Etiology of Fever and Associated Outcomes Among Adults Receiving Chemotherapy for the Treatment of Solid Tumors in Uganda
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PROVIDER: S-EPMC10633783 | biostudies-literature | 2023 Oct
REPOSITORIES: biostudies-literature
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| S-EPMC10043746 | biostudies-literature
Project description:PurposeThe objective of this study was to evaluate the short- and long-term outcomes of adult patients with solid tumors receiving chemotherapy in the intensive care unit (ICU).MethodsThis was a retrospective single-center study comparing the outcomes of patients with solid tumors who received chemotherapy in the ICU with a matched cohort of ICU patients (by age, sex, and tumor type) who did not receive chemotherapy. Conditional logistic regression and shared frailty Cox regression were used to assess short-term (ICU and hospital) mortality and death by 12-month post-hospital discharge, respectively.ResultsSeventy-three patients with solid tumors who received chemotherapy in the ICU were successfully matched. The most common solid tumors included thoracic (30%), genitourinary (26%), and breast (16%). The ICU, hospital, and 12-month (post discharge) mortality rates of patients who recieved chomtherapy in the ICU were 23%, 36%, and 43%, respectively. When compared to the matched cohort of patients who did not receive chemotherapy, patients who received chemotherapy had a significantly longer length of stay in the ICU (median 7 vs. 4 days, p < 0.001) and hospital (median 15 vs. 11 days, p = 0.011) but similar short-term ICU and hospital mortality rates (23% vs. 18% and 36% vs. 38%, respectively). Patients who received chemotherapy in the ICU were at a lower risk of death by 12 months (HR 0.31, p < 0.001) compared to the matched cohort on multivariable analysis.ConclusionsPatients with solid tumors who received chemotherapy had increased ICU and hospital length of stay compared to patients who did not. Although short-term mortality did not differ, patients who received chemotherapy in the ICU had improved long-term survival. Our data can inform critical care triage decisions to include patients who are to receive chemotherapy in the ICU.
| S-EPMC8286144 | biostudies-literature
Project description:BACKGROUND:The decision whether to treat older adults with advanced cancer with standard therapy (ST) or reduced therapy (RT) is complicated by heterogeneity in aging. We assessed the potential utility of the chemotherapy toxicity risk score (CTRS) [J Clin Oncol 2011;29:3457-3465] for treatment decisions in older adults. MATERIALS AND METHODS:This was a prospective observational study of patients aged ≥65 years receiving first-line chemotherapy for advanced cancer for which combination chemotherapy is the standard of care. Patients were categorized as high risk (CTRS ≥10), for whom RT (dose-reduced combination or single-agent chemotherapy) is deemed appropriate, or nonhigh risk (CTRS <10), for whom ST is deemed appropriate for toxicity. The primary objective was to estimate the agreement in chemotherapy choice (ST vs. RT) between the treating physician and the CTRS using a κ statistic. RESULTS:Fifty-eight patients (median age, 71 years) were enrolled. Thirty-eight patients received ST (21 had CTRS <10, and 17 had CTRS ≥10), and 20 patients received RT (12 had CTRS ≥10, and 8 had CTRS <10), with minimal agreement in chemotherapy choice (κ = 0.14; 95% CI, -0.10 to 0.38). Grade 3-4 toxicity and hospitalization occurred in 60% and 27% of 55 patients with follow-up data, respectively. Among patients receiving ST, patients with CTRS ≥10 had a higher incidence of toxicity (88% vs. 40%, p = .006) and hospitalization (50% vs. 15%, p = .03) than those with CTRS <10. CONCLUSION:Older patients with cancer with a high CTRS who receive combination chemotherapy have an exceedingly high rate of severe toxicity and hospitalization. IMPLICATIONS FOR PRACTICE:The potential utility of the chemotherapy toxicity risk score (CTRS) in old adults with advanced solid tumors receiving first-line chemotherapy was assessed. Little agreement was found between chemotherapy treatment decisions based on the clinical impression versus what was recommended based on the CTRS. Among patients treated with standard-dose combination chemotherapy, patients with CTRS ≥10 had a very high incidence of grade 3-4 toxicities and hospitalization, which was significantly greater than that of patients with a low CTRS (<10). These findings suggest that the addition of CTRS to the clinical impression has a potential to improve treatment decisions.
