Cancer in older adults: understanding cause and effects of chemotherapy-related toxicities.
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ABSTRACT:
SUBMITTER: Bhatt VR
PROVIDER: S-EPMC7857338 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
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Cancer in older adults: understanding cause and effects of chemotherapy-related toxicities.
Future oncology (London, England) 20190724 22
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Project description:ImportanceAlthough geriatric assessment-driven intervention improves patient-centered outcomes, its influence on chemotherapy-related toxic effects remains unknown.ObjectiveTo assess whether specific geriatric assessment-driven intervention (GAIN) can reduce chemotherapy-related toxic effects in older adults with cancer.Design, setting, and participantsA randomized clinical trial enrolled 613 participants from a National Cancer Institute-designated cancer center between 2015 and 2019. Patients were 65 years and older with a solid malignant neoplasm, were starting a new chemotherapy regimen, and completed a geriatric assessment. Patients were followed up until chemotherapy completion or 6 months after initiation, whichever occurred first. Data analysis was done by intention-to-treat principle.InterventionsPatients were randomized (2:1) to either the GAIN (intervention) or standard of care (SOC) arm. In the GAIN arm, a geriatrics-trained multidisciplinary team composed of an oncologist, nurse practitioner, social worker, physical/occupation therapist, nutritionist, and pharmacist reviewed geriatric assessment results and implemented interventions based on prespecified thresholds built into the geriatric assessment's domains. In the SOC arm, geriatric assessment results were sent to treating oncologists for consideration.Main outcomes and measuresThe primary outcome was incidence of grade 3 or higher chemotherapy-related toxic effects (graded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0). Secondary outcomes included advance directive completion, emergency department visits, unplanned hospitalizations, average length of stay, unplanned hospital readmissions, chemotherapy dose modifications, and early discontinuation. Overall survival analysis was performed up to 12 months after chemotherapy initiation.ResultsAmong the 605 eligible participants for analysis, median (range) age was 71 (65-91) years, 357 (59.0%) were women, and 432 (71.4%) had stage IV disease. Cancer types included gastrointestinal (202 [33.4%]), breast (136 [22.5%]), lung (97 [16.0%]), genitourinary (91 [15.0%]), gynecologic (54 [8.9%]), and other (25 [4.1%]). Incidence of grade 3 or higher chemotherapy-related toxic effects was 50.5% (95% CI, 45.6% to 55.4%) in the GAIN arm and 60.6% (95% CI, 53.9% to 67.3%) in the SOC arm, resulting in a significant 10.1% reduction (95% CI, -1.5 to -18.2%; P = .02). A significant absolute increase in advance directive completion of 28.4% with GAIN vs 13.3% with SOC (P < .001) was observed. No significant differences were observed in emergency department visits, unplanned hospitalizations, average length of stay, unplanned readmissions, chemotherapy dose modifications or discontinuations, or overall survival.Conclusions and relevanceIn this randomized clinical trial, integration of multidisciplinary GAIN significantly reduced grade 3 or higher chemotherapy-related toxic effects in older adults with cancer. Implementation of GAIN into oncology clinical practice should be considered among older adults receiving chemotherapy.Trial registrationClinicalTrials.gov Identifier: NCT02517034.
| S-EPMC8485211 | biostudies-literature
Project description:PurposeTo evaluate the association between renal function (RF) and chemotherapy-related toxicity (CRT) in older adults with cancer and to compare the effect of different RF formulas and body weight measurements on this association.MethodsThis is a secondary analysis of data from a prospective multicenter study of patients ≥ age 65 who were starting a new chemotherapy regimen. RF was estimated with 4 formulas (modified Jelliffe [Jelliffe], Cockcroft-Gault [CG], Wright, and Modification of Diet in Renal Disease [MDRD]), using actual, ideal and adjusted body weights for 492 patients. The association between baseline RF and grade 3-5 CRT was evaluated by unconditional logistic regression.ResultsAs a continuous variable, decreased creatinine clearance (CrCl) calculated by CG with actual body weight was associated with increased odds of CRT (OR 1.12, P<0.01; 95% CI 1.04-1.20) indicating that on average for every 10mL/min decrease in CrCl the odds of CRT increased by 12%. Very low RF (in the lowest 10%) with all formulas (CG, Jelliffe, Wright and MDRD) was associated with increased odds for CRT. This association is independent of the type of chemotherapy received (those requiring dose adjustment for renal function vs not). Neither primary dose reduction nor chemotherapy duration was associated with CRT. Serum creatinine alone was not associated with increased odds of CRT (OR 0.67, P=0.15).ConclusionsDecreased RF is associated with increased odds of CRT and should be considered when assessing risk of CRT in older adults with cancer. Serum creatinine alone is not adequate for risk assessment.
