Associated Factors to Efficacy and Tolerance of Immunotherapy in Older Patients with Cancer Aged 70 Years and Over: Impact of Coprescriptions.

BACKGROUND: Immunotherapy with immune checkpoint blockers (ICB) significantly improves the prognosis for an increasing number of cancers. However, data on geriatric populations taking ICB are rare. OBJECTIVE: This study aimed to identify factors associated with the efficacy and tolerance of ICB in an older population. PATIENTS AND METHODS: This retrospective monocentric study included consecutive patients aged ≥ 70 years with solid cancer who received ICB between January 2018 and December 2019. Efficacy was assessed by progression-free survival (PFS) and tolerance was defined as cessation of immunotherapy due to the occurrence of any adverse event. RESULTS: One hundred and five patients (65.7% men) were included, mainly at the metastatic stage (95.2%); 50.5% had lung cancer. Most (80%) patients were treated with anti-PD1 (nivolumab, pembrolizumab), 19.1% with anti-PD-L1 (atezolizumab, durvalumab, and avelumab) and 0.9% with anti-CTLA4 ICB (ipilimumab). Median PFS was 3.7 months [95% confidence interval (CI) (2.75-5.70)]. PFS was shorter in univariate analysis when ICB was taken concomitantly with an antiplatelet agent (AP) [hazard ratio (HR) = 1.93; 95% CI (1.22-3.04); p = 0.005]. Tolerance was lower in univariate analysis for lung cancer [odds ratio (OR) = 3.03; 95% CI (1.07-8.56), p < 0.05] and in patients taking proton pump inhibitors (PPI) [OR = 5.50; 95% CI (1.96-15.42), p < 0.001]. There was a trend toward poorer tolerance among patients living alone [OR = 2.26; 95% CI (0.76-6.72); p = 0.14]. CONCLUSIONS: In older patients taking ICB for solid cancers, concomitant AP may influence efficacy and concomitant PPI may influence tolerance. Further studies are needed to confirm these results.

Long-term quality of life and sexual function of elderly people with endometrial or ovarian cancer.

BACKGROUND: With the growing number of older endometrial cancer (EC) and ovarian cancer (OC) survivors, data on long-term health-related quality of life (HRQoL) became an important issue in the management of older patients. So, the aim of this study was to describe and compare according to age long-term HRQoL, sexual function, and social deprivation of adults with either EC or OC. METHODS: A cross-sectional study was set up using data from the Côte d'Or gynecological cancer registry. A series of questionnaires assessing HRQoL (SF-12), sexual function (FSFI), anxiety/depression (HADS), social support (SSQ6) and deprivation (EPICES) were offered to women with EC or OC diagnosed between 2006 and 2013. HRQoL, sexual function, anxiety/depression, social support and deprivation scores were generated and compared according to age (< 70 years and ≥ 70 years). RESULTS: A total of 145 women with EC (N = 103) and OC (N = 42) participated in this study. Fifty-six percent and 38% of EC and OC survivors respectively were aged 70 and over. Treatment did not differ according to age either in OC or EC. The deprivation level did not differ between older and younger survivors with OC while older survivors with EC were more precarious. The physical HRQoL was more altered in older EC survivors. This deterioration concerned only physical functioning (MD = 24, p = 0.012) for OC survivors while it concerned physical functioning (MD = 30, p < 0.0001), role physical (MD = 22, p = 0.001) and bodily pain (MD = 21, p = 0.001) for EC survivors. Global health (MD = 11, p = 0.011) and role emotional (MD = 12, p = 0.018) were also deteriorated in elderly EC survivors. Sexual function was deteriorated regardless of age and cancer location with a more pronounced deterioration in elderly EC survivors for desire (p = 0.005), arousal (p = 0.015) and orgasm (p = 0.007). Social support, anxiety and depression were not affected by age regardless of location. CONCLUSION: An average 6 years after diagnosis, the impact of cancer on HRQoL is greatest in elderly survivors with either EC or OC.

Therapeutic drug monitoring as a tool to optimize 5-FU-based chemotherapy in gastrointestinal cancer patients older than 75 years.