| S-EPMC5947449 | biostudies-literature
Project description:ObjectivesTo estimate the risk of thrombocytopenia in various cancers and chemotherapy regimens.MethodsStructured patient-level data from the Flatiron Health Electronic Health Record database were used to identify adult patients who received chemotherapy for a solid tumor or hematologic malignancy from 2012 to 2017. Three-month cumulative incidence of thrombocytopenia was assessed based on platelet counts, overall and by grade of thrombocytopenia. Co-occurrence of anemia, neutropenia, and leukopenia was evaluated.ResultsOf 15,521 patients with solid tumors, 13% had thrombocytopenia within 3 months (platelet count < 100 × 109 /L); 4% had grade 3 (25 to < 50 × 109 /L), and 2% grade 4 (<25 × 109 /L) thrombocytopenia. Of 2537 patients with hematologic malignancies, 28% had any thrombocytopenia, 16% with grade 3, and 12% with grade 4. Among patients with thrombocytopenia, it occurred without another cytopenia in 18% of solid tumors and 7% of hematologic malignancies.ConclusionsIn a large, US-representative sample of patients undergoing chemotherapy in clinical practice, thrombocytopenia incidence varied across tumor and regimen types. Despite recommendations to alter chemotherapy to avoid severe thrombocytopenia, 4% of patients with solid tumors and 16% with hematologic malignancies experienced grade 3 thrombocytopenia. Prediction and prevention of thrombocytopenia may help oncologists avoid dose modifications and their adverse effects on survival.
| S-EPMC8248430 | biostudies-literature
Project description:The serine/threonine kinase AKT, also known as protein kinase B (PKB), is the major substrate to phosphoinositide 3-kinase (PI3K) and consists of three paralogs: AKT1 (PKBα), AKT2 (PKBβ) and AKT3 (PKBγ). The PI3K/AKT pathway is normally activated by binding of ligands to membrane-bound receptor tyrosine kinases (RTKs) as well as downstream to G-protein coupled receptors and integrin-linked kinase. Through multiple downstream substrates, activated AKT controls a wide variety of cellular functions including cell proliferation, survival, metabolism, and angiogenesis in both normal and malignant cells. In human cancers, the PI3K/AKT pathway is most frequently hyperactivated due to mutations and/or overexpression of upstream components. Aberrant expression of RTKs, gain of function mutations in PIK3CA, RAS, PDPK1, and AKT itself, as well as loss of function mutation in AKT phosphatases are genetic lesions that confer hyperactivation of AKT. Activated AKT stimulates DNA repair, e.g. double strand break repair after radiotherapy. Likewise, AKT attenuates chemotherapy-induced apoptosis. These observations suggest that a crucial link exists between AKT and DNA damage. Thus, AKT could be a major predictive marker of conventional cancer therapy, molecularly targeted therapy, and immunotherapy for solid tumors. In this review, we summarize the current understanding by which activated AKT mediates resistance to cancer treatment modalities, i.e. radiotherapy, chemotherapy, and RTK targeted therapy. Next, the effect of AKT on response of tumor cells to RTK targeted strategies will be discussed. Finally, we will provide a brief summary on the clinical trials of AKT inhibitors in combination with radiochemotherapy, RTK targeted therapy, and immunotherapy.
| S-EPMC7169978 | biostudies-literature
Project description:Reactivation of hepatitis B or C virus can occur in patients undergoing chemotherapy. Recommendations for selective or systematic hepatitis B virus testing prior chemotherapy for solid tumors differ. The primary aim was to determine the seroprevalence of hepatitis B or C in a low endemic country. The second objective was to assess the relevance of a questionnaire on hepatitis B/C risk factors to consider a selective screening.Patients were prospectively tested for hepatitis B/C markers. HBs antigen positive patients and isolated anti-HBc positive patients with detectable viral load received antiviral preventive treatment. Patients or physicians completed the questionnaire on infection risk factors.Among the 450 patients included, 388 were tested for all serological markers and had gastrointestinal (63.7%), lung (31.2%) and skin (4.6%) cancers. The prevalence of subjects exposed to hepatitis B virus was 8.5% (33/388). One patient tested positive for HBs antigen and received preventive treatment. Prevalence of subjects exposed to hepatitis C was 1.3% (5/388). The questionnaire sensitivity was 45.5%, 100% and 50% for detecting carriers of hepatitis B, C and one or the other, respectively.Seroprevalence of hepatitis B was low. Selective screening with the questionnaire was insufficiently sensitive. Systematic screening with serological tests prior to chemotherapy in patients with solid tumors is therefore relevant.