| S-EPMC5373948 | biostudies-literature
Project description:BackgroundAbundant evidences have shown that newly developed chemotherapy regimens improved 5-year survival rate of colorectal cancer (CRC) patients over the past two decades. However, their impact on risk of death from leading causes among elderly patients is still poorly understood.Patients and methodsA retrospective cohort study of 69 718 elderly CRC patients with their first primary tumors in 1992-2009, identified from the 12 areas of Surveillance, Epidemiology, and End Results-Medicare linked database with their Medicare claims up to 2010. Multivariate Cox regression models were used to assess the effect of newly developed chemotherapy regimens, comorbidities, and chemotherapy related toxicities on cause-specific death and their temporal patterns among elderly CRC patients.ResultsThe leading causes of death among CRC patients were CRC, circulation disorders, and secondary cancers, which accounted for 51.4%, 25%, and 4.6% of all-cause death, respectively. Patients diagnosed in more recent diagnostic time periods were significantly less likely to die of CRC [period 2: 5-year hazard ratio = 0.94, 95% confidence interval (CI) 0.90-0.97; period 3: 0.86, 0.83-0.90], circulation disorders (period 2: 0.94, 0.88-1.00; period 3: 0.80, 0.75-0.87), and more likely to die of secondary cancer (period 3: 1.42, 1.20-1.68) compared with those diagnosed in period 1. Charlson comorbidities index and the selected pre-existing comorbidities were significantly associated with increased 5-year risk of death from all three leading causes. Both hematological and gastric toxicity were associated with reduced risk of death from CRC and circulation disorders. The association between diagnostic time period and risk reduction in death from CRC depended on chemotherapy treatment (P < 0.0001). Subgroup analyses showed that the chemotherapy-dependent significant risk reduction was seen in patients with stage II-III CRC, patients without comorbidities, and patients without toxicities (P < 0.0001 for all).ConclusionThe newly developed chemotherapy regimens were associated with the decreased risk of mortality from CRC.
| S-EPMC4110447 | biostudies-literature
Project description:This study aimed to investigate the effects of a multidomain intervention on gene expression profile of older adults with cognitive frailty in Selangor, Malaysia, using mRNA gene sequencing. The intervention included a combination of dietary changes, exercise, and psychosocial support. By analyzing gene expression profile in both groups, this study explores how multidomain interventions may influence mrna in older adults. The findings could provide insights into the role of lifestyle factors on the CF in aging populations.
2025-05-31 | GSE298126 | GEO
Project description:ObjectiveChemotherapy preference refers to a patient's interest in receiving chemotherapy. This study examined whether chemotherapy preference was associated with toxicity, efficacy, quality of life (QoL), and functional outcomes during and after completion of adjuvant chemotherapy in older women with breast cancer.Materials and methodsThis study is a secondary analysis of CALGB 49907, a randomized trial that compared standard adjuvant chemotherapy versus capecitabine in patients age 65 years or older with breast cancer. A subset of 145 patients completed a questionnaire to describe chemotherapy preference pre-treatment. The association of this pre-treatment preference with the patient's perception of self-health, predicted and actual QoL, patient- and professional-reported toxicity, mental health, self-rated function, and survival was studied during and after treatment.ResultsThe median age of patients was 71 years and 47% had a high preference for chemotherapy. On baseline demographics, the low preference group had a higher proportion of white patients (95% vs. 78%, p = 0.004). Before treatment, low chemotherapy preference was associated with greater nausea/vomiting (p = 0.008). Mid-treatment, low preference was associated with lower QoL, worse social, emotional and physical function (all p ≤ 0.02) and worse nausea/vomiting, cancer symptoms and financial worries (all p < 0.05). The association noted mid-treatment, resolved after treatment completion except with financial worries which persisted at 24 months. Low preference was associated with higher rates of grade 3-5 adverse events (53% vs. 34%, p = 0.02) but was not associated with survival.ConclusionsLow chemotherapy preference prior to treatment initiation was associated with lower QoL, worse physical symptoms and self-rated function and more adverse events mid-treatment. There is no association of chemotherapy preference with survival.