AIMS: Most clinical trials exclude elderly people, leading to a limited understanding of the benefit-to-risk ratio in this population. Despite existing data regarding the oncological management of elderly receiving fluorouracil (5-FU)-based regimen, our objective was to investigate 5-FU exposure/toxicity relationship in patients ≥75 years and compare the effectiveness of 5-FU therapeutic drug monitoring between elderly and younger patients. METHODS: Hundred fifty-four patients (31 of whom are older than 75 years) with gastrointestinal cancers, who were to receive 5-FU-based regimens, were included in our study. At cycle 1 (C1), the 5-FU dose was calculated using patient's body surface area, then a blood sample was drawn to measure 5-FU concentration and 5-FU dose was adjusted at the subsequent cycles based on C1 concentration. Assessments of toxicity were performed at the beginning of every cycle. RESULTS: Seventy-one percent of elderly patients required dose adjustments after C1, compared with 50% for younger patients. Percentages of patients within 5-FU area under the curve range at cycle 2 were 64% and 68%, respectively, for elderly and younger patients. The proportion of elderly patients experiencing severe toxicities fell from 15% at C1 to only 5% at cycle 3. CONCLUSION: Pharmacokinetic-guided 5-FU-dosing algorithm, leading to an improved tolerability while remaining within therapeutic concentration range, is even more valuable for patients older than 75 years than in younger patients.

Management of elderly patients suffering from cancer: Assessment of perceived burden and of quality of life of primary caregivers.

OBJECTIVE: To evaluate the perceived burden and the quality of life (QoL) at 3 and 6months of the primary caregiver (PC) of patients aged 70 and over suffering from cancer and the predictors of QoL in this population. METHODS: In this prospective observational study, 98 patients aged 70 and older with cancer and 96 PCs were included between 01/06/2014 and 18/03/2015. The Medical Outcomes Study 12-item Short Form Health Survey (SF-12) was used to assess the QoL of PCs and the Zarit Burden Interview (ZBI) was used to measure the perceived burden at 3 and 6months. The major determinants of QoL were identified using mixed linear models for the dimensions of the SF-12 that showed an average difference of at least 5 points between baseline and follow-up at 6months. RESULTS: The QoL scores of PCs showed a decrease in the dimensions "role emotional" and "bodily pain" over 6months. In multivariate analysis, the main determinants of QoL for "role emotional" were the PC's age (p=0.005), a low perceived burden (p<0.0001) and a functionally independent patient (p=0.01), and for "bodily pain" was a low perceived burden (p<0.0001) and the non-use of hormone therapy during the treatment (p<0.0001). CONCLUSION: The main determinants of the QoL of PCs concerned factors inherent to the PC (age and perceived burden) and patient (functional independence).

Folfirinox in elderly patients with pancreatic or colorectal cancer-tolerance and efficacy.

AIM: To study the tolerance and the efficiency of FOLFIRINOX in elderly patients diagnosed with colorectal or pancreatic cancer. METHODS: This retrospective study included elderly patients aged over 70 years of age treated at Georges-Francois Leclerc Center by FOLFIRINOX for histological proved colorectal or pancreatic cancer between January 2009 and January 2015. Chemotheapy regimen consisted of oxaliplatin (85 mg/m2 in over 120 min) followed by leucovorin (400 mg/m2 in over 120 min), with the addition, after 30 min of irinotecan (180 mg/m2 in over 90 min) then 5 fluorouracil (5FU) (400 mg/m2 administred intravenous bolus), followed by 5FU (2400 mg/m2 intraveinous infusion over 46 h) repeated every 2 wk. Geriatric parameters were recorded at the beginning. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events 4.03. Tumor response was evaluated by CT scan. Treatment continued until disease progression, unacceptable toxicities or patient refusal. RESULTS: Fifty-two patients aged from 70 to 87 years were treated by FOLFIRINOX, 34 had colorectal cancer and 18 had pancreatic cancer. Most of them were in good general condition, 82.7% had a 0-1 performance status and 61.5% had a Charlson Comorbidity Index < 10. The most frequent severe toxicities were neutropenia (17 patients, n = 32.7%) and diarrhea (35 patients n = 67.3%); 10 of the case of neutropenia and 5 of diarrhea registered a grade 4 toxicity. Thirty-nine patients (75%) initially received an adapted dose of chemotherapy. The dosage was adjusted for 26% of patients during the course of treatment. Tumor response evaluated by RECIST criteria showed a controlled disease for 25 patients (48.1%), a stable disease for 13 and a partial response for 12 patients. Time under treatment was higher for colorectal cancer with a median time of 2.44 mo (95%CI: 1.61-3.25). Overall survival was 43.88 mo for colorectal cancer and 12.51 mo for pancreatic cancer. In univariate or multivariate analysis, none of geriatric parameters were linked to overall survival. Only the type of tumor (pancreatic/colorectal) was linked in both analysis. CONCLUSION: For people over 70 years old, FOLFIRINOX regimen seems to induce manageable toxicities but similar, even higher, median survival rates compared to younger people.

