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Simple Summary: Peritoneal metastases have a poor prognosis, and one potential treatment option is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). The specific role of HIPEC is still poorly defined. In this cross-sectional study, we systematically analyzed all HIPEC trials registered on ClinicalTrials.gov to identify current research areas and to provide a perspective on expected outcomes. Only 11% (n = 26) of HIPEC trials registered on ClinicalTrials.gov (n = 234) have been published. The registered trials are very heterogeneous regarding methodological approaches and study designs. Currently, research is being conducted on 20 different drugs. The most studied cancers in HIPEC trials are peritoneal metastatic colorectal tumors, gastric cancer, and ovarian cancer. Introduction: Over the past two decades, cytoreductive surgery and HIPEC has improved outcomes for selected patients with peritoneal metastasis from various origins. This is a cross-sectional study with descriptive analyses of HIPEC trials registered on ClinicalTrials.gov. This study aimed to characterize clinical trials on HIPEC registered on ClinicalTrials.gov with the primary objective of identifying a trial focus and to examine whether trial results were published. Methods: The search included trials registered from 1 January 2001 to 14 March 2022. We examined the associations of exposure variables and other trial features with two primary outcomes: therapeutic focus and results reporting. Results: In total, 234 clinical trials were identified; 26 (11%) were already published, and 15 (6%) trials have reported their results but have not been published as full papers. Among ongoing nonpublished trials, 81 (39%) were randomized, 30 (14%) were blinded, n = 39 (20%) were later phase trials (i.e., phases 3 and 4), n = 152 (73%) were from a single institution, and 91 (44%) had parallel groups. Most of the trials were recruiting at the time of this analysis (75, 36%), and 39 (20%) were completed but had yet to publish results. In total, 68% of the trials focused on treatment strategies, and 53% investigated the oncological outcome. The most studied neoplasms for HIPEC trials were peritoneally metastasized colorectal cancer (32%), gastric cancer (29%), and ovarian cancer (26%). Twenty different drugs were analyzed in these clinical trials. Conclusions: Many study results are awaited from ongoing HIPEC trials. Most HIPEC trials focused on gastric, colorectal, or ovarian cancer. Many clinical trials were identified involving multiple entities and chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Simple Summary: Given the wide usage of Bevacizumab in current oncological practice, it is very important to compare the "real-world" results to those obtained in controlled clinical trials. This study aims to describe the clinical experience of using Bevacizumab in a large cohort of cancer patients in "non-controlled real-world" conditions regarding effectiveness, safety, and cost of therapy. For this purpose, we conducted an open, observational, retrospective study involving all patients treated for solid malignant tumors in the Bucharest Institute of Oncology with "Prof. Dr. Al. Trestioreanu" with Bevacizumab-based systemic therapy, between 2017 and 2021. Bevacizumab re-mains a high-cost therapy, but it can add to clinical benefits (like overall survival, progression-free survival, and response rate) when used in conjunction with standard chemotherapy. Similar results as those presented in various controlled trials are observable even on unselected cohorts of patients in the uncontrolled conditions of "real-world" oncological practice. Overall, it is estimated that more than 3,500,000 patients have received Bevacizumab as part of systemic oncologic treatment. Bevacizumab and its biosimilars are currently marketed in over 130 countries. Given the wide usage of Bevacizumab in current oncological practice, it is very important to compare the "real-world" results to those obtained in controlled clinical trials. This study aims to describe the clinical experience of using Bevacizumab in a large cohort of cancer patients in "non-controlled real-world" conditions with regard to effectiveness, safety, and cost of therapy. Methods: For this purpose, we conducted an open, observational, retrospective study involving all patients treated for solid malignant tumors in the Bucharest Institute of Oncology with "Prof. Dr. Al. Trestioreanu" with Bevacizumab-based systemic therapy, between 2017 and 2021. Results: The study consisted of 657 treatment episodes in 625 patients (F/B = 1.62/1, with a median age of 57.6 years) which were treated for