Johan Menten

Phase II Study of First-Line Chemotherapy With Temozolomide in Recurrent Oligodendroglial Tumors: The European Organization for Research and Treatment of Cancer Brain Tumor Group Study 26971

PURPOSE Oligodendroglial tumors are chemotherapy-sensitive tumors, with two thirds of patients responding to combination chemotherapy with procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ), a new alkylating and methylating agent, has demonstrated high response rates in patients with recurrent anaplastic astrocytoma. We investigated TMZ as first-line chemotherapy in recurrent oligodendroglial tumors (OD) and mixed oligoastrocytomas (OA) after surgery and radiation therapy. PATIENTS AND METHODS In a prospective, nonrandomized, multicenter, phase II trial, patients were treated with 200 mg/m2 of TMZ on days 1 through 5 in 28-day cycles for 12 cycles. Patients with a recurrence after prior surgery and radiotherapy, and with measurable and enhancing disease on magnetic resonance imaging (MRI) were eligible for this study. Patients with large lesions and mass effect or with new clinical deficits were not eligible. Pathology and the MRI scans of all responding patients were centrally reviewed. RESULTS Thirty-eight eligible patients were included. In three patients, pathology review did not confirm the presence of an OD or OA. TMZ was generally well tolerated. The most frequent side effects were hematologic; only one patient discontinued treatment for toxicity. In 20 (52.6%) of 38 patients (95% exact confidence interval, 35.8% to 69.0%), a complete (n = 10) or partial response to TMZ was observed. The median time to progression was 10.4 months for all patients and 13.2 months for responding patients. At 12 months from the start of treatment, 40% of patients were still free from progression. CONCLUSION TMZ provides an excellent response rate with good tolerability in chemotherapy-naive patients with recurrent OD. A randomized phase III study comparing PCV with TMZ is warranted.

Cognitive status and quality of life after treatment for primary CNS lymphoma

Objective: To evaluate the cognitive status and quality of life (QOL) in a cohort of 19 consecutive patients treated in a prospective European Organization for Research and Treatment of Cancer study (20962) for primary CNS lymphoma (PCNSL). All patients were in complete remission after combined modality treatment with IV and intrathecal high-dose methotrexate (MTX)-based chemotherapy followed by whole brain radiotherapy (WBRT). Methods: An extensive neuropsychological assessment, including QOL measures, was conducted in 19 patients with PCNSL. The results were compared with matched control subjects with systemic hematologic malignancies treated with systemic chemotherapy or non-CNS radiotherapy. In addition, a neuroradiologic evaluation was carried out in 18 patients with PCNSL. Results: Cognitive impairment was found in 12 patients with PCNSL (63%) despite a complete tumor response. Four patients (21%) showed severe cognitive deficits, and the percentage of impaired test indices correlated with age. In comparison, only two control subjects (11%) showed cognitive dysfunction (p = 0.002). Forty-two percent of the patients with PCNSL, in contrast to 81% of the control subjects, resumed work. White matter abnormalities were observed in 14 patients with PCNSL, and 14 had cortical atrophy. Cortical atrophy correlated with cognitive functioning, age, and Karnofsky performance score. Group differences in cognitive status and QOL could not be explained by anxiety, depression, or fatigue. Conclusions: Combined modality treatment for primary CNS lymphoma is associated with cognitive impairment even in patients aged <60 years.

Salvage PCV chemotherapy for temozolomide-resistant oligodendrogliomas

The authors investigated the results of PCV chemotherapy within a cohort of 24 patients treated within the EORTC study 26971 on temozolomide chemotherapy in recurrent oligodendroglioma. The genotype of the tumors was assessed with fluorescent in situ hybridization with locus specific probes for the region 1p36. Four of the 24 patients responded (17%). Fifty percent of patients were still free from progression at 6 months and 21% were free from progression at 12 months. Although a clear relation existed between loss of 1p and response to temozolomide chemotherapy, this relation was absent in salvage PCV chemotherapy.

