Stratégies d’immunothérapie dans les cancers colorectaux

Recent studies have underlined the close link between immune response and prognosis of patients with colorectal cancer (CRC). Immune response understanding combined with biotechnology progress of the last years has allowed development of immunotherapy strategies in CRC. Immunotherapy strategies are divided in “active” or “passive” strategies (patients immune system stimulation or not) and considering the activation of antigen specific immune response or not. These immunotherapy strategies are well tolerated and induced cellular and humoral response correlated with clinical response. Many monoclonal antibodies targeting signalisation pathways or angiogenic growth factors have demonstrated their efficacy in CRC. Multiple vaccine strategies, using different tumour associated antigens, have demonstrated a biological efficacy but with poor clinical results. Results are more promising in adjuvant setting but need to be confirmed by randomized trials. Adoptive immunotherapy with transfer of tumour associated antigen specific T cell is probably the most promising strategy. Actually, except monoclonal antibodies, immunotherapy is not used in clinical practice in CRC due to the lack of results and absence of standardisation.     

Réflexions sur les critères d’évaluation des traitements anticancéreux lors des procédures d’autorisation de mise sur le marché

Although clear and validated recommendations exist concerning the evaluation of cancer treatments at the international level, the criteria retained to obtain the marketing authorization (MA) are multiple and heterogeneous. This qualitative survey explores the opinion related to the assessment of cancer treatment among the several concerned population. By the way of semi-structured interviews, our aim was to elicit perceptions toward the criteria which should be retained during the process of MA, by patients, oncologists, members of the pharmaceutical industry, health decision-makers and general population. Our survey emphasizes the variability of the significations associated with the criteria of efficiency of cancer treatments according to the characteristics of the respondents. We also have observed some common expectations from patients and oncologists toward the economic and political aspect, but also from the whole respondents toward the importance of the comfort of the patients. Lastly, the necessity to define specific criteria related to clinical cases emerges.     

Psychothérapie de la dignité: une intervention pour réduire la détresse psychologique chez les personnes en soins palliatifs

This study examined the feasibility of the introduction of a new intervention, dignity therapy, in a palliative care setting and evaluated the satisfaction of the participants regarding this intervention. This intervention was administered to 33 French-speaking persons attending a palliative care center in Quebec City. Results confirmed the relevance of this intervention and showed that it is associated with a high-level of satisfaction for participants and family members.     

Perception de l’activité physique adaptée par les parents d’enfants hospitalisés en oncologie-hématologie pédiatrique

The role of adapted physical activity (APA) in adult oncology is becoming increasingly important due to its effect on fatigue and quality of life, but also on patient survival. In contrast, there is very little data concerning children. Our study reports the results of the perception of parents regarding adapted physical activity implemented in a paediatric onco-haematology department for children sometimes in sterile rooms. Although the effect is low (N = 13), it would appear that the timing of the sessions (particularly for young children) and the initial state of tiredness of the children are significant factors for parents. With regards to parent satisfaction, overall they appear to be satisfied without any correlation between satisfaction and the number of sessions being observed. Notions of independence, potential, pleasure in relationships and relaxation appear in the positive evaluation. This activity seems to enable parents to change their perceptions about their child and their relationship to him/her. These initial results suggest the implementation of a wider study.     

Inégalités géographiques observées dans la survie pour la période 1990-1994: les résultats d’Eurocare 3

Résumé: Les analyses de survie réalisées à partir des données provenant des registres de cancer permettent de juger de lefficacité globale du système de soins. La dernière analyse de grande envergure parue fait partie du projet Eurocare. Elle permet de connaître et de comparer la survie de patients atteints dun cancer dans 22 pays européens (100 millions dhabitants). Les survies, mesurées en terme de survie relative (prise en compte de la mortalité naturelle) sont très différentes en fonction des pays, surtout pour les localisations cancéreuses de bon pronostic. Toutefois, il ne faut pas attribuer toutes les différences à une meilleure prise en charge thérapeutique, les meilleures survies sont souvent associées à une plus grande précocité des diagnostics.     