malignant tumors (majority colorectal, non-small cell lung, ovarian, and breast cancer). First-line treatment was administered in 229 patients, and the rest received Bevacizumab as second or subsequent lines of treatment. The overall response rate to Bevacizumab-based therapies was around 60–65% across all indication except for subsequent treatment lines in colorectal and ovarian cancers, where lower values were recorded (27.1%, and 31.5% respectively). Median PFS for the entire cohort was 8.2 months (95% CI 6.8–9.6), and the median OS was 13.2 months (95% CI 11.5–14.9). Usual bevacizumab-related toxicities were observed, including bleeding, hypertension, wound-healing complications, gastrointestinal perforation, other types of fistulas, septic complications, and thromboembolic events. Although the clinical benefits are undeniable, the addition of Bevacizumab to standard chemotherapy increased the overall treatment cost by 213%. Conclusions: Bevacizumab remains a high-cost therapy, but it can add to clinical benefits (like overall survival, progression-free survival, and response rate) when used in conjunction with standard chemotherapy. Similar results as those presented in various controlled trials are observable even on unselected cohorts of patients in the uncontrolled conditions of "real-world" oncological practice. Off-label usage is encountered in clinical practice, and this aspect should be monitored given the potential adverse effects of the therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer is one of the most commonly diagnosed cancers worldwide with a high probability of developing metastasis over the course of the disease. Only certain patients with colorectal liver metastases can be treated by surgical resection. Different interventional treatments such as laser-induced thermotherapy, microwave ablation, as well as transarterial chemoembolization can be applied for treating colorectal liver metastases. These therapies have been discussed in various studies. However, the current medical literature is still lacking research from large long-term studies. This retrospective monocentric study includes 2140 patients with colorectal liver metastases treated by different locoregional treatments. It is based upon data collected over a period of more than 26 years at the University Hospital Frankfurt of Goethe University. The aim of this study was to analyze the long-term results of different locoregional treatments for colorectal cancer liver metastases (CRLM), including transarterial chemoembolization (TACE), laser-induced thermotherapy (LITT) and microwave ablation (MWA). A total of 2140 patients with CRLM treated at our department between 1993 and 2020 were included in this retrospective study. The patients were divided into the following groups: LITT (573 patients; median age: 62 years), TACE + LITT (346 patients; median age: 62 years), MWA (67 patients; median age: 59 years), TACE + MWA (152 patients; median age: 65 years), and TACE (1002 patients; median age: 62 years). Median survival was 1.9 years in the LITT group and 1.7 years in the TACE + LITT group. The median survival times in the MWA group and TACE + MWA group were 3.1 years and 2.1 years, respectively. The median survival in the TACE group was 0.8 years. The 1-, 3-, and 5-year survival rates were 77%, 27%, and 9% in the LITT group and 74%, 18%, and 5% in the TACE + LITT group, respectively. The corresponding survival rates were 80%, 55%, and 33% in the MWA group, 74%, 36%, and 20% in the TACE + MWA group and 37%, 3%, and 0% in the TACE group, respectively. The long-term results of this study demonstrate the efficacy of locoregional treatments in treating patients with CRLM. The longest survival was found in the MWA group, followed by the combination therapy of TACE and MWA. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal adenoma formation has multiple contributing factors and how these risk factors interact is not precise. Past studies have demonstrated that increased weight is one of the risk factors of colorectal adenoma formation, but does not mean participants with normal body weight are not concerned about colorectal adenoma formation. We aimed to explore the specific risk factors for colorectal adenomas in individuals with normal body weight, who are often overlooked, and the interaction between these risk factors. Background: We aimed to evaluate the interaction between colorectal adenoma risks among asymptomatic individuals in terms of metabolic health status and obesity, and examine the normal waist-to-hip ratio (WHR) in adults with colorectal adenoma risk. Methods: A cross-sectional, retrospective study was conducted at MacKay Memorial Hospital