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.
Project description:BACKGROUND:Abundant 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 METHODS:A 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. RESULTS:The 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). CONCLUSION:The newly developed chemotherapy regimens were associated with the decreased risk of mortality from CRC.
Project description:OBJECTIVE:Chemotherapy 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 METHODS:This 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. RESULTS:The 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. CONCLUSIONS:Low 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.
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.
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.
Project description:A 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.Sixty-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-.Demographics 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).13q- RB patients had a higher incidence of neutropenia requiring chemotherapy dose reductions, but did not have increased treatment failure.
Project description:Because the elderly are underrepresented on clinical trials, physicians have few sources of information to estimate the risks (ie, toxicities) and benefits of chemotherapy administration to the elderly.Our goal was to determine whether the standard measures of toxicity used in clinical trials could be captured from observational Medicare claims data.We identified 175 elderly clinical trial patients treated on 2 Cancer and Leukemia Group B (CALGB) trials (9344, adjuvant breast study and 9730, advanced lung cancer study) and merged participants' CALGB data with their Medicare data. From CALGB data, we identified the most frequent Extended Clinical Toxicity Critieria grade III/IV toxicities. We reviewed diagnostic and procedure codes from Medicare manuals, developed algorithms to measure the toxicities, and then finalized the algorithms after empiric review of patients' codes. We compared results of Medicare algorithms to gold standard CALGB toxicity information to calculate test characteristics.CALGB data documented that 15 grade III/IV chemotherapy-related toxicities occurred in > or =3% of the 175 patients: white blood cell, hemoglobin, platelets, anorexia, nausea, vomiting, diarrhea, stomatitis, sensory neuropathy, motor neuropathy, motor or sensory neuropathy, dyspnea, hyperglycemia, infection, and malaise. Vomiting was the only toxicity identified by the Medicare-based algorithm with a sensitivity, specificity, and area under the receiver operator curve of > or =80%.The results of this preliminary study suggest that Medicare diagnostic and procedure codes may be of only limited value in measuring clinically significant chemotherapy-related toxicities in elderly Medicare beneficiaries. Future research includes confirming these findings in a larger and more diverse sample.
Project description:Background/objectiveExercise interventions improve anxiety and mood disturbances in patients with cancer. However, studies are limited in older adults with cancer. We assessed the effects of exercise on anxiety, mood, and social and emotional well-being in older patients with cancer during their first 6 weeks of chemotherapy.DesignExploratory secondary analysis of a randomized controlled trial (RCT).SettingCommunity oncology practices.ParticipantsOlder patients (aged 60 years or older) undergoing chemotherapy (N = 252).InterventionPatients were randomized to Exercise for Cancer Patients (EXCAP) or usual care (control) for the first 6 weeks of chemotherapy. EXCAP is a home-based, low- to moderate-intensity progressive walking and resistance training program.MeasurementsAnalysis of covariance, with study arm as the factor, baseline value as the covariate, and study arm × baseline interaction, was used to evaluate arm effects on postintervention anxiety (State Trait Anxiety Inventory [STAI]), mood (Profile of Mood States [POMS]), and social and emotional well-being (Functional Assessment of Cancer Therapy-General subscales) after 6 weeks.ResultsMedian age was 67 years; 77% had breast cancer. Statistically significant group differences were observed in the STAI score (P = .001), POMS score (P = .022), social well-being (P = .002), and emotional well-being (P = .048). For each outcome, EXCAP patients with worse baseline scores had larger improvements at 6 weeks; these improvements were clinically significant for STAI score and social well-being.ConclusionsAmong older cancer patients receiving chemotherapy, a 6-week structured exercise program improved anxiety and mood, especially among those participants with worse baseline symptoms. Additional RCTs are needed to confirm these findings and evaluate the appropriate exercise prescription for managing anxiety, mood, and well-being in this patient population. J Am Geriatr Soc 67:1005-1011, 2019.
Project description:High-dose chemotherapy and autologous hematopoietic cell transplantation is an effective consolidation therapy in lymphoma; however, its use in elderly patients has been limited because of concerns for greater toxicity in this group. We investigated the toxicities of carmustine, etoposide, cytarabine, and melphalan (BEAM) and autologous hematopoietic cell transplantation (AHCT) in 346 patients in 2 age groups: 279 patients aged 60 to 69 years and 67 patients aged ≥70 years. The majority developed severe toxicities; the most common were febrile neutropenia, gastrointestinal, infections, and cardiovascular. Older patients were at higher risk for grade ≥3 cardiovascular toxicities (hazard ratio [HR], 3.36; 95% confidence interval [CI], 2.25-5.00; P < .001) and skin toxicities (HR, 2.45; 95% CI, 1.08-5.54, P = .032). In the older group, nonrelapse mortality at 100 days and at 2 years was 2.99% (95% CI, 0.55-9.32) and 6.2% (95% CI, 1.97-13.95), respectively, vs 1.79% (95% CI, 0.68-3.92) and 2.91% (95% CI, 1.37-5.42), respectively, in the younger group. When adjusting for the number of grade ≥3 toxicities within the first 100 days, older patients had a 1.71-fold (95% CI, 1.08-2.71) increased risk for progression or death relative to younger patients. Although BEAM followed by AHCT is effective, it is associated with significant organ toxicities, especially in patients aged ≥70 years. Interventions to mitigate toxicities while maintaining efficacy are much needed.
Project description:PurposeGiven the biological differences between females and males, sex-specific evaluations should be carried out to obtain better cancer prevention, diagnosis, and treatment strategies. To this purpose, our aim was to evaluate sex differences for toxicity in a cohort of colorectal cancer (CRC) patients undergoing chemotherapy.MethodsWe performed a retrospective study in 329 CRC patients. Differences between males and females were tested performing the Mann-Whitney U test or the Fisher exact test. Multivariate logistic regression models were computed to evaluate the association between sex and risk of chemotherapy agent-related toxicity.ResultsAccording association sex toxicity, significant differences were observed in the median number of episodes of nausea (p = 0.044), vomit (p = 0.007), heartburn (p = 0.022), thrombocytopenia (p = 0.005), mucositis (p = 0.024). Moreover, statistically significant differences between males and females were observed in the distribution of the highest toxicity grades of nausea (p = 0.024), heartburn (p = 0.016), and thrombocytopenia (p = 0.034). Females have an increased risk of vomit (p = 0.002), alopecia (p = 0.035), heartburn (p = 0.005), mucositis (p = 0.003), and lower risk for thrombocytopenia (p = 0.005).ConclusionAccording to the association of sex chemotherapy agent-related toxicities, females resulted on average at a significant increased risk of more common adverse events (constipation, dysgeusia, alopecia, heartburn, vomit, asthenia, nausea, pain events, and mucositis). Sex-tailored CRC chemotherapy treatment is necessary to obtain efficacy avoiding toxicity, based on patients' biological and genetic characteristics, a vision that would change CRC setting, a stable disease but still orphan of a real tailored approach.