| S-EPMC5967401 | biostudies-literature
Project description:Chemotherapy-related cognitive impairment (CRCI) can occur during or after chemotherapy and represents a concern for many patients with cancer. Among older patients with cancer, in whom there is little clinical trial evidence examining side effects like CRCI, many unanswered questions remain regarding risk for and resulting adverse outcomes from CRCI. Given the rising incidence of cancer with age, CRCI is of particular concern for older patients with cancer who receive treatment. Therefore, research related to CRCI in older patients with cancers is a high priority. In this manuscript, we discuss current gaps in research highlighting the lack of clinical studies of CRCI in older adults, the complex mechanisms of CRCI, and the challenges in measuring cognitive impairment in older patients with cancer. Although we focus on CRCI, we also discuss cognitive impairment related to cancer itself and other treatment modalities. We highlight several research priorities to improve the study of CRCI in older patients with cancer.
| S-EPMC4969145 | biostudies-literature
Project description:ImportanceHeat exposure is known to have a complex set of physiological effects on multiple organ systems, but current understanding of the health effects is mostly based on studies investigating a small number of prespecified health outcomes such as cardiovascular and respiratory diseases.ObjectivesTo identify possible causes of hospital admissions during extreme heat events and to estimate their risks using historical data.Design, setting, and populationMatched analysis of time series data describing daily hospital admissions of Medicare enrollees (23.7 million fee-for-service beneficiaries [aged ≥65 years] per year; 85% of all Medicare enrollees) for the period 1999 to 2010 in 1943 counties in the United States with at least 5 summers of near-complete (>95%) daily temperature data.ExposuresHeat wave periods, defined as 2 or more consecutive days with temperatures exceeding the 99th percentile of county-specific daily temperatures, matched to non-heat wave periods by county and week.Main outcomes and measuresDaily cause-specific hospitalization rates by principal discharge diagnosis codes, grouped into 283 disease categories using a validated approach.ResultsRisks of hospitalization for fluid and electrolyte disorders, renal failure, urinary tract infection, septicemia, and heat stroke were statistically significantly higher on heat wave days relative to matched non-heat wave days, but risk of hospitalization for congestive heart failure was lower (P < .05). Relative risks for these disease groups were 1.18 (95% CI, 1.12-1.25) for fluid and electrolyte disorders, 1.14 (95% CI, 1.06-1.23) for renal failure, 1.10 (95% CI, 1.04-1.16) for urinary tract infections, 1.06 (95% CI, 1.00-1.11) for septicemia, and 2.54 (95% CI, 2.14-3.01) for heat stroke. Absolute risk differences were 0.34 (95% CI, 0.22-0.46) excess admissions per 100,000 individuals at risk for fluid and electrolyte disorders, 0.25 (95% CI, 0.12-0.39) for renal failure, 0.24 (95% CI, 0.09-0.39) for urinary tract infections, 0.21 (95% CI, 0.01-0.41) for septicemia, and 0.16 (95% CI, 0.10-0.22) for heat stroke. For fluid and electrolyte disorders and heat stroke, the risk of hospitalization increased during more intense and longer-lasting heat wave periods (P < .05). Risks were generally highest on the heat wave day but remained elevated for up to 5 subsequent days.Conclusions and relevanceAmong older adults, periods of extreme heat were associated with increased risk of hospitalization for fluid and electrolyte disorders, renal failure, urinary tract infection, septicemia, and heat stroke. However, the absolute risk increase was small and of uncertain clinical importance.
| S-EPMC4319792 | biostudies-literature
Project description:ImportanceCancer care has inherent complexities in older adults, including balancing risks of cancer and noncancer death. A poor understanding of cause-specific outcomes may lead to overtreatment and undertreatment.ObjectiveTo examine all-cause and cancer-specific death throughout 5 years for older adults after cancer resection.Design, setting, and participantsThis population-based cohort study was conducted in Ontario, Canada, using the administrative databases stored at ICES (formerly the Institute for Clinical Evaluative Sciences). All adults 70 years or older who underwent resection for a new diagnosis of cancer between January 1, 2007, and December 31, 2017, were included. Patients were followed up until death or censored at date of last contact of December 31, 2018.ExposuresCancer resection.Main outcome and measuresUsing a competing risks approach, the cumulative incidence of cancer and noncancer death was estimated and stratified by important prognostic factors. Multivariable subdistribution hazard models were fit to explore prognostic factors.ResultsOf 82 037 older adults who underwent surgery (all older than 70 years; 52 119 [63.5%] female), 16 900 of 34 044 deaths (49.6%) were cancer related at a median (interquartile range) follow-up of 46 (23-80) months. At 5 years, estimated cumulative incidence of cancer death (20.7%; 95% CI, 20.4%-21.0%) exceeded noncancer death (16.5%; 95% CI, 16.2%-16.8%) among all patients. However, noncancer deaths exceeded cancer deaths starting at 3 years after surgery in breast, prostate, and melanoma skin cancers, patients older than 85 years, and those with frailty. Cancer type, advancing age, and frailty were independently associated with cause-specific death.Conclusions and relevanceAt the population level, the relative burden of cancer deaths exceeds noncancer deaths for older adults selected for surgery. No subgroup had a higher burden of noncancer death early after surgery, even in more vulnerable patients. This cause-specific overall prognosis information should be used for patient counseling, to assess patterns of over- or undertreatment in older adults with cancer at the system level, and to guide targets for system-level improvements to refine selection criteria and perioperative care pathways for older adults with cancer.