Tolérance et efficacité de la radiothérapie préopératoire chez les patients âgés atteints d’un cancer du rectum

PurposeTo retrospectively assess the impact of age on tolerance and oncologic outcomes treated by neoadjuvant treatment for patients of 70 years old or above with locally advanced rectal cancer.Patients and methodsNinety-one consecutive patients were divided into three groups: group 1 from 70 to 75 years (n = 31); group 2: 76 to 79 years (n = 31) and group 3, patients aged 80 years or above (n = 29). Radiation therapy was delivered according two schemes: 25 Gy in five fractions (short scheme) or 45 to 50 Gy with a classical fractionation (long scheme). Long scheme patients received a concomitant chemotherapy with 5-fluoro-uracile alone or associated with oxaliplatin.ResultsThe three groups were comparable for performance status, Charlson's score and T staging. Long scheme radiation therapy and chemotherapy were performed in 77.5, 74.5 and 48.3% of patients (P = 0.03) and 77.4, 71 and 41.4% (P = 0.006) in the groups 1, 2 and 3, respectively. All patients treated with the short scheme irradiation received the treatment without any acute toxicity. In the long scheme group, 65% of patients received the treatment on time and grade 3 or above toxicity was observed in 12% of patients who did not receive oxaliplatin and in 48% of patients who received oxaliplatin. The overall survival rate at 3 and 5 years was 66.9% and 60.8% in the group 1, 90.5% and 75.9% in the group 2 and 80.5% and 73.8% in the group 3 (P = 0.15).ConclusionNeoadjuvant treatment is feasible with encouraging survival rates for patients aged 70 years and older. Short scheme radiation therapy seems to be an interesting option in this population.     

La radiothérapie (conformationnelle avec modulation d’intensité) adaptative est-elle nécessaire pour les carcinomes du col utérin ?

PurposeTo observe on ten patients, the changes of different pelvic structures during a Stade IB2-IIB cervix cancer tomotherapy course delivering 60 Gy over 5.5 weeks and evaluate the rationale of adaptive treatments.Materials and methodsEach of the six weekly mega voltage CT-scan (MVCT) exams performed the same day of the week were analyzed. The centro-pelvic CTV volume was contoured as well as the organs at risk (OAR). The dose delivered was recalculated while those to 2%, 50% and 98% of the centro-pelvic CTV as well as to 2 cm³, 10 cm³ and 50 cm³ of the OAR were analyzed.ResultsThe mean decrease in volume of the centro-pelvic CTV was 13% and non-significant (P > 0.2). However four tumors decreased from 21% to 42%. This decrease was centripetal. Likewise, the fraction doses to 2%, 50% and 98% were respectively 2.14 ± 0.08 Gy, 2.02 ± 0.14 Gy, 1.8 ± 0.34 Gy at week 1 and 2.13 ± 0.1 Gy, 2.06 ± 0.12 Gy, 1.88 ± 0.24 Gy at week 6 (P > 0.2). The doses delivered to 2 cm³, 10 cm³ and 50 cm³ of the different OAR did not change at a significant level (P > 0.05) too, except the dose to 50 cm³ of non-sigmoid bowel moving from 1.69 ± 0.16 Gy at week 1 to 1.78 ± 0.14 Gy at week 6 (P = 0.05).ConclusionAs a whole, adaptive therapy does not seem mandatory in this population of stages IB2-IIB cancers. A complementary study on more advanced stages is however necessary.     