Assessment of the interest of the geriatric oncology consultation among French general practitioners.

OBJECTIVE: We assessed the interest of the geriatric oncology (GO) consultation (GOC) among general practitioners (GPs). MATERIALS AND METHODS: We conducted a survey among GPs whose patients had had a GOC in 2012. A questionnaire was sent to GPs. The 1st part collected GPs' characteristics including medical education in geriatrics and GO, and knowledge of GOC. The following parts concerned the GOC and included the cancer type, GOC report and care plan. RESULTS: One-hundred twenty-six questionnaires corresponding to 94 GPs were collected. Concerning the GPs' characteristics, age range 50-59 (44.7%), men (62.8%) and urban practice (79.8%) were the most represented, 80.8% had no expertise in geriatrics, 60.6% knew of the existence of GOCs, and 14.9% had received medical education in GO. The most frequent cancer location was gynecological (40.7%) (82.6% were breast cancers). Of the GPs, 69.8% had received a GOC report and 92% were (very) satisfied with the delivery time. A care plan was proposed after the GOC in 83% of cases. It was satisfactory in 96.4% of cases, and applied by 74.7% of GPs. Sixteen percent of GPs were called by the GO team. The less the GP was satisfied with the GOC, the more he or she wanted phone contact (p=0.02); 94% of GPs considered the GOC (very) satisfactory. Sixty-seven percent of GPs wanted to be trained in GO. CONCLUSION: Very few GPs had been trained in geriatrics and/or GO. They were mostly satisfied with GOC and expressed a wish to be trained in GO.

In breast cancer, are treatments and survival the same whatever a patient's age? A population-based study over the period 1998-2009.

AIM: The present study aimed to describe treatments, relative survival and prognostic factors in breast cancer patients according to age. METHODS: All women with primary invasive breast cancer, diagnosed from 1998 to 2009 in the department of Côte d'Or, were retrospectively selected. Variations in treatments administered according to age (<50 years, 50-74 years, >74 years) and period were assessed using Cochran-Armitage trend tests and χ(2) -tests, respectively. Prognostic factors according to age were estimated using a generalized linear model with a Poisson error structure. RESULTS: Overall, 4305 women were included. The oldest women (aged >74 years) were more likely than the youngest women to have comorbidities, advanced stage tumors, hormone receptor-positive tumors and be human epidermal growth factor receptor 2-negative. The use of breast conserving surgery plus adjuvant therapy decreased in older women (>74 years), whereas the proportions of women without treatments and with adjuvant hormone therapy increased with age. Multivariate relative survival analyses according to age showed an increased risk of death in women aged 50-74 years and >74 years with comorbidities compared with those without comorbidities; relative excess risks were 1.85 (1.13-3.02) and 3.23 (1.26-8.31), respectively. In contrast, a decreased risk of death was observed in women aged 50-74 years diagnosed by medical imaging compared with those diagnosed by clinical signs; relative excess risks 0.44 (0.22-0.89). CONCLUSION: Elderly women compared with the youngest women were diagnosed with more favorable tumor biology (hormone receptor-positive tumors, human epidermal growth factor receptor 2-negative). However, survival was poor in elderly women who had comorbid conditions, did not attend screening mammography examinations and were undertreated.

Influence of geriatric oncology consultation on the management of breast cancer in older women: a French population-based study.

