The Impact of the COVID-19 Pandemic on Incidence and Short-Term Survival for Common Solid Tumours in the United Kingdom: A Cohort Analysis.

Purpose: The COVID-19 pandemic profoundly affected healthcare systems and patients. There is a need to comprehend the collateral effects of the pandemic on non-communicable diseases. We examined the impact of the pandemic on short-term survival for common solid tumours, including breast, colorectal, head and neck, liver, lung, oesophageal, pancreatic, prostate, and stomach cancer in the UK. Methods: This was a population-based cohort study of electronic health records from the UK primary care Clinical Practice Research Datalink GOLD database. In sum, 12,259,744 eligible patients aged ≥18 years with ≥1 year's history identified from January 2000 to December 2022 were included. We estimated age-standardised incidence and short-term (one- and two-year) survival for several common cancers from 2000 to 2019 (in five-year strata) and compared these to 2020-2022 using the Kaplan-Meier method. Results: Incidence decreased for most cancers in 2020 and recovered to different extents in 2021-2022. Short-term survival improved for most cancers between 2000 and 2019, but then declined, albeit minimally, for those diagnosed in 2020-2022. This was most pronounced for colorectal cancer, with one-year survival falling from 78.8% (95% CI 78%-79.6%) in 2015-2019 to 77% (95% CI 75.6-78.3%) for those diagnosed in 2020-2022. Conclusion: Short-term survival for many cancers was impacted, albeit minimally, by the pandemic in the UK, with reductions in survivorship from colorectal cancer equivalent to returning to the mortality seen in the first decade of the 2000s. While data on longer-term survival are needed to fully comprehend the impact of COVID-19 on cancer care, our findings illustrate the need for an urgent and substantial commitment from the UK National Health Service to address the existing backlog in cancer screening and diagnostic procedures to improve cancer care and mortality.

Time From Colorectal Cancer Surgery to Adjuvant Chemotherapy: Post Hoc Analysis of the SCOT Randomized Clinical Trial.

Importance: The timing of adjuvant chemotherapy after surgery for colorectal cancer and its association with long-term outcomes have been investigated in national cohort studies, with no consensus on the optimal time from surgery to adjuvant chemotherapy. Objective: To analyze the association between the timing of adjuvant chemotherapy after surgery for colorectal cancer and disease-free survival. Design, Setting, and Participants: This is a post hoc analysis of the phase 3 SCOT randomized clinical trial, from 244 centers in 6 countries, investigating the noninferiority of 3 vs 6 months of adjuvant chemotherapy. Patients with high-risk stage II or stage III nonmetastatic colorectal cancer who underwent curative-intended surgery were randomized to either 3 or 6 months of adjuvant chemotherapy consisting of fluoropyrimidine and oxaliplatin regimens. Those with complete information on the date of surgery, treatment type, and long-term follow-up were investigated for the primary and secondary end points. Data were analyzed from May 2022 to February 2024. Intervention: In the post hoc analysis, patients were grouped according to the start of adjuvant chemotherapy being less than 6 weeks vs greater than 6 weeks after surgery. Main Outcomes and Measures: The primary end point was disease-free survival. The secondary end points were adverse events in the total treatment period or the first cycle of adjuvant chemotherapy. Results: A total of 5719 patients (2251 [39.4%] female; mean [SD] age, 63.4 [9.3] years) were included in the primary analysis after data curation; among them, 914 were in the early-start group and 4805 were in the late-start group. Median (IQR) follow-up was 72.0 (47.3-88.1) months, with a median (IQR) of 56 (41-66) days from surgery to chemotherapy. Five-year disease-free survival was 78.0% (95% CI, 75.3%-80.8%) in the early-start group and 73.2% (95% CI, 72.0%-74.5%) in the late-start group. In an adjusted Cox regression analysis, the start of adjuvant chemotherapy greater than 6 weeks after surgery was associated with worse disease-free survival (hazard ratio, 1.24; 95% CI, 1.06-1.46; P = .01). In adjusted logistic regression models, there was no association with adverse events in the total treatment period (odds ratio, 0.82; 95% CI, 0.65-1.04; P = .09) or adverse events in the first cycle of treatment (odds ratio, 0.77; 95% CI, 0.56-1.09; P = .13). Conclusions and Relevance: In this international population of patients with high-risk stage II and stage III colorectal cancer, starting adjuvant chemotherapy more than 6 weeks after surgery was associated with worse disease-free survival, with no difference in adverse events between the groups. Trial Registration: isrctn.org Identifier: ISRCTN59757862.

