Gilbert B. Zulian

Are Older French Patients As Willing As Older American Patients to Undertake Chemotherapy

PURPOSE A view often held in Europe is that older Europeans are less willing than older Americans to undertake chemotherapy. This study assesses whether this view is valid. PATIENTS AND METHODS Three-hundred twenty outpatients aged 70 years and older were interviewed via anonymous questionnaires: French patients with and without cancer and American patients with and without cancer. The response rate was 61% (195 of 320 questionnaires). Ages ranged from 70 to 95 years (29% aged 80 years and older). Two scenarios were presented: a strong chemotherapy (platinum/taxane combination-like) and a milder chemotherapy (weekly vinorelbine-like). The options were to refuse chemotherapy or to accept for a threshold chance of cure, of life prolongation, or of symptom relief. Functional status, education, self-rated health, and depression were controlled for. RESULTS French noncancer patients (34%) were less willing to accept the strong chemotherapy than French cancer patients (77.8%), American noncancer patients (73.8%), and American cancer patients (70.5%) (P <.001 for each pair). This was also true for the moderate chemotherapy (67.9% v 100%, 95.2%, and 88.5%, respectively; P <.001). Age and sex did not correlate with response, but self-rated health, cancer status, and nationality did. Thresholds varied from patient to patient. CONCLUSION Whereas older French people without cancer are more reluctant than older Americans to envision chemotherapy, older cancer patients in both countries have the same amenability to treatment. Chemotherapy options should be fully discussed with older cancer patients, given that most are willing to consider them.

Multidisciplinary Approach to the Geriatric Oncology Patient

Given the dramatic demographic shift observed in developed countries, the medical community, especially oncologists, geriatricians, and primary care providers, are confronted with the expanding challenge of the management of elderly people with cancer. Ageing is associated with the accumulation of multiple and various medical and social problems. With a prevalence comparable to that of other chronic conditions in this age group, such as diabetes or dementia, cancer holds a prominent place among diseases of the elderly. The care of elderly cancer patients is fundamentally interdisciplinary. Communication and collaboration between geriatricians/primary care providers and oncologists represent key features of effective care in geriatric oncology. The combination of the disease-oriented approach of oncologists and the patient-oriented approach of geriatricians is the most powerful way to better serve this specific population. The medical approach of elderly cancer patients should ideally be under the lead of geriatricians or primary care providers sensitive to geriatric issues. Oncologists should manage the biologic consequences of the interplay between cancer and ageing. Close collaboration between clinicians will help promote active dedicated clinical research and the development of guidelines on the management of elderly people with cancer.

Symptom assessment in elderly cancer patients receiving palliative care

BACKGROUND The purpose of this study is to examine the concordance of symptom assessment among the multiple raters in French-speaking elderly patients with an advanced cancer benefiting from palliative care. PATIENTS AND METHODS This study was conducted in a geriatric hospital with palliative care specificity. During 6 months, patient, nurse and physician completed the Edmonton symptom assessment system on two consecutive days. RESULTS 42 patients with an advanced oncological disease were included. Mean age was 72+/-9.04 (range 52-88) and 23 were females. Mean mini mental status examination (MMSE) was 27.5+/-1.6. First assessment was completed at a median of day 8 after admission. Nurses, physicians and patients assessments were reproducible between days 1 and 2 (P>0.05). Pearson correlation coefficient significantly associated nurse assessment with patient assessment for pain, depression, anxiety, drowsiness, appetite and wellbeing (P<0.05). Physician assessment was associated with patient assessment for pain, depression, drowsiness, appetite, wellbeing and shortness of breath (P<0.05). However, regression analysis looking for patient score from both physicians and nurses scores weakly correlated all these factors (R2<0.6), except for appetite (R2 for day 1/day 2: 0.79/0.64). CONCLUSIONS French-speaking elderly cancer patients without cognitive failure and in stable general condition are consistent in their symptom assessment, and they have to be considered as the gold standard. Nevertheless, interdisciplinary assessment is probably a valid surrogate to self-assessment by the patient but only when the latter is truly impossible.

Role of advance directives in palliative care units: a prospective study:

Advance directives (ADs) might be useful in achieving improved communication and satisfaction with decision making at the end-of-life. Our aims were to better characterise patients with advanced oncological disease who decided to complete ADs and to measure the effect of ADs completion on the satisfaction level with end-of-life care from both patients and their relatives. A prospective study was conducted in three palliative care units. Patients with advanced cancer were included if they met the following criteria: an estimated life expectancy of <6 months, fluency in French, Mini Mental State Examination >20 and not yet completed ADs. All the patients received information about ADs and decided whether to complete ADs or not. The level of satisfaction with involvement in the decision process concerning end-of-life care was assessed by means of a written questionnaire. In all, 53 of 228 patients were included, and 12 decided to complete ADs. Patients who completed ADs had statistically less depression one week after inclusion (P = 0.030), had a lower anxiety score on the second week and had a lower depression score on the third week. There was a trend towards a higher satisfaction level with the involvement of the patients in end-of-life care for those completing ADs (P = 0.878). In conclusion, each patient with an advanced progressive disease should be informed about ADs and be encouraged to complete the ADs with the aim to ease many fears as well as to improve communication.

