Multiple Myeloma in Patients over 80: A Real World Retrospective Study of First Line Conservative Approach with Bortezomib Dexamethasone Doublet Therapy and Mini-Review of Literature.

Data on octogenarian patients with MM are scarce, and optimal management remains controversial. We report a retrospective cohort of unselected octogenarian patients with NDMM treated with bortezomib dexamethasone (Vd). Seventy-four patients were treated with an initial doublet therapy (Vd regimen, 2−3 cycles, induction). A dose escalation with an adjunction of melphalan or cyclophosphamide was proposed for patients who had an insufficient response after induction and who could tolerate it. In responders, the treatment was continued until progression or a plateau response for 6 months (consolidation). The overall response rate was 73%. After a median follow-up of 31.4 months, median progression-free survival (PFS) and overall survival (OS) were 13.2 and 26.9 months, respectively. PFS and OS of patients with ECOG PS < 3 (25.4 and 54.9 months, respectively) were better in comparison to PFS and OS of patients with ECOG PS ≥ 3 (9.3 and 11.3 months, respectively). Thirteen patients (17.6%) died during induction. Twelve patients (16.2%) died during consolidation. In conclusion, a conservative therapeutic strategy based on Vd resulted in a good response rate. However, the survival remains poor in the population of patients with an ECOG PS ≥ 3, mainly because of early mortality not related to progressive disease.

Utilization of intravenous or subcutaneous immunoglobulins in secondary immune deficiency (ULTIMATE): A retrospective multicenter study.

INTRODUCTION: We conducted a retrospective multicenter cohort study of patients receiving Immunoglobulin replacement therapy (IgRT) for secondary immune deficiency (SID) during 2012. METHODS: Data were retrospectively collected from the first dose of Ig administered in 2012 to 1 year afterward in terms of the indication for IgRT, as well as efficacy and safety. RESULTS: In total, 16 hospitals participated in the study, and 368 patients were included. Indications for IgRT were non-Hodgkin lymphoma (82 [22.3%] patients), multiple myeloma (76 [20.7%]), chronic lymphocytic leukemia (64 [17.4%]) and other (79 [21.5%]). Only 89 (24.2%) patients received IgRT according to 2011 European Medical Agency (EMA) recommendations; 196 (53.3%) received prophylactic antibiotics and 262 (76.2%) had an IgG level < 4 g/L before IgRT initiation. CONCLUSION: In this study, whatever the criteria, only 24.2% of patients with SID who received IgRT met EMA recommendations, which suggests a misuse of IgRT in SID.

Multicenter phase III randomized trial comparing laparoscopy and laparotomy for colon cancer surgery in patients older than 75 years: the CELL study, a Fédération de Recherche en Chirurgie (FRENCH) trial.

BACKGROUND: Several multicenter randomized controlled trials comparing laparoscopy and conventional open surgery for colon cancer have demonstrated that laparoscopic approach achieved the same oncological results while improving significantly early postoperative outcomes. These trials included few elderly patients, with a median age not exceeding 71 years. However, colon cancer is a disease of the elderly. More than 65% of patients operated on for colon cancer belong to this age group, and this proportion may become more pronounced in the coming years. In current practice, laparoscopy is underused in this population. METHODS: The CELL (Colectomy for cancer in the Elderly by Laparoscopy or Laparotomy) trial is a multicenter, open-label randomized, 2-arm phase III superiority trial. Patients aged 75 years or older with uncomplicated colonic adenocarcinoma or endoscopically unresectable colonic polyp will be randomized to either colectomy by laparoscopy or laparotomy. The primary endpoint of the study is overall postoperative morbidity, defined as any complication classification occurring up to 30 days after surgery. The secondary endpoints are: 30-day and 90-day postoperative mortality, 30-day readmission rate, quality of surgical resection, health-related quality of life and evolution of geriatric assessment. A 35 to 20% overall postoperative morbidity rate reduction is expected for patients operated on by laparoscopy compared with those who underwent surgery by laparotomy. With a two-sided α risk of 5% and a power of 80% (ß = 0.20), 276 patients will be required in total. DISCUSSION: To date, no dedicated randomized controlled trial has been conducted to evaluate morbidity after colon cancer surgery by laparoscopy or laparotomy in the elderly and the benefits of laparoscopy is still debated in this context. Thus, a prospective multicenter randomized trial evaluating postoperative outcomes specifically in elderly patients operated on for colon cancer by laparoscopy or laparotomy with curative intent is warranted. If significant, such a study might change the current surgical practices and allow a significant improvement in the surgical management of this population, which will be the vast majority of patients treated for colon cancer in the coming years. TRIAL REGISTRATION: ClinicalTrials.gov NCT03033719 (January 27, 2017).

