To determine factors associated with early functional decline during first-line chemotherapy in older patients.
Patients age ≥ 70 years receiving first-line chemotherapy for cancer were prospectively ...considered for inclusion across 12 centers in France. Functional decline was defined as a decrease of ≥ 0.5 points on the Activities of Daily Living (ADL) scale between the beginning of chemotherapy and the second cycle. Factors associated with functional decline were sought from pretreatment abbreviated comprehensive geriatric assessment, including ADL, Instrumental ADL (IADL), Mini-Nutritional Assessment (MNA), Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS15), and Timed Get Up and Go (GUG) test, and from comorbidities (Cumulative Illness Rating Scale-Geriatrics), MAX2 index, and baseline biologic and clinical information.
Of 364 included patients, 50 experienced functional decline (16.7%; median, 0.5 points). Abnormal preadmission performance status, IADL, GDS15, MMSE, GUG, and MNA were associated with increased likelihood of functional decline (univariate analysis). In the multivariate model adjusted for baseline ADL and MAX2 index, high baseline GDS (odds ratio OR, 2.16; 95% CI, 1.09 to 4.30; P = .03) and low IADL scores (OR, 2.87; 95% CI, 1.06 to 7.79; P = .04) were independently associated with increased risk of functional decline.
Our results outline associations between baseline depression, instrumental dependencies, and early functional decline during chemotherapy for older patients. ADL should be sequentially evaluated early during treatment. Baseline evaluation of GDS15 and IADL may be proposed to anticipate this event.
BACKGROUND
Sarcomas are rare, heterogeneous, ubiquitously localized malignancies with many histologic subtypes and genomic patterns. The survival of patients with sarcoma has rarely been described ...based on this heterogeneity; therefore, the authors' objective was to estimate survival outcomes in patients who had sarcomas using the 2020 version of the World Health Organization classification of soft tissue and bone tumors.
METHODS
Patients older than 15 years who had incident sarcoma diagnosed between 2005 and 2010 were extracted from 14 French population‐based cancer registries covering 18% of the French metropolitan population. Vital status for each patient was actively followed up to June 30, 2013. Net survival (NS) was estimated using the unbiased Pohar‐Perme method.
RESULTS
Overall, 4202 patients were included. NS declined with increasing age at diagnosis. According to topographic groups, large 5‐year NS disparities were observed, ranging from 47% among women with gynecologic sarcomas to 89% among patients with skin sarcomas. Patients with soft tissue, bone, and gastrointestinal sarcomas had 5‐year NS rates of 53%, 61%, and 70%, respectively. Similar heterogeneity was observed according to histologic subtypes, with 5‐year NS ranging from 19% for patients with angiosarcomas to 96% for patients with dermatofibrosarcomas. Patients with sarcoma who displayed missense mutations had a better 5‐year NS (74%); those with MDM2‐amplified sarcomas had the worst NS (45%).
CONCLUSIONS
NS rates in patients with sarcoma are presented here for the first time based on the 2020 World Health Organization classification applied to population‐based registry data. Large prognostic heterogeneity was observed based on age, topographic and histologic groups, and genomic alteration profiles, constituting a benchmark for future studies and clinical trials.
In this study based on the 2020 version of the World Health Organization classification of soft tissue and bone tumors applied to the French population‐based cancer registries, large survival heterogeneity of sarcomas was observed on age, topographic and histologic groups, and genomic alteration profiles. This study emphasized the major determinants of survival in patients with sarcoma, providing a new benchmark for future studies or clinical trials.
To explore mortality of French professional male firefighters.
Standardized mortality ratios (SMR) were calculated for 10,829 professional male firefighters employed in 1979 and compared with the ...French male population between 1979-2008. Firefighters were identified from 89 French administrative departments (93% of population).
One thousand six hundred forty two deaths were identified, representing significantly lower all-cause mortality than in the general population (SMR = 0.81; 95%CI: 0.77-0.85). SMR increased with age and was not different from 1 for firefighters >70 years. No significant excess of mortality was observed for any specific cause, but a greater number of deaths than expected were found for various digestive neoplasms (rectum/anus, pancreas, buccal-pharynx, stomach, liver, and larynx).
We observed lower all and leading-cause mortality likely due to the healthy worker effect in this cohort, with diseases of the respiratory system considerably lower (SMR = 0.57). Non-significant excesses for digestive neoplasms are notable, but should not be over-interpreted at this stage.