| S-EPMC4688993 | biostudies-other
Project description:BackgroundRheumatic heart disease is the largest contributor to cardiac-related mortality in children worldwide. Outcomes in endemic settings after its antecedent illness, acute rheumatic fever, are not well understood. We aimed to describe 3-5 year mortality, acute rheumatic fever recurrence, changes in carditis, and correlates of mortality after acute rheumatic fever.MethodsWe conducted a prospective cohort study of Ugandan patients aged 4-23 years who were diagnosed with definite acute rheumatic fever using the modified 2015 Jones criteria from July 1, 2017, to March 31, 2020, enrolled at three rheumatic heart disease registry sites in Uganda (in Mbarara, Mulago, or Lira), and followed up for at least 1 year after diagnosis. Patients with congenital heart disease were excluded. Patients underwent annual review, most recently in August, 2022. We calculated rates of mortality and acute rheumatic fever recurrence, tabulated changes in carditis, performed Kaplan-Meier survival analyses, and used Cox regression models to identify correlates of mortality.FindingsData were collected between Sept 1 and Sept 30, 2022. Of 182 patients diagnosed with definite acute rheumatic fever, 156 patients were included in the analysis. Of these 156 patients (77 [49%] male and 79 (51%) female; data on ethnicity not collected), 25 (16%) died, 21 (13%) had a cardiac-related death, and 17 (11%) had recurrent acute rheumatic fever over a median of 4·3 (IQR 3·0-4·8) years. 16 (24%) of the 25 deaths occurred within 1 year. Among 131 (84%) of 156 survivors, one had carditis progression by echo. Moderate-to-severe carditis (hazard ratio 12·7 [95% CI 3·9-40·9]) and prolonged PR interval (hazard ratio 4·4 [95% CI 1·7-11·2]) at acute rheumatic fever diagnosis were associated with increased cardiac-related mortality.InterpretationThese are the first contemporary data from sub-Saharan Africa on medium-term acute rheumatic fever outcomes. Mortality rates exceeded those reported elsewhere. Most decedents already had chronic carditis at initial acute rheumatic fever diagnosis, suggesting previous undiagnosed episodes that had already compounded into rheumatic heart disease. Our data highlight the large burden of undetected acute rheumatic fever in these settings and the need for improved awareness of and diagnostics for acute rheumatic fever to allow earlier detection.FundingStrauss Award at Cincinnati Children's Hospital, American Heart Association, and Wellcome Trust.
| S-EPMC10882210 | biostudies-literature
Project description:In oncologic patients fever is a non-specific clinical marker of different clinical settings. Procalcitonin (PCT) seems to be the most promising infection marker. We aimed to define the potential role of PCT as an earlier diagnostic marker in patients with fever and solid tumor. This retrospective study enrolled 431 patients. All of them performed hemoculture (HE) and basal PCT assessment (reference laboratory cut-off: ≤0.5 or >0.5 ng/dL) before starting antibiotic therapy. Gram positive (G+), negative (G-) or Fungi infection were detected. A statistically significant difference in PCT levels between patients with positive and negative HE was observed (P < 0.0001). Moreover comparing PCT values in patients with positive and negative HE, we obtain in the positive HE subpopulation an AUC of 0.7 and a cut-off of 1.52 ng/dL reached high sensitivity (61.6%) and specificity (70.1%). Using this last cut-off, instead of the normal reference value, we achieve a risk reduction to overestimate an infection status of 23.4%. We support the clinic usefulness of serum PCT dosage in febrile advanced solid tumor patients. A PCT cut-off of 1.52 ng/dL could be helpful in the management of the antibiotic therapy preventing delays of oncologic treatments.
| S-EPMC4911581 | biostudies-other
Project description:PurposeThere is limited data on third-line chemotherapy in patients with metastatic gastric cancer (MGC). This study was conducted to assess third-line treatment patterns, outcomes, and clinical parameters related to survival outcomes in patients with MGC.MethodsUsing the Korean Health Insurance Review and Assessment Service (HIRA) database, a nationwide population-based outcomes study was conducted. From the HIRA database, patients newly diagnosed in 2010 with MGC were identified (N = 1,871), and of these, 229 patients who had received third-line chemotherapy were finally selected for this study.ResultsPrior to third-line chemotherapy, more than 90% of patients received fluoropyrimidine and platinum, and 43.7% and 40.6% received taxane and irinotecan, respectively. Various third-line chemotherapy regimens containing taxane (docetaxel or paclitaxel), irinotecan, or oxaliplatin were prescribed. The median overall survival (OS) of all patients receiving third-line chemotherapy was 4.4 months. The median time from the start date of first-line chemotherapy to the start date of third-line chemotherapy (TF1T3) was 9.5 months, and a longer TF1T3 was the only factor that was significantly associated with an increased OS. The median OS of patients who had received fluoropyrimidine, platinum, and taxane followed by third-line irinotecan-based therapy was similar to that of patients who had received fluoropyrimidine, platinum, and irinotecan followed by third-line taxane-based therapy (p = 0.894).ConclusionIn patients with MGC receiving third-line chemotherapy, TF1T3 was the only significant factor associated with OS. The sequence of using taxane and irinotecan as subsequent therapy after first-line failure was not shown to impact survival outcome.
| S-EPMC5991719 | biostudies-literature
Project description: Not available
| S-EPMC8260907 | biostudies-literature