involving 16,996 participants who underwent bidirectional gastrointestinal endoscopy between 2013 and 2023. The study recorded important clinicopathological characteristics, including age, body mass index and WHR, Framingham Risk Score (FRS), blood glucose level, and Helicobacter pylori (H. pylori) infection status. Results: Multivariate logistic regression analysis demonstrated that elevated hemoglobin A1C (HbA1c), increased FRS, positive H. pylori infection, and WHR ≥ 0.9 are independent risk factors for colorectal adenoma. In examining the interaction between FRS and WHR using multivariate logistic regression to evaluate adenoma risk, the OR for the interaction term was 0.95, indicating a decline in adenoma risk when considering the interaction between these two factors. Incorporating HbA1c into the analysis, evaluating the interaction between FRS and WHR still demonstrated a statistically significant impact on adenoma risk (OR 0.96, p < 0.001). Participants with WHR < 0.9, elevated FRS, positive H. pylori infection, and increased HbA1c levels were associated with a higher risk of colorectal adenoma formation. Remarkably, the increased risk of adenoma due to rising HbA1c levels was statistically significant only for those with a WHR < 0.9. Conclusions: An increase in FRS and HbA1c or a positive H. pylori infection still warrants vigilance for colorectal adenoma risk when WHR is 0.9. These factors interacted with each other and were found to have a minimal decline in adenoma risk when considering the interaction between WHR and FRS. [ABSTRACT FROM AUTHOR]

Simple Summary: There is little evidence about the optimal timing of systemic chemotherapy (SC) in patients treated with cytoreductive surgery (CRS) and HIPEC for colorectal peritoneal metastases (CRC-PM). Due to the lack of evidence in this field, a systematic literature search and a meta-analysis of relevant studies were performed. Twenty-one studies were included in the systematic review and fifteen in the quantitative analysis (4523 patients). Postoperative SC was associated with increased overall survival compared to no SC or a preoperative SC regimen, whereas SC (pre or post) and pre-SC compared to surgery alone were not. Similar results were found for disease-free survival. Preoperative SC was not associated with an increased risk of severe surgical complications. Background. For patients with colorectal cancer (CRC) peritoneal metastases (PM) who are eligible for cytoreductive surgery (CRS), the indication and timing of systemic chemotherapy (SC) are still under debate. This study aims to analyze the role of pre, post or perioperative SC on the survival and surgical complications of patients treated with CRS-HIPEC. Methods. After a systematic search in MEDLINE, Cochrane Database of Systematic Reviews, Scopus, Web of Science and Embase, a meta-analysis was performed to compare postoperative complications, disease-free survival (DFS) and overall survival (OS) according to SC administration and timing. PROSPERO: CRD42023478977. Results. Of 1203 studies screened, 15 were included in the meta-analysis (4523 patients). Post-operative SC was associated with increased overall survival (post-SC vs. no post-SC: HR 0.81, p = 0.00001, I2 = 0%; pre-SC vs. post-SC: HR 0.65, p = 0.01, I2 = 28%), whereas SC (pre or post) or pre-SC compared to surgery alone was not (SC vs. no SC: p = 0.29, I2 = 80%; pre-SC vs. no pre-SC: p = 0.59, I2 = 58%). Similar results were seen for DFS. SC was not associated with an increased complication rate (p = 0.47, I2 = 64%). Conclusions. Systemic chemotherapy administration in patients undergoing radical surgery for colorectal peritoneal metastases is associated with increased survival only in the adjuvant/post-operative setting. Considering the limitations of the included studies, further trials are needed to answer this unresolved question. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver transplantation is emerging as a treatment option for patients with colorectal liver metastases. Due to the lack of liver donors, patient selection is vital. In this study, we report on the predictive value of combining metabolic tumor volume obtained from the pre-transplantation 18F-FDG PET/CT with the radiological measurements of tumor load (size, number, and tumor burden score) to select patients with the probability of long-term survival. Patients with low metabolic tumor volume have long disease-free survival, overall survival, and survival after relapse despite a high number of liver metastases and a high tumor burden score. This underlines the prognostic properties of metabolic active-tumor burden beyond conventional measurements. The aim of the present study is to report