Carine Bellera

Detection of frailty in elderly cancer patients: Improvement of the G8 screening test

OBJECTIVEnThe G8 is a screening test to identify frail elderly patients with cancer. Objectives were to design and evaluate the performance of alternative tests taking into account other predictive domains for frailty.nnnMETHODSnWe conducted a literature review to identify predictive factors of frailty. Using a Delphi consensus, we collected 24 European experts opinions to validate the most relevant items to improve the G8. Alternative tests were created and performance assessed on a development population (ONCODAGE cohort). The highest performing test was compared to the G8, and validated through both an internal and an external population validation (Aquitaine Geriatric Oncology cohort).nnnRESULTSnThe study population consisted of 1435 patients (ONCODAGE cohort) and 364 patients (Aquitaine Geriatric Oncology cohort). Twenty-three experts validated two items with a strong consensus (>75%): modification of the threshold for the G8 polypharmacy item to six drugs per day and replacement of the G8 item on neuropsychological problems by four Instrumental Activities of Daily Living (IADL) items predictive of incident dementia, creating three modified G8 tests (addition of either item, or both). Only the G8 IADL-modified test had better performance than the G8 when tested on the ONCODAGE cohort: sensitivity=77%, specificity=67%. This test was validated on the internal (sensitivity=78%, specificity=71%) and external (sensitivity=88%, specificity=69%) validation populations.nnnCONCLUSIONnAdding the four IADL items improves the performance of the G8. We have developed and validated a G8-modified test that is more specific than the G8 to detect frail elderly, while still sensitive and feasible in less than 10 min.

Barriers to inclusion of older adults in randomised controlled clinical trials on Non-Hodgkin's lymphoma: a systematic review.

BACKGROUNDnThe majority of Non-Hodgkins lymphoma (NHL) patients are over 65 years. Management is challenging, especially for aggressive lymphoma, and appropriate assessment of efficacy and tolerance specific to this population is crucial.nnnOBJECTIVESnTo assess the representation of older patients in randomised controlled trials (RCT) in NHL, examining whether trial eligibility criteria prevent participation, and whether appropriate primary endpoints such as toxicity, quality of life, or geriatric assessment scores are used.nnnMETHODSnWe searched Medline for articles published in English or French between 1 January 2005 and 31 December 2011 reporting on phase II/III RCT evaluating therapeutic strategies for NHL. Articles were categorised as including or excluding (directly or indirectly) older adults, and features of RCT that included or excluded older patients are compared.nnnRESULTSnWe identified 87 relevant RCT: 9 (10.3%) focussed exclusively on patients >65 years, 22 (25.3%) directly excluded patients >65 years, 47 (54.0%) indirectly excluded older adults through selective inclusion criteria (ECOG status, liver or kidney function, and comorbidities), and 9 (10.3%) did not directly or indirectly exclude patients >65 years (although two excluded patients >70 years). Proportions of older patients included do not reflect incidence. Trials including older adults were published in journals with lower impact factors and few RCT used appropriate endpoints for older adults.nnnCONCLUSIONSnOlder adults are poorly represented in NHL RCT both due to direct age-based exclusion and restrictive inclusion criteria. This situation needs rapid correction to better represent older patients and thus improve cancer management in this highly prevalent population.

Phase-II trials in osteosarcoma recurrences: A systematic review of past experience

BACKGROUNDnThe most appropriate design of Phase-II trials evaluating new therapies in osteosarcoma remains poorly defined.nnnOBJECTIVEnTo study consistency in phase-II clinical trials evaluating new therapies for osteosarcoma recurrences with respect to eligibility criteria, response assessment, end-points, statistical design and reported results.nnnMETHODSnSystematic review of clinical trials registered on clinicaltrials.gov, clinicaltrialsregister.euxa0and French National Cancer Institute websitexa0or referenced in PubMed and American Society of Clinical Oncology websites, between 2003 and 2016, using the following criteria: (osteosarcoma OR bone sarcoma) AND (Phase-II).nnnRESULTSnAmong the 99 trials identified, 80 were Phase-II, 17 I/II and 2 II/III, evaluating mostly targeted therapy (nxa0=xa040), and chemotherapy alone (nxa0=xa026). Results were fully (nxa0=xa028) or partially (abstract, nxa0=xa06) published. Twenty-four trials were dedicated to osteosarcoma, 22 had an osteosarcoma stratum. Twenty-eight out of 99 trials refer to the age range observed at recurrence (28%). Overall, 65 trials were run in multicentre settings, including 17 international trials. Only 9 trials were randomised. The primary end-point was tumour response in 71 trials (response rate, nxa0=xa040 or best response, nxa0=xa031), with various definitions (completexa0+xa0partialxa0±xa0minor response and stable disease), mainly evaluated with RECIST criteria (nxa0=xa069); it was progression-free survival in 24 trials and OS in 3. In single-arm trials evaluating response rate, the null hypothesis tested (when available, nxa0=xa012) varied from 5% toxa025%.nnnCONCLUSIONnNo robust historical data can currently be derived from past efficacy Phase-II trials. There is an urgent need to develop international randomised Phase-II trials across all age ranges with standardised primary end-point.

