 patients with head and neck, and 2 patients with breast cancers were treated. Twenty-eight patients had primary and 15 recurrent tumors; 14 had received prior external irradiation to the same site. The doses per pulse at the prescription isodose were 0.4-1 Gy (median 0.5 Gy), delivered using a single cable-driven 0.3-1.0 Ci 192-iridium source (PDR Nucletron Micro-Selectron). RESULTS: The median treated volumes (at the prescribed isodose) were 28 cc for pelvic, 8.33 cc for head and neck, and 40 cc for breast malignancies. Of 14,499 source and 14,499 dummy source transfer procedures, 3 technical machine failure events were observed (0.02%). Grade 3 acute toxicities were seen in 5/43 patients (4 oral stomatitis, 1 vaginal mucositis) and grade 4 acute toxicity in one patient (rectovaginal fistula). Grade 3-4 late complications were observed in 4/41 (9.8%) patients: 1 pubic fracture, 1 rectovaginal fistula, 1 vesicovaginal fistula and 1 local necrosis. With a median follow-up of 18 months, 10/41 patients progressed locoregionally (6 pelvic, 4 head and neck), 3 developed local recurrence and distant metastasis (3 pelvic), 3 only distant metastasis (2 pelvic, 1 head and neck). Two patients are lost to follow-up. CONCLUSION: PDR interstitial brachytherapy for pelvic, head and neck, and breast malignancies is feasible and the acute and late toxicities seem acceptable. Although the physical advantages of PDR are clear, further follow-up is required to determine how results compare with those obtained with standard LDR brachytherapy.

Combined chemoradiotherapy for invasive bladder cancer: a feasibility approach in a non selected population.

BACKGROUND: We aimed to evaluate the tolerance and response rate to neo-adjuvant combined chemo-radiotherapy and to determine the possibilities of conservative treatment in patients (pts) with muscle invasive bladder cancer. METHODS: Thirty-nine T1-4, NO-3 pts were enrolled in this study. After 2 cycles of treatment, responders at intermediate assessment were treated by either additional chemotherapy +/- radiotherapy or radical cystectomy. If there was evidence of persistent tumour, radical cystectomy was performed whenever possible. RESULTS: Thirty-five (90%) pts completed the pre-operative treatment, 26/39 (67%) were in remission at intermediate assessment and 8 of them underwent a radical cystectomy. The median follow-up was 87 months, and 15 pts are alive without evidence of tumour and 5 with bladder preservation. The 3 and 5-year survival was 51 and 40%, respectively. Median survival differences between the responding operated or non-operated pts were not statistically different. CONCLUSIONS: Neo-adjuvant chemo-radiotherapy for invasive bladder cancer is effective with acceptable toxicity, and inoperable patients can benefit from such treatment.

[Sarcoidosis: apropos of a case of isolated myopathy]. / Sarcoïdose: à propos d'un cas de myopathie isolée.

We report the case of a 69 year old female, who in 1979 presented with a granulomatous myositis confirmed by muscular biopsy. The histology is typical for sarcoidosis, but tests on other organs remained negative for eight years. Up to 1987, 79 cases of sarcoid myopathy have been published in medical journals, of which 44% had an isolated muscular involvement. We discuss the differential diagnosis, the histology, pathology, etiology and the manifestations shown by the EMG of this rare illness, as well as our patient's peculiar signs.

[Schoenlein-Henoch syndrome in adults--current aspects]. / Le syndrome de Schoenlein-Henoch de l'adulte--aspects actuels.

Schoenlein-Henoch purpura is characterized clinically by palpable purpura, mainly on the legs, with varying degrees of gastrointestinal, articular and renal involvement. Renal involvement is often more severe in the adult than in children and it often determines the outcome of the disease. Schoenlein-Henoch purpura is also characterized by an IgA-vasculitis, which may be triggered by several non-specific antigenic factors. Its pathogenesis is still unclear, but a dysfunction of the IgA immune system has been demonstrated. We discuss the anatomo-clinical, therapeutic and etiopathogenic aspects of this syndrome according to today's knowledge.

[Adenocarcinoma of the ethmoid sinus in a woodworker: apropos of a case]. / Adénocarcinome de l'ethmoïde chez les travailleurs sur bois: à propos d'un cas.

We report the case of a 69 year old male who developed an ethmoidal adenocarcinoma in 1984, after having worked as a woodworker for 35 years. Although the relationship between wood dust and ethmoidal cancer has been known since 1965, the exact etiological agent is not identified up to now. A good knowledge of the clinical picture together with the means of screening and the investigations which are available make it possible to identify up to 86% of localised tumours.