AIM: The objective of the present population-based study was to assess the impact of geriatric oncology consultation on the management of elderly patients with breast cancer and to identify the predictive factors of breast cancer treatment in this population. METHODS: A total of 206 women aged 75 years and older with breast cancer, diagnosed from January 2007 to December 2009 were included. The independent impact of geriatric oncology consultation on treatment was analyzed using multivariate logistic regression with adjustment for the other predictive factors of treatment. RESULTS: Patients who had a geriatric oncology consultation (19.4%) had more comorbidities (Charlson Comorbidity Index ≥ 1; P = 0.02), more advanced tumors (P = 0.025), more aggressive tumors (P = 0.029), were more likely to receive mastectomy and adjuvant therapy (P < 0.0001); and less likely to be treated by breast-conserving surgery and adjuvant therapy (P = 0.003). Regarding the geriatric oncology database, 36 of the 40 patients consulted a geriatrician about oncological treatment, and 27 of these 36 patients received the treatment suggested by the geriatrician. For the whole population, geriatric oncology consultation remained a positive predictor for mastectomy and adjuvant therapy (odds ratio 2.32, P = 0.043), and a negative predictor for breast-conserving surgery and adjuvant therapy (odds ratio 0.38, P = 0.048). CONCLUSIONS: In the present study, we found that treatment of patients who underwent a geriatric oncology consultation generally followed the geriatricians' recommendations. The geriatric oncology consultation was a positive predictor of mastectomy and adjuvant therapy, and a negative predictor of breast-conserving surgery and adjuvant therapy.

Population-based study of breast cancer in older women: prognostic factors of relative survival and predictors of treatment.

BACKGROUND: A large proportion of women with breast cancer (BC) are elderly. However, there is a lack of information regarding BC prognostic factors and care in this population. The aims of this study were to assess the prognostic factors of relative survival (RS) among women with BC aged ≥ 75 years old and to identify the predictive factors of treatments administered to this population. METHODS: A population-based study was performed using data from the Cote d'Or breast and gynaecological cancer registry. Women aged 75 years and older with primary invasive BC and resident in Cote d'Or at the time of diagnosis made between January 1998 and December 2008 were retrospectively selected. Prognostic factors of RS were estimated in a generalized linear model with a Poisson error structure. RS rate for the whole population was given at 5 years. Logistic regression models were used to identify the predictors of the treatments administered. RESULTS: Six hundred and eighty-one women were included. Median age at diagnosis was 80. Comorbidities (p = 0.02), pT stage (p = 0.04), metastases (p =< 0.001), having a family doctor (p = 0.03) and hormone-receptor status (p = 0.006) were independent prognostic factors of RS. The RS rate at 5 years for the whole population was 78.2%, 95%CI = [72.2-83.0]. Age, pT stage, metastases, histoprognostic SBR grade, hormone receptor status and comorbidities were frequently found to be predictors of treatment with surgery alone, hormone therapy alone, breast conserving surgery plus adjuvant therapy and mastectomy plus adjuvant therapy. CONCLUSIONS: Comorbid conditions adversely affect survival in older women with breast cancer. Moreover the results of this study showed that there are numerous predictors of the type of treatment administered, and that the most important were age and comorbidities.

A case of meningitis due to Achromobacter xylosoxidans denitrificans 60 years after a cranial trauma.

BACKGROUND: Achromobacter xylosoxidans (AX) is a non-fermentative aerobic gram-negative bacillus. It is an opportunistic pathogen and the causative agent of various infections. We report an original case of late posttraumatic meningitis due to AX denitrificans. CASE REPORT: An 83-year-old man was hospitalized for acute headache, nausea and vomiting. The emergency brain computer tomography (CT) scan did not reveal any anomaly. In his medical history, there was an auditory injury due to a cranial trauma incurred in a skiing accident 60 years earlier. Cytobiochemical analysis of the cerebrospinal fluid (CSF) revealed increased levels of neutrophils and proteins. The CSF bacterial culture was positive: the Gram stain showed a gram-negative bacillus, oxidase + and catalase +, and the biochemical pattern using the API 20 NE strip revealed AX dentrificans. Late posttraumatic meningitis on a possible osteomeningeal breach was diagnosed even though the breach was not confirmed because the patient declined a second brain CT scan. The patient was successfully treated with meropenem. CONCLUSIONS: This report demonstrates the importance of searching for unusual or atypical organisms when the clinician encounters meningitis in a particular context, as well as the importance of adequate follow-up of craniofacial traumas.