on the ability of metabolic tumor volume (MTV) of liver metastases from pre-transplant 18F-FDG PET/CT in combination with conventional radiological measurements from CT scans to predict long-term disease-free survival (DFS), overall survival (OS), and survival after relapse (SAR) after liver transplantation for colorectal liver metastases. The total liver MTV was obtained from the 18F-FDG PET/CT, and the size of the largest metastasis and the total number of metastases were obtained from the CT. DFS, OS, and SAR for patients with a low and high MTV, in combination with a low and high size, number, and tumor burden score, were compared using the Kaplan–Meier method and log–rank test. Patients with a low number of metastases and low MTV had a significantly longer OS than those with a high MTV, with a median survival of 151 vs. 26 months (p = 0.010). Patients with a high number of metastases and low MTV had significantly longer DFS, OS, and SAR than patients with a high MTV (p = 0.034, 0.006, and 0.026). The tumor burden score of group/zone 3, in combination with a low MTV, had a significantly improved DFS, OS, and SAR compared to those with a high MTV (p = 0.034, <0.001, and 0.006). Patients with a low MTV of liver metastases had a long DFS, OS, and SAR despite a high number of liver metastases and a high tumor burden score. [ABSTRACT FROM AUTHOR]

Simple Summary: Third-line or further treatments are rarely given to patients with refractory mCRC. In this regard, two noteworthy innovative therapy options, with varying toxicity profiles and statistically significant improvements in overall survival (OS), progression-free survival (PFS), and disease control, are regorafenib (R) and trifluridine/tipiracil (T). This study is a subset analysis of a larger retrospective study that we have already published, with the aim of evaluating patient outcomes when R and T were administered in that order. The purpose of this analysis was to evaluate the relationship between survival outcomes and the first drug treatment duration (<3 months, 3 to <6 months, and ≥6 months) in patients who had received the regorafenib-to-trifluridine/tipiracil sequence or vice versa. Our substudy found that administering R three to six months prior to T can prolong both OS and PFS in comparison to the opposite sequence. Background: Patients with refractory metastatic colorectal cancer (mCRC) rarely receive third-line or further treatment. In this context, regorafenib (R) and trifluridine/tipiracil (T) are two important novel therapeutic choices with statistically significant increases in overall survival (OS), progression-free survival (PFS), and disease control, with different toxicity profiles. This study is a subgroup analysis of our larger retrospective study, already published, whose objective was to assess the outcomes of patients when R and T were given sequentially. Patients and Methods: The study involved thirteen Italian cancer centers on a 10-year retrospective observation (2012–2022). In this subgroup analysis, we focused our attention on the correlation between the first drug treatment duration (<3 months, 3 to <6 months and ≥6 months) and survival outcomes in patients who had received the sequence regorafenib-to-trifluridine/tipiracil, or vice versa. Results: The initial study included 866 patients with mCRC who received sequential T/R, or R/T, or T or R alone. This analysis is focused on evaluating the impact of the duration of the first treatment in the sequence on clinical outcomes (OS, PFS) and includes 146 and 116 patients of the T/R and R/T sequences, respectively. Based on the duration of the first drug treatment, subgroups for the T/R sequence included 27 patients (18.4%) who received T for <3 months, 86 (58.9%) treated for 3 to <6 months, and 33 (22.6%) treated for ≥6 months; in the reverse sequence (R as the first drug), subgroups included 18 patients (15.5%) who received their first treatment for <3 months, 62 (53.4%) treated for 3 to <6 months, and 35 (31.0%) treated for ≥6 months. In patients who received their first drug treatment for a period of 3 to <6 months, the R/T sequence had a significantly longer median OS (13.7 vs. 10.8 months, p = 0.0069) and a longer median PFS (10.8 vs. 8.5 months, p = 0.0003) than the T/R group. There were no statistically significant differences between groups with first drug treatment durations of <3 months and ≥6 months. Conclusions: Our analysis seems to suggest that the administration of R for a period of 3 to <6 months before that of T can prolong both OS and PFS, as compared to the opposite sequence. [ABSTRACT FROM AUTHOR]

