Phase II study of cisplatin and oral VP16 in patients with refractory or relapsed Ewing sarcoma.

BACKGROUND: Phase II trials demonstrate the activity of cisplatin in patients with refractory Ewing sarcoma family tumours (ESFT) and also the feasibility of giving cisplatin with oral VP16 in a variety of different cancers. This trial was conducted to evaluate the activity and toxicity profile of this combination delivered as outpatient therapy in patients with refractory/relapsed ESFT. METHODS: Cisplatin was administered on days 1, 8 and 15 and days 29, 36 and 43 (70 mg/m(2)/dose for patients <21 years of age and 50 mg/m(2)/dose ≥21 years). VP16 was administered at a dose of 50 mg/m(2) on days 1-15 and days 29-43 inclusive. A three-stage Fleming statistical design was used for analysis. RESULTS: Between January 2003 and October 2006, 45 patients aged between 5 and 46 years (median 19) were enrolled. Thirty-eight were evaluable for response. Patients had previously received one to three lines of chemotherapy (median = one). Seventy-three per cent of the patients had grade 3/4 neutropenia, 20 % developed fever, 40 % had grade 3/4 anaemia, 68 % grade 3/4 thrombocytopenia and 16 % grade 2/3 ototoxicity. Measured response after 2 cycles: 0 CR, 7 PR (18 %), 13 SD (34 %), 18 PD (48 %). There was excellent concordance between unidimensional and bidimensional criteria in 31 of 33 responses (94 %). PFS at 1 year was 39 %, with a median PFS of 6 months. Overall survival at 1 year was 44 %; median survival was 11 months. CONCLUSIONS: Cisplatin combined with oral VP16 is well tolerated and has acceptable side effects, but limited clinical activity in refractory/relapsed ESFT.

[Brain metastasis of breast cancer; imaging evaluation]. / Métastases cérébrales et méningées des cancers du sein. Évaluation radiologique Entretiens du DOM de l'Institut Curie 17 mars 2010.

CNS involvement in breast cancer modifies the prognosis and the treatment of the disease. Imaging plays a leading role for the diagnosis, the pretherapeutic assessment and the follow-up. MRI is the most sensitive modality for the detection of infraclinic lesions, reported in about 15% of metastatic breast cancers. In addition to conventional MR study, diffusion MR, perfusion MR and spectroscopy have a diagnostic value with specificity of more than 95%; 3D study is required if neurosurgical resection or stereotactic radiosurgery is contemplated. The use of new drugs in clinical trials needs a precise and accurate follow up to assess their usefulness; appreciation of the response is based on the precise measure of the number of targets and of their size; The WHO and recently the RECIST have established the guidelines for measurement of the tumoral targets and to assess the response to treatments. Brain modifications related to surgery or stereotactic radiosurgery are well studied by MRI.

Does a geriatric oncology consultation modify the cancer treatment plan for elderly patients?

BACKGROUND: This study was performed to describe the treatment plan modifications after a geriatric oncology clinic. Assessment of health and functional status and cancer assessment was performed in older cancer patients referred to a cancer center. PATIENTS AND METHODS: Between June 2004 and May 2005, 105 patients 70 years old or older referred to a geriatric oncology consultation at the Institut Curie cancer center were included. Functional status, nutritional status, mood, mobility, comorbidity, medication, social support, and place of residence were assessed. Oncology data and treatment decisions were recorded before and after this consultation. Data were analyzed for a possible correlation between one domain of the assessment and modification of the treatment plan. RESULTS: Patient characteristics included a median age of 79 years and a predominance of women with breast cancer. About one half of patients had an independent functional status. Nearly 15% presented severe undernourishment. Depression was suspected in 53.1% of cases. One third of these patients had >2 chronic diseases, and 74% of patients took > or =3 medications. Of the 93 patients with an initial treatment decision, the treatment plan was modified for 38.7% of cases after this assessment. Only body mass index and the absence of depressive symptoms were associated with a modification of the treatment plan. CONCLUSION: The geriatric oncology consultation led to a modification of the cancer treatment plan in more than one third of cases. Further studies are needed to determine whether these modifications improve the outcome of these older patients.

Phase II study of vinflunine in malignant pleural mesothelioma.

PURPOSE: Malignant pleural mesothelioma (MPM) is a disease of increasing incidence for which treatment options are limited. This study reports the clinical efficacy data for vinflunine, a novel microtubule inhibitor, in MPM. PATIENTS AND METHODS: Patients with a histologically confirmed diagnosis of MPM were eligible for enrollment onto this multicenter phase II trial if they had not received prior chemotherapy or radiotherapy and had measurable lesions by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Vinflunine 320 mg/m2 by 10-minute intravenous infusion was administered on day 1 of 21-day cycles. Modifications of dose and schedule were made according to National Cancer Institute Common Toxicity Criteria version 2.0. Efficacy was assessed by an external, independent radiologist. The one-sample multiple testing procedure of Fleming was applied at the predetermined recruitment stages of 20 and 40 assessable patients. RESULTS: Sixty-seven patients were enrolled. Five patients were not assessable for tumor response. The response rate was 13.8% (95% CI, 6.5% to 24.7%). The median survival was 10.8 months (95% CI, 7.8 to 12.0 months). The most common adverse events were anemia, neutropenia, fatigue, constipation, and nausea. Of grade 3 and 4 toxicities, neutropenia and constipation were the most common (45% and 9% of patients, respectively). CONCLUSION: Vinflunine can be delivered with high-dose intensity in patients with MPM. The response rate and median survival are encouraging for a single agent. These data suggest that vinflunine should be further evaluated in the management of MPM.