Objectives
Due to COVID-19, a lockdown took place between March 17 and May 1, 2020, in France. This study evaluates the impact of the lockdown on the diagnosis and staging of breast cancers in a ...tertiary cancer centre.
Methods
Our database was searched for all consecutive invasive breast cancers diagnosed in our institution during the lockdown (36 working days), during equivalent periods of 36 working days before and after lockdown and a reference period in 2019. The number and staging of breast cancers diagnosed during and after lockdown were compared to the pre-lockdown and reference periods. Tumour maximum diameters were compared using the Mann–Whitney test. Proportions of tumour size categories (T), ipsilateral axillary lymph node invasion (N) and presence of distant metastasis (M) were compared using Fisher’s exact test.
Results
Compared to the reference period (
n
= 40 in average), the number of breast cancers diagnosed during lockdown (
n
= 32) decreased by 20% but increased by 48% after the lockdown (
n
= 59). After the lockdown, comparatively to the reference period, breast cancers were more often symptomatic (86% vs 57%;
p
= 0.001) and demonstrated bigger tumour sizes (
p
= 0.0008), the rates of small tumours (T1) were reduced by 38%, locally advanced cancers (T3, T4) increased by 80% and lymph node invasion increased by 64%.
Conclusion
The COVID-19 lockdown was associated with a 20% decrease in the number of diagnosed breast cancers. Because of delayed diagnosis, breast cancers detected after the lockdown had poorer prognosis with bigger tumour sizes and higher rates of node invasion.
Key Points
•
The number of breast cancer diagnosed in a large tertiary cancer centre in France decreased by 20% during the first COVID-19 lockdown.
•
Because of delayed diagnosis, breast cancers demonstrated bigger tumour size and more frequent axillary lymph node invasion after the lockdown.
•
In case of a new lockdown, breast screening programme and follow-up examinations should not be suspended and patients with clinical symptoms should be encouraged to seek attention promptly.
The Cox model relies on the proportional hazards (PH) assumption, implying that the factors investigated have a constant impact on the hazard - or risk - over time. We emphasize the importance of ...this assumption and the misleading conclusions that can be inferred if it is violated; this is particularly essential in the presence of long follow-ups.
We illustrate our discussion by analyzing prognostic factors of metastases in 979 women treated for breast cancer with surgery. Age, tumour size and grade, lymph node involvement, peritumoral vascular invasion (PVI), status of hormone receptors (HRec), Her2, and Mib1 were considered.
Median follow-up was 14 years; 264 women developed metastases. The conventional Cox model suggested that all factors but HRec, Her2, and Mib1 status were strong prognostic factors of metastases. Additional tests indicated that the PH assumption was not satisfied for some variables of the model. Tumour grade had a significant time-varying effect, but although its effect diminished over time, it remained strong. Interestingly, while the conventional Cox model did not show any significant effect of the HRec status, tests provided strong evidence that this variable had a non-constant effect over time. Negative HRec status increased the risk of metastases early but became protective thereafter. This reversal of effect may explain non-significant hazard ratios provided by previous conventional Cox analyses in studies with long follow-ups.
Investigating time-varying effects should be an integral part of Cox survival analyses. Detecting and accounting for time-varying effects provide insights on some specific time patterns, and on valuable biological information that could be missed otherwise.
Cytochrome P450 1B1 (CYP1B1) is mostly expressed in tumours and displays unusual properties. Its two polymorphic forms were differently associated with anticancer drug sensitivity. We decipher here ...the role of this polymorphism in anticancer drug efficacy in vitro, in vivo and in the clinical setting.
From head-and-neck squamous cell carcinoma cell lines not expressing CYP1B1, we generated isogenic derivatives expressing the two forms. Proliferation, invasiveness, stem cell characteristics, sensitivity to anticancer agents and transcriptome were analysed. Tumour growth and chemosensitivity were studied in vivo. A prospective clinical trial on 121 patients with advanced head-and-neck cancers was conducted, and a validation-retrospective study was conducted.
Cell lines expressing the variant form displayed high rates of in vitro proliferation and invasiveness, stemness features and resistance to DNA-damaging agents. In vivo, tumours expressing the variant CYP1B1 had higher growth rates and were markedly drug-resistant. In the clinical study, overall survival was significantly associated with the genotypes, wild-type patients presenting a longer median survival (13.5 months) than the variant patients (6.3 months) (p = 0.0166).
This frequent CYP1B1 polymorphism is crucial for cancer cell proliferation, migration, resistance to chemotherapy and stemness properties, and strongly influences head-and-neck cancer patients' survival.