[Analysis of 736 blood transfusions in a geriatric teaching hospital]. / Seuils et objectifs transfusionnels chez des patients de plus de 75ans : analyse de 736 transfusions de culots globulaires et comparaison aux recommandations.

BACKGROUND: Red blood cell transfusion in elderly patients with anemia requires taking into account a hemoglobin threshold, as well as comorbidities that may be decompensated by anemia. In the absence of consensual indications for blood transfusion in the elderly population, it seems important to evaluate the practical approach of blood transfusion in geriatrics. We analyzed prescriptions of red blood cell transfusion in very old patients hospitalized in a geriatric teaching hospital. METHODS: This retrospective study was based on information collected during one year in 736 red blood cell transfusion prescriptions. Hemoglobin levels, numbers of red blood cell units and clinical informations notified by prescribing physicians have been collected and analyzed. RESULTS: The mean hemoglobin level before red blood cell transfusion was 8.45±0.94g/dL. Two variables were significantly associated with an increase of the transfusion threshold above 9g/dL: the poor tolerance of anemia (P<10(-4)) and clinical situations at risk for poor tolerance of anemia (P=0.0076). The most frequent symptoms of poor tolerance of anemia were cardiovascular symptoms and also acute neuropsychiatric symptoms that could be considered as specific criteria for the red cell transfusion in the elderly. The mean number of red blood cell units prescribed for each transfusion was 1.88±0.55 and the only predictive factor was the hemoglobin level (P<0.001). PERSPECTIVES: In our geriatric practice, transfusion thresholds and target hemoglobin levels after transfusion seemed to be comparable with the thresholds recommended in the only available French guidelines edited in 2002 by the Afssaps. However, our study pointed out specific geriatric particularities in red blood cell transfusion prescriptions with the use of some tolerance criteria that seem related to non-cardiovascular comorbidities. Future prospective interventional studies could be conducted in order to evaluate the clinical relevance of these potential specific geriatric criteria in transfusion indications.

Anemia in the elderly: usefulness of an easy and comprehensive laboratory screen.

Anemia, the most common hematological disorder in the elderly, increases the risk of mortality and morbidity and adversely affects quality of life. However, few studies focused specifically on anemia in the elderly, especially regarding the underlying causes. The main objective of this prospective study was to evaluate the causes of anemia in non-institutionalized elderly patients. We included 190 consecutive patients ≥70 years, admitted to a geriatric short-stay unit over a 1-year period. When the hemoglobin level was <120 g/L, the following serum assays were performed routinely: iron, ferritin, transferrin saturation, folate, vitamin B12, C-reactive protein, TSH, albumin, and haptoglobin. When these tests were normal, bone marrow aspiration was performed to look for myelodysplastic syndrome. Hemoglobin was <120 g/L in 83 (43.7%) of 190 included patients. Patients with anemia had a mean hemoglobin level of 105 ± 11 g/L. The most common potential causes of anemia were inflammation, severe renal impairment, severe malnutrition, and iron deficiency; each of these causes was found in at least one-third of patients with anemia. Myelodysplastic syndrome was found in all anemic patients with a normal serum screen (12/83, 14.5%). Anemia was multifactorial in most patients: the mean number of potential causes per patient was 1.85 ± 1, and 65.4% of the patients had two to four concomitant causes. The serum screen used in our study is easy to perform in ambulatory patients and identifies potential causes of anemia for which safe and effective treatments are available. Second-line bone marrow aspiration adds to the diagnostic yield.