Simple Summary: Oxaliplatin-based chemotherapy remains the mainstay of first-line therapy in patients with metastatic colorectal cancer (mCRC). Unfortunately, only approximately 60% of treated patients achieve response, and half of responders will experience an early onset of disease progression. Furthermore, some individuals will develop a mixed response due to the emergence of resistant tumor subclones. The ability to predicting which patients will acquire resistance could help them avoid the unnecessary toxicity of oxaliplatin therapies. Furthermore, sorting out lesions that do not respond, in the context of an overall good response, could trigger further investigation into their mutational landscape, providing mechanistic insight towards the planning of a more comprehensive treatment. In this study, we validated a delta-radiomics signature capable of predicting response to oxaliplatin-based first-line treatment of individual liver colorectal cancer metastases. Findings could pave the way to a more personalized treatment of patients with mCRC. The purpose of this paper is to develop and validate a delta-radiomics score to predict the response of individual colorectal cancer liver metastases (lmCRC) to first-line FOLFOX chemotherapy. Three hundred one lmCRC were manually segmented on both CT performed at baseline and after the first cycle of first-line FOLFOX, and 107 radiomics features were computed by subtracting textural features of CT at baseline from those at timepoint 1 (TP1). LmCRC were classified as nonresponders (R−) if they showed progression of disease (PD), according to RECIST1.1, before 8 months, and as responders (R+), otherwise. After feature selection, we developed a decision tree statistical model trained using all lmCRC coming from one hospital. The final output was a delta-radiomics signature subsequently validated on an external dataset. Sensitivity, specificity, positive (PPV), and negative (NPV) predictive values in correctly classifying individual lesions were assessed on both datasets. Per-lesion sensitivity, specificity, PPV, and NPV were 99%, 94%, 95%, 99%, 85%, 92%, 90%, and 87%, respectively, in the training and validation datasets. The delta-radiomics signature was able to reliably predict R− lmCRC, which were wrongly classified by lesion RECIST as R+ at TP1, (93%, averaging training and validation set, versus 67% of RECIST). The delta-radiomics signature developed in this study can reliably predict the response of individual lmCRC to oxaliplatin-based chemotherapy. Lesions forecasted as poor or nonresponders by the signature could be further investigated, potentially paving the way to lesion-specific therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: The treatment and prognosis of colorectal cancer (CRC) patients vary depending on their disease stage at diagnosis. Understanding the processes of tumorigenesis and disease development can reveal new therapeutic targets and guide patient management. On the basis of this, we investigated the molecular profiles of 237 patients with stage III CRC enrolled in the international IDEA study. We also correlated the molecular profile with Toll-like and vitamin D receptor polymorphisms, clinicopathological and epidemiological characteristics, and patient outcomes. This study suggests that the molecular characterization of tumor cells may contribute to the understanding of the biological disease course. Mutations can serve as promising prognostic biomarkers leading to better treatment options. If the results are confirmed in larger patient cohorts, then this is expected to guide clinical decision-making and personalized and improved care, and reduce treatment toxicity and patient and health system costs. Background: This study aimed to investigate the molecular profiles of 237 stage III CRC patients from the international IDEA study. It also sought to correlate these profiles with Toll-like and vitamin D receptor polymorphisms, clinicopathological and epidemiological characteristics, and patient outcomes. Methods: Whole Exome Sequencing and PCR-RFLP on surgical specimens and blood samples, respectively, were performed to identify molecular profiling and the presence of Toll-like and vitamin D polymorphisms. Bioinformatic analysis revealed mutational status. Results: Among the enrolled patients, 63.7% were male, 66.7% had left-sided tumors, and 55.7% received CAPOX as adjuvant chemotherapy. Whole exome sequencing identified 59 mutated genes in 11 different signaling pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) CRC panel. On average, patients had 8 mutated genes (range, 2–21 genes). Mutations in ARAF and MAPK10 emerged as independent prognostic factors for reduced DFS (p = 0.027 and p < 0.001, respectively), while RAC3 and RHOA genes emerged as