Laurent Zelek

Using ONCODOC as a Computer-Based Eligibility Screening System to Improve Accrual onto Breast Cancer Clinical Trials

While clinical trials offer cancer patients the optimum treatment, historical accrual of such patients has not been very successful. OncoDoc is a decision support system designed to provide best therapeutic recommendations for breast cancer patients. Developed as a browsing tool of a knowledge base structured as a decision tree, OncoDoc allows physicians to control the contextual instantiation of patient characteristics to build the best formal equivalent of an actual patient. Used as a computer-based eligibility screening system, depending on whether instantiated patient parameters are matched against guideline knowledge or available clinical trial protocols, it provides either evidence-based therapeutic options or relevant patient-specific clinical trials. Implemented at the Gustave Roussy Institute and routinely used at the point of care during a 4-month period, it significantly improved physician compliance with guideline recommendations and enhanced physician awareness of open trials while increasing patient enrollment to clinical trials by 50%. But, when analyzing reasons of non-accrual of potentially eligible patients, it appeared that physicians psychological reluctance to refer patients to clinical trials, measured during the experiment at 25%, may not be resolved by the simple dissemination of clinical trial information at the point of care.

Physiopathology and management of osteonecrosis of the jaws related to bisphosphonate therapy for malignant bone lesions. A French expert panel analysis

Bisphosphonates (BP) are the current standard of care for preventing malignant skeletal related-events. Recent reports have documented the relationship between osteonecrosis of the jaws (ONJ) and the use of BPs. Based on the opinion of experts, the purpose of our analysis was to summarize current knowledge, to propose therapeutic options, and to define areas of research. Identified risk factors were long-lasting exposure to BPs, intravenous nitrogen-containing BPs, and poor dental status. Three major hypotheses could explain the genesis of ONJ: excess of bone turnover inhibition, antiangiogenic effect, and local infection. Before the onset of therapy, the dental status must be controlled, and followed during treatment. Dental procedures could worsen the risk of ONJ, and indications must be well evaluated. When an ONJ occurs, the management should be adapted according to its extent. Thereby, a customization of BP therapy should be applied taking into account the aggressiveness of the underlying disease.

Fixed-dose rate gemcitabine in elderly patients with advanced pancreatic cancer: an observational study.

Pancreatic cancer represents one of the most lethal cancers and treatment of advanced disease remains palliative. Age-related physiologic changes can increase chemotherapys toxicity but the use of gemcitabine in elderly patients has not been properly evaluated. This observational prospective study evaluated patients aged 70 years and over, receiving gemcitabine for an advanced pancreatic carcinoma. Gemcitabine was delivered according to the usual fixed-dose rate schedule (1000mg/(m(2)week) over 100min, every week, 3 weeks over 4). Thirty-nine patients (median age 74) were treated between November 1999 and August 2004. Twenty-three patients (59%) received 100% of the planned dose-intensity. Grade 3-4 toxicities were neutropenia (38% of patients), thrombocytopenia (28%), anemia (18%) and alopecia (18%). Four partial responses (10%) and 13 stabilizations (33%) were observed. Eight patients (20%) experienced clinical benefit. The median progression free and overall survivals were 7 and 10 months, respectively. Gemcitabine can be administered in selected elderly patients.

SALTO: a randomized, multicenter study assessing octreotide LAR in inoperable bowel obstruction

This phasexa0II, multicenter, randomized, double-blind, non-comparative study assessed the efficacy and safety of immediate-release octreotide and octreotide LAR, in combination with corticosteroids and standard medical care, on the symptoms of inoperable malignant bowel obstruction (MBO) due to peritoneal carcinomatosis. The primary efficacy endpoint was success at dayxa014 defined as a composite endpoint including the absence of a nasogastric tube, and vomiting less than twice per day and no use of anticholinergic agents. Patients in the octreotide arm received octreotide LAR 30u2009mg intramuscular (im) on daysxa01,xa029 andxa057, as well as daily immediate-release octreotide 600u2009μg per day plus methylprednisolone on days 1 to 6. Placebo-treated patients received methylprednisolone and matched placebo instead of octreotide. Difficulties associated with enrolling patients at palliative-care stage meant only 64xa0patients (instead of the planned 102xa0patients) were randomized, 32xa0to octreotide and 32xa0to placebo. Despite randomization, more patients in the octreotide arm (46.4%) than in the placebo arm (21.9%) had a baseline Karnofsky score less thanxa050. An intention-to-treat analysis showed that in the octreotide and placebo arms, 12xa0(38%) and nine (28%), respectively, patients were successfully treated at dayxa014, which increased to 9/15 (60%) and 7/25 (28%), respectively, among patients with a baseline Karnofsky score greater or equal toxa050. Octreotide-treated patients reported three drug-related adverse events (AEs), and no drug-related serious AEs or deaths. Octreotide LAR may have a key role in treating patients with a MBO due to peritoneal carcinomatosis, particularly in those with moderately severe disease.