| S-EPMC8117065 | biostudies-literature
Project description:BackgroundA total of 5-10% of patients with retinoblastoma (RB) harbor deletion of the long arm (q) chromosome 13 (13q-). The treatment-related toxicities in this population have not been described.MethodsSixty-eight RB patients on a single institutional protocol (RET5) from 2005 to 2010 were reviewed. Genetic screening identified 11 patients (seven female) with 13q-. Patients with early (Reese-Ellsworth [R-E] group I-III) disease (6/23 with 13q-) received eight courses of vincristine/carboplatin (VC). Patients with advanced (R-E group IV-V) bilateral disease (2/27 with 13q-) received two courses of vincristine/topotecan (VT) followed by nine courses of alternating VT/VC. Patients undergoing upfront enucleation received histopathology-based chemotherapy: intermediate risk (2/8 with 13q-) or high risk (1/10 with 13q-). Dose reductions were mandated for >7 day delay in two consecutive courses following hematologic toxicity. Grades 3 and 4 hematologic, infectious, and gastrointestinal toxicities were compared between RET5 patients with and without 13q-.ResultsDemographics were similar between groups. When present, prolonged neutropenia (median 7 days, range 0-14 days) delayed chemotherapy and resulted in more frequent dose reductions among 13q- patients (5/11) than non-13q- patients (4/57) (P < 0.01). GI toxicity was similar between groups (5/11 13q- vs. 13/57 non-13q-; P = 0.14), but halted chemotherapy in one 13q- patient. Infectious complications and disease outcomes were similar between groups. At follow-up, all patients are alive (median 6.1 years, range 7.6 months-9.5 years).Conclusions13q- RB patients had a higher incidence of neutropenia requiring chemotherapy dose reductions, but did not have increased treatment failure.
| S-EPMC5683082 | biostudies-literature
Project description:BackgroundCurrently available predictive models for chemotherapy-related toxicity are not sufficiently discriminative in older patients with cancer and do not consider moderate toxicities. The purpose of this study was to identify factors associated with moderate and severe chemotherapy toxicities in older patients with cancer.Materials and methodsPatients aged 70+ recruited in the prospective ELCAPA cohort were analyzed. A total of 837 patients with data on toxicities had received chemotherapy without other systemic treatment and were included between 2015 and 2022. To adjust for any imbalances in the distribution of covariates between patients receiving single-agent chemotherapy vs combination chemotherapy, we applied overlap weighting (a propensity-score-based technique). We used multinomial logistic regression.ResultsMedian (interquartile range) age was 81 (77-84). Forty-one percent experienced moderate toxicity, and 33% experienced severe toxicity. Hematologic toxicities accounted for 53% of severe toxicities and 66% of moderate toxicities. Age <80 years, cancer type, metastatic status, Eastern Cooperative Oncology Group performance status (ECOG-PS) >1, no cognitive impairment were associated with combination chemotherapy decision. In a univariate analysis with overlap weighting, no factors were associated with moderate toxicity. Hemoglobin < 10 g/dL and a CIRS-G score >12 were associated with severe toxicity. In a multivariate analysis, only hemoglobin < 10 g/dL was independently associated with severe toxicity, adjusted OR 2.96 (95% CI, 1.20-7.29).ConclusionBy addressing indication bias for combination chemotherapy decision, only anemia and not cancer type, combination chemotherapy was predicting for severe chemotherapy-related toxicity in older patients with cancer. We did not find any predictors of moderate chemotherapy-related toxicity.
| S-EPMC11546720 | biostudies-literature