the role of radiotherapy for limited stage Hodgkin's disease in 1999: limitations and perspectives]

The role of radiotherapy in limited stage Hodgkin's disease (HD) has been gradually changing in the past few decades, resulting in the almost complete disappearance of exclusive irradiation treatment. In reality, exclusive radiotherapy yielded satisfactory results in terms of long-term survival, but in 1999 it was becoming impossible not to take into account the late mortality rates observed in all large cohorts of HD patients. This increased mortality rate has been shown to be related to 1) cardiac toxicity of irradiation, and 2) secondary radiation-induced solid tumors. Thus, the search for efficient but less toxic new strategies can no longer be avoided. For clinically staged, limited HD, precisely defined according to specific prognostic factors, the association of chemotherapy and radiotherapy appears more and more as a standard, and with this therapeutic burden comes parallel efforts for its alleviation. The Previous Radiotherapy experience has shown that, after a chemotherapy-induced complete remission, irradiation of only the initially involved areas was enough. Ongoing trials are now exploring the possibility of a dose de-escalation, from the conventional 36 Gy to 20 Gy (as for children HD), and to maybe 0 Gy (no radiotherapy at all). In parallel, deescalation in the number of chemotherapy cycles is also being investigated. For unfavorable cases, the problem is slightly different, as a higher percentage of cases still appears to be refractory to treatment in this subgroup. Thus, while chemo-radiotherapy has clearly became the standard strategy, efforts are essentially being devoted to identify new--and hopefully more efficient--chemotherapy schemes. In Europe, most of these pending questions will be addressed in the recently initiated trials of the EORTC/GELA and of the GHSG (German Hodgkin Study Group), with the aim of offering to patients treatment which could be at least as efficient as the present schedules, and less toxic in the long term.     

Ischemic preconditioning increases the tolerance of Fatty liver to hepatic ischemia-reperfusion injury in the rat

Hepatic steatosis is a major risk factor in ischemia-reperfusion. The present study evaluates whether preconditioning, demonstrated to be effective in normal livers, could also confer protection in the presence of steatosis and investigates the potential underlying protective mechanisms. Fatty rats had increased hepatic injury and decreased survival after 60 minutes of ischemia compared with lean rats. Fatty livers showed a degree of neutrophil accumulation and microcirculatory alterations similar to that of normal livers. However, in presence of steatosis, an increased lipid peroxidation that could be reduced with glutathione-ester pretreatment was observed after hepatic reperfusion. Ischemic preconditioning reduced hepatic injury and increased animal survival. Both in normal and fatty livers, this endogenous protective mechanism was found to control lipid peroxidation, hepatic microcirculation failure, and neutrophil accumulation, reducing the subsequent hepatic injury. These beneficial effects could be mediated by nitric oxide, because the inhibition of nitric oxide synthesis and nitric oxide donor pretreatment abolished and simulated, respectively, the benefits of preconditioning. Thus, ischemic preconditioning could be an effective surgical strategy to reduce the hepatic ischemia-reperfusion injury in normal and fatty livers under normothermic conditions, including hepatic resections, and liver transplantation.     

When disaster strikes,acute stress disorder may follow

During and immediately following a traumatic event, people may manifest a pattern of dissociative and anxiety symptoms and other reactions, referred to as Acute Stress Disorder. A review of the empirical literature on psychological reactions to trauma suggest that this pattern of symptoms has often been identified across different kinds of traumatic events. It is likely to constitute a psychological adaptation to a stressful event, limiting painful thoughts and feelings associated with the event and allowing the person to function at least minimally. Continuation of these symptoms, however, may impair the person's quality of life and disrupt social and other functioning. If symptoms last beyond a month following the traumatic event, Post Traumatic Stress Disorder (PTSD) may ensue, continuing for months or even years after the precipitating event. Hence, it is important to be able to identify this pattern of reactions that may be manifested in reaction to trauma, so that appropriate intervention can be provided. Although it was not officially recognized in the 3rd edition Diagnostic and Statistical Manual (DSM-III-R), Acute Stress Disorder is included as a separate diagnosis in the DSM-IV.     

Isoxaben Soil Biodegradation in Pear Tree Orchard After Repeated High Dose Application

During the past nine years, each of the plots of a pear tree orchard were treated annually with the same herbicide treatment. The following herbicide treatments were compared, each being made by application of a mixture of two or three herbicides: 1a, no herbicide at all, weeds being hoed (control 1a); 2, diuron + paraquat 3 + 1 kg/ha; 3, simazine + paraquat 2 + 1 kg/ha; 4, isoxaben + diuron + paraquat 0.5 + 1.6 + 1 kg/ha; and 5, isoxaben + simazine + paraquat 0.5 + 1.25 + 1 kg/ha. In March 1996, one year after the final orchard herbicide treatment, isoxaben could not be detected in the soils of any field plots; isoxaben was incorporated at 0.74 mg/kg in the loamy soils sampled separately in each of the field plots, and the soils were incubated in the laboratory. Isoxaben soil half-lives were 92 days in the soils treated previously with herbicide treatments 1a, 2, or 3 and 42 days in the soils treated with herbicide treatments 4 and 5. The repeated isoxaben treatments applied in the past thus enhanced the isoxaben soil biodegradation; diuron, simazine, and paraquat had no influence on this rate enhancement. On the other hand, herbicide treatments 4 and 5 were applied in the orchard in April 1996 on the corresponding plots treated in this manner for the last nine years. Isoxaben + paraquat 0.5 + 1 kg/ha was applied simultaneously on other plots (control 1b) not treated in the past with isoxaben. During the growth season in the orchard, the isoxaben soil half-lives in the control plots 1b was 101 days, and 41 days in the plots where herbicide treatments 4 or 5 were applied. Received: 25 March 1997/Accepted: 15 July 1997     

