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A B S T R A C T PurposeFluourouracil (FU) is a mainstay of chemotherapy, although toxicities are common. Genetic biomarkers have been used to predict these adverse events, but their utility is uncertain. Patients and MethodsWe tested candidate polymorphisms identified from a systematic literature search for associations with capecitabine toxicity in 927 patients with colorectal cancer in the Quick and Simple and Reliable trial (QUASAR2). We then performed meta-analysis of QUASAR2 and 16 published studies (n ϭ 4,855 patients) to examine the polymorphisms in various FU monotherapy and combination therapy regimens. ResultsGlobal capecitabine toxicity (grades 0/1/2 v grades 3/4/5) was associated with the rare, functional DPYD alleles 2846TϾA and *2A (combined odds ratio, 5.51; P ϭ .0013) and with the common TYMS polymorphisms 5ЈVNTR2R/3R and 3ЈUTR 6bp ins-del (combined odds ratio, 1.31; P ϭ 9.4 ϫ 10 Ϫ6 ). There was weaker evidence that these polymorphisms predict toxicity from bolus and infusional FU monotherapy. No good evidence of association with toxicity was found for the remaining polymorphisms, including several currently included in predictive kits. No polymorphisms were associated with toxicity in combination regimens. ConclusionA panel of genetic biomarkers for capecitabine monotherapy toxicity would currently comprise only the four DPYD and TYMS variants above. We estimate this test could provide 26% sensitivity, 86% specificity, and 49% positive predictive value-better than most available commercial kits, but suboptimal for clinical use. The test panel might be extended to include additional, rare DPYD variants functionally equivalent to *2A and 2846A, though insufficient evidence supports its use in bolus, infusional, or combination FU. There remains a need to identify further markers of FU toxicity for all regimens.

Topo1 immunohistochemistry identified subpopulations that did or did not benefit from irinotecan, and possibly also from oxaliplatin. If verified independently, this information will contribute to the individualization of treatment for colorectal cancer.

These results do not support the routine clinical use of the evaluated polymorphisms, including UGT1A1*28. Further investigation of XRCC1, ERCC2, and GSTP1 as potential predictors of irinotecan toxicity is warranted.

As the therapeutic options for the treatment of colorectal cancer have expanded over the past 20 years, so has the complexity of decision making. The goals of treatment in the palliative, adjuvant and neoadjuvant settings vary and it is not only the efficacy of drugs that influence treatment decisions. Age, performance status, the presence of significant comorbidities and the different treatment regimens and strategies provide medical oncologists with an array of options to attempt to maximize patients' quality of life and longevity.

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The SARS-CoV-2-infection can be seen as a single disease but also affects patients with relevant comorbidities who may have an increased risk of a severe course of infection. In this report, we present a 77-year old patient with a heart transplant under relevant immunosuppressive therapy who was tested positive for SARS-CoV-2 after several days of dyspnoea, dry cough and light general symptoms. The CTscan confirmed an interstitial pneumonia. The patient received an antiviral therapy with hydroxychloroquine showing no further deterioration of the clinical state. After 12 days of hospitalisation the patient was released SARS-CoV-2 negative and completely asymptomatic. Anamnesis Accepted Article

Adjuvant chemotherapy (ACT) for stage III colon cancer is well-established. This study aimed to explore determinants of ACT use and between-hospital variation within the English National Health Service. 11,932 patients (diagnosed 2014-2017) with pathological stage III colon cancer in the English NHS were identified from the National Bowel Cancer Audit. Records were linked to Systemic Anti-Cancer Therapy and Hospital Episode Statistics databases.Multi-level logistic regression analyses were performed to estimate independent factors for ACT use including age, sex, deprivation, comorbidities, performance status, ASA, surgical urgency, surgical access, TNM staging, re-admission and hospital-level factors (University teaching hospital, on-site chemotherapy and high-volume centre). A random intercept was modelled for each English NHS hospital (n=142).Between-hospital variation was explored using funnel plot methodology. Fullyadjusted random-intercept models were fitted separately in young (<70 years) and elderly (≥70 years) patients, and intra-class correlation coefficients estimated. 60.7% of patients received ACT. Age was the strongest determinant. Compared to patients <60 years, those aged 60-64 (adjusted odds ratio (aOR) 0.76 (95%