Summary Background Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is used to treat patients with non-Hodgkin lymphoma. Interval decrease from 3 weeks of treatment (CHOP-21) to 2 ...weeks (CHOP-14), and addition of rituximab to CHOP-21 (R-CHOP-21) has been shown to improve outcome in elderly patients with diffuse large B-cell lymphoma (DLBCL). This randomised trial assessed whether six or eight cycles of R-CHOP-14 can improve outcome of these patients compared with six or eight cycles of CHOP-14. Methods 1222 elderly patients (aged 61–80 years) were randomly assigned to six or eight cycles of CHOP-14 with or without rituximab. Radiotherapy was planned to sites of initial bulky disease with or without extranodal involvement. The primary endpoint was event-free survival; secondary endpoints were response, progression during treatment, progression-free survival, overall survival, and frequency of toxic effects. Analyses were done by intention to treat. The trial is registered on National Cancer Institute website, number NCT00052936 and as EU-20243. Findings 3-year event-free survival was 47·2% after six cycles of CHOP-14 (95% CI 41·2–53·3), 53·0% (47·0–59·1) after eight cycles of CHOP-14, 66·5% (60·9–72·0) after six cycles of R-CHOP-14, and 63·1% (57·4–68·8) after eight cycles of R-CHOP-14. Compared with six cycles of CHOP-14, the improvement in 3-year event-free survival was 5·8% (−2·8–14·4) for eight cycles of CHOP-14, 19·3% (11·1–27·5) for six cycles of R-CHOP-14, and 15·9% (7·6–24·2) for eight cycles of R-CHOP-14. 3-year overall survival was 67·7% (62·0–73·5) for six cycles of CHOP-14, 66·0% (60·1–71·9) for eight cycles of CHOP-14, 78·1% (73·2–83·0) for six cycles of R-CHOP-14, and 72·5% (67·1–77·9) for eight cycles of R-CHOP-14. Compared with treatment with six cycles of CHOP-14, overall survival improved by −1·7% (−10·0–6·6) after eight cycles of CHOP-14, 10·4% (2·8–18·0) after six cycles of R-CHOP-14, and 4·8% (−3·1–12·7) after eight cycles of R-CHOP-14. In a multivariate analysis that used six cycles of CHOP-14 without rituximab as the reference, and adjusting for known prognostic factors, all three intensified regimens improved 3-year event-free survival (eight cycles of CHOP-14: RR relative risk 0·76 0·60–0·95, p=0·0172; six cycles of R-CHOP-14: RR 0·51 0·40–0·65, p<0·0001; eight cycles of R-CHOP-14: RR 0·54 0·43–0·69, p<0·0001). Progression-free survival improved after six cycles of R-CHOP-14 (RR 0·50 0·38–0·67, p<0·0001), and eight cycles of R-CHOP-14 (RR 0·59 0·45–0·77, p=0·0001). Overall survival improved only after six cycles of R-CHOP-14 (RR 0·63 0·46–0·85, p=0·0031). In patients with a partial response after four cycles of chemotherapy, eight cycles were not better than six cycles. Interpretation Six cycles of R-CHOP-14 significantly improved event-free, progression-free, and overall survival over six cycles of CHOP-14 treatment. Response-adapted addition of chemotherapy beyond six cycles, though widely practiced, is not justified. Of the four regimens assessed in this study, six cycles of R-CHOP-14 is the preferred treatment for elderly patients, with which other approaches should be compared.
•SARS-CoV-2 rapid antigen tests provide fast identification of infectious patients•Prediction models for identification of false negative test results were developed•One investigated clinical model ...reached an area under the curve of 0.971•Prediction models can be routinely applied in the healthcare sector•The prevention of nosocomial infections positively influences the pandemic's course
SARS-CoV-2 rapid antigen tests (RAT) provide fast identification of infectious patients when RT-PCR results are not immediately available. We aimed to develop a prediction model for identification of false negative (FN) RAT results.
In this multicenter trial, patients with documented paired results of RAT and RT-PCR between October 1st 2020 and January 31st 2021 were retrospectively analyzed regarding clinical findings. Variables included demographics, laboratory values and specific symptoms. Three different models were evaluated using Bayesian logistic regression.
The initial dataset contained 4,076 patients. Overall sensitivity and specificity of RAT was 62.3% and 97.6%. 2,997 cases with negative RAT results (FN: 120; true negative: 2,877; reference: RT-PCR) underwent further evaluation after removal of cases with missing data. The best-performing model for predicting FN RAT results containing 10 variables yielded an area under the curve of 0.971. Sensitivity, specificity, PPV and NPV for 0.09 as cut-off value (probability for FN RAT) were 0.85, 0.99, 0.7 and 0.99.
FN RAT results can be accurately identified through ten routinely available variables. Implementation of a prediction model in addition to RAT testing in clinical care can provide decision guidance for initiating appropriate hygiene measures and therefore helps avoiding nosocomial infections.
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