Camille Chakiba

Functional Decline in Older Patients With Cancer Receiving First-Line Chemotherapy

PURPOSE To determine factors associated with early functional decline during first-line chemotherapy in older patients. PATIENTS AND METHODS Patients age ≥ 70 years receiving first-line chemotherapy for cancer were prospectively considered for inclusion across 12 centers in France. Functional decline was defined as a decrease of ≥ 0.5 points on the Activities of Daily Living (ADL) scale between the beginning of chemotherapy and the second cycle. Factors associated with functional decline were sought from pretreatment abbreviated comprehensive geriatric assessment, including ADL, Instrumental ADL (IADL), Mini-Nutritional Assessment (MNA), Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS15), and Timed Get Up and Go (GUG) test, and from comorbidities (Cumulative Illness Rating Scale-Geriatrics), MAX2 index, and baseline biologic and clinical information. RESULTS Of 364 included patients, 50 experienced functional decline (16.7%; median, 0.5 points). Abnormal preadmission performance status, IADL, GDS15, MMSE, GUG, and MNA were associated with increased likelihood of functional decline (univariate analysis). In the multivariate model adjusted for baseline ADL and MAX2 index, high baseline GDS (odds ratio [OR], 2.16; 95% CI, 1.09 to 4.30; P = .03) and low IADL scores (OR, 2.87; 95% CI, 1.06 to 7.79; P = .04) were independently associated with increased risk of functional decline. CONCLUSION Our results outline associations between baseline depression, instrumental dependencies, and early functional decline during chemotherapy for older patients. ADL should be sequentially evaluated early during treatment. Baseline evaluation of GDS15 and IADL may be proposed to anticipate this event.

Immune checkpoint inhibitors and elderly people: A review

Immune checkpoint inhibitors, including targeting programmed cell death 1, programmed cell death ligand 1, and cytotoxic T lymphocyte antigen 4 pathways, are a new type of cancer treatment. This approach of targeting the immune system has demonstrated dramatic efficacy for several cancers, and various drugs have been approved by health authorities and are used in clinical practice. Elderly patients (≥65 years) represent most of the cancers diagnosed and deaths by age group, with an increase expected over the next decade. However, this subgroup of patients is under-represented in clinical trials. Ageing is also associated with a decrease in the effectiveness of the immune system and in alterations to it. Few specific trials have been carried out for immunotherapy in elderly people, with most patients considered to be fit. In this review, we discuss the impact of ageing and immunosenescence on immune system functions, and we assess the safety and efficacy of immune checkpoint inhibitors in elderly patients, principally from the data of pivotal clinical trials with subgroup analysis. Tolerance in elderly patients seems similar to younger people, but efficacy seems different between younger and elderly patients according to the type of cancer, some showing no difference and others less efficacy in the elderly subgroup. However, the numbers in elderly groups are small and more investigation is needed, with specific clinical trials for elderly cancer patients.

Dynamic contrast enhanced MRI-derived parameters are potential biomarkers of therapeutic response in bladder carcinoma

OBJECTIVES To evaluate the performance of dynamic contrast enhanced (DCE) magnetic resonance (MR) imaging to assess the histological response after chemotherapy on bladder carcinoma. METHODS From 2008 to 2010, 12 patients presenting localized urothelial carcinoma of the bladder were prospectively evaluated by DCE-MR imaging before and after two courses of cisplatin-based neoadjuvant chemotherapy. Size and thickness of tumours were measured. Relative enhancement at the arterial (rSI35s) and venous phases (rSI80s) of each tumour was obtained. Histological response was assessed and outcomes were recorded. RESULTS Histological examination after neoadjuvant chemotherapy concluded as pathological complete response (pCR) for 6 out of 12 patients. Five patients developed recurrences (4/6 no pCR and 1/6 pCR). Significant differences, between before and after treatment, were found for patients with complete pathological response after chemotherapy for all MR quantitative values. Tumours decreased in size and thickness (both P=0.03). After treatment, rSI80s was significantly different between pCR and non-pCR patients (P=0.04) with a cut-off value of 40%. For this cut-off, sensitivity, specificity and accuracy were 83.33%. Similar recurrence free survivals were obtained if applying the MR cut-off value or the histopathological findings. CONCLUSION Our results suggest that DCE-MR imaging may be a useful biomarker for patients with localized bladder carcinoma, improving selection before surgery.