[Measurement of tumour response to cancer treatment: morphologic imaging role]. / Evaluation de la réponse thérapeutique en cancérologie: le rôle de l'imagerie morphologique.

New forms of cancer chemotherapy are tested in therapeutic trials (phase I, phase II or phase III) while chemotherapeutic agents whose efficacy has already been demonstrated are used, in routine clinical practice, in the context of protocols. The overall survival rate is the best objective parameter of efficacy of the treatments tested, but this parameter is obtained too late, as the effect on the tumour must be determined as soon as possible in order to institute another treatment if necessary. Tumour response, or objective response, is based on changes in the number and size of measurable primary or secondary tumour "targets". These parameters are obtained more rapidly than survival data, but their reliability is highly dependent on the quality of comparative clinical and especially radiological measurements of tumour targets. Medical imaging plays an essential role in these assessments. The absence of standardized techniques, poor selection of targets and inaccurate measurements can bias the results, particularly those of therapeutic trials. In view of the economic, scientific and patient-related stakes involved, a very rigorous approach is essential, directly implicating the responsibility of radiologists performing assessment examinations. The World Health Organization (WHO) guidelines defining the method of measurement of solid tumours and response criteria are no longer adapted to technical progress in imaging. Recently these guidelines have been updated and a new set of criteria has been proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Group, taking into account progress in imaging. They remain based on measurement of the size of the target lesion. The use of this single criterion of size to evaluate response to treatment needs to be discussed in the light of new technologies able to provide information on tumour composition, metabolism or neovascularization, modifications of which reflect response to treatment before a reduction in tumour volume can be detected.

Monitoring therapeutic efficacy in breast carcinomas.

The aim of imaging during and after neoadjuvant therapy is to document and quantify tumor response: has the tumor size been accurately measured? Certainly, the most exciting information for the oncologists is: can we identify good or nonresponders, and can we predict the pathological response early after the initiation of treatment? This review article will discuss the role and the performance of the different imaging modalities (mammography, ultrasound, magnetic resonance imaging and FDG-PET imaging) for evaluating this therapeutic response. It is important to emphasize that, at this time, clinical examination and conventional imaging (mammography and ultrasound) are the only methods recognized by the international criteria. Magnetic resonance imaging and FDG-PET imaging are very promising for predicting the response early after the initiation of neoadjuvant chemotherapy.

MRI for surgical planning in patients with breast cancer who undergo preoperative chemotherapy.

OBJECTIVE: Accurate presurgical evaluation of residual disease appears essential for successful clinical outcome in patients with breast cancer who are undergoing chemotherapy. Our objective was to study the impact on surgical planning of adding serial MRI evaluations of the tumor to standard non-MRI assessments. MATERIALS AND METHODS: MR images of breast tumors obtained before, during, and after preoperative chemotherapy were reviewed in 30 patients. Tumor response was assessed using both size and morphologic MRI criteria. We compared the actual surgical decisions made prospectively on the basis of standard (clinical, mammographic, and sonographic) assessments of response with decisions that would have been made had MRI findings also been considered. MRI investigators were blinded to the ultimate surgical results. Successful breast-conserving surgery was judged on pathologic confirmation of excision margins that were negative for cancer. RESULTS: The standard evaluation led to 16 successful breast-conserving and 14 mastectomy procedures. Using MRI results would have led to major beneficial therapeutic changes in six (20%) of the 30 patients: five patients undergoing primary mastectomy (chemotherapy avoided) and one patient undergoing postchemotherapy mastectomy (unsuccessful breast-conserving surgery avoided). MRI would have added valuable information in 14 (46.7%) of the 30 patients. In seven (23.3%) of the 30 patients, the decision to perform postchemotherapy mastectomy would have been unchanged. In one patient (3.3%), MRI results would not have prevented unsuccessful breast-conserving surgery. In two patients (6.6%), MRI results would have prevented successful breast-conserving surgery from being performed. CONCLUSION: Although the ultimate incidence of breast conservation was potentially similar for the patients (16/30, 53%) in whom the standard evaluation was used and for the patients (14/30, 47%) in whom the MRI-added evaluation was used, MRI was useful in establishing the final treatment earlier in the process, avoiding unnecessary preoperative chemotherapy, or selecting high-risk breast-conserving procedures.

Imaging of malignant tumours of the long bones in children: monitoring response to neoadjuvant chemotherapy and preoperative assessment.

This review focuses on imaging of osteosarcoma and Ewing's sarcoma of the long bones in children during preoperative neoadjuvant chemotherapy. Morphological criteria on plain films and conventional static MRI are insufficiently correlated with histological response. We review the contribution of dynamic MRI, diffusion-weighted MR and nuclear medicine (18FDG-PET) to monitor tumoural necrosis. MRI is currently the best method to evaluate local extension prior to tumour resection, especially to assess the feasibility of conservative surgery. Quantitative models in dynamic MRI and 18FDG-PET are currently being developed in order to find new early prognostic criteria, but for the time being, treatment protocols are still based on the gold standard of histological response.