PREMIUM: A French prospective multicenter observational study of factors impacting on efficacy and compliance to cetuximab treatment in first-line KRAS wild-type metastatic colorectal cancer.

BACKGROUND: Cetuximab improves progression-free survival (PFS) and overall survival (OS) in patients with KRAS wild type (wt) metastatic colorectal cancer (mCRC). Few data are available on factors impacting both efficacy and compliance to cetuximab treatment, which is, in combination with chemotherapy, a standard-of-care first-line treatment regimen for patients with KRAS wt mCRC. PATIENTS AND METHODS: PREMIUM is a prospective, French multicenter, observational study that recruited patients with KRAS wt mCRC scheduled to receive cetuximab, with or without first-line chemotherapy, as part of routine clinical practice, between October 28, 2009 and April 5, 2012 (ClinicalTrials.gov Identifier: NCT01756625). The main endpoints were the factors impacting on efficacy and compliance to cetuximab treatment. Predefined efficacy endpoints were PFS and safety. RESULTS: A total of 493 patients were recruited by 94 physicians. Median follow-up was 12.9 months. Median progression-free survival was 11 months [9.6-12]. In univariate analyses, ECOG performance status (PS), smoking status, primary tumor location, number of metastatic organs, metastasis resectability, surgery, folliculitis, xerosis and paronychia maximum grade, and acne preventive treatment were statistically significant. In multivariate analysis (Hazard Ratios of multivariate stepwise Cox models), ECOG PS, surgery, xerosis and folliculitis were positive prognostics factors for longer PFS. Among all patients, 69 (14%) were non-compliant. In multivariate analysis, no variables were statistically significant. The safety profile of cetuximab was consistent with previous studies. CONCLUSIONS: ECOG PS <2, surgical treatment performed, and maximum grade xerosis or folliculitis developed were predictive factors of cetuximab efficacy on KRAS wt mCRC patients. Unfortunately, we failed in identifying predictive factors for compliance in these patients.

[The patient care experience in radiotherapy: perspectives for better patient support]. / Les enjeux du vécu de la radiothérapie: perspectives pour un meilleur accompagnement des malades.

This paper reports the patient care experience during the course of the radiotherapy. Plights are multiple. Patients are confronted with a complex and unknown distressing space, an irrelavant information, a banalization of side effects, an isolation with a frequent inadequate support of their family or the caregivers team, with the fear of a definitive abandonment at the end of the treatment without comforting follow-up. It is imperative to state a real policy in order to improve the patient support. Sensibilization and training of the caregivers, in spite of a frequent overbooking technical work, is required in a pluridisciplinary approach to provide a relevant reception with the collaboration of psychologists, social workers and self care groups and associations. The personal implication of the physicians and technologists is also essential. The simple smile is the intangible proof of the reliable emotional support.

[Fractionated radiotherapy of intracranial meningiomas and neurinomas]. / Radiothérapie fractionnée des méningiomes et des neurinomes intracrâniens.

In most institutions, surgical excision remains the standard treatment of meningiomas and neurinomas; the aim of surgery is complete resection. However, total removal is not always feasible without significant morbidity and in some cases, the patient's condition contraindicates surgery. For incompletely excised tumors, recurrences will have consequences on neurological functions. There are now many reports in the literature confirming the fact that radiotherapy significantly decreases the incidence of recurrence of incompletely resected benign tumors and that it can replace surgery in some situations where an operation would involve considerable danger or permanent neurological damage: about 80 to 90% of such tumors are controlled with fractionated radiotherapy. Stereotaxic and three-dimensional treatment planning techniques increase local control and central nervous system tolerance so that the respective place of surgery and radiotherapy needs to be redefined, considering efficacy and morbidity of these two therapeutic means. In this article, we limit our remarks to fractionated radiotherapy and, after a review of the literature, we discuss the indications, volume evaluations and the techniques currently used.

[Fractionated radiotherapy of intracranial meningiomas: 15 years' experience at the Bordeaux University Hospital Center]. / Radiothérapie fractionnée des méningiomes intracrâniens: 15 ans d'expérience au centre hospitalier universitaire de Bordeaux.

PURPOSE: To evaluate the long-term results of external fractionated radiation therapy (RT) in the treatment of intracranial meningiomas. PATIENTS AND METHODS: From January 1981 to December 1996, 156 patients with intracranial meningiomas were treated with external fractionated RT. Median age was 57. Indications for radiation therapy were as follows: (1) completely excised histologically aggressive tumors (12 patients); (2) incomplete surgical resection (37 patients); (3) medically inoperable or basilar tumors where operation would involve considerable danger or permanent neurological damage (77 patients); and, (4) tumor recurrences (30 patients). Most patients were irradiated with 6 to 9 MV photon beams. A three to four-field technique with coned-down portals was used. Since 1993, 71 patients had a three dimensional dosimetry. Doses were calculated on the 95% or 98% isodoses, all fields were treated every day, five days a week, for a median total dose of 50 Gy (1.8 Gy/Fraction). RESULTS: Median follow-up from radiation therapy was 40 months. Acute tolerance was excellent; an early clinical improvement during radiation therapy was noted in 19 patients (17.8%). Clinical improvement or stabilization was observed in 130 patients (83.4%). Radiologically, local control was obtained in 124 cases (79.4%) and tumor recurrences occurred in 21 cases (ten progressions in the treated volume, five borderline, six new locations). Overall and cause specific-survival rates were 75% and 89% at five years, and 45 and 76% at 10 years, respectively. CONCLUSION: These results reassess the role of fractionated RT in the treatment of intracranial meningiomas. Long-term tolerance is excellent for a majority of patients. The study of recurrences confirms the importance of the definition of the target volume, and asks questions about total given doses.

[Central nervous system. Experience of the Bordeaux University Hospital Center and review of the literature]. / Les dysgerminomes du système nerveux central. Expérience du Centre Hospitalier Universitaire de Bordeaux et analyse de la littérature.

PURPOSE: Retrospective analysis of 17 patients with intracranial germ cell tumors treated in a multidisciplinary consultation at the Bordeaux University Hospital a and literature review. MATERIALS AND METHODS: Seventeen consecutive patients were treated from 1978 to 1995 for a primary intracranial germ cell tumor. Median age was 14 (range 3-29 years). There were two malignant teratoma, six proved germinoma and nine presumed germinoma (diagnostic based on biological, radiological and treatment criteria). All received radiotherapy from 30 to 60 Gy (median 40 Gy) in different volumes. Chemotherapy was administered in 15 cases, three after surgery and 12 after radiotherapy. RESULTS: All tumours were in complete remission after initial treatment. The two malignant teratomas recurred in non-irradiated area after nine and 48 months, and the patients died. None of the germinoma recurred within a follow-up period of two to 17 years (median 65 months). Five and 10 year actuarial overall survival rates were the same: 84% for all histologies and 100% for germinomas. Only two patients developed school difficulties and six presented an hypopituitarism, of which one was consecutive to radiotherapy. Chemotherapy was well tolerated. CONCLUSION: This retrospective study and literature analysis are in favor of limited dose and volume of radiation therapy associated with chemotherapy.