Enregistrement et publication du critère d’évaluation principal dans les essais contrôlés randomisés en oncologie

PurposeTo improve the quality of reporting of randomized clinical trials (RCTs), international registries for RCTs and guidelines for primary endpoint (PEP) analysis were established. The objectives of this systematic review were to evaluate concordance of PEP between publication and the corresponding registry and to assess the intrapublication consistency in PEP reporting.MethodsAll adult oncology RCTs in solid tumors published in 10 journals between 2005 and 2009 were reviewed. Registration information was extracted from international trial registries.ResultsA total 366 RCTs were identified. Trial registration was found for 215 trials and the rate increased from 43% in 2005 to 82% in 2009 (P < 0.001). There were 134 RCTs with clearly defined PEPs in registry, with the rate increasing from 15 to 67% (P < 0.001). PEP differs between registration and final publication in 14% trials with clearly defined PEPs. Reporting issues in methodology were found in 15% RCTs, mainly due to inadequate reporting of PEP or of sample size calculation. Problems with the interpretation of trial results were found in 22% publications, mostly due to negative superiority studies being interpreted as showing equivalence.ConclusionThe rates of trial registration and of trials with clearly defined PEP have improved over time, however 14% of these trials reported a different PEP in the final publication. Intrapublication inconsistencies in PEP reporting are frequent. Our findings highlight the need for investigators, peer reviewers and readers for increased awareness and scrutiny of reporting outcomes of oncology RCTs.     

L'hadronthérapie: les ions carbone

Carbon ion therapy is an innovative radiation therapy. It has been first proposed in the forties by Robert Wilson, however the first dedicated centres for human care have been build up only recently in Japan and Germany. The interest of carbon ion is twofold: 1) the very sharp targeting of the tumour with the so called spread out Bragg peak that delivers most of the beam energy in the tumour and nothing beyond it, sparing very efficiently the healthy tissues; 2) the higher relative biological efficiency compared to X rays or protons, able to kill radioresistant tumour cells. Both properties make carbon ions the elective therapy for non resectable radioresistant tumours loco-regionally threatening. The technical and clinical experience accumulated during the recent decades is summarized in this paper along with a detailed presentation of the elective indications. A short comparison between conventional radiotherapy and hadrontherapy is proposed for the indications which are considered as priority for carbon ions.     

Radiothérapie en conditions stéréotaxiques : les prérequis

Indications of treatment by stereotactic body radiotherapy are dramatically increasing due to new potential indications. The conditions associated with the treatment delivery are multiple. The first step of the process is crucial. It is related to the validation of the indication proposed during the multidisciplinary meeting as regard the evidence-based proof of the concept. These emerging techniques mainly extracranial stereotactic body irradiation do not benefit from long-term evaluation in terms of efficiency as well as normal tissue late toxicities. Priority should be given to prospective independent clinical trials, validated by an independent scientific committee, performed under a relevant and well dedicated multicentric quality assurance program aiming to improve knowledge and selection of indications. The SFRO is still working with others professionals on the definition of the conditions for the implementation of such treatments and actively collaborates with the authorities to define the appropriate conditions to preserve the quality of the treatment delivery under these specific conditions.     

Place de la chirurgie dans les métastases cérébrales

Surgical excision in brain metastases has been well evaluated in unique metastases. Two randomized phase III trials have shown that combined with adjuvant whole brain radiotherapy, it significantly improves overall survival. However, even in the presence of multiple brain metastases, surgery may be useful in large, symptomatic or life-threatening lesions (posterior fossa tumor with mass effect). Also, even in lesions amenable to radiosurgery, surgical resection is preferred when tumors displayed cystic or necrotic aspect with important edema or when located in highly eloquent areas or cortico-subcortically. Furthermore, surgery may have a diagnostic role, in the absence of histological documentation of the primary disease, if the radiological aspect is atypical to rule out differential diagnosis (brain abscess, lymphoma, primary tumor of the central nervous system) or in case of suspicion of progression after irradiation to differentiate radionecrosis from a genuine progression of brain disease. Finally, the issue of biological documentation of brain disease may arise in situations where a specific targeted therapy can be proposed. If the surgical indications are relatively well defined, the selection of patients who will really benefit from surgery should take into account three factors, clinical and functional status of the patient, systemic disease status and characteristics of intracranial metastases. Given the improved survival of cancer patients due to the advent of effective targeted therapies on systemic disease, a renewed interest has been given to local therapy (surgery or radiosurgery) in brain metastases. Surgical resection currently represents a valuable tool in the armamentarium of brain metastases but has also become a diagnostic and decision tool that can affect therapeutic strategies in these patients.