Colorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC (mCRC) has improved greatly due not only to an increase in the number of patients being referred for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. This reflects the increase in the number of patients that are being managed within a multidisciplinary team environment and specialist cancer centres, and the emergence over the same time period not only of improved imaging techniques but also prognostic and predictive molecular markers. Treatment decisions for patients with mCRC must be evidence-based. Thus, these ESMO consensus guidelines have been developed based on the current available evidence to provide a series of evidence-based recommendations to assist in the treatment and management of patients with mCRC in this rapidly evolving treatment setting.
Background Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness.Methods In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing. FindingsOf 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57-76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1•84, 95% CI 1•53-2•21), male sex (1•63, 1•07-2•48), smoking status (former smoker vs never smoked: 1•60, 1•03-2•47), number of comorbidities (two vs none: 4•50, 1•33-15•28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3•89, 2•11-7•18), active cancer (progressing vs remission: 5•20, 2•77-9•77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2•93, 1•79-4•79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0•24, 0•07-0•84) or the US-Midwest (0•50, 0•28-0•90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality. Interpretation Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments.
A B S T R A C T PurposePrior reports have indicated that patients with colon cancer who demonstrate high-level microsatellite instability (MSI-H) or defective DNA mismatch repair (dMMR) have improved survival and receive no benefit from fluorouracil (FU) -based adjuvant therapy compared with patients who have microsatellite-stable or proficient mismatch repair (pMMR) tumors. We examined MMR status as a predictor of adjuvant therapy benefit in patients with stages II and III colon cancer. MethodsMSI assay or immunohistochemistry for MMR proteins were performed on 457 patients who were previously randomly assigned to FU-based therapy (either FU ϩ levamisole or FU ϩ leucovorin; n ϭ 229) versus no postsurgical treatment (n ϭ 228). Data were subsequently pooled with data from a previous analysis. The primary end point was disease-free survival (DFS). Results Overall, 70 (15%) of 457 patients exhibited dMMR. Adjuvant therapy significantly improved DFS (hazard ratio [HR], 0.67; 95% CI, 0.48 to 0.93; P ϭ .02) in patients with pMMR tumors. Patients with dMMR tumors receiving FU had no improvement in DFS (HR, 1.10; 95% CI, 0.42 to 2.91; P ϭ .85) compared with those randomly assigned to surgery alone. In the pooled data set of 1,027 patients (n ϭ 165 with dMMR), these findings were maintained; in patients with stage II disease and with dMMR tumors, treatment was associated with reduced overall survival (HR, 2.95; 95% CI, 1.02 to 8.54; P ϭ .04). ConclusionPatient stratification by MMR status may provide a more tailored approach to colon cancer adjuvant therapy. These data support MMR status assessment for patients being considered for FU therapy alone and consideration of MMR status in treatment decision making.
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