Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

BACKGROUND: Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer. PATIENTS AND METHODS: A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts. RESULTS: Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings. CONCLUSION: The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT.

Phase I/II study of preoperative cetuximab, capecitabine, and external beam radiotherapy in patients with rectal cancer.

BACKGROUND: To assess the safety and preliminary efficacy of concurrent radiotherapy, capecitabine, and cetuximab in the preoperative treatment of patients with rectal cancer. PATIENTS AND METHODS: Forty patients with rectal cancer (T3-T4, and/or N+, endorectal ultrasound) received preoperative radiotherapy (1.8 Gy, 5 days/week for 5 weeks, total dose 45 Gy, three-dimensional conformal technique) in combination with cetuximab [initial dose 400 mg/m(2) intravenous given 1 week before the beginning of radiation followed by 250 mg/m(2)/week for 5 weeks] and capecitabine for the duration of radiotherapy (650 mg/m(2) orally twice daily, first dose level; 825 mg/m(2) twice daily, second dose level). RESULTS: Four and six patients were treated at the first and second dose level of capecitabine, respectively. No dose-limiting toxicity occurred. Thirty additional patients were treated with capecitabine at 825 mg/m(2) twice daily. The most frequent grade 1/2 side-effects were acneiform rash (87%), diarrhea (65%), and fatigue (57%). Grade 3 diarrhea was found in 15%. Three grade 4 toxic effects were recorded: one myocardial infarction, one pulmonary embolism, and one pulmonary infection with sepsis. Two patients (5%) had a pathological complete response. CONCLUSIONS: Preoperative radiotherapy in combination with capecitabine and cetuximab is feasible with some patients achieving pathological downstaging.

Phase II study of preoperative oxaliplatin, capecitabine and external beam radiotherapy in patients with rectal cancer: the RadiOxCape study.

BACKGROUND: Preoperative radiotherapy has been shown to decrease the local recurrence rate of patients with locally advanced rectal cancer. Capecitabine and oxaliplatin are both active anticancer agents in the treatment of patients with advanced colorectal cancer and have radiosensitizing properties. Therefore, these drugs would be expected to improve effectiveness of preoperative radiotherapy in terms of local control and prevention of distant metastases. PATIENTS AND METHODS: Forty patients with rectal cancer (T3-T4 and/or N+) received radiotherapy (1.8 Gy, 5 days a week over 5 weeks, total dose 45 Gy, 3D conformational technique) in combination with intravenous oxaliplatin 50 mg/m2 once weekly for 5 weeks and oral capecitabine 825 mg/m2 twice daily on each day of radiation. Surgery was performed 6-8 weeks after completion of radiotherapy. The main end points were safety and efficacy as assessed by the pathological complete response (pCR). RESULTS: The most frequent grade 3/4 adverse event was diarrhea, occurring in 30% of patients. pCR was found in five (14%) patients. According to Dworak's classification, good regression was found in six (18%) additional patients. CONCLUSIONS: Combination of preoperative radiotherapy with capecitabine and oxaliplatin is feasible for downstaging rectal cancer.

The Place of Whole-Body PET FDG for the Diagnosis of Distant Recurrence of Breast Cancer.

Purpose: To study the role of positron emission tomography 18F-fluorodeoxyglucose (PET FDG) imaging in patients with a suspicion of breast cancer recurrence.Procedures: Whole-body PET FDG was performed in 39 women. Thirty-four were included because of asymptomatic tumor marker increase. PET findings were confirmed by oriented imaging or by biopsy. Follow-up data were collected over a period of at least 12 months.Results: PET FDG depicted 37/39 sites in 31/33 patients with recurrence. PET missed one locoregional recurrence and in one patient peritoneal carcinomatosis developed 6 months after a negative PET. False positive PET FDG corresponded to lung infection, degenerative bone disease, and reconstruction artifact. The conventional imaging work-up depicted sites of recurrence in 6/33 patients.Conclusion: Whole-body PET FDG is highly sensitive for the detection of distant breast cancer recurrence. Prospective studies are mandatory to address its potential impact on patient management and survival.

[Radiotherapy treatment of subfoveal retinal neovascularization related to age]. / Traitement par radiothérapie des néo-vaisseaux sous-rétiniens rétrofovéolaires liés à l'âge.

Thirty-three patients who underwent low dose of radiation therapy for subfoveal choroidal membranes were studied after a mean follow-up of 16 months. The evaluated parameters were the visual outcome and the choroidal neovascularization evolution. In this study, the efficacy of low-dose radiation delivered to the macular region as an alternative treatment in subfoveal membrane was limited.

Neutron therapy of bladder carcinoma: can a high rate of severe complications be avoided in neutron therapy?

We reviewed retrospectively a series of 58 patients with deeply invasive bladder cancer treated with fast neutron therapy (p(65) + Be) in order to evaluate its tolerance and side effects. Patients were divided into three groups according to treatment technique. Patients of group A received whole pelvis irradiation up to 50 Gy photon equivalent followed by a boost to the bladder up to 57-66 Gy photon equivalent (40-56 days). Group B patients were treated by a split course regimen of 30 Gy photon equivalent on the whole pelvis at 3-4 weeks interval (66-108 days). Group C patients, not suitable for radical treatment, received only 40-54 Gy photon equivalent (26-70 days). The overall 5-year actuarial survival rate was 30% (SE 8%). As expected, T stage was a statistically significant prognostic factor. The overall local control rate reached 21% at 4 years. Acute and late side effects were minimal to moderate. These results suggest that high-energy neutron beam treatment is at least as effective as photon beam treatment for bladder carcinoma, without a higher incidence of major side effects.

Dramatic response of recurrent invasive thymoma to high doses of corticosteroids.

We report the case of a widely invasive thymoma non-associated with myasthenia gravis which responded only to high doses of corticosteroids. We review the other few reported cases of complete response achieved by this treatment and we stress the possible use of high doses of corticosteroids in the management of recurrent invasive thymoma.

Malignant lymphoma in systemic rheumatic diseases. A report of five cases.

We describe five patients suffering from systemic rheumatic diseases who developed a malignant lymphoma. Two patients, one with systemic lupus erythematosus and another with systemic necrotizing vasculitis, suffered from Hodgkin's disease and three other patients, one with lupus and two with Sjögren's syndrome, developed non-Hodgkin's lymphoma. Only one of these patients had been treated with immunosuppressive drugs before the onset of the lymphoproliferative malignancy. Four patients were given combination chemotherapy and complete remission was achieved in the three patients for whom follow-up data were available. We discuss the relationships between systemic rheumatic diseases and lymphoma.

Radiotherapy as salvage treatment in patients with Hodgkin's disease or non-Hodgkin's lymphoma relapsing after initial chemotherapy.

The prognosis of relapsing Hodgkin's disease (HD) and high grade aggressive non-Hodgkin's lymphoma (NHL) is generally poor since many of these patients fail to respond to second line chemotherapy. Radiation therapy has been reported as an effective but seldom used, alternative treatment. We have observed very encouraging results with salvage radiotherapy in a highly selected group of eight lymphoma patients (six with HD and two with high grade NHL), suffering mainly from nodal relapse. The literature on the use of radiation therapy after chemotherapy failures in HD and NHL is reviewed.

Successful treatment of a pineal endodermal sinus tumor. Case report.

A patient with a pineal endodermal sinus tumor is presented who was successfully treated by a combination of surgery, adjuvant chemotherapy, and craniospinal irradiation. Two years after diagnosis, he is free of any disease. A review of the literature shows that such an outcome is very unusual. A multidisciplinary treatment is recommended for this rare tumor, using chemotherapy as adjuvant treatment.