S. Mathoulin-Pelissier

DNA topoisomerase IIα expression and the response to primary chemotherapy in breast cancer

The α isoform of Topoisomerase IIα (Topo IIα) is a proliferation marker as well as a target for several chemotherapeutic agents such as anthracyclines. In vitro studies have demonstrated the relationship between the Topo IIα expression level and chemosensitivity of target cancer cells. To verify this effect in vivo, we selected 125 patients presenting with T2>3 cm and T3 N0–1 M0 breast tumours who were treated by six cycles of primary chemotherapy, including epirubicin before any surgery. Therapy response was assessed by clinical and X-ray mammogram measurements of tumour shrinkage. The pretherapeutic core biopsies were immunostained with a monoclonal antibody (Ki-S7) against Topo IIα. Ki-S7 positivity ranged from 0 to 50% (median, 15%). A high percentage of Ki-S7-positive cells (>15%) was associated with tumour regression under chemotherapy (OR=2.88, CI: 1.3–6.4, P=0.004). Ki-S7 further emerged as an independent predictor of tumour regression (OR=3.34, CI: 1.41–7.93, P=0.006), together with tumour size of less than 40 mm (OR=3.82, CI: 1.58–9.25, P=0.002) and negative oestrogen receptor (ER) status (OR=3.35, CI: 1.43–7.86, P=0.005), in a multivariate analysis including tumour size, SBR grade, ER and PR status, Ki-67, p53 and Her-2/neu. Our clinical results confirm in vitro data on the relationship between Topo IIα expression and tumour chemosensitivity and thus may have important practical implications.

Prognostic significance of immunohistochemically detected breast cancer node metastases in 218 patients

Axillary lymph node metastases detected by immunohistochemistry in standard node-negative patients with breast carcinomas (13 out of 129 infiltrating ductal carcinomas and 37 out of 89 infiltrating lobular carcinomas) do not have any prognostic significance in patients followed up for a long time (respectively 24 and 18 years). Moreover, their pejorative significance in the literature is debatable since the groups and events taken into account are heterogeneous.

DNA topoisomerase IIα expression and the response toprimary chemotherapy in breast cancer

The α isoform of Topoisomerase IIα (Topo IIα) is a proliferation marker as well as a target for several chemotherapeutic agents such as anthracyclines. In vitro studies have demonstrated the relationship between the Topo IIα expression level and chemosensitivity of target cancer cells. To verify this effect in vivo, we selected 125 patients presenting with T2>3 cm and T3 N0–1 M0 breast tumours who were treated by six cycles of primary chemotherapy, including epirubicin before any surgery. Therapy response was assessed by clinical and X-ray mammogram measurements of tumour shrinkage. The pretherapeutic core biopsies were immunostained with a monoclonal antibody (Ki-S7) against Topo IIα. Ki-S7 positivity ranged from 0 to 50% (median, 15%). A high percentage of Ki-S7-positive cells (>15%) was associated with tumour regression under chemotherapy (OR=2.88, CI: 1.3–6.4, P=0.004). Ki-S7 further emerged as an independent predictor of tumour regression (OR=3.34, CI: 1.41–7.93, P=0.006), together with tumour size of less than 40 mm (OR=3.82, CI: 1.58–9.25, P=0.002) and negative oestrogen receptor (ER) status (OR=3.35, CI: 1.43–7.86, P=0.005), in a multivariate analysis including tumour size, SBR grade, ER and PR status, Ki-67, p53 and Her-2/neu. Our clinical results confirm in vitro data on the relationship between Topo IIα expression and tumour chemosensitivity and thus may have important practical implications.

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

BACKGROUND The 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. OBJECTIVES To 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. METHODS We 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. RESULTS We 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. CONCLUSIONS Older 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.

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

OBJECTIVE Current 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. DESIGN In 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. RESULTS Forty-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. CONCLUSIONS Results 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.