independent prognostic factors for reduced OS (p = 0.029 and p = 0.006, respectively). Right-sided tumors were also identified as independent prognostic factors for reduced DFS (p = 0.019) and OS (p = 0.043). Additionally, patients with tumors in the transverse colon had mutations in genes related to apoptosis, PIK3-Akt, Wnt, and MAPK signaling pathways. Conclusions: Molecular characterization of tumor cells can enhance our understanding of the disease course. Mutations may serve as promising prognostic biomarkers, offering improved treatment options. Confirming these findings will require larger patient cohorts and international collaborations to establish correlations between molecular profiling, clinicopathological and epidemiological characteristics and clinical outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Patient-Reported Outcome Measures (PROMs) provide reports from patients on their own health, quality of life, or functional status associated with their disease, and the care they have received. In treating metastatic colorectal cancer (CRC), it is important to obtain information about the impact of a treatment on various aspects of patients' lives besides overall survival. We performed a review on the use of PROMs in phase III clinical trials started between 2010 and 2021, evaluating systemic therapy in patients with metastatic CRC. We demonstrate that the quality of reporting on PROMs has increased over the last decade, but is still not optimal. Moreover, PROM results are underreported in studies on metastatic CRC, impeding the optimal incorporation of trial and PROM results into daily clinical practice. Purpose: To perform a scoping review on the use of Patient-Reported Outcome Measures (PROMs) in randomized trials on systemic therapy in patients with metastatic colorectal cancer (mCRC) between 2010 and 2021. Methods: First, a search on clinicaltrials.gov was performed, looking for randomized trials in mCRC. The use of PROMs was analyzed quantitatively. Subsequently, we assessed the completeness of PROM reporting based on the CONSORT PRO extension in publications related to the selected trials acquired using Embase and PubMed. Results: A total of 46/176 trials were registered on clinicaltrials.gov used PROMs. All these trials used validated PROM instruments. The EORTC QLQ-C30 was most frequently used (37 times), followed by the EQ-5D (21 times) and the EORTC QLQ-CR29 (six times). A total of 56/176 registered trials were published. In 35% (n = 20), the results of the PROMs were available. Overall, 7/20 (35%) trials documented all items of the CONSORT PRO extension and quality of reporting according to the CONSORT PRO extension was higher than in the period 2004–2012. In 3/20 (15%) of the published trials, the results of PROMs were not discussed nor included in the positioning of the new treatment compared to the reference treatment. Conclusion: When PROMs are used, the quality of reporting on patient-reported outcomes is improving, but this must continue in order to optimize the translation of trial results to individual patient values. [ABSTRACT FROM AUTHOR]

Simple Summary: Mismatch repair (MMR) system deficiency results in increased mutation rates with consequent microsatellite instability (MSI) and susceptibility to carcinogenesis. Clinically, testing MSI status contributes not only to early Lynch syndrome detection, which is associated with an increased risk of various cancers, but also to predicting the biomarkers of response to immune checkpoint inhibitors. In addition, it works prognostically because patients with the MSI phenotype or deficient MMR system (MSI-H or dMMR) characteristics show improved overall survival compared to patients with microsatellite stability or a proficient MMR system (MSS or pMMR). Here, we compare the two methods for MSI testing and outline the pros and cons of both methodologies, as well as examine their sensitivity, complementation, and degree of concordance to clarify to clinicians the ultimate methodology for MSI testing for different cancer types. Both methods are generally known to produce false negative results under certain circumstances, even in technically ideal situations. It is recommended that both methods ought to be established for determining MSI-H and dMMR status, respectively, for all cancer types as a first-line screening test, regarding the substantial agreement of the two methods in the present study. MMR gene germline mutations are considered a major genetic disorder in patients with hereditary nonpolyposis colon cancer (HNPCC) or Lynch syndrome; A total of 15% of sporadic colon carcinomas are MSI-High. MSI has also been observed in other cancers, such as endometrial, gastric, and