Current targeted therapies in breast cancer: clinical applications in the elderly woman.

The incidence of breast cancer is two to three times higher in women aged ≥65 years than in the whole population, whereas their mortality rate is threefold to fourfold higher. Targeted therapies allow significantly longer disease-free survival times. Nevertheless, in an elderly population, these treatments need to be prescribed with caution. This paper reviews the treatments of breast cancer in the elderly, and the issues of targeted therapies and their toxicities. Patients with human epidermal growth factor receptor (HER)-2(+) breast cancer benefit from trastuzumab; although cardiotoxic effects are observed in <5% of patients when given alone, they affect ~25% of patients when combined with anthracyclines. Bevacizumab leads to a longer progression-free survival time and lower risk for progression in patients with metastatic breast cancer when added to paclitaxel or docetaxel. Although generally well tolerated, it is associated with a higher risk for arterial thromboembolism and hypertension. Lapatinib is approved for the treatment of advanced or metastatic breast cancer in patients not responding to trastuzumab, combined with capecitabine chemotherapy. The most frequent side effects concern the gastrointestinal system and dermatologic symptoms. The life expectancy of breast cancer patients should be taken into account to determine the appropriateness of treatments. The quality of life of elderly cancer patients must be assessed with an appropriate tool. Older patients exhibit greater vulnerability, suggesting identification and exclusion of patients at high cardiac risk. Future recommendations for the treatment of elderly women with breast cancer should include a multidisciplinary approach and a global geriatric assessment before treatment with anti-HER-2 therapy or bevacizumab.

Influence of geriatric consultation with comprehensive geriatric assessment on final therapeutic decision in elderly cancer patients.

Elderly patients represent a heterogeneous population in which decisions on cancer treatment are often difficult. The present study aims to report a 2-year period of the activity of geriatric assessment consultations and the impact on treatment decisions. Since January 2007, we have systematically carried out geriatric consultations, using well-known international scales, for elderly patients in whom treatment decisions appear complex to oncologists. From January 2007 to November 2008, 161 patients (57 men, 104 women; median age 82.4 years, range 73-97) were seen at geriatric consultations. Most of the patients (134/161) were undergoing first-line treatment and cancer was metastatic in 86 patients (53%). Geriatric assessment found severe comorbidities (grade 3 or 4 in CIRS-G scale) in 75 patients, dependence for at least one activity of daily living (ADL) in 52 patients, cognitive impairment in 42 patients, malnutrition in 104 patients (65%) and depression in 39 patients. According to the oncologists' prior decisions, there were no changes in treatment decisions in only 29 patients. Cancer treatment was changed in 79 patients (49%), including delayed therapy in 5 patients, less intensive therapy in 29 patients and more intensive therapy in 45 patients. Patients for whom the final decision was delayed or who underwent less intensive therapy had significantly more frequent severe comorbidities (23/34, p<0.01) and dependence for at least one ADL (19/34, p<0.01). In this study, we have found that comprehensive geriatric evaluation did significantly influence treatment decisions in 82% of our older cancer patients.

[Elderly patients with myelodysplastic syndrome with del 5q receiving lenalidomide: two case reports with poor prognosis]. / Patients âgés atteints de syndrome myélodysplasique avec anomalie 5q- traités par lénalidomide : à propos de deux observations avec évolution défavorable.