Encouraging Trends in Modern Phase 1 Oncology Trials

Benefits of Phase 1 Oncology Trials Historically, phase 1 trials have been aimed at defining the toxic effects of an agent. With the advent of targeted therapies and immunotherapies, response rates...

GREB1-CTNNB1 fusion transcript detected by RNA-sequencing in a uterine tumor resembling ovarian sex cord tumor (UTROSCT): a novel CTNNB1 rearrangement

Mutations of CTNNB1 have been implicated in tumorigenesis in many organs. However, tumors harboring a CTNNB1 translocation are extremely rare and this translocation has never been reported in a uterine mesenchymal neoplasm. We report a novel translocation t(2;3)(p25;p22) involving the GREB1 (intron 8) and CTNNB1 (exon 3) in a uterine tumor resembling ovarian sex cord tumor (UTROSCT), which exhibited extrauterine metastasis. The translocation detected by RNA‐sequencing was validated by RT‐PCR, and resulted in nuclear expression of β‐catenin. Juxtapositioning with GREB1, which is overexpressed in response to estrogens, resulted in overexpression of a truncated and hypophosphorylated nuclear β‐catenin in the primary and recurrent tumors. This accumulation of nuclear β‐catenin results in a constitutive activation of the Wnt/β‐catenin signaling pathway with a major oncogenic effect. The CTNNB1 gene fusion, promoted by an estrogen‐responsive gene (GREB1), could be a potential driver of tumorigenesis in this case and a therapeutic target with adapted inhibitors. RT‐PCR and immunohistochemistry performed on 11 additional UTROSCTs showed no CTNNB1 fusion transcript or nuclear β‐catenin immunoreactivity.

Genomic complexity in pediatric synovial sarcomas (Synobio study): the European pediatric soft tissue sarcoma group (EpSSG) experience

A genomic index (GI) tool using array comparative genomic hybridization (aCGH) on tumor cells has emerged as independent prognostic factor associated with the risk of metastatic relapse in synovial sarcoma (SS). The aim was to assess GI in pediatric patients with SS, to determine its value as a prognostic factor. All pediatric/adolescent/young adults’ (<25 years) with localized SS prospectively included in the European EpSSG‐NRSTS05 protocol with a contributive aCGH were selected. Definition of GI was A2/C, where A is the total number of alterations (segmental gains and losses) and C is the number of involved chromosomes on aCGH results. GI1 group corresponds to cases with no copy number alterations (flat profile, GI = 0) and GI2 group cases with at least one or more copy number alterations (rearranged profile; GI ≥ 1). Samples were available from 61 patients. The median age of the cohort was 13 years (range: 4–24). Overall, 55.7% were GI1 group, and 44.3% GI2. After a median follow‐up of 62 months (range: 0.1–112), 10 tumor events occurred and five patients died. Respectively, for GI1 versus GI2 groups, five‐year event‐free survival (EFS) was 93.8 ± 4.2% versus 64.9 ± 10.1% (P < 0.006) and five‐year Metastatic‐Free Survival (MFS) 93.8 ± 4.2% versus 72.9 ± 9.5% (P < 0.04). In multivariate analysis, GI status as adjusted for IRS group, patient age, site, and tumor size remain independent prognostic for EFS with a relative risk (RR) of 6.4 [1.3–31.9] (P < 0.01) and RR for MFS is 4.8 [0.9–25.7] (P < 0.05). Genomic complexity evaluated through GI may explain the metastatic behavior of pediatric SS.

Risks and benefits of phase 1 oncology trials in the era of personalized medicine.

e18116Background: Although crucial to developing new anti-cancer treatments, phase I trials in oncology remain ethically controversial. Critics argue that they have no therapeutic intent and offer ...

General Considerations on Treatment in Older Patients with Hematological Malignancies

Standard treatment relates to disease, not to patients. The question in older patients is consequently most often to adapt standard treatment to the specific situation of the patient through a strict evaluation of risks and benefits since higher risks may consume benefits.