ovarian cancer. The aim of the current study was to correlate and outline the optimal method between the molecular testing of the instability of microsatellite DNA regions (MSI status) and the loss of protein expression by immunehistochemistry (MMR). A total of 242 paraffin-embedded tissues from gastrointestinal, gynecological, genitourinary, lung, breast, and unknown primary cancer patients were analyzed for the expression of MLH1/MSH2/MSH6/PMS2 by immunohistochemistry, as well as for the molecular analysis of MSI status using PCR-based molecular fragment analysis. A total of 29 MSI-High patients were detected molecularly, while 23 patients were detected by immunohistochemistry, with rates that are comparable according to the literature. Based on the agreement coefficient of the two methods, a substantial agreement emerged (Kappa = 0.675 with standard error = 0.081, p < 0.001). Despite the substantial agreement, both methods ought to be established to determine MSI-H/dMMR status in all cancer types as a first-line screening test. [ABSTRACT FROM AUTHOR]

Simple Summary: The rapid spread of the new Coronavirus-19 disease (COVID-19) has led to the implementation of unprecedented confinement measures, while healthcare systems were restructured in order to confront the pandemic; these radical measures have prevented people from seeking medical advice. At the same time, oncology and surgery societies altered treatment guidelines, favoring postponement of surgery. The aim of the present study is to determine the impact of the pandemic in the management of colorectal cancer patients. We confirmed that during the pandemic, patients were more likely to present with metastatic cancer, often requiring emergent or palliative interventions. In addition, neoadjuvant therapy and conventional open surgery utilization rates were increased in the pandemic era. These observed changes in clinical practice may be associated with tumor upstaging, which carries significant implications regarding the long-term oncologic survival of patients with colorectal neoplasias. (1) Background: To determine the impact of the COVID-19 pandemic in the management of colorectal cancer patients requiring surgery and to examine whether the restructuring of healthcare systems led to cancer stage upshifting or adverse treatment outcomes; (2) Methods: A systematic literature search of the MedLine, Scopus, Web of Science, and CNKI databases was performed (PROSPERO ID: CRD42021288432). Data were summarized as odds ratios (OR) or weighted mean differences (WMDs) with 95% confidence intervals (95% CIs); (3) Results: Ten studies were examined, including 26,808 patients. The number of patients presenting with metastases during the pandemic was significantly increased (OR 1.65, 95% CI 1.02–2.67, p = 0.04), with no differences regarding the extent of the primary tumor (T) and nodal (N) status. Patients were more likely to have undergone neoadjuvant therapy (OR 1.22, 95% CI 1.09–1.37, p < 0.001), while emergency presentations (OR 1.74, 95% CI 1.07–2.84, p = 0.03) and palliative surgeries (OR 1.95, 95% CI 1.13–3.36, p = 0.02) were more frequent during the pandemic. There was no significant difference recorded in terms of postoperative morbidity; (4) Conclusions: Patients during the pandemic were more likely to undergo palliative interventions or receive neoadjuvant treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: In colorectal cancer (CRC), mutations may occur in short, repeated DNA sequences, known as microsatellite instability (MSI). Tumor DNA methylation is another molecular change now recognized as an important biomarker in CRC. In a genome-wide scale, for the first time, we explored whether DNA methylation is associated with MSI status in CRC. We analyzed 250 paired samples (tumor and corresponding normal) from 125 CRC patients (m = 72, f = 53) at different stages. We found that many genes were methylated in tumor tissue compared to normal tissue. However, almost four times more genes showed such methylation changes in the tumor if the patient who also had MSI compared to patients without MSI. Our study shows an association of MSI and DNA methylation in CRC. The study also indicates an opportunity for potential use of certain immune checkpoint inhibitors (CTLA4 and HAVCR2 inhibitors) in CRC with MSI. In colorectal cancer (CRC), the role of microsatellite instability (MSI) is well known. In a genome-wide scale, for the first time, we explored whether differential methylation is associated with MSI. We analyzed 250 paired samples from 125 CRC patients (m = 72, f = 53) at different stages. Of them, 101 had left-sided CRC, 30 had MSI, 34 had somatic mutation in KRAS