Using formal concept analysis to discover patterns of non-compliance with clinical practice guidelines: a case study in the management of breast cancer

Clinical decision support systems (CDSSs) may be appropriate tools to promote the use of clinical practice guidelines (CPGs). However, compliance with CPGs is a multifactorial process that relies on the CPGs to be implemented, the physician(s) in charge of the decision, and the patient to manage. Formal concept analysis (FCA) allows to derive implicit relationships from a set of objects described by their attributes, based on the principle of attribute sharing between objects.We used FCA to elicit patient-based formal concepts related to the non-conformity of multidisciplinary staff meetings (MSMs) decisions with CPGs in the domain of breast cancer management. We developed a strategy for selecting attributes and make lattices manageable. We found that when not using the guideline-based CDSS OncoDoc2, patients with bad prognostic factors were associated with non-compliant decisions. This was corrected when the system was used during MSMs.

Cancer du sein métastatique

RésuméSi la prise en charge du cancer du sein précoce est relativement bien codifiée, il n’en est pas de même pour le cancer du sein métastatique où les attitudes sont extrêmement variables. Les recommandations édictées pour la prise en charge du cancer du sein métastatique visent essentiellement à établir une liste des molécules disponibles et des traitements possibles en fonction du statut ménopausique et des récepteurs hormonaux (RH). Si l’on considère tous les éléments pouvant influencer la décision thérapeutique, l’objectif de la présente réflexion a été de s’orienter vers une attitude consensuelle chez les patientes ayant un cancer du sein métastatique. Les facteurs pronostiques décisionnels retenus ont été l’intervalle libre sans maladie, la localisation viscérale des métastases, les RH et éventuellement les LDH. Les facteurs prédictifs acquis de la réponse au traitement sont les RH et le statut HER2. Le choix de ces facteurs prédictifs et l’agressivité de la maladie ont conditionné les options thérapeutiques de première ligne à savoir chimiothérapie (mono-ou polychimiothérapie, concomitante ou séquentielle), hormonothérapie ou hormonochimiothérapie.AbstractAlthough the treatment of early breast cancer is relatively well-defined, therapeutic options for metastatic breast cancer remains controversial. The published guidelines for the management of metastatic breast cancer mainly aim to draw up a list of available agents and treatments according to menopausal status and hormone receptors (HR). Taking into account all the variables influencing therapeutic decision-making, the purpose of the present study was to find a consensus with respect to patients with metastatic breast cancer. The selected prognostic factors were disease-free duration, visceral metastasis, HR, and possibly LDH. The validated predictive factors of response to treatment were HR and HER2 status. The choice of these predictive factors as well as the disease’s level of aggressiveness were the basis for the choice of first-line treatment i.e. chemotherapy (mono-or polychemotherapy, concomitant or sequential), hormonotherapy, or chemoendocrine therapy.

Cancers du Sein Métastatique

Résumé:La prise en charge des patientes atteintes d’un cancer du sein métastatique devient de plus en plus complexe. L’évolution actuelle des traitements adjuvants est en train demodifier l’étendue de l’arsenal thérapeutique disponible une fois le stade métastatique atteint. En l’absence de consensus, cet article a pour objectif de présenter les options thérapeutiques à notre disposition en termes de chimiothérapie de 1ère ligne pour le cancer du sein métastatique en tenant compte des caractéristiques de la patiente, de sa tumeur, ainsi que des traitements préalablement reçus en situation adjuvante. A partir d’une analyse de la littérature, nous avons établi un arbre décisionnel afin d’orienter les stratégies thérapeutiques envisageables et tenter de répondre au mieux à la question «quelle chimiothérapie de 1ère ligne et pour quelle patiente?».Abstract:The management of metastatic breast cancer patients is becoming increasingly complex. The present development of adjuvant therapy is modifying the range of available treatments for once the metastatic stage is reached. Bearing in mind the lack of consensus, the purpose of this article is to highlight current options for metastatic breast cancer first-line chemotherapy taking into account the characteristics of the patient and the tumor as well as previous adjuvant treatments received. The analysis of literature has guided us to establish a treatment algorithm that considers possible therapeutic choices, and tries to provide an optimal answer to “which first-line chemotherapy for which patient?”

Which patients may benefit from the use of a decision support system to improve compliance of physician decisions with clinical practice guidelines: a case study with breast cancer involving data mining.

OncoDoc2 is a guideline-based clinical decision support system (CDSS) for breast cancer management. It has been used as an intervention in a randomized controlled trial carried out to evaluate the impact of using a CDSS upon the compliance with clinical practice guidelines (CPGs) of multidisciplinary staff meeting decisions. Data mining was used to discover multi-criteria regularities as emerging patterns (EPs) associated with compliance and non-compliance with CPGs when using and not using OncoDoc2 and to assess which patients may benefit from the use of the CDSS. Decision data was collected from all participating centers. The number of EPs associated with non-compliance is smaller in the intervention arm, which suggests a practice harmonization effect of OncoDoc2. EPs associated with compliant decisions in both arms of the trial correspond to situations well identified in CPGs. EPs associated with non-compliant decisions when the system is not used are associated with compliance when the system is used except in clinical situations where evidence is lacking.

CT and MRI in radiotherapy

In radiotherapy, the use of cross sectional imaging for planning the treatment planes has the advantage of combining precise anatomical details (tumor volume, critical organs) with the differences in tissue density necessary for dose calculations. A diagnostically targeted CT is used to choose the number and position of sections necessary for calculating the distributions of the dose.