Recombinant human erythropoietin as adjuvant treatment for autologous blood donation in elective surgery with large blood needs (> or = 5 units): a randomized study.

BACKGROUND: Autologous blood transfusion presents no infectious or immunologic side effects. The aim of this randomized study was to determine the impact of recombinant human erythropoietin (rHuEPO) on the donation of 5 units of autologous blood by nonanemic patients who were candidates for elective surgery with transfusion requirements of > or = 5 units. STUDY DESIGN AND METHODS: Starting on Day -35, 420 mL of blood was taken weekly. All patients received 200 mg of iron saccharose complex intravenously at each visit and six subcutaneous injections of rHuEPO (141 U/kg) or placebo between Days -21 and -7. RESULTS: Of 50 patients, 45 completed the study (placebo, 21; rHuEPO, 24). Total red cell production was higher in the rHuEPO group (p = 0.001). Donation of 5 units was possible for 67 percent (placebo group) and 79 percent (rHuEPO group) of patients (p = 0.5). The mean number of blood units donated was 4.6 (placebo group) and 4.7 (rHuEPO group). More patients in the placebo group received allogeneic blood (9/21 [43%] vs. 6/23 [26%]), although the difference did not reach significance (p = 0.34). CONCLUSION: In nonanemic patients donating 5 units of blood, rHuEPO associated with intravenous iron increased total red cell production. However, no difference was found between the rHuEPO and placebo groups with regard to the number of units of autologous blood donated of the number of patients receiving allogeneic blood transfusion.

[Schoenlein-Henoch syndrome in adults and skin infection]. / Syndrome de Schoenlein-Henoch de l'adulte et infection cutanée.

Schoenlein-Henoch purpura is a rare disease in adults clinically characterized by palpable purpura, mainly on the legs, with varying degrees of gastrointestinal, articular and renal involvement. This syndrome is also characterized by IgA-vasculitis and its pathogenesis is still unclear, although it appears frequently after a viral or bacterial infection especially in the ORL sphere. We report here the cases of three adult patients who developed Schoenlein-Henoch purpura shortly after a bacterial infection of the skin, notably by Staphylococcus aureus.

Hepatitis C virus acute exacerbation during chemotherapy and radiotherapy for oesophageal carcinoma.

AIMS: We report the first case of an hepatitis C virus positive patient presenting with a solid tumor and developing an exacerbation of his hepatitis C after chemotherapy. CASE REPORT: A 56-year-old white male, previously infected with hepatitis C virus and treated for epidermoid carcinoma of the oesophagus, developed hepatitis (alamine aminotransferase 2376 U/l and aspartate aminotransferase 2262 U/l) after chemotherapy with cisplatin and vinblastine. METHODS: Polymerase chain reaction detected hepatitis C virus RNA in the serum during the acute phase, which returned to negative 14 weeks later. DISCUSSION: Viral replication was probably increased during immunosuppression induced by chemotherapy. Enhanced cellular immune response in the recovery phase was the most likely cause of the hepatitis. CONCLUSIONS: More attention should be paid to liver function tests in patients with a previous history of hepatitis C virus infection. Polymerase chain reaction identification of hepatitis C virus RNA can be a very useful tool that permits rapid diagnosis and appropriate management of such cases.

A randomized double-blind trial to compare the clinical efficacy of granisetron with metoclopramide, both combined with dexamethasone in the prophylaxis of chemotherapy-induced delayed emesis.

BACKGROUND: The prophylactic use of 5-HT(3) receptor antagonists (setrons), after the first 24 h (acute phase) of exposure to emetic chemotherapy, to decrease the incidence of 'delayed phase' emesis increases costs. We designed a study to evaluate the efficacy of a setron (granisetron) in the delayed phase, compared with metoclopramide, each combined with a corticosteroid. PATIENTS AND METHODS: Patients on their first course of single-day emetic chemotherapy (cisplatin, carboplatin, doxorubicin, cyclophosphamide and others) received granisetron 2 mg p.o. and dexamethasone 8 mg p.o. on day 1, followed for 5 days by dexamethasone 4 mg p.o. od combined with either metoclopramide 20 mg p.o. tds or granisetron 1 mg bd in a double-blinded double-dummy protocol. Patients evaluated the results using a diary card. Randomization was stratified by institution, sex, emetic chemotherapy naïve versus previous, alcohol consumption and platinum versus non-platinum regimen. RESULTS: 131 evaluable patients received granisetron in the delayed phase, and 127 received metoclopramide. Control of acute emesis in both arms was similar (86% granisetron; 85% metoclopramide). The 35 patients experiencing acute emesis had poor control in the delayed phase, with only four granisetron and three metoclopramide patients having no or mild nausea and no vomiting. CONCLUSIONS: In daily practice, a combination of oral dexamethasone and oral granisetron achieves an extremely high control of acute emesis (86% protection). Our data suggest that routine prescription of setrons for delayed phase control is not advisable as it increases costs without any benefit for the majority of patients. Delayed emesis in the rare patients with acute phase emesis remains an unsolved problem.