What do hospital professionals report as helping in overcoming obstacles for ACP decision-making? A qualitative study

Background: Advance Care Planning (ACP) can be defined as an ongoing process of communication between patients and (in-) formal caregivers to help an individual identify, reflect upon, discuss, and express her or his values, beliefs, goals, and priorities to guide individual care and treatment decision making when nearing end of life. Studies suggest ACP is not well implemented in the hospital setting. This contrast sharply to the necessity of those conversations in hospitals: treatment decisions are made which potentially have a big impact on the patient’s and families quality of life. AIMS: In order to facilitate the implementation of the ACP decision making process in hospital, it might be interesting to know what helps hospital professionals to overcome challenges. Methods: 24 semi-structured interviews were taken from hospital physicians, nurses, psychologists and social workers and analyzed using content analysis based upon grounded theory principles. Results: Participants reported that finding consensus about treatment and care was difficult. Furthermore, finding consensus on when to start decision making conversations with patients was difficult. Helping factors are multidisciplinary cooperation and strategies to convince one another, like the use of rhetoric’s. Also, working closely together is also seen to be advantageous, because opinions can be checked and one can learn from more experienced colleagues. Conclusion: This study gives an insight in how ACP is conducted in hospital practice and what is experienced as helping to overcome obstacles. Results can be used to facilitate implementation, for example by educating professionals. Correspondence to: Birgit Vanderhaeghe, Palliative Support Team, University Hospitals Leuven, B-3000 Leuven, Belgium, E-mail: birgit.vanderhaeghen@kuleuven.be Received: April 06, 2017; Accepted: May 07, 2017; Published: May 10, 2017 Introduction In recent history, calls for the strengthening of individual patient rights and participation in decision-making, have led to the development of the concept Advance Care Planning [1]. Advance Care Planning (ACP) can be defined as an ongoing process of communication between patients and (in-)formal caregivers to help an individual identify, reflect upon, discuss, and express her or his values, beliefs, goals, and priorities to guide individual care and treatment decision making when nearing end of life [2]. The ACP decision-making process is important in the hospital setting for many reasons. A first argument is that an important goal of ACP decision-making is guaranteeing continuation of care throughout the different care settings [3]. Second, in order to prevent hospital admissions for palliative patients, health services often focus on the implementation of ACP in the primary care setting and nursing homes [4–11]. However, still many palliative patients reside and die in the hospital setting [12–16]. When admitted to the hospital, palliative patients often experience the disease and treatment burden strongly. In these moments, questions concerning the meaning of treatment and disease may arise in patients. It is not a remote theoretical discussion that doesn’t concern them [17–20]. In this setting, treatment decisions are made which potentially have a big impact on the palliative patient’s daily life and might even cause or hasten death [21]. The biggest treatment decisions indeed concern hospital treatments (e.g. starting chemo therapy, stopping hemodialysis, placement of defibrillator ...) [22]. Furthermore, if the palliative patient loses competence in hospital, life-sustaining measures including cardiopulmonary resuscitation (CPR) are routinely implemented [23]. In the absence of advance directives (AD’s) or medical instructions, this may lead to unwanted resuscitation [24]. Studies show that a lack of ACP discussions in hospital may lead to patients feeling overly optimistic about their prognosis, thereby choosing too aggressive medical treatment with a high burden of toxicity or side effects a high likelihood of an undesirable outcome [25,26]. However, studies suggest ACP is not well implemented in this setting for palliative patients [10,27–30]. Implementation literature emphasizes the importance of a good understanding of experienced barriers and helpful factors [31–38]. In order to implement ACP more easily in hospital, it is valuable to have a better understanding of the ways in which hospital professionals deal with, and overcome these barriers [31]. In this article, we focus on what is seen as helpful Vanderhaeghen B (2017) What do hospital professionals report as helping in overcoming obstacles for ACP decision-making? A qualitative study Volume 1(1): 2-5 Int Clin Med, 2017 doi: 10.15761/ICM.1000104 for hospital professionals to overcome experienced obstacles for ACP discussions. The research question of the study is: ‘What is seen as helpful by hospital professionals to overcome challenges for the implementation of ACP conversations with patient and their families?’