Do brain T2/FLAIR white matter hyperintensities correspond to myelin loss in normal aging? A radiologic-neuropathologic correlation study

BackgroundWhite matter hyperintensities (WMH) lesions on T2/FLAIR brain MRI are frequently seen in healthy elderly people. Whether these radiological lesions correspond to irreversible histological changes is still a matter of debate. We report the radiologic-histopathologic concordance between T2/FLAIR WMHs and neuropathologically confirmed demyelination in the periventricular, perivascular and deep white matter (WM) areas.ResultsInter-rater reliability was substantial-almost perfect between neuropathologists (kappa 0.71 - 0.79) and fair-moderate between radiologists (kappa 0.34 - 0.42). Discriminating low versus high lesion scores, radiologic compared to neuropathologic evaluation had sensitivity / specificity of 0.83 / 0.47 for periventricular and 0.44 / 0.88 for deep white matter lesions. T2/FLAIR WMHs overestimate neuropathologically confirmed demyelination in the periventricular (p < 0.001) areas but underestimates it in the deep WM (0 < 0.05). In a subset of 14 cases with prominent perivascular WMH, no corresponding demyelination was found in 12 cases.ConclusionsMRI T2/FLAIR overestimates periventricular and perivascular lesions compared to histopathologically confirmed demyelination. The relatively high concentration of interstitial water in the periventricular / perivascular regions due to increasing blood–brain-barrier permeability and plasma leakage in brain aging may evoke T2/FLAIR WMH despite relatively mild demyelination.

Management of Prostate Cancer in Elderly Patients: Recommendations of a Task Force of the International Society of Geriatric Oncology

CONTEXT Prostate cancer is the most frequent male cancer. Since the median age of diagnosis is 66 yr, many patients require both geriatric and urologic evaluation if treatment is to be tailored to individual circumstances including comorbidities and frailty. OBJECTIVE To update the 2014 International Society of Geriatric Oncology (SIOG) guidelines on prostate cancer in men aged >70 yr. The update includes new material on health status evaluation and the treatment of localised, advanced, and castrate-resistant disease. DATA ACQUISITION A multidisciplinary SIOG task force reviewed pertinent articles published during 2013-2016 using search terms relevant to prostate cancer, the elderly, geriatric evaluation, local treatments, and castration-refractory/resistant disease. Each member of the group proposed modifications to the previous guidelines. These were collated and circulated. The final manuscript reflects the expert consensus. DATA SYNTHESIS Elderly patients should be managed according to their individual health status and not according to age. Fit elderly patients should receive the same treatment as younger patients on the basis of international recommendations. At the initial evaluation, screening for cognitive impairment is mandatory to establish patient competence in making decisions. Initial evaluation of health status should use the validated G8 screening tool. Abnormal scores on the G8 should lead to a simplified geriatric assessment that evaluates comorbid conditions (using the Cumulative Illness Score Rating-Geriatrics scale), dependence (Activities of Daily Living) and nutritional status (via estimation of weight loss). When patients are frail or disabled or have severe comorbidities, a comprehensive geriatric assessment is needed. This may suggest additional geriatric interventions. CONCLUSIONS Advances in geriatric evaluation and treatments for localised and advanced disease are contributing to more appropriate management of elderly patients with prostate cancer. A better understanding of the role of active surveillance for less aggressive disease is also contributing to the individualisation of care. PATIENT SUMMARY Many men with prostate cancer are elderly. In the physically fit, treatment should be the same as in younger patients. However, some elderly prostate cancer patients are frail and have other medical problems. Treatment in the individual patient should be based on health status and patient preference.

Transfusion-associated graft-versus-host disease in a patient treated with Cladribine (2-chlorodeoxyadenosine): demonstration of exogenous DNA in various tissue extracts by PCR analysis.