[Effect of administration of recombinant human erythropoietin in acute normovolemic hemodilution on transfusion needs during total hip prosthesis implantation]. / Effet de l'administration de la r-HuEpo associée à l'hémodilution normovolémique aiguë sur les besoins transfusionnels lors d'interventions pour prothèse totale de hanche.

Acute normovolaemic haemodilution (ANH) is used to avoid perioperative blood loss and consists of the withdrawal of whole blood just before or just after anaesthesia induction and its simultaneous replacement by synthetic colloids and crystalloid solutions. In an attempt to improve the efficiency of this technique while at the same time avoiding cardiovascular complications, we set up a pilot study to test the association of rHuEpo/ANH during elective surgery for total hip replacement. Five patients (3 males, 2 females) were included in this study. The amount of whole blood drawn was 3 x 450 ml from the men and 2 x 450 ml from the women. Before blood was taken, the mean increase in haemoglobin was 1.2 +/- 0.9 g/dl and mean increase in reticulocytes 106 +/- 34 G/l. No patient received homologous transfusion during the perioperative period; 3 patients received the totality of predonated blood and one patient 2 of the 3 units taken. The mean fall in haemoglobin at day 1 post-surgery was 3.6 g/dl. In conclusion, the stimulation of erythropoiesis by rHuEpo in the pre-surgery phase led on average to a 1 g/dl gain in haemoglobin, permitting an isovolaemic withdrawal of 900 to 1350 ml of blood depending on body weight without the development of severe anaemia. It was thus possible to perform total hip replacement in all the patients without homologous blood support and with a post-surgery haemoglobin value of > 10 g/dl. This protocol should be further tested in a prospective randomised study (rHuEpo versus placebo) in order to assess the real benefit of rHuEpo.

Histiocytic necrotizing lymphadenitis or Kikuchi's disease. Anatomo-clinical study of 4 cases.

Histiocytic necrotizing lymphadentis (HNL) is an uncommon clinical and histologic entity, essentially diagnosed in Japan since 1972. The clinical picture is usually characterized by cervical lymphadenopathy and fever, females being more often affected. Leukopenia and elevated erythrocyte sedimentation rate are frequent. The etiology is still unknown, but a viral origin is most likely. The clinical course is always favorable without treatment, except in one case. The histological picture, with necrotic foci surrounded by histiocytes, immunoblasts, small T lymphocytes and plasmacytoid monocytes (so-called plasmacytoid T cells), is characteristic. Nevertheless, HNL may be mistaken for malignant lymphoma both clinically and histologically. We report 4 cases of HNL. One of these presented severe leukothrombopenia; the serum of this patient significantly suppressed the maturation of granulocytic precursor cells in the bone marrow.

Combined chemotherapy and radiotherapy, followed or not by surgery, in squamous cell carcinoma of the esophagus.

BACKGROUND: This study was designed to evaluate the feasibility of a neo-adjuvant combined chemo-radiotherapy in patients with localized squamous cell carcinoma of the esophagus. PATIENTS AND METHODS: Forty-two patients with squamous cell carcinoma of the esophagus, stages II and III (or stage I if considered to be poor candidates for immediate curative surgery), age less than 70 years and WHO performance status 0 to 2, were enrolled in a study of radiotherapy combined with chemotherapy, consisting of 2 (operated patients) or 3 (nonoperated patients) courses of cisplatin, vindesine, mitomycin-C or cisplatin, vinblastine. Surgery was routinely proposed to patients. RESULTS: Thirty-seven patients (88%) received full preoperative therapy. Of 30 patients responding to this preoperative therapy, 12 had a third cycle of treatment and 15 had esophagectomy. Three of the operated patients had no pathological evidence of residual tumour. Median survival of all 42 patients is 11 months and the 2-year survival rate is 29%. There is no difference in survival among responding operated or non-operated patients. Our group represents 95% of all eligible cases of squamous cell carcinoma of the esophagus occurring in Geneva during the study period. CONCLUSION: Our series gives a realistic view of the median survival of a population of patients eligible for neo-adjuvant therapy of esophagus cancer, and suggests that secondary surgery might not improve the patient survival. Furthermore, non-selected patients are at high risk for therapy-related death.