proto-oncogene (KRAS), and 6 had B-Raf proto-oncogene (BRAF) exon 15p.V600E mutation. MSI was more frequent in right-sided tumors (54% vs. 17%, p = 0.003). Among the microsatellite stable (MSS) CRC, a paired comparison revealed 1641 differentially methylated loci (DML) covering 686 genes at FDR 0.001 with delta beta ≥ 20%. Similar analysis in MSI revealed 6209 DML covering 2316 genes. ANOVA model including interaction (Tumor*MSI) revealed 23,322 loci, where the delta beta was different among MSI and MSS patients. Our study shows an association between MSI and tumor DNA methylation in the pathogenesis of CRC. Given the interaction seen in this study, it may be worth considering the MSI status while looking for methylation markers in CRC. The study also indicates an opportunity for potential use of certain immune checkpoint inhibitors (CTLA4 and HAVCR2 inhibitors) in CRC with MSI. [ABSTRACT FROM AUTHOR]

Simple Summary: Most patients with metastatic colorectal cancer (mCRC) are treated with chemotherapy alone; however, increasingly, addition procedures such as surgery, radiotherapy, and ablation of metastases are being used with the aim of improving survival. We aimed to review all patients with mCRC receiving chemotherapy at the University College London Hospital (UCLH) in order to determine the survival outcomes of those who received additional procedures versus those who received chemotherapy alone, but also to understand which procedures provided the most benefit and to whom. We found that additional procedures improved survival of patients with mCRC compared to chemotherapy alone, and the more procedures performed, the greater the survival benefit. Surgical removal of metastases were associated with the most improved survival; however, repeated procedures in the same organ did not improve outcomes. We hope these results may help guide cancer specialists in the decision-making process for the management of patients with mCRC. Background: Despite notable advances in the management of metastatic colorectal cancer (mCRC) over the last two decades, treatment intent in the vast majority of patients remains palliative due to technically unresectable disease, extensive disease, or co-morbidities precluding major surgery. Up to 30% of individuals with mCRC are considered potentially suitable for primary or metastasis-directed multimodal therapy, including surgical resection, ablative techniques, or stereotactic radiotherapy (RT), with the aim of improving survival outcomes. We reviewed the potential benefits of multimodal therapy on the survival of patients with mCRC treated at the UCLH. Methods: Clinical data on baseline characteristics, multimodal treatments, and survival outcomes were retrospectively collected from all patients with mCRC receiving systemic chemotherapy between January 2013 and April 2017. Primary outcome was the impact of multimodal therapy on overall survival, compared to systemic therapy alone, and the effect of different types of multimodal therapy on survival outcome, and was assessed using the Kaplan–Meier approach. All analyses were adjusted for age, gender, and side of primary tumour. Results: One-hundred and twenty-five patients with mCRC were treated during the study period (median age: 62 years (range 19–89). The liver was the most frequent metastatic site (78%; 97/125). A total of 52% (65/125) had ≥2 lines of systemic chemotherapy. Of the 125 patients having systemic chemotherapy, 74 (59%) underwent multimodal treatment to the primary tumour or metastasis. Median overall survival (OS) was 25.7 months [95% Confidence Interval (CI) 21.5–29.0], and 3-year survival, 26%. Univariate analysis demonstrated that patients who had additional procedures (surgery/ablation/RT) were significantly less likely to die (Hazard Ratio (HR) 0.18, 95% CI 0.12–0.29, p < 0.0001) compared to those receiving systemic chemotherapy alone. Increasing number of multimodal procedures was associated with an incremental increase in survival—with median OS 28.4 m, 35.7 m, and 64.8 m, respectively, for 1, 2, or ≥3 procedures (log-rank p < 0.0001). After exclusion of those who received systemic chemotherapy only (n = 51), metastatic resections were associated with improved survival (adjusted HR 0.36, 95% CI 0.20–0.63, p < 0.0001), confirmed in multivariate analysis. Multiple single-organ procedures did not improve survival. Conclusion: Multimodal therapy for metastatic bowel cancer is associated with significant survival benefit. Resection/radical RT of the primary and resection of metastatic disease should be considered to improve survival outcomes following multidisciplinary team (MDT) discussion and individual assessment of fitness. [ABSTRACT FROM AUTHOR]