Evaluation of efficacy and safety of FOLFIRI for elderly patients with gastric cancer: A first-line phase II study

OBJECTIVEnCurrent chemotherapy protocols for gastric cancer present high toxicity. The FOLFIRI regimen has shown promising results with elderly colorectal cancer patients and for gastric cancer patients but this is the first report on elderly gastric cancer patients.nnnDESIGNnIn this multicenter non-randomized phase II trial, we administered the FOLFIRI chemotherapy protocol (irinotecan [180 mg/m(2)], fluorouracil [5-FU] [400 mg/m(2)] and folinic acid 400 mg/m(2) or 200mg/m(2) of l-folinic acid) to patients aged over 70 years with locally-advanced or metastatic gastric cancer combined with Comprehensive Geriatric Assessment (CGA). Responses were assessed at 2 months.nnnRESULTSnForty-two patients received eight cycles of the FOLFIRI regimen, with 82.5% of patients showing disease control: 10 patients (26%) showing objective (partial or complete) responses and 23 (57.5%) showing stable disease. One-year overall survival (OS) was 41.5% [95%CI 26.5-56.0] and one-year progression-free survival (PFS) was 31.8% [95%CI 18.4-46.1%]. We observed 10 Grade 3/4 hematologic toxicities with one febrile neutropenia. CGA data demonstrated that geriatric functions were not altered by treatment and that nutritional status improved over treatment.nnnCONCLUSIONSnResults show excellent disease control and relatively high survival rates with limited toxicity similar to younger patients indicating that this regimen should be considered as a possible treatment in advanced gastric cancer of the elderly.

Chemotherapy treatment for older women with metastatic breast cancer: What is the evidence?

While the over-representation of the elderly in the breast cancer population is projected to dramatically increase within the next two decades, data on chemotherapy for elderly patients with metastatic breast carcinoma (MBC) remain very limited. The aim of the present study is to investigate whether elderly patients included in clinical studies for MBC are representative of the population seen during usual clinical practice. Firstly, a review of the literature was performed identifying 39 publications about chemotherapy for MBC focusing on elderly patients and we examined patient characteristics in each of these publications. Comparison of the age distribution of patients included in these studies with that of a large cohort of consecutive MBC patients aged 65years who received chemotherapy in our institution over the last ten years (n=573) indicated that trials tend to include relatively younger patients. Furthermore, criteria to assess external validity of the results are seldom reported. Possible ways to improve the applicability of results such as increasing the minimum age for inclusion and the use of CGA are proposed.

Complications de l’ablathermie par radiofréquences peropératoires (ARFPO) des métastases hépatiques : enseignements de la courbe d’apprentissage (100)

Introduction L’ARFPO attend sa validation des resultats definitifs des essais CLOCC et ARF2003 actuellement en cours d’analyse. L’analyse des complications observees a ce jour doit toutefois nous permettre de valider les limites d’indications que nous avons retenues pour definir ainsi un rapport benefice /risque pertinent pour le patient. Patients et Methode Patients operes par ARFPO avec ou sans resection combinee dans le cadre d’une decision de RCP, de janvier 2000 a decembre 2008. Le choix entre resection et ARFPO etait realise lesion par lesion, apres echographie peroperatoire, selon des criteres anterieurement publies (EJSO 2008 ; 34 : 185-190). Des clampages vasculaires porte ou sus-hepatique pouvaient etre realises pour traiter des lesions paravasculaires cave ou sus-hepatique. Les aiguilles etaient droites (Integra ® ) utilisees en strategie de recouvrement de champs, avec tirs multiples. Les resultats etaient collectes prospectivement sur une base Medlog et analyses retrospectivement sur le logiciel SPSS 8.0 ® . La classification de Dindo et Clavien a ete utilisee pour decrire les complications. Resultats Ont beneficies d’une ARFPO (21-98 ans), 113 patients, pour le traitement de 282 metastases. Un antecedent d’hepatectomie majeure etait note dans 12 %. Les maladies etaient colorectales dans 70 % et etaient synchrones dans 56 %. Des metastases extra-hepatiques etaient presentes dans 26 %. Une chimiotherapie neo-adjuvante etait administree dans 66 %. Un geste extra-hepatique a ete associe dans 26 %. Une resection etaient associee dans 49 % des cas. Ont eu respectivement une morbidite de garde 1 : 19 patients (16,8 %) ; de grade 2 : 10 (8,8 %) patients traites medicalement ; de grade 3a : 13 (11,5 %) patients traites de maniere invasive mais non chirurgicale ; de grade 3b : 5 patients (4,4 %) avec reprise chirurgicale (3 saignements de tranches, une ischemie colique, une evisceration sur atcd d’eventrations multiples) ; de grade 4 : 2 patients (1,8) pour une defaillance hepatique et une defaillance respiratoire, toutes deux d’evolution favorable ; de grade 5, 3 patients decedes (2,6 %). Une patiente de 78 ans, ASA 3 est decedee au 5eme jour d’un choc septique. Un patient de 38 ans en 4eme ligne de recidive d’un sarcome est decede des suites d’une perforation d’ulcere gastrique. Enfin, plus specifique, un patient de 58 ans, est decede au 4 e jour d’une insuffisance hepatocellualaire apres traitement de 4 lesions par ARFPO et d’une bisegmentectomie 2/3. Sont apparues comme facteurs pronostiques de survenue de complications : 1) l’existence d’un geste extra-hepatique (Odd Ratio = 3,1 [1,18-8,41], p xa0=xa00,018) ; 2) l’ouverture du tube digestif (Odd Ratio = 4,6 [1,55 - 13,75], p xa0=xa00,004) et la duree operatoire > 4 heures (Odd Ratio = 6,3, p Conclusion l’ARFPO ne parait pas dans cette serie ajouter de morbidite specifique majeure malgre la lourdeur et la complexite des situations metastatiques prises en compte (morbidite grade 3-5 = 20,3 %). Les limites de ses indications etant des lors connues (moins de 30 mm de diametre, a distance d’une voie biliaire principale), elle offre dans ce perimetre un ratio benefice/risque interessant pour etendre de champ des indications de la resection seule et traiter ainsi davantage de patients.