Transfusion-associated graft-versus-host disease can occur in both immunocompetent and immunocompromised hosts. Cladribine is a synthetic analogue of adenine used in the treatment of lymphoid malignancies, commonly associated with a decrease in T lymphocytes. Cladribine was given for a low-grade non-Hodgkins lymphoma with thrombocytopenia as the main side-effect. Six units of pooled non-irradiated platelets were transfused from six unrelated donors; 10 d later a clinical picture typical of graft-versus-host disease resulted. Polymerase chain reaction of the highly polymorphic DNA minisatellites and HLA-DR oligotyping were used to demonstrate the exogenous DNA. In the patients blood and tissues, only the pattern of donor 5 was found. The patient (DRB1*0301/1101; DRB3*0101/02) and this donor (DRB1*0301/1104; DRB3*02) by chance shared a partial common haplotype. This complication highlights the sensitivity of DNA minisatellite analysis. It further raises the question of transfusion and of prophylactic irradiation of all blood products in immunosuppressed patients and those treated with cladribine. This case represents a previously unreported situation where an immunosuppressed patient was able to eliminate cells from five totally HLA-DR dissimilar donors but not from one heterozygous donor with strong HLA-DR similarity.

Palliative care education in Swiss undergraduate medical curricula: a case of too little, too early

Palliative medicine education is an important strategy in ensuring that the needs of terminally ill patients are met. A review was conducted in 2007 of the undergraduate curricula of all five of Switzerland’s medical schools to identify their palliative care-related content and characteristics. The average number of mandatory hours of palliative care education is 10.2 h (median 8 h; range 0–27 h), significantly short of the 40 h recommended by the European Palliative Care Association’s Education Expert Group. The median time allocated to designated palliative care blocks is 3 h (range 0–8 h). Most of the education occurs before the clinical years, and there are no mandatory clinical rotations. Three schools offer optional clinical rotations but these are poorly attended (<10% of students). Although a number of domains are covered, ethics-related content predominates; 21 of a total of 51 obligatory hours (41%). Communication related to palliative care is largely limited to ‘breaking bad news’. In two of the schools, the teaching is done primarily by palliative care physicians and nurses (70% or more of the teaching). In the others, it is done mostly by educators in other clinical specialties and ethics (approximately 90% of the teaching). These findings show significant deficiencies.

Acute myelogenous leukaemia

The incidence of acute myelogenous leukaemia (AML) increases steadily with age, more than 50% of the cases being diagnosed in subjects aged 60 years or over [1,2]. Age has been reported as an adverse prognostic indicator in AML affecting both remission rates and survival [1–3]. The overall unsatisfactory therapeutic results appear related to either host-related factors, (the impaired capacity of older patients to tolerate the toxic effects of dose-intense chemotherapy), and intrinsic differences in the biology of leukaemia itself (Table 1) [4,5]. First, AML in the elderly displays clonal involvement not only at level of the granulomonocytic lineage, as for most of de novo adult AMLs, but also erythroid and megakaryocytic progenitors are often involved [5]. These findings, along with the very frequent expression of the CD34 antigen, suggest that AML in older persons probably originates from a more primitive multipotent stem cell [5,6]. The multilineage involvement and the resulting functional impairment of the residual normal stem cell pool, might account for the reported longer duration of post-chemotherapy aplasia and for the increased risk of induction deaths in the elderly AML [2–5]. Second, unfavourable karyotypic abnormalities are more frequently detected in elderly than in younger AML patients, along with a low frequency of favourable cytogenetic patterns [5–7]. Third, the incidence of AML secondary to a preceding myelodysplastic syndrome (MDS), or the presence of bone marrow tri-lineage dysplastic changes in apparently de novo AMLs, are very elevated in older patients [1–5]. This fact carries an important prognostic significance since, independently from age, AMLs developing after MDS have a high rate of primary resistance to chemotherapy [4,5]. Fourth, FAB cytotypes associated with a poor prognosis (M1, M5 and M6), display a

SYMPTOM RELIEF IN THE LAST WEEK OF LIFE: IS DEMENTIA ALWAYS A LIMITING FACTOR?

older people, despite their being randomized, since the studies are often relatively small. However, this seems not to have been considered in the Cochrane Review for all included studies. For example in a study by Skelton et al., the effect regarding knee extensor strength, as presented in the review, was negative although the improvement from baseline to follow-up was considerably greater in the intervention group than in the control group (127% vs 13%). The calculations of SMD for this study seem to be based in the review on the unadjusted outcome values at the followup and do not take into consideration the fact that baseline values were lower in the intervention group than in the control group. An alternative way of calculating the effect size is to use the change in the outcome from baseline to follow up (both the difference between groups and the standard deviation), based on estimated marginal means for the outcome at the follow-up adjusted for baseline values. This approach takes into account differences between groups at baseline and variations in ability between participants. Hopefully, in future, a consensus will be reached concerning how to calculate effect sizes in randomized trials. For the present, it is recommended that effect sizes are presented but the definitions in the CONSORT statement, e.g., for continuous outcome ‘‘difference in means,’’ need to be clarified to ensure that the calculation is made in the same way in all studies.