Impacts des avis diagnostiques de cancérologie en Aquitaine. Étude quantitative, qualitative et médicoéconomique rétrospective sur une année

AIMS The goal of this work was to evaluate the impact of expert pathological second opinion on the diagnosis and management of patients with cancer, in a French region (Aquitaine) and with an economic point of view. MATERIAL AND METHODS The study was first quantitative, performed retrospectively on all cases of cancer, voluntary sent for a second opinion to an expert pathologist of two centers. Secondly, we restricted the study to lymphoid, melanocytic and soft tissue tumors sent for second opinion. We considered that the expert review had an important diagnostic impact either when the initial pathologist sent the specimen to identify or classify malignant tumor or hesitated between benign and malignant tumor or had no hypothesis, or if there were discordant diagnoses (malignant/benign) between the two pathologists. We considered that the expert review had a high therapeutic impact if the disagreement between initial and expert diagnoses induced a complete modification in therapy. We evaluated the cost of second opinion for the expert centers and the cost of care management. RESULTS Over the year 2006, the expert centers received 5077 lesions for consultation: 3769 specimens were sent by a pathologist for a second review, 1324 by pathologists of Aquitania and of these, 751 samples were submitted for lymphoid (55%), soft tissues (30%) or melanocytic tumors (15%). There was an important diagnostic impact for 75% of the samples; the impact of the expert review on patient management was considered high for 46% of specimens and the expert pathological diagnosis modified the clinical prognosis for 40% of the specimens. We estimated that for 53 discordant diagnoses (malignant/benign), second opinion allowed an economy of 500,000 euro. CONCLUSION Expert second opinion is very important not only for diagnosis and management for patient with cancer but also for economic reasons.

L’examen cytologique a-t-il encore sa place dans l’analyse extemporanée du ganglion sentinelle dans le cancer du sein ?

Intraoperative examination of sentinel lymph nodes (SLN) in breast cancer can avoid a new surgical procedure in case of positive SLN, but its value, efficacy and the methods used are still controversial. The aim of our study was to evaluate the imprint cytology intraoperative method of SLN analysis performed at our institution. We did a retrospective study of the sentinel lymph node procedures performed during a period of 24  months on cT1N0 unifocal breast cancers. Intraoperative procedure was mainly by imprint cytology (touch prep). A SLN procedure was performed on 187 women with 360 SLN. Two hundred and seventy-seven SLN among 156 women were analyzed intraoperatively by touch prep. 19/48 positive SLN were detected by intraoperative touch prep (sensitivity 39.6%; specificity 100%; positive predictive value 100%; negative predictive value 88.7%, accuracy 89.5%). False negative rate of cytological intraoperative examination of SLN was 11,2% by SLN and 18,3% by patient. By univariate analysis, this rate significantly increased with lymphovascular invasion, tumor size cT1b and c and histological SBR grade 2 or 3. By multivariate analysis, only lymphovascular invasion was a predictive factor of intraoperative touch prep failure (OR = 3.3; IC 1.3-8.4). Intraoperative imprint cytology of SLN in breast cancer is associated with a high rate of false negativity that questions its use in this setting.

Correlation of quality of life with nutritional status and autonomy in elderly cancer patients according to standard geriatric evaluation.

e19532 Background: Number of elderly people is growing and with them the possibility to develop cancer. Specific cares and particularly chemotherapy must allow to maintain their quality of life. Methods: From 2003 to 2006, cohort of 364 patients older than 70 years with cancer was evaluated by oncologist and geriatrician before chemotherapy in public and private hospitals in south-west of France. Quality of life of patients was appreciated by QLQ-C30 completion. Standard geriatric evaluation occurred and oncologic endpoints were collected . Global quality of life, functions and symptoms items were calculated according to Aaronson (JNCI 1993) using EORTC SAS Program provided. Results: Median age was 77.5 years [range 70-99.4] and sex ratio was 214/150 (M/F). Most of patients had metastatic status 65.6% (n = 231) among several cancer location. Creatinine clearance was <50ml/min in 42% (n = 153) and 29.9% presented one comorbidity grade 3-4 and 8.3% at least 2 comorbidities. Global quality of life was not re...