We report two cases of myelodysplastic syndrome (MDS) with del(5q) isolated cytogenetic abnormality in elderly patients: AREB-1 in Patient 1, "5q syndrome" in Patient 2. A first line of treatment including hematopoietic growth factors (darbepoetin alone or associated with G-CSF) failed after several months and a treatment with lenalidomide was initiated in both cases. The treatment was poorly tolerated (myelosuppression) in Patient 1 without an improvement of the quality of life; a progression of the disease was observed with an increase of the bone marrow blastosis and a new acquired karyotypic abnormality (t13;17), leading to the prescription of 5-azacytidine. Patient 2 had a good response to lenalidomide for several months with an increase in the haemoglobin level and a transfusion independence. The patient's prognosis suddenly worsened with the occurrence of a blood blastosis (10%): 5-azacytidine was thus initiated. These two case reports illustrate the recent advances in the management of patients with MDS with del(5q), including the use of lenalidomide.

[Geriatric oncology: epidemiological evidence]. / Oncogériatrie : une évidence épidémiologique.

In Europe, 60% of all cancers and 75% of all deaths from cancer occur in patients older than 65 years. The incidence of many cancers (prostate, colorectal, and hematological) either increases with age or remains high (breast and lungs). The two principal characteristics of cancer in the elderly are late diagnosis and comorbidity that requires specific geriatric assessment and cooperation between the oncologist and the geriatrician. Academic and pharmaceutical industry research must focus on the specificities of cancers in the elderly and of response to treatment according to functional abilities and comorbidity. Equal access to high quality medical care and procedures must be ensured, regardless of age; this is not currently the case everywhere.

Placement of the VenaTech LP caval filter in the elderly: feasibility and clinical benefits of insertion via the arm.

PURPOSE: To evaluate routine use of access sites in the arm for percutaneous caval filter placement (PCFP) in elderly patients. Neck arthritis, patient anxiety, access site thrombosis or fecal/urinary incontinence complicating jugular or femoral access may require alternative access sites in this population. METHODS: Access via the right arm was chosen for PCFP (VenaTech LP). The indication for PCFP was deep vein thrombosis, a history of pulmonary embolism, and a contraindication to anticoagulant therapy. Ultrasound-guided puncture was performed after diameter measurement of the arm veins (ØAV). The filter was inserted with standard imaging procedures. Procedural difficulty was graded and compared with ØAV and the angle from the arm vein to the superior vena cava (alphaAV/SVC). RESULTS: Over 2 years, 16 patients (14 women, 2 men) with an average age of 90 years (range 79-97 years) were included in the study. The average ØAV value of the basilic or brachial veins was 4.2 mm (range 3.0-5.1 mm). The minimal ØAV for successful access was determined after the first 15 patients. No hematoma occurred at the puncture sites. The average alphaAV/SVC value was 62 degrees (range 29 degrees -90 degrees ). Arm access was possible in 12 of 16 patients (75%) with ØAV >or= 3.5 mm and alphaAV/SVC >or= 29 degrees . Every procedure via the arm was graded "easy" by the operator, regardless of angulation values. Femoral access was used in one case due to the impossibility of traversing the heart (patient no. 2), and jugular access was used in 3 of 16 (19%) patients due to puncture failure (patient no. 4), small ØAV (3 mm) (patient no. 6), and stenosis of the distal right subclavian vein (patient no.16), respectively. CONCLUSION: PCFP via the arm can be routinely accomplished in patients older than 75 years, provided ØAV >or= 3.5 mm, and alphaAV/SVC >or= 29 degrees .

Valproic acid and all-trans retinoic acid for the treatment of elderly patients with acute myeloid leukemia.

Valproic acid (VPA) has been demonstrated to be able to inhibit histone deacetylase activity and to synergize with all-trans retinoic acid (ATRA) in inducing the differentiation of acute myeloid leukemia (AML) cells. A pilot study of the VPA/ATRA combination was performed in 11 elderly patients with de novo AML (median age, 82 years). Complete marrow response was observed in 3 patients, including 1 complete remission. Two additional patients had hematologic improvement.