Combined radiotherapy-chemotherapy for early stages non-Hodgkin's lymphoma: the 1975-1980 EORTC controlled lymphoma trial

Patients with stage I and II non-Hodgkin's lymphoma (NHL) are considered to have a relatively good prognosis. For this reason, they are seldom referred to specialized centers and the accrual of such patients in controlled studies is limited. Therefore, significant studies of homogeneously treated patients are difficult to collect and the management of these patients remains controversial. Some patients do very well after treatments with minimal toxicity while others require a much more aggressive approach. The Radiotherapy-Chemotherapy Group of the EORTC carried out its second controlled trial on patients with stage I and II NHL from 1975 to 1980. Its first aim was to assess the prognostic value of histologic classifications independently of treatment. The second aim was to compare two therapeutic options within each stage. In stage I, 124 patients were randomized to receive extended field radiotherapy (RT) either with or without adjuvant cyclophosphamide, vincristine prednisone (CVP) chemotherapy (CT). Relapse-free survival (RFS) was higher in patients who received adjuvant CVP but the total survival rates were not different. The RFS was lower in patients with diffuse than in those with follicular architectural histologies; in the former, RFS was not influenced by adjuvant CVP. Those patients who underwent a staging laparotomy had a higher 5-year total survival (TS) independent of the histologic type. Fifty-six stage II patients were included and extended field was randomized versus total nodal irradiation. Subsequently, adjuvant CVP was given to all patients. Results are good in follicular histologies but the advantage for total nodal irradiation is not significant. In diffuse histologies, results were unsatisfactory in both arms; a new therapeutic strategy was designed in which RT and CT are alternated and has been successfully tested in a pilot study.     

Ifosfamide/mesna related encephalopathy: a case report with a possible role of phenobarbital in enhancing neurotoxicity

A case of reversible encephalopathy after one dose of ifosfamide/mesna in an epileptic 15-year-old girl is reported. No other pathology could be responsible for the symptoms. An epilepsy or a toxicity induced by vincristine were discussed. Nevertheless, the possible role of phenobarbital, known to induce hepatic microsomal activity, seems the more probable mechanism.     

Alternating chemotherapy and radiotherapy for limited-stage intermediate and high-grade non-Hodgkin's lymphomas: Long-term results for 96 patients with tumors > 5 cm

BACKGROUND:: The role and timing of radiotherapy for optimal treatment oflocalized aggressive non-Hodgkin's lymphoma (NHL) is controversial.We report the long-term results of a single-institution pilotstudy of alternating chemotherapy (CT) and radiotherapy (RT)in patients with clinical stages I or II tumors exceeding 5cm. PATIENTS AND METHODS:: From 1981 to 1992, 96 patients with stages I-II aggressive NHLreceived an alternating regimen of CT and RT consisting of 8cycles of CT with 3 courses of RT interjected after the 2nd,3rd and 4th cycles of CT. The CT combined cyclophosphamide,doxorubicin, teniposide and prednisone every 28 days. Each RTcourse was started 8 to 10 days after CT (15 Gy in 6 fractionsto initially involved and contiguous areas). RESULTS:: The median age was 54 years. The disease predominantly locatedin the head and neck area was stage II in 63% of patients. Bulkytumors (10 cm or larger) were found in 24% of patients. Sixpatients discontinued CT because of acute toxicity (mucositis).The mean relative dose intensity achieved for doxorubicin, cyclophosphamideand teniposide were 72%, 82%, and 78%, respectively. Late toxicityconsisted mostly of severe xerostomia lasting more than 2 yearsin 7 patients irradiated in Waldeyer's ring. The complete response(CR) rate was 91%; 20 of the 86 patients in CR relapsed (3 locallyonly). The median follow-up was 61 months, and at 5 years, overallsurvival (OS) was 77%. Classification according to the InternationalPrognostic Factor Index was possible for 54 patients, all butthree of whom were in the ‘low risk’ grqup (0–1factor). Bulky disease was the only unfavorable prognostic factor(P < 0.001) for CR, freedom from progression (FFP) and OSrates; the low relative dose intensity of CT achieved in thisstudy did not affect outcome. CONCLUSION:: Alternating chemo-radiotherapy for localized aggressive NHLwas feasible and yielded long-term results comparable to thoseobtained with standard treatments, despite a reduction in doseintensity considerably below that of CHOP which suggested synergisticeffects of CT and RT in this scheme. CHVmP, combinedmodality therapy, non-Hodgkin's lymphoma, stage I-II     

Prolonged intravenous infusion chemotherapy. General review of theoretical bases and results

Continuous intravenous infusion of chemotherapy is now widely used to enhance the therapeutic index of cancer drugs. Cellular kinetics and pharmacological basis for protracted intravenous chemotherapy are reviewed for the main available drugs. From the increasingly published data it is now possible to separate routine and research utilization of protracted infusion chemotherapy.