The association of postoperative morbidity and age on 5-year survival after colorectal surgery in the elderly population: a nationwide cohort study.

AIM: This study aimed to evaluate the association of age and postoperative morbidity on 5-year overall survival (OS) after elective surgery for colorectal cancer. METHOD: Patients undergoing elective, curatively intended surgery for colorectal cancer Union for International Cancer Control Stages I-III between January 2014 and December 2019 were selected from four Danish nationwide healthcare databases. Patients were divided into four groups: group I 65-69 years old; group II 70-74 years old; group III 75-79 years old; and group IV ≥80 years old. Propensity score matching was used to reduce potential confounding bias. The primary outcome was the association of age and postoperative morbidity with 5-year OS. The secondary outcome was conditional survival, given that the patient had already survived the first 90 days after surgery. RESULTS: After propensity score matching with a 1:1 ratio, group II contained 2221 patients; group III 952 patients; and group IV 320 patients. There was no significant difference in 5-year OS between group I (reference) and groups II and III (P = 0.4 and P = 0.9, respectively). Patients with severe postoperative complications within 30 days after surgery had a significantly decreased OS (P < 0.01); however, when patients who died within the first 90 days were excluded from the analysis, the differences in 5-year OS were less pronounced across all age groups. CONCLUSION: Postoperative morbidity, and not patient age, was associated with a lower 5-year OS. Long-term survival for patients who experience a complication is similar to patients who did not have a complication when conditioning on 90 days of survival.

Prediction of 30-day, 90-day, and 1-year mortality after colorectal cancer surgery using a data-driven approach.

PURPOSE: To develop prediction models for short-term mortality risk assessment following colorectal cancer surgery. METHODS: Data was harmonized from four Danish observational health databases into the Observational Medical Outcomes Partnership Common Data Model. With a data-driven approach using the Least Absolute Shrinkage and Selection Operator logistic regression on preoperative data, we developed 30-day, 90-day, and 1-year mortality prediction models. We assessed discriminative performance using the area under the receiver operating characteristic and precision-recall curve and calibration using calibration slope, intercept, and calibration-in-the-large. We additionally assessed model performance in subgroups of curative, palliative, elective, and emergency surgery. RESULTS: A total of 57,521 patients were included in the study population, 51.1% male and with a median age of 72 years. The model showed good discrimination with an area under the receiver operating characteristic curve of 0.88, 0.878, and 0.861 for 30-day, 90-day, and 1-year mortality, respectively, and a calibration-in-the-large of 1.01, 0.99, and 0.99. The overall incidence of mortality were 4.48% for 30-day mortality, 6.64% for 90-day mortality, and 12.8% for 1-year mortality, respectively. Subgroup analysis showed no improvement of discrimination or calibration when separating the cohort into cohorts of elective surgery, emergency surgery, curative surgery, and palliative surgery. CONCLUSION: We were able to train prediction models for the risk of short-term mortality on a data set of four combined national health databases with good discrimination and calibration. We found that one cohort including all operated patients resulted in better performing models than cohorts based on several subgroups.

Endoscopic calcium electroporation for colorectal cancer: a phase I study.