[Anatomo-physiological aspects of the lower urinary tract in men and modifications related to ageing]. / Aspects anatomo-physiologiques de l'appareil vésico-sphinctérien chez l'homme et modifications liées au vieillissement.

MICTURITION AND INCONTINENCE: The lower urinary tract, composed of several organs necessary for micturition, is controlled by the encephalic and peripheral centres, which have a synergic effect and coordinate the lower urinary tract. Continence is ensured by the effect of the adrenergic sympathetic nerve that increases urethral sphincter tonus and maintains low pressure in the bladder during filling. Micturition appeals to the cholinergic system mediated by the muscarinic receptors situated in the bladder. AGEING OF THE PROSTATE: Under the influence of dihydrotestosterone and growth factors, ageing of the prostate is characterized by histological modifications leading to hypertrophy, obstructing the flow of urine. AGEING OF THE BLADDER: Electronic microscopy studies have shown the presence of degenerative lesions and, on urodynamic level, are characterised by over or under-activity. Ageing of the peripheral and central nervous centres is morphological and metabolic with the production of vascular and free radicals, involving the systems that control micturition and continence. The ageing kidney has a tendency to produce more urine at night because of the functional changes that intervene in the salt and water balance regulation systems.

[Clinical manifestations of urinary disorders and their treatment in ageing men]. / Manifestations cliniques des troubles urinaires chez l'homme vieillissant et leur traitement.

PROBLEMS OF THE PROSTATE: Benign hypertrophy of the prostate (BHP), when it occurs, is manifested by an obstruction or irritation related to overactivity of the bladder. The obstructive syndrome is defined by urodynamic tests. Urge incontinence and study of the pressure-flow ratio are the tests of choice. The functional handicap and impact on quality of life are assessed using the International Prostatism Symptoms Score (I-PSS). Efficient and fairly well tolerated medical treatment has reduced the indications for surgery. It relies on alpha-blockers, 5a-reductase inhibitors and phytotherapy. When indicated, the surgical treatment of choice is endoscopic resection of the prostate. Among the non-prostatic micturition disorders, urge micturition with, in extreme cases, incontinence are due to detrusor instability. This is of multifactor origin; enhanced by the local irritation or environmental factors, it usually occurs within a context of acute or chronic pathologies. Treatment is recommended with anticholinergic agents. New molecules have recently been launched, better tolerated than oxybutinine. Electrostimulation can be a good alternative in mentally normal patients. Micturition due to excess urine may be due to overactivity of the bladder, the major risk of which is acute urine retention. It can also be observed during neurological affections such as Parkinson's disease or during administration of certain drugs. Nocturnal polyuria is a frequent problem. However, simple hygiene and dietary measures and the control of certain concomitant diseases can usually relieve the symptoms. Medical treatment relies on desmopressine.

[Monoclonal gammopathy of undetermined significance]. / Les gammapathies monoclonales de signification indéterminée.

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic disorder with serum monoclonal immunoglobulin less than 30 g/l. It preferentially affects elderly patients; MGUS prevalence is about 1% in the general population and about 10% in patients aged over 80 years. MGUS diagnosis is based on elimination of other causes of serum monoclonal immunoglobulin, particularly multiple myeloma. Within the 20 years following diagnosis of MGUS, about 25% of patients will evolve towards myeloma or other malignant lymphoproliferative disorder. No factor has been identified to date which can efficiently predict this evolution. Recent data concerning immunophenotype, cytogenetics and molecular biology of plasma cells demonstrate the link between MGUS and multiple myeloma. MGUS clearly appears now as a plasma cell monoclonal pathology with reduced malignity. Soon, new biological data would help to discriminate patients with MGUS who will remain asymptomatic life-long from those who will evolve towards malignant lymphoproliferative disorder.