Prognostic value of comorbidities in older patients with cancer: the ELCAPA cohort study.

BACKGROUND: In older patients, comorbidities competed with cancer for mortality risk. We assessed the prognostic value of comorbidities in older patients with cancer. PATIENTS AND METHODS: We analysed all patients >70 years of age with colorectal, breast, prostate, or lung cancer included in the prospective ELCAPA cohort. The Cumulative Illness Rating Scale-Geriatrics (CIRS-G) score was used to assess comorbidities. The primary endpoint was overall survival (OS) at 3, 12, and 36 months. The adjusted difference in the restricted mean survival time (RMST) was used to assess the strength of the relationship between comorbidities and survival. RESULTS: Of the 1551 patients included (median age 82 years; interquartile range 78-86 years), 502 (32%), 575 (38%), 283 (18%), and 191 (12%) had colorectal, breast, prostate, and lung cancer, respectively, and 50% had metastatic disease. Hypertension, kidney failure, and cognitive impairment were the most common comorbidities (67%, 38%, and 29% of the patients, respectively). A CIRS-G score >17, two or more severe comorbidities, more than seven comorbidities, heart failure, and cognitive impairment were independently associated with shorter OS. The greatest effect size was observed for CIRS-G >17 (versus CIRS-G <11): at 36 months, the adjusted differences in the RMST (95% confidence interval) were -6.0 months (-9.3 to -2.6 months) for colorectal cancer, -9.1 months (-13.2 to -4.9 months) for breast cancer, -8.3 months (-12.8 to -3.9 months) for prostate cancer, and -5.5 months (-9.9 to -1.1 months) for lung cancer (P < 0.05 for all). CONCLUSIONS: Comorbidities' type, number, and severity were independently associated with shorter OS. A 17-point cut-off over 56 for the total CIRS-G score could be considered in clinical practice.

Enrollment of older metastatic breast cancer patients in first-line clinical trials: 9-year experience of the large-scale real-life multicenter French ESME cohort.

PURPOSE: Older cancer patients are underrepresented in clinical trials. We aimed to evaluate the enrollment of older women aged 70 years old (yo) or over with metastatic breast cancer (MBC) in clinical trials. METHODS: We used the national Epidemio-Strategy and Medical Economics MBC Data Platform, a French multi-center real-life database. We selected MBC women over 70yo, without central nervous system metastases, with at least one line of systemic treatment, between January 1st, 2008 and December 31st, 2016, and had no other cancer in the 5 years before MBC. The primary objective was to evaluate the proportion of patients enrolled in clinical trials according to their age. Secondary objective was to identify variables associated with enrollment in older ones. RESULTS: 5552 women were aged ≥ 70 (median 74yo; IQR 72-77). 14,611 were less than 70. Of the older ones, 239 (4%) were enrolled in a clinical trial during first line of treatment, compared with 1529 (10.5%) for younger ones. Multivariable analysis of variables predicting for enrollment during first line of treatment in older patients were younger age (OR 0.50 [95%CI 0.33-0.76] for the 80-85yo class; OR 0.17 [95%CI 0.06-0.39] for the 85yo and more class), good ECOG Performance Status (PS 0-1) (OR 0.15 [95%CI 0.08-0.27] for the PS 2-4 class), HER2 + disease (OR 1.78 [95%CI 1.27-2.48]), type of treatment (chemotherapy/targeted therapy/immunotherapy OR 5.01 [95%CI 3.13-8.18]), and period (OR 1.65 [95%CI 1.22-2.26] for 2012-2016, compared to 2008-2011). CONCLUSION: In this large database, few older MBC patients were enrolled in a trial compared with younger ones.

Combined differentiation therapy in myelodysplastic syndrome with retinoid acid, 1 alpha,25 dihydroxyvitamin D3, and prednisone.

The myelodysplastic syndrome (MDPS) provides an opportunity for identifying host factors (genetic, endocrine, immune) involved in initiation and progression of preleukemia into frank acute myeloid leukemia. The aim of this study was to identify bone marrow (BM) cellular and humoral dysfunctions central to the development of MDPS and useful in therapeutic follow-up studies. Our preclinical studies have shown that (1) the characteristic stromal cell composition of the normal BM microenvironment was impaired in MDPS and in AML in 67 and 86% of the cases, respectively; (2) the 1 alpha,25(OH)2D3 concentration in BM plasma was abnormal in 50% of MDPS and 30% of AML; and (3) an inverse correlation existed in MDPS between the 1 alpha,25(OH)2D3 concentration and the frequency of F-CFU, (r = 0.41, p < 0.02), suggestive of a regulatory interaction between this secosteroid hormone and BM stromal cells. The analysis of clonal extinction of BM blast cells in response to all trans retinoic acid (RA), 1 alpha,25(OH)2D3, and colony stimulating factors (PHA-LCM), either alone or in various combinations, revealed individual patterns of responses in the cases of MDPS or AML. The results indicate the necessity for preclinical studies to select patients for combined differentiation therapy. Our ongoing clinical trials suggest that RA (Roaccutan, 20 mg/day continuously) as induction therapy, followed at weeks 6 to 8 by prednisone (40 mg/day for 15 days) and 1 alpha,25(OH)2D3 (Rocaltrol, 3 x 0.25 micrograms/day for 3 months) may induce a long-lasting hematological remission in MDPS.