Background and study aims Colorectal cancer is one of the most common malignancies, with approximately 20 % of patients having metastatic disease. Local symptoms from the tumor remain a common issue and affect quality of life. Electroporation is a method to permeabilize cell membranes with high-voltage pulses, allowing increased passage of otherwise poorly permeating substances such as calcium. The aim of this study was to determine the safety of calcium electroporation for advanced colorectal cancer. Patients and methods Six patients with inoperable rectal and sigmoid colon cancer were included, all presenting with local symptoms. Patients were offered endoscopic calcium electroporation and were followed up with endoscopy and computed tomography/magnetic resonance scans. Biopsies and blood samples were collected at baseline and at follow-up, 4, 8, and 12 weeks after treatment. Biopsies were examined for histological changes and immunohistochemically with CD3/CD8 and PD-L1. In addition, blood samples were examined for circulating cell-free DNA (cfDNA). Results A total of 10 procedures were performed and no serious adverse events occurred. Prior to inclusion, patients reported local symptoms, such as bleeding (N = 3), pain (N = 2), and stenosis (N = 5). Five of six patients reported symptom relief. In one patient, also receiving systemic chemotherapy, clinical complete response of primary tumor was seen. Immunohistochemistry found no significant changes in CD3 /CD8 levels or cfDNA levels after treatment. Conclusions This first study of calcium electroporation for colorectal tumors shows that calcium electroporation is a safe and feasible treatment modality for colorectal cancer. It can be performed as an outpatient treatment and may potentially be of great value for fragile patients with limited treatment options.

The impact of time to surgery on oncological outcomes in stage I-III dMMR colon cancer - A nationwide cohort study.

INTRODUCTION: One of the considerations when investigating neoadjuvant interventions is the prolonging of time from diagnosis to curative surgery (i.e. the treatment interval [TI]). The aim of this study was to investigate the association between the length of TI and overall survival and disease-free survival in patients with deficient mismatch repair (dMMR) colon cancer. MATERIALS AND METHODS: This retrospective propensity score-adjusted study included all patients of ≥18 years of age undergoing elective curative surgery for stage I-III, dMMR colon cancer. Data were extracted from four Danish patient databases. Outcomes were investigated in groups with TIs of ≤14 days versus >14 days. Propensity scores were computed using all demographics, diagnoses and measurements. Matching was done in a 1:1 ratio. RESULTS: A total of 4130 patients were included in the study with a mean age of 73.8 years and a median follow-up time of 43.9 months. After matching, 2794 patients were included in the analysis of overall survival. No significant difference in overall survival was seen between patients with TIs of ≤14 days versus >14 days (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.81-1.17; p = 0.78). In the analysis of disease-free survival, 1798 patients were included after matching. This showed no significant difference between patients with TIs of ≤14 days versus >14 days (HR, 0.85; 95% CI, 0.69-1.06; p = 0.14). CONCLUSION: No associations were found between TI and overall survival and disease-free survival in patients with stage I-III, dMMR colon cancer undergoing elective curative surgery.

Expression of Circadian Clock Genes in Human Colorectal Cancer Tissues Using Droplet Digital PCR.

Increasing evidence indicates that disruption of circadian rhythms may be directly linked to cancer. Here we report that the expression levels of the core clock genes Per1 and Per3 measured by droplet digital polymerase chain reaction are significantly decreased in tumour tissue from 16 patients undergoing colorectal cancer surgery compared to paired normal mucosa. No differences were observed in the expression of Per2, Bmal1, and Clock. In conclusion, abnormal expression levels of the clock genes Per1 and Per3 in CRC tissue may be related to tumourigenesis and may provide future diagnostic and prognostic information.

[Individualized treatment of colon cancer].

The treatment of colon cancer has undergone a rapid development with improved surgical and medical regimes and the introduction of targeted treatments. This review offers insight into the current available tailored treatment of colon cancer, and some of the new tailored treatment possibilities with focus on preoperative-, surgical- and post-operative treatment are presented.