Few data are available on survival and predictive factors in early breast cancer (BC) patients treated with neoadjuvant endocrine therapy (NET).
This is a pooled analysis of two multicentre, ...randomised non-comparative phase 2 clinical trials evaluating neoadjuvant anastrozole and fulvestrant efficacy for postmenopausal HR+/HER2- breast cancer patients: HORGEN (NCT00871858) and CARMINA02 (NCT00629616) studies.
In total, 236 patients were included in CARMINA02 and HORGEN trials. Modified intention-to-treat analysis was available for 217 patients. Median follow-up was 65.2 months. Relapse-free survival (RFS) and overall survival (OS) at 5 years were 83.7% (95% CI: 77.9-88) and 92.7% (95% CI: 88.2-95.6), respectively, with no difference between treatment arms. On univariate analysis, tumour staging (T2 vs T3-4; p = 0.0001), Ki-67 at surgery (≤10% vs >10%; p = 0.0093), pathological tumour size (pT1-2 vs pT3-4; p = 0.0012) and node status (pN negative vs positive; p = 0.007), adjuvant chemotherapy (p = 0.0167) and PEPI score (PEPI group I + II vs III; p = 0.0004) were associated with RFS. No events were observed in patients with pathological response according to the Sataloff classification. Multivariate analysis showed that preoperative endocrine prognostic index (PEPI) group III was associated with significantly worse RFS (p = 0.0069, hazard ratio = 3.33 (95% CI: 1.39-7.98)).
Postmenopausal HR+/HER2- breast cancer patients receiving NET generally have a favourable outcome. The PEPI score identifies a subset of patients of poorer prognosis who are candidates for further additional treatment.
Owing to the natural evolution of a disease, several events often arise after a first treatment for the same subject. For example, patients with a primary invasive breast cancer and treated with ...breast conserving surgery may experience breast cancer recurrences, metastases or death. A certain proportion of subjects in the population who are not expected to experience the events of interest are considered to be ‘cured’ or non-susceptible. To model correlated failure time data incorporating a surviving fraction, we compare several forms of cure rate frailty models. In the first model already proposed non-susceptible patients are those who are not expected to experience the event of interest over a sufficiently long period of time. The other proposed models account for the possibility of cure after each event. We illustrate the cure frailty models with two data sets. First to analyse time-dependent prognostic factors associated with breast cancer recurrences, metastases, new primary malignancy and death. Second to analyse successive rehospitalizations of patients diagnosed with colorectal cancer. Estimates were obtained by maximization of likelihood using SAS proc NLMIXED for a piecewise constant hazards model. As opposed to the simple frailty model, the proposed methods demonstrate great potential in modelling multivariate survival data with long-term survivors (‘cured’ individuals).
Geriatric Assessment is an appropriate method for identifying older cancer patients at risk of life-threatening events during therapy. Yet, it is underused in practice, mainly because it is time- and ...resource-consuming. This study aims to identify the best screening tool to identify older cancer patients requiring geriatric assessment by comparing the performance of two short assessment tools the G8 and the Vulnerable Elders Survey (VES-13).
The diagnostic accuracy of the G8 and the (VES-13) were evaluated in a prospective cohort study of 1674 cancer patients accrued before treatment in 23 health care facilities. 1435 were eligible and evaluable. Outcome measures were multidimensional geriatric assessment (MGA), sensitivity (primary), specificity, negative and positive predictive values and likelihood ratios of the G8 and VES-13, and predictive factors of 1-year survival rate.
Patient median age was 78.2 years (70-98) with a majority of females (69.8%), various types of cancer including 53.9% breast, and 75.8% Performance Status 0-1. Impaired MGA, G8, and VES-13 were 80.2%, 68.4%, and 60.2%, respectively. Mean time to complete G8 or VES-13 was about five minutes. Reproducibility of the two questionnaires was good. G8 appeared more sensitive (76.5% versus 68.7%, P = 0.0046) whereas VES-13 was more specific (74.3% versus 64.4%, P<0.0001). Abnormal G8 score (HR = 2.72), advanced stage (HR = 3.30), male sex (HR = 2.69) and poor Performance Status (HR = 3.28) were independent prognostic factors of 1-year survival.
With good sensitivity and independent prognostic value on 1-year survival, the G8 questionnaire is currently one of the best screening tools available to identify older cancer patients requiring geriatric assessment, and we believe it should be implemented broadly in daily practice. Continuous research efforts should be pursued to refine the selection process of older cancer patients before potentially life-threatening therapy.
PDF
